#### Sample records for juhan judu aare

1. Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.

PubMed

Santos, Karine; Preussner, Marco; Heroven, Anna Christina; Weber, Gert

2015-11-01

In eukaryotes, the removal of nuclear noncoding sequences (pre-mRNA splicing) is catalyzed by the spliceosome, which consists of five ribonucleoprotein particles (U1, U2, U4, U5 and U6 snRNPs, each with a respective snRNA) and a plethora of protein factors that aid spliceosomal maturation, assembly, activation and disassembly. Recently, the U5 snRNP maturation factor Aar2p from baker's yeast has been characterized structurally and biochemically. Aar2p binds to the RNaseH (RH) and Jab1/MPN domains of the highly conserved U5-specific Prp8p, which forms a framework for the spliceosomal catalytic centre. Thereby, Aar2p sterically excludes Brr2p, a helicase essential for the catalytic activation of the spliceosome, from Prp8p binding. At the same time, Aar2p blocks U4/U6 di-snRNA binding to Prp8p. Aar2p therefore prevents premature spliceosome activation and its functions are regulated by reversible phosphorylation. To date, little is known about the hypothetical human Aar2 (hsAar2) orthologue C20ORF4. This study identifies C20ORF4 (i) as part of the HeLa proteome by Western blotting and (ii) as a true Aar2 orthologue which binds to the RH domain (hsRH) of Prp8 and corroborates an evolutionary link between yeast and human Aar2 function. An elaborate strategy was devised to crystallize hsAar2 in complex with hsRH. The analysis of initial weakly diffracting crystals obtained by in situ proteolysis and homology modelling guided the design of an hsAar2 construct in which an internal loop was replaced by three serines (hsAar2(Δloop)). A complex of hsAar2(Δloop) and hsRH crystallized in space group C2; the crystals diffracted to 2.35 Å resolution and were suitable for structure determination by molecular-replacement approaches. The study presented here suggests a connection between Aar2 and the spliceosome in human cells and paves the way for structural studies of human Aar2. PMID:26527271

2. Adult Attachment Ratings (AAR): An Item Response Theory Analysis

PubMed Central

Pilkonis, Paul A.; Kim, Yookyung; Yu, Lan; Morse, Jennifer Q.

2013-01-01

The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent attachment (excessive dependency, interpersonal ambivalence, and compulsive care-giving), 3 for avoidant attachment (rigid self-control, defensive separation, and emotional detachment), and 1 for secure attachment. The scales include items (ranging from 6–16 in their original form) scored by raters using a 3-point format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce a total score. Item response theory (IRT) analyses were conducted with data from 414 participants recruited from psychiatric outpatient, medical, and community settings to identify the most informative items from each scale. The IRT results allowed us to shorten the scales to 5-item versions that are more precise and easier to rate because of their brevity. In general, the effective range of measurement for the scales was 0 to +2 SDs for each of the attachment constructs; that is, from average to high levels of attachment problems. Evidence for convergent and discriminant validity of the scales was investigated by comparing them with the Experiences of Close Relationships–Revised (ECR–R) scale and the Kobak Attachment Q-sort. The best consensus among self-reports on the ECR–R, informant ratings on the ECR–R, and expert judgments on the Q-sort and the AAR emerged for anxious, ambivalent attachment. Given the good psychometric characteristics of the scale for secure attachment, however, this measure alone might provide a simple alternative to more elaborate procedures for some measurement purposes. Conversion tables are provided for the 7 scales to facilitate transformation from raw scores to IRT-calibrated (theta) scores. PMID:24033268

3. Adult Attachment Ratings (AAR): an item response theory analysis.

PubMed

Pilkonis, Paul A; Kim, Yookyung; Yu, Lan; Morse, Jennifer Q

2014-01-01

The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent attachment (excessive dependency, interpersonal ambivalence, and compulsive care-giving), 3 for avoidant attachment (rigid self-control, defensive separation, and emotional detachment), and 1 for secure attachment. The scales include items (ranging from 6-16 in their original form) scored by raters using a 3-point format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce a total score. Item response theory (IRT) analyses were conducted with data from 414 participants recruited from psychiatric outpatient, medical, and community settings to identify the most informative items from each scale. The IRT results allowed us to shorten the scales to 5-item versions that are more precise and easier to rate because of their brevity. In general, the effective range of measurement for the scales was 0 to +2 SDs for each of the attachment constructs; that is, from average to high levels of attachment problems. Evidence for convergent and discriminant validity of the scales was investigated by comparing them with the Experiences of Close Relationships-Revised (ECR-R) scale and the Kobak Attachment Q-sort. The best consensus among self-reports on the ECR-R, informant ratings on the ECR-R, and expert judgments on the Q-sort and the AAR emerged for anxious, ambivalent attachment. Given the good psychometric characteristics of the scale for secure attachment, however, this measure alone might provide a simple alternative to more elaborate procedures for some measurement purposes. Conversion tables are provided for the 7 scales to facilitate transformation from raw scores to IRT-calibrated (theta) scores.

4. Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii.

PubMed Central

Macinga, D R; Parojcic, M M; Rather, P N

1995-01-01

The aarP gene has been identified in a search for activators of the 2-N-acetyltransferase [encoded by aac(2')-Ia] in Providencia stuartii. Introduction of aarP into P. stuartii on a multicopy plasmid resulted in a 9.9-fold increase in the accumulation of beta-galactosidase from an aac(2')-lacZ fusion. Northern (RNA) blot analysis demonstrated that this increased aac(2')-Ia expression occurred at the level of mRNA accumulation. The deduced AarP protein was 15,898 Da in size and exhibited significant homology to a number of transcriptional activators in the AraC/XyIS family, including TetD,Rob, MarA, and SoxS. The similarity of AarP to the MarA and SoxS proteins prompted an investigation to determine whether AarP is involved in activation of genes in either the multiple antibiotic resistance (Mar) phenotype or redox stress (SoxRS) system. Introduction of aarP on a multicopy plasmid into either P. stuartii or Escherichia coli conferred a Mar phenotype with higher levels of resistance to tetracycline, chloramphenicol, and ciprofloxacin. Multiple copies of aarP in E. coli also resulted in activation of the endonuclease IV gene (nfo), a gene in the SoxRS regulon of E. coli. The function of aarP in its single-copy state was addressed by using allelic replacement to construct an aarP::Cm disruption, which resulted in a fivefold reduction in the accumulation of aac(2')-Ia mRNA. Analysis of aarP regulation showed that aarP mRNA accumulation was slightly increased by exposure to tetracycline and dramatically increased in cells containing the aarB3 (aar3) mutation, which was previously shown to increase transcription of the aac(2')-Ia gene. (P.N. Rather, E. Oroz, K.J. Shaw, R. Hare, and G. Miller, J. Bacteriol. 175:6492-6498). PMID:7768849

5. Characterization of aarA, a pleiotrophic negative regulator of the 2'-N-acetyltransferase in Providencia stuartii.

PubMed Central

Rather, P N; Orosz, E

1994-01-01

We have utilized transposon mutagenesis to obtain insertional mutations in Providencia stuartii that activate the chromosomal aac(2')-la gene. Two closely linked mini-Tn5Cm insertions were obtained in a locus designated aarA, and a single insertion was obtained in a separate locus, aarC. Nucleotide sequence analysis, complementation studies, and localization of the sites of mini-Tn5Cm insertion have allowed the identification of the aarA coding region. The deduced AarA protein had a molecular mass of 31,086 kDa and displayed characteristics of an integral membrane protein. A strain deleted for the aarA gene by allelic exchange showed at least a fourfold increase in the accumulation of aac(2')-la mRNA and an eightfold increase in aminoglycoside resistance. Mutations in aarA were pleiotrophic and also resulted in loss of pigmentation and a deficiency in cell separation during division. Images PMID:8051030

6. Alkali - Aggregate reaction (AAR) A brief history of discovery of tis basic chemistry

SciTech Connect

Leps, T.M.

1995-12-31

Alkali Aggregate Reaction (AAR), also variously known as Alkali Silica Reaction (ASR) and even Alkali Carbonate Reaction (ACR), has troubled and challenged those of us since the 1930s who would have liked to think of portland cement concrete and aggregates as a simple, reliable, inert, enduring construction material. Its complex and not easily understood chemistry successfully defied the understanding of the engineering fraternity for many decades. After all, civil engineers, architects, and construction engineers are not chemists or petrographers, and are only minimally laboratory-oriented or trained. Furthermore, the almost infinite variety of minerals which Nature has provided in the form of rocks and aggregates indeed constituted a nearly insurmountable challenge to the ready development of a credible understanding of the chemistry of expanding concrete. Accordingly, although a few talented pioneers such as E.A. Stephenson in 1916, J.C. Pearson & G.F. Loughlin in 1923, Professor R.J. Holden in 1935, and F. M. Lea & C.H. Desch in 1935, nibbled at the edges of understanding how gels were formed in the alkali-aggregate interaction process, it was not until 1940 when an engineer, Thomas E. Stanton, dared to publish a preliminary but understandable view of what causes portland cement concrete to expand. The writers interest in AAR began as far back as 1946 when the importance of the problem was repeatedly brought to his attention by Ralph W. Spencer, then Chief Civil Engineer of Southern California Edison Company, who was the writers supervisor in planning, designing and contracting the construction of many major projects, including dams. Previously as well as subsequently, the writers interest was enhanced by friendships and association with pioneers of AAR such as Professor Roy Carlson, Professor R.E. Davis, Lewis H. Tuthill, R.F. Blanks, and Roger Rhoades. The writer regrets never having met Thomas E. Stanton and his chief chemist, G.H.P.

7. Responses to the AAR-Teagle White Paper: "The Religious Studies Major in a Post-9/11 World"

ERIC Educational Resources Information Center

Webster, Jane S.; Buckley, James J.; Jensen, Tim; Floyd-Thomas, Stacey

2011-01-01

In October 2008 The American Academy of Religion published the findings of an eighteen month study (conducted with funding from the Teagle Foundation) on "The Religious Studies Major in a Post-9/11 World: New Challenges, New Opportunities." Re-published here, this AAR-Teagle White Paper provides the opportunity for four respondents to raise issues…

8. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR)

PubMed Central

Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J.; Laclette, Juan P.; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

2015-01-01

Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

9. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

NASA Technical Reports Server (NTRS)

2002-01-01

A NASA F/A-18 is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

10. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

PubMed

Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

2015-05-19

Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.

11. The Front of the Aar Massif: A Crustal-Scale Ramp Anticline?

NASA Astrophysics Data System (ADS)

Herwegh, Marco; Mock, Samuel; Wehrens, Philip; Baumberger, Roland; Berger, Alfons; Wangenheim, Cornelia; Glotzbach, Christoph; Kissling, Edi

2015-04-01

The front of the Aar Massif (Swiss Central Alps) is characterized by Paleozoic basement rocks exposed at altitudes of more than 4600m above sea level, followed by a steeply north dipping Mesozoic sedimentary cover and overlying Helvetic nappes. The sediments turn into subhorizontal orientations just few kilometers to the N, where the top of the basement is situated at depths of about 7000m below sea level. What is the origin of this vertical jump of about 12000m of the basement rocks over such short horizontal distances? Recent structural investigations at the Basement-Cover contact indicate a complex structural evolution involving reactivation of extensional faults and inversion of half-grabens during early compressional stages. In the internal parts of the Aar Massif a general steepening of the faults resulted with progressive compression. In the northern frontal part, however, a new spaced cleavage evolved, which is dipping with 20-30° to the SE. In places, the new cleavage in the basement rocks is intense and pervasive and correlates with a steepening of the basement-cover contact and its offsets of several tens to hundreds of meters. Hence strain is strongly partitioned in a large number of high strain zones, which cover a cumulative thickness of at least 2000m, eventually even much more considering subsurface continuation. The Mesozoic sediments affected by this large-scale deformation zone are either intensely ductile folded in the case of limestones or faulted and imbricated in the case of dolomites. These differences in deformation style result from the deformation conditions of about < 250-300°C, where calcite still deforms in a ductile manner, while dolomite and crystalline basement preferentially undergo brittle deformation in combination of dissolution-precipitation processes. In a large-scale point of view, we suggest that the high strain domain in the crystalline basement in fact represents a crustal-scale several kilometers wide shear zone, which

12. Halogen and trace element geochemistry in Mid-Ocean Ridge basalts from the Australian-Antarctic Ridge (AAR)

NASA Astrophysics Data System (ADS)

Yang, Y. S.; Seo, J. H.; Park, S. H.; Kim, T.

2015-12-01

Australian-Antarctic Ridge (AAR) is an extension of easternmost SE Indian Mid-Ocean Ridge (MOR).We collected volcanic glasses from the "in-axis" of the KR1 and KR2 MOR, and the overlapping zones of the KR1 MOR and the nearby seamounts ("KR1 mixing"). We determined trace and halogen elements in the glasses. Halogen concentrations and its ratios in the glasses are important to understand the mantle metasomatism and volatile recycling. 52 of the collected glasses are "primitive" (higher than 6 wt% MgO), while 3 of them have rather "evolved" composition (MgO wt% of 1.72, 2.95 and 4.15). K2O concentrations and Th/Sc ratios in the glasses show a negative correlation with its MgO concentration. Incompatible element ratios such as La/Sm are rather immobile during a magma differentiation so the ratios are important to understand mantle composition (Hofmann et al. 2003). La/Sm ratios in the glasses are 0.95 ~ 3.28 suggesting that the AAR basalts can be classified into T-MORB and E-MORB (Schilling et al., 1983). La/Sm ratios are well-correlated with incompatible elements such as U, Ba, Nb, and negatively correlated with compatible elements such as Sc, Eu2+, Mg. The AAR glasses contain detectable halogen elements. The "KR1 mixing" glasses in halogen elements are more abundant than "in-axis" the glasses. Cl is the least variable element compared to the other halogens such as Br and I in the AAR. The "KR1 mixing" glasses have the largest variations of Br/Cl ratios compared to the "in-axis" glasses. The Cl/Br and Th/Sc ratios in the "in-axis" glasses and in the "KR1 mixing" glasses show positive and negative correlations, respectively. The Br-rich glasses in the "KR1 mixing" zone might be explained by a recycled Br-rich oceanic slab of paleo-subduction or by a hydrothermal alteration in the AAR. I composition in the glasses does not show a correlation other trace elements. The K/Cl and K/Ti ratios in the AAR glasses are similar to the basalts from the Galapagos Spreading Center

13. A Recurrent Loss-of-Function Alanyl-tRNA Synthetase (AARS) Mutation in Patients with Charcot-Marie-Tooth Disease Type 2N (CMT2N)

PubMed Central

McLaughlin, Heather M.; Sakaguchi, Reiko; Giblin, William; Wilson, Thomas E.; Biesecker, Leslie; Lupski, James R.; Talbot, Kevin; Vance, Jeffery M.; Züchner, Stephan; Lee, Yi-Chung; Kennerson, Marina; Hou, Ya-Ming; Nicholson, Garth; Antonellis, Anthony

2011-01-01

Charcot-Marie-Tooth (CMT) disease comprises a heterogeneous group of peripheral neuropathies characterized by muscle weakness and wasting, and impaired sensation in the extremities. Four genes encoding an aminoacyl-tRNA synthetase (ARS) have been implicated in CMT disease. ARSs are ubiquitously expressed, essential enzymes that ligate amino acids to cognate tRNA molecules. Recently, a p.Arg329His variant in the alanyl-tRNA synthetase (AARS) gene was found to segregate with dominant axonal CMT type 2N (CMT2N) in two French families; however, the functional consequence of this mutation has not been determined. To investigate the role of AARS in CMT, we performed a mutation screen of the AARS gene in patients with peripheral neuropathy. Our results showed that p.Arg329His AARS also segregated with CMT disease in a large Australian family. Aminoacylation and yeast viability assays showed that p.Arg329His AARS severely reduces enzyme activity. Genotyping analysis indicated that this mutation arose on three distinct haplotypes, and the results of bisulfite sequencing suggested that methylation-mediated deamination of a CpG dinucleotide gives rise to the recurrent p.Arg329His AARS mutation. Together, our data suggest that impaired tRNA charging plays a role in the molecular pathology of CMT2N, and that patients with CMT should be directly tested for the p.Arg329His AARS mutation. PMID:22009580

14. Lake Biel Holocene sediment record before and after the Aare river deviation (1878 AD)

NASA Astrophysics Data System (ADS)

Jeannet, Alice; Corella, Juan Pablo; Kremer, Katrina; Girardclos, Stéphanie

2014-05-01

Lake sediments are excellent archives of environmental and climate changes as well as human impact on lake- and river-systems. Lake Biel is a medium-sized peri-alpine lake in Switzerland, with a maximum depth of 74 m, and lies at an altitude of 429 m a.s.l. Lake Biel, which formed during the Pleistocene by glacial erosion, is part of the Aare river system. Our study focuses on the south-west part of the lake basin where the lake sedimentation was originally (i.e. naturally) mainly controlled by autochthonous sedimentation. This area is currently under a strong influence of water and sediment input from this river catchment since the Aare river deviation through the Hagneck canal in 1878. A 10.05 m long composite sediment sequence, cored from a 52 m water depth in September 2011, was built from two long cores retrieved with the ETH Zurich/Eawag Uwitec system. A radiocarbon age model indicates that the retrieved sedimentary sequence spans the last 7500 years. The upper sediments were correlated to previous short core radionuclide stratigraphy for the 1.5 m upper part (Thevenon et al., 2013). Magnetic susceptibility and density were measured by Geotek MultiSensor Core Logger at 0.5 cm resolution. Granulometry was measured with a CILAS grain sizer every 10 cm, and X-ray fluorescence (XRF) was carried out using an Avaatech core scanner at 1-cm resolution. This technique provides semi-quantitative information of the sediment elemental composition and shows how runoff and river input (Ti, Al, Si) or redox conditions (Fe/Mn) vary through time. Lake Biel sediment record suggests marked environmental changes with runoff decrease linked to climate and vegetation change during Atlantic chronobiozone, as well as a complex climate-human impact during the 'La Tène' and Roman cultural times. The most prominent recorded feature is the 10-times increase of sediment rate that occurred after the Aare river deviation through the Hagneck canal into Lake Biel in 1878. This artificial

15. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

NASA Technical Reports Server (NTRS)

2002-01-01

A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

16. GAMMA DETECTOR RESPONSE/SOIL CONCENTRATION CORRELATION STUDY AT THE AAR MANUFACTURING, INC. SITE, LIVONIA, MICHIGAN

SciTech Connect

ALTIC, NICK A

2013-03-22

At the NRC's request, ORAU conducted surveys of the AAR Manufacturing site during the period of September 25 through September 27, 2012. The survey activities included walkover surveys and sampling activities. Once the survey team was onsite, the NRC personnel decided to forgo survey activities in the New Addition and the pickling area. Areas of the planned study boundary were inaccessible due to overgrowth/large pieces of concrete covering the soil surface; therefore, the study boundary was redefined. Gamma walkover scans of the site boundary and front yard identified multiple areas of elevated gamma radiation. As a result, two judgmental samples were collected. Sample results were above thorium background levels The answer to the PSQ relating to the relationship between thorium concentration in soil and NaI instrument response is Yes. NaI instrument response can be used as a predictor of Th-232 concentration in the 0 to 1 m layer. An R2 value of 0.79 was determined for the surface soil relationship, thus satisfying the DQOs. Moreover, the regression was cross-checked by comparing the predicted Th-232 soil core concentration to the average Th-232 concentration (Section 5.3.2). Based on the cross-check, the regression equation provides a reasonable estimate for the Th-232 concentration at the judgmental locations. Consideration must be given when applying this equation to other soil areas of the site. If the contamination was heterogeneously distributed, and not distributed in a discrete layer as it was in the study area, then using the regression equation to predict Th-232 concentration would not be applicable.

17. Internal structure of the Aar Massif: What can we learn in terms of exploration for deep geothermal energy?

NASA Astrophysics Data System (ADS)

Herwegh, Marco; Baumberger, Roland; Wehrens, Philip; Schubert, Raphael; Berger, Alfons; Maeder, Urs; Spillmann, Thomas

2014-05-01

The successful use of deep geothermal energy requires 3D flow paths, which allow an efficient heat exchange between the surrounding host rocks and the circulating fluids. Recent attempts to exploit this energy resource clearly demonstrate that the new technology is facing sever problems. Some major problems are related to the prediction of permeability, the 3D structure of the flow paths and the mechanical responses during elevated fluid pressures at depths of several kilometers. Although seemingly new in a technical perspective, nature is facing and solving similar problems since the beginning of the Alpine orogeny. Based on detailed studies in the Hasli Valley (Aar Massif) we can demonstrate that deformation and fluid flow are strongly localized along mechanical anisotropies (e.g. lithological variations, brittle and ductile faults). Some of them already evolved during Variscan and post-Variscan times. Interestingly, these inherited structures are reactivated over and over again during the Alpine orogeny. Their reactivation occurred at depths of ~13-15 km with elevated temperatures (400-475°C) and involved both ductile and brittle deformation processes. Brittle deformation in form of hydrofracking was always present due to the circulating fluids. It is this process, which was and still is responsible for seismic activity. With progressive uplift and exhumation of the Aar Massif, ductile deformation structures became replaced by brittle cataclasites and fault gouges during fault activity at shallower crustal levels. Existing hydrotest data from the Grimsel Test Site (Nagra's underground research laboratory) indicate that these brittle successors of the ductile shear zones are domains of enhanced recent fluid percolation. Note that although being exposed today, the continuation of these fault structures are still active at depth in both brittle and ductile deformation modes, a fact that can be inferred from recent uplift rates and the active seismicity. On the

18. Adaptive on-line classification for EEG-based brain computer interfaces with AAR parameters and band power estimates.

PubMed

Vidaurre, C; Schlögl, A; Cabeza, R; Scherer, R; Pfurtscheller, G

2005-11-01

We present the result of on-line feedback Brain Computer Interface experiments using adaptive and non-adaptive feature extraction methods with an on-line adaptive classifier based on Quadratic Discriminant Analysis. Experiments were performed with 12 naïve subjects, feedback was provided from the first moment and no training sessions were needed. Experiments run in three different days with each subject. Six of them received feedback with Adaptive Autoregressive parameters and the rest with logarithmic Band Power estimates. The study was done using single trial analysis of each of the sessions and the value of the Error Rate and the Mutual Information of the classification were used to discuss the results. Finally, it was shown that even subjects starting with a low performance were able to control the system in a few hours: and contrary to previous results no differences between AAR and BP estimates were found.

19. Magnetic fabric (AMS, AAR) of the Santa Marta batholith (northern Colombia) and the shear deformation along the Caribbean Plate margin

NASA Astrophysics Data System (ADS)

Salazar, Carlos A.; Bustamante, Camilo; Archanjo, Carlos J.

2016-10-01

Anisotropy of low-field magnetic susceptibility (AMS) and anhysteretic remanence (AAR) were measured in the Santa Marta Batholith formed by subduction of the Caribbean Plate beneath the northern South America. The batholith, elongated in the N-S direction, records multiple pulses of quartzdiorite to tonalite and granodiorite magmas between 58 and 49 Ma. The high mean magnetic susceptibility (4 × 10-3 SI) combined with thermomagnetic and partial magnetic remanence measurements indicate that the magnetic susceptibility depends on Ti-poor magnetite. AMS is defined by ellipsoids that are dominantly oblate. The foliation was used to distinguish a narrow band of E-trending magnetic structures that separate the batholith in two lobes. The southern lobe is characterized by foliations that are broadly parallel to the contact with the wall rocks, while the northern lobe by foliations oblique to the batholith elongation. Late tonalitic magmas dated at c. 50 Ma record, in turn, a fabric apparently controlled by E-trending tectonic events. Partial AAR indicates that the subfabrics of magnetite with different grain sizes are nearly parallel to AMS, therefore discarding the possibility of superposed fabrics with different orientations. The magnetic fabric pattern is consistent with a magma emplaced in an arc setting deformed by a dextral shear. Synthetic extensional shear bands localize the magmatic deformation along East-trending corridors that probably were exploited to emplace the late magmatic pulses. Accretion of the Eocene batholith and the Late Cretaceous metasedimentary host-rocks to the South American continent defines a major strike-slip shear suture that resulted from the oblique convergence of the Caribbean Plate.

20. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation

PubMed Central

Euro, Liliya; Konovalova, Svetlana; Asin-Cayuela, Jorge; Tulinius, Már; Griffin, Helen; Horvath, Rita; Taylor, Robert W.; Chinnery, Patrick F.; Schara, Ulrike; Thorburn, David R.; Suomalainen, Anu; Chihade, Joseph; Tyynismaa, Henna

2015-01-01

The accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs) and the mitochondrial DNA-encoded tRNAs. The recent advances in whole-exome sequencing have revealed the importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is now recognized as a disease gene for mitochondrial disease. Typically, defects in each mtARS have been identified in one tissue-specific disease, most commonly affecting the brain, or in one syndrome. However, mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) have been reported both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. We present here an investigation of the effects of the described mutations on the structure of the synthetase, in an effort to understand the tissue-specific outcomes of the different mutations. The mtAlaRS differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged with incorrect amino acids. We show that the cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. Nevertheless, our structural analysis predicts that all mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. According to our model, the cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. These predictions provide a hypothesis for the molecular basis of the distinct tissue-specific phenotypic outcomes. PMID:25705216

1. Lake Biel sediment record during the last 7500 years and impact of the Aare river deviation in 1878 AD.

NASA Astrophysics Data System (ADS)

Jeannet, Alice; Corella, Juan Pablo; Reusch, Anna; Kremer, Katrina; Girardclos, Stéphanie

2013-04-01

Lake sediments are excellent archives of environmental and climate changes as well as human impact on lake- and river-systems. Lake Biel is a medium-sized peri-alpine lake (Switzerland) with a maximum depth of 74 m and lies at 429 m asl. Our study focuses on the south-west basin, where the lake sedimentation was naturally mainly controlled by autochthonous sedimentation, and is now, since the artificial Aare river deviation through the Hagneck canal in 1878 AD, under the strong influence of water and sediment input from its catchment. A 10.05-m-long composite sediment sequence, cored in 2011 at 52 m water depth, was built from two cores retrieved with an Uwitec system. The cored sedimentary sequence begins in 1975 and spans the last 7500 years, as dated by seven 14C analyses and 210Pb/137Cs activity profiles. Magnetic susceptibility and density were measured with a Geotek MSCL at 0.5 cm resolution, granulometry with a CILAS grain sizer every 10 cm and X-ray fluorescence measurements were carried out using an Avaatech core scanner at 1-cm resolution. Lake Biel sediment record is subdivided in four main units. The lowest Unit A (651-1005 cm; 7355 to 5075 BP), with dark greyish clayey silty laminated layers and sedimentation rates between 0.10 to 0.29 cm/yr, shows stable low values for almost all proxies, excepted for allochtonous elements which increase between 7000-6000 BP. By analogy with Unit C facies (see below), Unit A is interpreted as influenced by the Aare river which probably flew into the south-west basin at that time. Unit B1 (651-343 cm, 5075 to 2036 BP) has lower sedimentation rate (0.10 cm/yr), high Ca/Ti ratio, light sediment color, constant clayey silty grain size and varying elemental profiles which point to the dominant influence of autochtonous lake processes influenced by climate. From the beginning of Unit B2 (343-147 cm, 2036 to 1878 AD) sediment grain size increases which possibly reflects a human influence over the lake system. The greatest

2. Estimating the gas transfer velocity: a prerequisite for more accurate and higher resolution GHG fluxes (lower Aare River, Switzerland)

NASA Astrophysics Data System (ADS)

Sollberger, S.; Perez, K.; Schubert, C. J.; Eugster, W.; Wehrli, B.; Del Sontro, T.

2013-12-01

Currently, carbon dioxide (CO2) and methane (CH4) emissions from lakes, reservoirs and rivers are readily investigated due to the global warming potential of those gases and the role these inland waters play in the carbon cycle. However, there is a lack of high spatiotemporally-resolved emission estimates, and how to accurately assess the gas transfer velocity (K) remains controversial. In anthropogenically-impacted systems where run-of-river reservoirs disrupt the flow of sediments by increasing the erosion and load accumulation patterns, the resulting production of carbonic greenhouse gases (GH-C) is likely to be enhanced. The GH-C flux is thus counteracting the terrestrial carbon sink in these environments that act as net carbon emitters. The aim of this project was to determine the GH-C emissions from a medium-sized river heavily impacted by several impoundments and channelization through a densely-populated region of Switzerland. Estimating gas emission from rivers is not trivial and recently several models have been put forth to do so; therefore a second goal of this project was to compare the river emission models available with direct measurements. Finally, we further validated the modeled fluxes by using a combined approach with water sampling, chamber measurements, and highly temporal GH-C monitoring using an equilibrator. We conducted monthly surveys along the 120 km of the lower Aare River where we sampled for dissolved CH4 (';manual' sampling) at a 5-km sampling resolution, and measured gas emissions directly with chambers over a 35 km section. We calculated fluxes (F) via the boundary layer equation (F=K×(Cw-Ceq)) that uses the water-air GH-C concentration (C) gradient (Cw-Ceq) and K, which is the most sensitive parameter. K was estimated using 11 different models found in the literature with varying dependencies on: river hydrology (n=7), wind (2), heat exchange (1), and river width (1). We found that chamber fluxes were always higher than boundary

3. A one- and two-dimensional cross-section sensitivity and uncertainty path of the AARE (Advanced Analysis for Reactor Engineering) modular code system

SciTech Connect

Davidson, J.W.; Dudziak, D.J.; Higgs, C.E.; Stepanek, J.

1988-01-01

AARE, a code package to perform Advanced Analysis for Reactor Engineering, is a linked modular system for fission reactor core and shielding, as well as fusion blanket, analysis. Its cross-section sensitivity and uncertainty path presently includes the cross-section processing and reformatting code TRAMIX, cross-section homogenization and library reformatting code MIXIT, the 1-dimensional transport code ONEDANT, the 2-dimensional transport code TRISM, and the 1- and 2- dimensional cross-section sensitivity and uncertainty code SENSIBL. IN the present work, a short description of the whole AARE system is given, followed by a detailed description of the cross-section sensitivity and uncertainty path. 23 refs., 2 figs.

4. An attempt to validate the ultra-accelerated microbar and the concrete performance test with the degree of AAR-induced damage observed in concrete structures

SciTech Connect

Leemann, Andreas; Merz, Christine

2013-07-15

There is little knowledge about the relation between AAR-induced damage observed in structures and the expansion potential obtained with accelerated tests. In this study, aggregates used in structures damaged by AAR were tested with the microbar test (MBT/AFNOR XP 18-594) and the concrete performance test (CPT/AFNOR P18-454). After the tests, the samples were examined using optical and scanning electron microscopy. Based on the results, the significance of the microbar test has to be examined very critically. The agreement of measured expansion, reacted rock types and the composition of the reaction products between the on-site concrete and the reproduced concrete subjected to the CPT clearly indicates that the reaction mechanisms in the structure and in the concrete performance test are comparable. As such, the concrete performance test seems to be an appropriate tool to test the potential reactivity of specific concrete mixtures.

5. This NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No

NASA Technical Reports Server (NTRS)

2002-01-01

A NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No. 847) is acting as an in-flight refueling tanker in the study to develop analytical models for an automated aerial refueling system for unmanned vehicles. A 300-gallon aerodynamic pod containing air-refueling equipment is seen beneath the fuselage. The hose and refueling basket are extended during an assessment of their dynamics on the F/A-18A.

6. Tectonic control on the late stage exhumation of the Aar Massif (Switzerland): Constraints from apatite fission track and (U-Th)/He data

NASA Astrophysics Data System (ADS)

Reinecker, John; DanišíK, Martin; Schmid, Claudia; Glotzbach, Christoph; Rahn, Meinert; Frisch, Wolfgang; Spiegel, Cornelia

2008-12-01

We examine the hypothesis that Pliocene exhumation of the external massifs in the central Alps is controlled by climatic change. New thermochronological data from the western Gastern-Aar massif are used to investigate the timing, extent, and reasons for Neogene exhumation. Our data reveal that exhumation was constant with 0.5 km/Ma over the last 10 Ma in the north. In the southern part, exhumation was of the same order until ˜3.5 Ma but then increased gradually toward the south to values of up to 1.2 km/Ma, resulting in overall northward tilting of the western Aar massif. We explain this accelerated exhumation in the south after ˜3.5 Ma mainly by tectonic denudation in the footwall of the Rhône-Simplon fault and discuss changes in deep crustal configuration, which may have triggered south directed normal faulting. We propose that the Rhône river was structurally trapped by the Rhône-Simplon normal fault zone, which additionally enhanced erosion in the southern section of the Aar massif. Climatic forcing may have an impact in the very late stage of exhumation due to Alpine glaciation in the late Pliocene.

7. GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas

PubMed Central

Moro-Rodríguez, Ernesto; Figols, Javier; Alvira, Mariano; Uranga-Ocio, José A; García-Poblete, Eduardo

2008-01-01

Objective This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. Study design Surgical specimens from 24 patients with oligodendrogliomas during the period 1981–2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor), diameters (max, mean and min.), radius (max. and min.) margination, ratio of perimeter-area, roundness and sizes (length and width). In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. Results Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 μm2 vs. GIII 43.45 μm2 p-value = 0.02), aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03), axis minor (GII 6.66 μm vs. GIII 6.01 μm p-value = 0.003), diameter minor (GII 5.93 μm vs. GIII 5.27 μm p-value = 0.002), radius minor (GII 2.64 μm vs. GIII 2.25 μm p-value = 0,003), perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04), size width (GII 6.60 μm vs. GIII 5.96 μm p-value = 0,003), and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05) were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01) and the intensity of alpha1a-AR (p-value = 0.01) were statistically significant in predicting survival. Conclusion These results suggest that some nuclear morphometrical features and the

8. A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti.

PubMed

Mullins, Elwood A; Francois, Julie A; Kappock, T Joseph

2008-07-01

Microbes tailor macromolecules and metabolism to overcome specific environmental challenges. Acetic acid bacteria perform the aerobic oxidation of ethanol to acetic acid and are generally resistant to high levels of these two membrane-permeable poisons. The citric acid cycle (CAC) is linked to acetic acid resistance in Acetobacter aceti by several observations, among them the oxidation of acetate to CO2 by highly resistant acetic acid bacteria and the previously unexplained role of A. aceti citrate synthase (AarA) in acetic acid resistance at a low pH. Here we assign specific biochemical roles to the other components of the A. aceti strain 1023 aarABC region. AarC is succinyl-coenzyme A (CoA):acetate CoA-transferase, which replaces succinyl-CoA synthetase in a variant CAC. This new bypass appears to reduce metabolic demand for free CoA, reliance upon nucleotide pools, and the likely effect of variable cytoplasmic pH upon CAC flux. The putative aarB gene is reassigned to SixA, a known activator of CAC flux. Carbon overflow pathways are triggered in many bacteria during metabolic limitation, which typically leads to the production and diffusive loss of acetate. Since acetate overflow is not feasible for A. aceti, a CO(2) loss strategy that allows acetic acid removal without substrate-level (de)phosphorylation may instead be employed. All three aar genes, therefore, support flux through a complete but unorthodox CAC that is needed to lower cytoplasmic acetate levels.

9. MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting

PubMed Central

Tian, Ting; Zhou, Yu; Feng, Xiao; Ye, Shicai; Wang, Hao; Wu, Weiyun; Tan, Wenkai; Yu, Caiyuan; Hu, Juxiang; Zheng, Rong; Chen, Zonghao; Pei, Xinyu; Luo, Hesheng

2016-01-01

MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene expression by targeting the 3′-untranslated region of their target genes. Altered expression of miR-16 is reported in human ulcerative colitis (UC), but its role in the development of the disease remains unclear. Adenosine through adenosine A2a receptor (A2aAR) could inhibit nuclear factor-kappaB (NF-κB) signaling pathway in inflammation. Here we identified overexpression of miR-16 and down-regulation of A2aAR in the colonic mucosa of active UC patients. We demonstrated that miR-16 negatively regulated the expression of the A2aAR at the post-transcriptional level. Furthermore, transfection of miR-16 mimics promoted nuclear translocation of NF-κB p65 protein and expression of pro-inflammatory cytokines, IFN-γ and IL-8 in colonic epithelial cells. Treatment with miR-16 inhibitor could reverse these effects in cells. The A2aAR-mediated effects of miR-16 on the activation of the NF-κB signaling pathway were confirmed by the A2aAR knockdown assay. Our results suggest that miR-16 regulated the immune and inflammatory responses, at least in part, by suppressing the expression of the A2aAR to control the activation of the NF-κB signaling pathway. PMID:27476546

10. Quantitative assessment of alkali-reactive aggregate mineral content through XRD using polished sections as a supplementary tool to RILEM AAR-1 (petrographic method)

SciTech Connect

Castro, Nelia; Sorensen, Bjorn E.; Broekmans, Maarten A.T.M.

2012-11-15

The mineral content of 5 aggregate samples from 4 different countries, including reactive and non-reactive aggregate types, was assessed quantitatively by X-ray diffraction (XRD) using polished sections. Additionally, electron probe microanalyzer (EPMA) mapping and cathodoluminescence (CL) were used to characterize the opal-CT identified in one of the aggregate samples. Critical review of results from polished sections against traditionally powdered specimen has demonstrated that for fine-grained rocks without preferred orientation the assessment of mineral content by XRD using polished sections may represent an advantage over traditional powder specimens. Comparison of data on mineral content and silica speciation with expansion data from PARTNER project confirmed that the presence of opal-CT plays an important role in the reactivity of one of the studied aggregates. Used as a complementary tool to RILEM AAR-1, the methodology suggested in this paper has the potential to improve the strength of the petrographic method.

11. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study.

PubMed

Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

2015-12-20

BACKGROUND Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. MATERIAL AND METHODS All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. RESULTS A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506-0.6 and 0.539-0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601-0.664 and 0.596-0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627-0.69 and 0.607-0.692, respectively. CONCLUSIONS APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis.

12. Distribution and inferred age of exfoliation joints in the Aar Granite of the central Swiss Alps and relationship to Quaternary landscape evolution

NASA Astrophysics Data System (ADS)

Ziegler, Martin; Loew, Simon; Moore, Jeffrey R.

2013-11-01

deepest exfoliation joint generation is associated with erosion of the inner glacial troughs of the upper Aar valley, which likely occurred during the mid-Pleistocene Revolution. Our study shows how exfoliation joint episodes can be dated, and, conversely, that better knowledge of the distribution of exfoliation joint sets can reveal unique information about the morphological evolution of an Alpine valley.

13. Cluster AAR Campaign Summary Plots

NASA Astrophysics Data System (ADS)

Fazakerley, A. N.; Walsh, A. P.; Garza, K. J.; Christopher, I.; Sadeghi, S.; Lindqvist, P.; Mihaljcic, B.; Forsyth, C.; Pickett, J. S.; Marklund, G. T.; Lucek, E. A.; Dandouras, I. S.

2010-12-01

Since late 2008 the Cluster spacecraft have been making the first four-point measurements of the Auroral Acceleration Region, opening up an exciting new opportunity for the auroral science, Cluster and wider magnetospheric physics communities. In order to stimulate auroral research with Cluster and aid in event selection, we have produced a set of summary plots for those Cluster perigee passes best suited for addressing open questions in auroral physics. The plots incorporate data from WBD, FGM, EFW, PEACE and CIS and are available from the Cluster PEACE website.

14. The influence of snow cover on alpine floods reconstructed from the analysis of satellite images. The case of the Hasli-Aare river basin, Berner Oberland (1987-2012)

NASA Astrophysics Data System (ADS)

Cabrera-Medina, Paula; Schulte, Lothar; Carvalho, Filipe; Peña, Juan Carlos; García, Carles

2016-04-01

Regarding the hydrological hazards in the Hasli-Aare river over the last century, instrumental and documentary data show that flood frequency and magnitude increased since 1977. One of the main water inputs contributing to peak discharges is given by the thaw of the stored snow. Therefore, the knowledge of the evolution of snow cover is considered essential for the assessment of alpine floods. Snow cover studies can be made by different approaches such as the analysis of data provided by field work or by nivometeorological stations. However, these methods are usually expensive and do not present adequate spatial or temporal coverage data. For this reason, satellite images with different spatial and temporal resolution are an interesting complementary source for the understanding of the snow cover dynamics. The aim of the paper is to study the influence of snow cover variations during years of severe floods that occurred in the upper Aare basin from 1987 to 2012. Three satellite images have been selected for each of the 9 studied events: 1) maximum snow cover during winter, 2) the last image before the event and 3) the first image after the flood. Each image has been processed with the ArcGIS software applying a statistical method of supervised classification. This image processing allows the spatial quantification of the variation of the snow cover in the Aare headwater catchment. Because the melting of snow cover is related to the changes of weather situations before and during the flood episode, it is important to analyse also the nivometeorological data of stations located in the catchment (snow depth, temperature and precipitation). From these data we determined 4 types of flood, which can be classified according to their nivometeorological variables and synoptic situation (500 hPa geopotential and Sea Level Pressure) into two patterns. The first group of events can be associated to an Atlantic pattern recording decreasing temperatures, moderate to high

15. Calibration of amino acid racemization (AAR) kinetics in United States mid-Atlantic Coastal Plain Quaternary mollusks using 87Sr/ 86Sr analyses: Evaluation of kinetic models and estimation of regional Late Pleistocene temperature history

USGS Publications Warehouse

Wehmiller, J. F.; Harris, W.B.; Boutin, B.S.; Farrell, K.M.

2012-01-01

The use of amino acid racemization (AAR) for estimating ages of Quaternary fossils usually requires a combination of kinetic and effective temperature modeling or independent age calibration of analyzed samples. Because of limited availability of calibration samples, age estimates are often based on model extrapolations from single calibration points over wide ranges of D/L values. Here we present paired AAR and 87Sr/ 86Sr results for Pleistocene mollusks from the North Carolina Coastal Plain, USA. 87Sr/ 86Sr age estimates, derived from the lookup table of McArthur et al. [McArthur, J.M., Howarth, R.J., Bailey, T.R., 2001. Strontium isotopic stratigraphy: LOWESS version 3: best fit to the marine Sr-isotopic curve for 0-509 Ma and accompanying Look-up table for deriving numerical age. Journal of Geology 109, 155-169], provide independent age calibration over the full range of amino acid D/L values, thereby allowing comparisons of alternative kinetic models for seven amino acids. The often-used parabolic kinetic model is found to be insufficient to explain the pattern of racemization, although the kinetic pathways for valine racemization and isoleucine epimerization can be closely approximated with this function. Logarithmic and power law regressions more accurately represent the racemization pathways for all amino acids. The reliability of a non-linear model for leucine racemization, developed and refined over the past 20 years, is confirmed by the 87Sr/ 86Sr age results. This age model indicates that the subsurface record (up to 80m thick) of the North Carolina Coastal Plain spans the entire Quaternary, back to ???2.5Ma. The calibrated kinetics derived from this age model yield an estimate of the effective temperature for the study region of 11??2??C., from which we estimate full glacial (Last Glacial Maximum - LGM) temperatures for the region on the order of 7-10??C cooler than present. These temperatures compare favorably with independent paleoclimate information

16. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part I

NASA Astrophysics Data System (ADS)

Wetter, Oliver; Tuttenuj, Daniel

2016-04-01

systematically analysed the period from 1446-1542 and could prove a large number of pre-instrumental flood events of river Rhine, Birs, Birsig and Wiese in Basel. All in all the weekly led account books contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results for river Emme and Saane (see Abstract Daniel Tuttenuj), whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs-, Birsig-, Rhine- and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see also Abstract of Daniel Tuttenuj).

17. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part II.

NASA Astrophysics Data System (ADS)

Tuttenuj, Daniel; Wetter, Oliver

2016-04-01

contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results of river Emme and Saane, whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs, Birsig, Rhine and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see Abstract Oliver Wetter).

18. AAR in concrete of Asejire spillway (OYO state - Nigeria)

SciTech Connect

Lamaudiere, J.P.; Spaeti, F.

1995-12-31

The Asejire dam at Ibadan, Nigeria was constructed in the late sixties for the purpose of providing water for the city of Ibadan (presently about 4,5 million inhabitants). It is located on the Oshun river approximately fifteen miles from the city. In 1982 cracks were observed on the wing walls and although these continued to develop, no attempt was made at that time to investigate their causes and no repair was carried out. In 1989 the SGI ENGINEERING Group of Geneva, Switzerland was appointed as the consultant for the complete refurbishment of the Asejire water scheme. The consortium Degremont-Poat-Clemessy was awarded the contract for the project. The African Development Bank and the Nigerian Government have provided the loan to finance the project.

19. F/A-18 Automated Aerial Refueling (AAR) Phase 1

NASA Video Gallery

Engineers at NASA's Dryden Flight Research Center are evaluating the capability of an F/A-18A aircraft as an in-flight refueling tanker to develop analytical models for an automated aerial refuelin...

20. The contribution of quartz and the role of aluminum for understanding the AAR with greywacke

SciTech Connect

Huenger, Klaus-Juergen E-mail: huenger@tu-cottbus.de

2007-08-15

Precambrian Greywacke from Lower Lusatia (Germany) has been well known as an alkali sensitive aggregate for several years. It can cause considerable damages in concrete buildings due to an Alkali-Aggregate-Reaction. The investigations are focused on quartz as the main releaser of silica, its characterization and its behavior in an alkaline solution. But there are no relations between quartz properties and the alkali sensitivities of greywacke samples. To understand this fact the role of aluminum which greywacke releases in different amounts into the alkaline solution too must be considered. Aluminum affects the silica concentration by three different mechanisms. The result is always a decrease of the silica concentration in the solution caused by an alumino silicate formation. The silica bound by alumino silicate structures can be quantified by {sup 27}Al-NMR-spectroscopy. The expansions of concrete samples can now be described much well as a function of a so called 'free' silica. Based on this results a direct test method for the assessment of the alkali sensitivity of greywackes could be created and suggestions for an inhibition can be given.

1. The NASA Dryden AAR Project: A Flight Test Approach to an Aerial Refueling System

NASA Technical Reports Server (NTRS)

Hansen, Jennifer L.; Murray, James E.; Campos, Norma V.

2004-01-01

The integration of uninhabited aerial vehicles (UAVs) into controlled airspace has generated a new era of autonomous technologies and challenges. Autonomous aerial refueling would enable UAVs to travel further distances and loiter for extended periods over time-critical targets. The NASA Dryden Flight Research Center recently has completed a flight research project directed at developing a dynamic hose and drogue system model to support the development of an automated aerial refueling system. A systematic dynamic model of the hose and drogue system would include the effects of various influences on the system, such as flight condition, hose and drogue type, tanker type and weight, receiver type, and tanker and receiver maneuvering. Using two NASA F/A-18 aircraft and a conventional hose and drogue aerial refueling store from the Navy, NASA has obtained flight research data that document the response of the hose and drogue system to these effects. Preliminary results, salient trends, and important lessons are presented.

2. 76 FR 47612 - AAR Manufacturing, Inc.; Completion of Radiological Survey Activities at CSX Transportation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-05

... potential doses to the public from the residual radioactivity at the site, it was determined that..., Radiological Criteria for License Termination,'' are not being met and residual radioactivity at the site...

3. Structural determinants characteristic to AARS subclasses and tRNA-splicing endonuclease in eukaryotes.

PubMed

Mallick, Bibekanand; Ghosh, Zhumur; Chakrabarti, Jayprokas

2008-10-01

We compare and analyse the whole set of cytoplasmic, nonorganellar transfer RNA genes from 22 eukaryal genomes. Grouping this whole set into sets of isoacceptors we have elucidated structural elements that are characteristic to individual isoacceptor tRNAs within the subclasses of aminoacyl tRNA synthetases. Further, we have observed structural motifs straddling the exon-intron boundaries, which includes selective occurrence of both symmetric- 3-4-3 and asymmetric-3-4-(4, 5) bulge-helix-bulge-like structural motifs. Among all the tRNA isoacceptors, Ile, Leu, Ser, Pro, Met, Arg, and Tyr harbor BHB-like secondary structures at exon-intron boundaries. The structural signatories at the exon-intron boundaries appear to contribute to the specificity of splice site recognition. PMID:18597544

4. A Service for Emotion Management: Turkish Version of the Adolescent Anger Rating Scale (AARS)

ERIC Educational Resources Information Center

Aslan, A. Esra; Sevincler-Togan, Seyhan

2009-01-01

An individual's activities are closely related with his/her communication abilities. One's awareness of his feelings and needs and to what extend he can control such feelings are the key factors which effect communication abilities. Webster (1996) defines anger as, "a strong emotion; a feeling that is oriented toward some real or supposed…

5. AarF Domain Containing Kinase 3 (ADCK3) Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation

PubMed Central

Cullen, Jason K.; Abdul Murad, Norazian; Yeo, Abrey; McKenzie, Matthew; Ward, Micheal; Chong, Kok Leong; Schieber, Nicole L.; Parton, Robert G.; Lim, Yi Chieh; Wolvetang, Ernst; Maghzal, Ghassan J.; Stocker, Roland; Lavin, Martin F.

2016-01-01

Autosomal recessive ataxias are a clinically diverse group of syndromes that in some cases are caused by mutations in genes with roles in the DNA damage response, transcriptional regulation or mitochondrial function. One of these ataxias, known as Autosomal Recessive Cerebellar Ataxia Type-2 (ARCA-2, also known as SCAR9/COQ10D4; OMIM: #612016), arises due to mutations in the ADCK3 gene. The product of this gene (ADCK3) is an atypical kinase that is thought to play a regulatory role in coenzyme Q10 (CoQ10) biosynthesis. Although much work has been performed on the S. cerevisiae orthologue of ADCK3, the cellular and biochemical role of its mammalian counterpart, and why mutations in this gene lead to human disease is poorly understood. Here, we demonstrate that ADCK3 localises to mitochondrial cristae and is targeted to this organelle via the presence of an N-terminal localisation signal. Consistent with a role in CoQ10 biosynthesis, ADCK3 deficiency decreased cellular CoQ10 content. In addition, endogenous ADCK3 was found to associate in vitro with recombinant Coq3, Coq5, Coq7 and Coq9, components of the CoQ10 biosynthetic machinery. Furthermore, cell lines derived from ARCA-2 patients display signs of oxidative stress, defects in mitochondrial homeostasis and increases in lysosomal content. Together, these data shed light on the possible molecular role of ADCK3 and provide insight into the cellular pathways affected in ARCA-2 patients. PMID:26866375

6. Large scale 3D geometry of deformation structures in the Aar massif and overlying Helvetic nappes (Central Alps, Switzerland) - A combined remote sensing and field work approach

NASA Astrophysics Data System (ADS)

Baumberger, R.; Wehrens, Ph.; Herwegh, M.

2012-04-01

Allowing deep insight into the formation history of a rock complex, shear zones, faults and joint systems represent important sources of geological information. The granitic rocks of the Haslital valley (Switzerland) show very good outcrop conditions to study these mechanical anisotropies. Furthermore, they permit a quantitative characterisation of the above-mentioned deformation structures on the large-scale, in terms of their 3D orientation, 3D spatial distribution, kinematics and evolution in 3D. A key problem while developing valid geological 3D models is the three-dimensional spatial distribution of geological structures, particularly with increasing distance from the surface. That is especially true in regions, where only little or even no "hard" underground data (e.g. bore holes, tunnel mappings and seismics) is available. In the study area, many subsurface data are available (e.g. cross sections, tunnel and pipeline mappings, bore holes etc.). Therefore, two methods dealing with the problems mentioned are developed: (1) A data acquisition, processing and visualisation method, (2) A methodology to improve the reliability of 3D models regarding the spatial trend of geological structures with increasing depth: 1) Using aerial photographs and a high-resolution digital elevation model, a GIS-based remote-sensing structural map of large-scale structural elements (shear zones, faults) of the study area was elaborated. Based on that lineament map, (i) a shear zone map was derived and (ii) a geostatistical analysis was applied to identify sub regions applicable for serving as field areas to test the methodology presented above. During fieldwork, the shear zone map was evaluated by verifying the occurrence and spatial distribution of the structures designated by remote sensing. Additionally, the geometry of the structures (e.g. 3D orientation, width, kinematics) was characterised and parameterised accordingly. These tasks were partially done using a GPS based Slate PC and the FieldMoveTM software, in order to ease the subsequent data processing. 2) Findings from the field work were visualised in 3D using the MoveTM software suite. Applying its specific tools and incorporating own field data, the structure's near-surface 3D settings was modelled. In a second step, the combined use of surface and subsurface data helped to predict their trend with increasing distance from the surface, bypassing a height difference of partially more than 2000m. Field work shows that the remote-sensing structural map fits very well with the field observations. Nevertheless, the shear zone map underwent an iterative refinement process, based on own observations in the field as well as on already existing maps. It now clearly describes the lithological subdivision of the study area. The incorporation of the data into the 3D modelling software points towards the fact, that own large-scale data fits very well with small-scale structures provided by recent studies in the same area. Yet, their exact interplay in terms of orientation, kinematics and evolution is not clear. Additional analysis is needed in order to gain more detailed insight into the deformation history of the rocks in the study area.

7. Adipose afferent reflex: sympathetic activation and obesity hypertension.

PubMed

Xiong, X-Q; Chen, W-W; Zhu, G-Q

2014-03-01

Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension.

8. The comparative effect of subjective and objective after-action reviews on team performance on a complex task.

PubMed

Villado, Anton J; Arthur, Winfred

2013-05-01

The after-action review (AAR; also known as the after-event review or debriefing) is an approach to training based on a review of trainees' performance on recently completed tasks or performance events. Used by the military for decades, nonmilitary organizations' use of AARs has increased dramatically in recent years. Despite the prevalence of AARs, empirical research investigating their effectiveness has been limited. This study sought to investigate the comparative effectiveness of objective AARs (reviews based on an objective recording and playback of trainees' recent performance) and subjective AARs (reviews based on a subjective, memory-based recall of trainees' recent performance). One hundred eighty-eight individuals, participating in 47 4-person teams, were assigned to 1 of 3 AAR conditions and practiced and tested on a cognitively complex performance task. Although there were no significant differences between objective and subjective AAR teams across the 5 training outcomes, AAR teams had higher levels of team performance, team efficacy, openness of communication, and cohesion than did non-AAR teams but no differences in their levels of team declarative knowledge. Our results suggest that AARs are effective at enhancing training outcomes. Furthermore, AARs may not be dependent on objective reviews and therefore may be a viable training intervention when objective reviews are not feasible or possible.

9. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

PubMed Central

Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

2016-01-01

Abstract Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning. Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370. Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)—especially rash (59.74%)—were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae. Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is

10. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning.

PubMed

Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

2016-03-01

Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning.Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370.Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)-especially rash (59.74%)-were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae.Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is higher with Ultravist

11. Determination of the myocardial area at risk with pre- versus post-reperfusion imaging techniques in the pig model.

PubMed

Mewton, Nathan; Rapacchi, Stanislas; Augeul, Lionel; Ferrera, René; Loufouat, Joseph; Boussel, Loic; Micolich, Alejandra; Rioufol, Gilles; Revel, Didier; Ovize, Michel; Croisille, Pierre

2011-11-01

The purpose of this study was to compare the accuracy of post-reperfusion cardiac magnetic resonance (CMR) and pre-reperfusion multidetector computed tomography (MDCT) imaging to measure the size of the area at risk (AAR), using pathology as a reference technique in a porcine acute myocardial infarction model. Fifteen pigs underwent balloon-induced coronary artery occlusion for 40 min followed by reperfusion. The AAR was assessed with arterial enhanced MDCT performed during occlusion, while two different T2 weighted (T2W) CMR imaging sequences and the contrast-enhanced (ce-) CMR endocardial surface length (ESL) were performed after 90 min of reperfusion. Animals were euthanized and the AAR was assessed by pathology. Additional measurements of the myocardial water content in the AAR, remote and the AAR border zones were performed. AAR by pathology best correlated with measurements made by MDCT (R(2) = 0.88; p < 0.001) with little bias on Bland-Altman plots (bias 2.5%, SD 6.1% LV area). AAR measurements obtained by T2W STIR, T2W ACUTE sequences or the ESL on ce-CMR showed a fair correlation with pathology (R(2) = 0.72, R(2) = 0.65 and R(2) = 0.69, respectively; all p ≤ 0.001), but significantly overestimated the size of the AAR with important bias (17.4 ± 10.8% LV area; 11.7 ± 11.0% LV area; 13.0 ± 10.3% LV area, respectively). The myocardial water content in the AAR border zones was significantly higher than the remote (82.8 vs. 78.8%; p < 0.001). Our data suggest that post-reperfusion imaging methods overestimated the AAR likely due to the presence of edema outside of the boundaries of the AAR. Pre-reperfusion arterial enhanced MDCT showed the greatest accuracy for the assessment of the AAR. PMID:21874556

12. Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats.

PubMed

Pelassa, Ilaria; Fiumara, Ferdinando

2015-01-01

Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as "junk" sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in shaping

13. Angiographic validation of magnetic resonance assessment of myocardium at risk in non-ST-elevation myocardial infarction.

PubMed

Buckert, Dominik; Mariyadas, Manuela; Walcher, Thomas; Rasche, Volker; Wöhrle, Jochen; Rottbauer, Wolfgang; Bernhardt, Peter

2013-08-01

In the setting of acute myocardial ischemia, the hypoperfused portion of the myocardium is in danger of becoming irreversibly injured. This portion is called the area at risk (AAR). It is of clinical interest to be able to estimate the AAR for further evaluation and improvement of different revascularization strategies. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) has been shown to be a jeopardy score with a good performance for angiographic assessment of the myocardium supplied by a coronary vessel, representing the AAR. Recently, cardiac magnetic resonance imaging (CMR) has been demonstrated to also provide good results in determining the AAR, especially in the setting of acute ST-elevation infarction patients. Therefore, the aim of our trial was to compare T2-weighted CMR imaging for assessment of AAR in patients with non-ST-elevation myocardial infarction (NSTEMI) and to validate this approach against the angiographic APPROACH-score. We enrolled sixty-four patients presenting with acute NSTEMI that underwent coronary X-ray angiography within 72 h of symptom onset. Two blinded readers performed offline angiographic AAR assessment using the modified APPROACH-score, as being described elsewhere. Furthermore, with the use of a semi-automatic T2w-CMR approach, the AAR was quantified by two fully blinded readers. The resulting mean AAR determined by the modified APPROACH-score was 28.6 ± 10.0 %. The mean CMR derived AAR was 27.6 ± 12.7 %. CMR assessment tended to slightly underestimate the AAR in comparison to angiographic scoring (difference -0.09 ± 7.6 %). There is a good correlation between the AAR assessed by CMR and by angiography (r = 0.65, p < 0.001). T2-weigthed CMR is able to quantify the AAR with very good correlation to the angiographic APPROACH-score in NSTEMI patients.

14. 77 FR 37879 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

.../AAR-57(V)7 Common Missile Warning Systems, 15 AN/AVR-2B Laser Detecting Sets, 15 AN/APR-39A(V)4 Radar..., 26 T700-GE-701D Engines (24 installed and 2 spares), 15 AN/AAR-57(V)7 Common Missile Warning Systems... sale: a. The AN/AAR-57(V)7 Common Missile Warning System (CMWS) detects energy emitted by...

15. Activation of the amino acid response modulates lineage specification during differentiation of murine embryonic stem cells

PubMed Central

Shan, Jixiu; Hamazaki, Takashi; Tang, Tiffany A.; Terada, Naohiro

2013-01-01

In somatic cells, a collection of signaling pathways activated by amino acid limitation have been identified and referred to as the amino acid response (AAR). Despite the importance of possible detrimental effects of nutrient limitation during in vitro culture, the AAR has not been investigated in embryonic stem cells (ESC). AAR activation caused the expected increase in transcription factors that mediate specific AAR pathways, as well as the induction of asparagine synthetase, a terminal AAR target gene. Neither AAR activation nor stable knockdown of activating transcription factor (Atf) 4, a transcriptional mediator of the AAR, adversely affected ESC self-renewal or pluripotency. Low-level induction of the AAR over a 12-day period of embryoid body differentiation did alter lineage specification such that the primitive endodermal, visceral endodermal, and endodermal lineages were favored, whereas mesodermal and certain ectodermal lineages were suppressed. Knockdown of Atf4 further enhanced the AAR-induced increase in endodermal formation, suggesting that this phenomenon is mediated by an Atf4-independent mechanism. Collectively, the results indicate that, during differentiation of mouse embryoid bodies in culture, the availability of nutrients, such as amino acids, can influence the formation of specific cell lineages. PMID:23736538

16. Cloning, DNA sequencing and heterologous expression of the gene for thermostable N-acylamino acid racemase from Amycolatopsis sp. TS-1-60 in Escherichia coli.

PubMed

Tokuyama, S; Hatano, K

1995-03-01

The gene encoding the novel enzyme N-acylamino acid racemase (AAR) was cloned in recombinant phage lambda-4 from the DNA library of Amycolatopsis sp. TS-1-60, a rare actinomycete, using antiserum against the enzyme. The cloned gene was subcloned and transformed in Escherichia coli JM105 using pUC118 as a vector. The AAR gene consists of an open-reading frame of 1104 nucleotides, which specifies a 368-amino-acid protein with a molecular mass of 39411Da. The molecular mass deduced from the AAR gene is in good agreement with the subunit molecular mass (40kDa) of AAR from Amycolatopsis sp. TS-1-60. The guanosine plus cytosine content of the AAR gene was about 70%. Although the AAR gene uses the unusual initiation codon GTG, the gene was expressed in Escherichia coli using the lac promoter of pUC118. The amount of the enzyme produced by the transformant was 16 times that produced by Amycolatopsis sp. TS-1-60. When the unusual initiation codon GTG was changed to ATG, the enzyme productivity of the transformant increased to more than 37 times that of Amycolatopsis sp. TS-1-60. In the comparison of the DNA sequence and the deduced amino acid sequence of AAR with those of known racemases and epimerases in data bases, no significant sequence homology was found. However, AAR resembles mandelate racemase in that requires metal ions for enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

17. Utilization of Participatory Electronic Technology in Group Communication and Decision-Making Processes. AIR 1983 Annual Forum Paper.

ERIC Educational Resources Information Center

Roberts, Adrian R.; Garg, Devendra P.

The use of an electronic feedback system, the Anonymous Audience Response System (AARS), in educational decision making is described, and the results of use studies in North Carolina are discussed. The AARS insures anonymity of an individual participant's responses, and at the same time, provides immediate feedback of the group's collective…

18. 75 FR 38114 - [Docket ID FEMA-2010-0008

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... publication of the 60-day Federal Register Notice at 75 FR 13775, March 23, 2010. OMB Number: 1660-NEW. Form...) After Action Report (AAR) Improvement Plan (IP) AGENCY: Federal Emergency Management Agency, DHS. ACTION...) After Action Report (AAR) Improvement Plan (IP). SUMMARY: The Federal Emergency Management Agency...

19. 75 FR 13775 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

...; Comment Request, 1660-NEW; Homeland Security Exercise and Evaluation Program (HSEEP) After Action Report... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP). SUMMARY... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP)....

20. Defining Educational Research: A Perspective of/on Presidential Addresses and the Australian Association for Research in Education

ERIC Educational Resources Information Center

Lingard, Bob; Gale, Trevor

2010-01-01

This paper is concerned with the definition of the field of educational research and the changing and developing role of the Australian Association for Research in Education (AARE) in representing and constituting this field. The evidence for the argument is derived from AARE Presidential Addresses across its 40-year history. The paper documents…

1. 77 FR 42704 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... (LONGBOW component), 12 AN/APR-48A Radar Frequency Interferometers, 28 AN/AAR-57(V)7 Common Missile Warning...-48A Radar Frequency Interferometers, 28 AN/AAR-57(V)7 Common Missile Warning Systems, 30 AN/AVR-2B... Common Missile Warning System (CMWS) detects energy emitted by threat missile in-flight,...

2. 49 CFR 179.400-8 - Thickness of plates.

Code of Federal Regulations, 2010 CFR

2010-10-01

... tensile strength of the plate material, as prescribed in AAR Specifications for Tank Cars, appendix M... inches; S = minimum tensile strength of the plate material, as prescribed in AAR Specifications for Tank... = inside knuckle radius, in inches; S = minimum tensile strength of plate material, as prescribed in...

3. 76 FR 76217 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

...)(3), which requires that end platforms on boxcars be centered on each end of car between inner ends... inches. AAR and ASLRRA stated that more than 18,000 cars and 20 different car owners are affected. The cars were manufactured between 1977 and 2001 as provided in an attachment to the petition. AAR...

4. 76 FR 35026 - Weather Shield Manufacturing, Inc. Corporate Office, Medford, WI; Notice of Amended Negative...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... published in the Federal Register on August 2, 2009 (75 FR 45163). AAR 77. The authority for these issuances... Register on September 21, 2009 (75 FR 57519). AAR 120. In response to the Plaintiff's complaint filed with... Employment and Training Administration TA-W-72,673 Weather Shield Manufacturing, Inc. Corporate...

5. 78 FR 30896 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

... Aircraft, 11 Small Laser Transmitter Assemblies, 3 System Processors/ Repeaters, 14 AN/AAR-54 Missile... Small Laser Transmitter Assemblies, 3 System Processors/Repeaters, 14 AN/AAR-54 Missile Warning Sensors... jamming infrared-seeker equipped missiles with aimed bursts of laser energy. 2. LAIRCM system...

6. Atlantoaxial Rotatory Subluxation after Removal of a Ventriculoperitoneal Shunt in the Supine-Lateral Position.

PubMed

Hashide, Shusei; Aihara, Yasuo; Nagahara, Ayumi; Mitsuyama, Tetsuryu; Okada, Yoshikazu

2015-01-01

Atlantoaxial rotatory subluxation (AARS) is an uncommon disease with a greater prevalence in children than adults. So far there has only been one report of AARS after surgery related to ventriculoperitoneal (VP) shunting. We present a new case of AARS closed reduction treatment after VP shunt removal in an 8-year-old girl with wound pain on the back of her head and torticollis after surgery. Her head was rotated in the spine-lateral position during surgery. The diagnosis of AARS was established by 3D-computed tomography. The rotatory subluxation was cured after cervical traction therapy. The successful closed reduction was the consequence of early detection and conservative treatment, which are important constituents in the management of AARS. PMID:26202450

7. Potential role of A2A adenosine receptor in traumatic optic neuropathy.

PubMed

Ahmad, Saif; Fatteh, Nadeem; El-Sherbiny, Nehal M; Naime, Mohammad; Ibrahim, Ahmed S; El-Sherbini, Ahmed M; El-Shafey, Sally A; Khan, Sohail; Fulzele, Sadanand; Gonzales, Joyce; Liou, Gregory I

2013-11-15

In traumatic optic neuropathy (TON), apoptosis of retinal ganglion cells is closely related to the local production of reactive oxygen species and inflammatory mediators from activated microglial cells. Adenosine receptor A2A (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in TON. In the present study, we examined the role of A2AAR in retinal complications associated with TON. Initial studies in wild-type mice revealed that treatment with the A2AAR agonist resulted in marked decreases in the TON-induced microglial activation, retinal cell death and releases of reactive oxygen species and pro-inflammatory cytokines TNF-α and IL-6. To further assess the role of A2AAR in TON, we studied the effects of A2AAR ablation on the TON-induced retinal abnormalities. A2AAR-/- mice with TON showed a significantly higher mRNA level of TNF-α, Iba1-1 in retinal tissue, and ICAM-1 expression in retinal sections compared with wild-type mice with TON. To explore a potential mechanism by which A2AAR-signaling regulates inflammation in TON, we performed additional studies using hypoxia- or LPS-treated microglial cells as an in vitro model for TON. Activation of A2AAR attenuates hypoxia or LPS-induced TNF-α release and significantly repressed the inflammatory signaling, ERK in the activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in TON and suggests that the retinal protective effect of A2AAR is mediated by attenuating the inflammatory response that occurs in microglia via interaction with MAPKinase pathway.

8. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity

PubMed Central

Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

2016-01-01

Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity. PMID:27694818

9. Forebrain pathway for auditory space processing in the barn owl.

PubMed

Cohen, Y E; Miller, G L; Knudsen, E I

1998-02-01

The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway. PMID:9463450

10. ADRA2A is involved in neuro-endocrine regulation of bone resorption

PubMed Central

Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

2015-01-01

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

11. Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway

PubMed Central

Copik, Alicja. J.; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill; Raymond, John R.; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.

2015-01-01

The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK

12. 49 CFR 1135.1 - Quarterly adjustment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

13. 49 CFR 1135.1 - Quarterly adjustment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

14. 49 CFR 1135.1 - Quarterly adjustment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

15. 49 CFR 1135.1 - Quarterly adjustment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

16. Concrete modelling for expertise of structures affected by alkali aggregate reaction

SciTech Connect

Grimal, E.; Sellier, A.; Multon, S.; Le Pape, Y.; Bourdarot, E.

2010-04-15

Alkali aggregate reaction (AAR) affects numerous civil engineering structures and causes irreversible expansion and cracking. In order to control the safety level and the maintenance cost of its hydraulic dams, Electricite de France (EDF) must reach better comprehension and better prediction of the expansion phenomena. For this purpose, EDF has developed a numerical model based on the finite element method in order to assess the mechanical behaviour of damaged structures. The model takes the following phenomena into account: concrete creep, the stress induced by the formation of AAR gel and the mechanical damage. A rheological model was developed to assess the coupling between the different phenomena (creep, AAR and anisotropic damage). Experimental results were used to test the model. The results show the capability of the model to predict the experimental behaviour of beams subjected to AAR. In order to obtain such prediction, it is necessary to take all the phenomena occurring in the concrete into consideration.

17. 49 CFR 234.109 - Recordkeeping.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION GRADE CROSSING SIGNAL SYSTEM SAFETY AND STATE ACTION PLANS Response to Reports... system malfunction: (1) Location of crossing (by highway name and DOT/AAR Crossing Inventory Number);...

18. 49 CFR 234.109 - Recordkeeping.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION GRADE CROSSING SIGNAL SYSTEM SAFETY AND STATE ACTION PLANS Response to Reports... system malfunction: (1) Location of crossing (by highway name and DOT/AAR Crossing Inventory Number);...

19. 77 FR 58615 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-21

... frogs guard check and face gage dimensions. The heavy-point frog is a unique design, which has a thicker... standards for Class 4 track frogs guard check and face gage dimensions. AAR states that waiver denial...

20. 49 CFR 1135.1 - Quarterly adjustment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

1. The AST/ALT (De-Ritis) ratio

PubMed Central

Rief, Peter; Pichler, Martin; Raggam, Reinhard; Hafner, Franz; Gerger, Armin; Eller, Philipp; Brodmann, Marianne; Gary, Thomas

2016-01-01

Abstract The aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients. In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI. In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9–28.23] vs median 4.3 mg/L [2.0–11.5]) and fibrinogen (median 427.5 mg/dL [344.25–530.0] vs 388.0 mg/dL [327.0–493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7–2.3) for CLI even after adjustment for other well-established vascular risk factors. An increased AAR is significantly

2. ATF4-dependent Regulation of the JMJD3 Gene during Amino Acid Deprivation Can Be Rescued in Atf4-deficient Cells by Inhibition of Deacetylation*

PubMed Central

Shan, Jixiu; Fu, Lingchen; Balasubramanian, Mukundh N.; Anthony, Tracy; Kilberg, Michael S.

2012-01-01

Following amino acid deprivation, the amino acid response (AAR) induces transcription from specific genes through a collection of signaling mechanisms, including the GCN2-eIF2-ATF4 pathway. The present report documents that the histone demethylase JMJD3 is an activating transcription factor 4 (ATF4)-dependent target gene. The JMJD3 gene contains two AAR-induced promoter activities and chromatin immunoprecipitation (ChIP) analysis showed that the AAR leads to enhanced ATF4 recruitment to the C/EBP-ATF response element (CARE) upstream of Promoter-1. AAR-induced histone modifications across the JMJD3 gene locus occur upon ATF4 binding. Jmjd3 transcription is not induced in Atf4-knock-out cells, but the AAR-dependent activation was rescued by inhibition of histone deacetylation with trichostatin A (TSA). The TSA rescue of AAR activation in the absence of Atf4 also occurred for the Atf3 and C/EBP homology protein (Chop) genes, but not for the asparagine synthetase gene. ChIP analysis of the Jmjd3, Atf3, and Chop genes in Atf4 knock-out cells documented that activation of the AAR in the presence of TSA led to specific changes in acetylation of histone H4. The results suggest that a primary function of ATF4 is to recruit histone acetyltransferase activity to a sub-set of AAR target genes. Thus, absolute binding of ATF4 to these particular genes is not required and no ATF4 interaction with the general transcription machinery is necessary. The data are consistent with the hypothesis that ATF4 functions as a pioneer factor to alter chromatin structure and thus, enhance transcription in a gene-specific manner. PMID:22955275

3. Cloning of genes responsible for acetic acid resistance in Acetobacter aceti.

PubMed

Fukaya, M; Takemura, H; Okumura, H; Kawamura, Y; Horinouchi, S; Beppu, T

1990-04-01

Five acetic acid-sensitive mutants of Acetobacter aceti subsp. aceti no. 1023 were isolated by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Three recombinant plasmids that complemented the mutations were isolated from a gene bank of the chromosome DNA of the parental strain constructed in Escherichia coli by using cosmid vector pMVC1. One of these plasmids (pAR1611), carrying about a 30-kilobase-pair (kb) fragment that conferred acetic acid resistance to all five mutants, was further analyzed. Subcloning experiments indicated that a 8.3-kb fragment was sufficient to complement all five mutations. To identify the mutation loci and genes involved in acetic acid resistance, insertional inactivation was performed by insertion of the kanamycin resistance gene derived from E. coli plasmid pACYC177 into the cloned 8.3-kb fragment and successive integration into the chromosome of the parental strain. The results suggested that three genes, designated aarA, aarB, and aarC, were responsible for expression of acetic acid resistance. Gene products of these genes were detected by means of overproduction in E. coli by use of the lac promoter. The amino acid sequence of the aarA gene product deduced from the nucleotide sequence was significantly similar to those of the citrate synthases (CSs) of E. coli and other bacteria. The A. aceti mutants defective in the aarA gene were found to lack CS activity, which was restored by introduction of a plasmid containing the aarA gene. A mutation in the CS gene of E. coli was also complemented by the aarA gene. These results indicate that aarA is the CS gene.

4. Is amino acid racemization a useful tool for screening for ancient DNA in bone?

PubMed Central

Collins, Matthew J.; Penkman, Kirsty E. H.; Rohland, Nadin; Shapiro, Beth; Dobberstein, Reimer C.; Ritz-Timme, Stefanie; Hofreiter, Michael

2009-01-01

Many rare and valuable ancient specimens now carry the scars of ancient DNA research, as questions of population genetics and phylogeography require larger sample sets. This fuels the demand for reliable techniques to screen for DNA preservation prior to destructive sampling. Only one such technique has been widely adopted: the extent of aspartic acid racemization (AAR). The kinetics of AAR are believed to be similar to the rate of DNA depurination and therefore a good measure of the likelihood of DNA survival. Moreover, AAR analysis is only minimally destructive. We report the first comprehensive test of AAR using 91 bone and teeth samples from temperate and high-latitude sites that were analysed for DNA. While the AAR range of all specimens was low (0.02–0.17), no correlation was found between the extent of AAR and DNA amplification success. Additional heating experiments and surveys of the literature indicated that d/l Asx is low in bones until almost all the collagen is lost. This is because aspartic acid is retained in the bone within the constrained environment of the collagen triple helix, where it cannot racemize for steric reasons. Only if the helix denatures to soluble gelatin can Asx racemize readily, but this soluble gelatine is readily lost in most burial environments. We conclude that Asx d/l is not a useful screening technique for ancient DNA from bone. PMID:19493899

5. Size specific steady-state accumulation-area ratio: an improvement for equilibrium-line estimation of small palaeoglaciers

NASA Astrophysics Data System (ADS)

Kern, Zoltán; László, Péter

2010-09-01

Characteristic distribution of the steady-state accumulation-area ratio (AAR 0) of valley and corrie glaciers was investigated in a global dataset comprised of 46 glaciers. There is a positive relationship between AAR 0 and glacier area with smaller glaciers having lower values of AAR 0 compared with larger glaciers. The relationship between glacier area (S) and steady-state AAR of studied glaciers can be optimally described by a logarithmic regression equation. This relationship is thought to be a globally valid approximation if the size of the glacier is not smaller than 10 -1 km 2. In the case of palaeoglaciers an AAR 0 value of 0.44 ± 0.07 is best applied on glaciers with areas in the range 0.1-1 km 2, 0.54 ± 0.07 for glaciers covering areas between 1 and 4 km 2 and 0.64 ± 0.04 for glaciers larger than 4 km 2. This assumes insignificant debris cover for the investigated palaeoglaciers. The proposed size-specific AAR 0 values take into account the geometric/hypsometric properties of (palaeo)glaciers. The results have major importance for palaeoglaciological reconstructions in many regions of former marginal/niche glaciation characterized by small former glaciers.

6. Cluster in the Auroral Acceleration Region

NASA Technical Reports Server (NTRS)

Pickett, Jolene S.; Fazakerley, Andrew N.; Marklund, Gorun; Dandouras, Iannis; Christopher, Ivar W.; Kistler, Lynn; Lucek, Elizabeth; Masson, Arnaud; Taylor, Matthew G.; Mutel, Robert L.; Santolik, Ondrej; Bell, Timothy F.; Fung, Shing; Pottelette, Raymond; Hanasz, Jan; Schreiber, Roman; Hull, Arthur J.

2010-01-01

Due to a fortuitous evolution of the Cluster orbit, the Cluster spacecraft penetrated for the first time in its mission the heart of Earth's auroral acceleration region (AAR) in December 2009 and January 2010. During this time a special AAR campaign was carried out by the various Cluster instrument teams with special support from ESA and NASA facilities. We present some of the first multi-spacecraft observations of the waves, particles and fields made during that campaign. The Cluster spacecraft configuration during these AAR passages was such that it allowed us to explore the differences in the signatures of waves, particles, and fields on the various spacecraft in ways not possible with single spacecraft. For example, one spacecraft was more poleward than the other three (C2), one was at higher altitude (C1), and one of them (0) followed another (C4) through the AAR on approximately the same track but delayed by three minutes. Their separations were generally on the order of a few thousand km or less and occasionally two of them were lying along the same magnetic field line. We will show some of the first analyses of the data obtained during the AAR campaign, where upward and downward current regions, and the waves specifically associated with those regions, as well as the auroral cavities, were observed similarly and differently on the various spacecraft, helping us to explore the spatial, as well as the temporal, aspects of processes occurring in the AAR.

7. α(2A) adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction.

PubMed

Chen, Yunjia; Peng, Yin; Che, Pulin; Gannon, Mary; Liu, Yin; Li, Ling; Bu, Guojun; van Groen, Thomas; Jiao, Kai; Wang, Qin

2014-12-01

Accumulation of amyloid β (Aβ) peptides in the brain is the key pathogenic factor driving Alzheimer's disease (AD). Endocytic sorting of amyloid precursor protein (APP) mediated by the vacuolar protein sorting (Vps10) family of receptors plays a decisive role in controlling the outcome of APP proteolytic processing and Aβ generation. Here we report for the first time to our knowledge that this process is regulated by a G protein-coupled receptor, the α(2A) adrenergic receptor (α(2A)AR). Genetic deficiency of the α(2A)AR significantly reduces, whereas stimulation of this receptor enhances, Aβ generation and AD-related pathology. Activation of α(2A)AR signaling disrupts APP interaction with a Vps10 family receptor, sorting-related receptor with A repeat (SorLA), in cells and in the mouse brain. As a consequence, activation of α(2A)AR reduces Golgi localization of APP and concurrently promotes APP distribution in endosomes and cleavage by β secretase. The α(2A)AR is a key component of the brain noradrenergic system. Profound noradrenergic dysfunction occurs consistently in patients at the early stages of AD. α(2A)AR-promoted Aβ generation provides a novel mechanism underlying the connection between noradrenergic dysfunction and AD. Our study also suggests α(2A)AR as a previously unappreciated therapeutic target for AD. Significantly, pharmacological blockade of the α(2A)AR by a clinically used antagonist reduces AD-related pathology and ameliorates cognitive deficits in an AD transgenic model, suggesting that repurposing clinical α(2A)R antagonists would be an effective therapeutic strategy for AD.

8. alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.

PubMed

Doze, Van A; Handel, Evelyn M; Jensen, Kelly A; Darsie, Belle; Luger, Elizabeth J; Haselton, James R; Talbot, Jeffery N; Rorabaugh, Boyd R

2009-08-18

Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive-compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of alpha(1)-adrenergic receptors (alpha(1)-ARs). Yet, it is unclear whether increased alpha(1)-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant alpha(1A)-ARs (CAM alpha(1A)-AR) or CAM alpha(1B)-ARs were used to examine the effects of alpha(1A)- and alpha(1B)-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM alpha(1A)-AR mice, but not CAM alpha(1B)-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective alpha(1)-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an alpha(1A)-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM alpha(1A)-AR mice but not in CAM alpha(1B)-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM alpha(1A)-AR, and CAM alpha(1B)-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that alpha(1A)- and alpha(1B)-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that alpha(1A)-ARs may be a useful therapeutic target for the treatment of depression.

9. Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline.

PubMed

Akinaga, Juliana; Lima, Vanessa; Kiguti, Luiz Ricardo de Almeida; Hebeler-Barbosa, Flávia; Alcántara-Hernández, Rocío; García-Sáinz, J Adolfo; Pupo, André Sampaio

2013-04-01

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that α1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the α1B and α1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent α1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that this property of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed α1A-AR regulation. OXY shows functional selectivity relative to NE and PE at α1A-ARs, leading to significant receptor desensitization and internalization, which is important in view of the therapeutic vasoconstrictor effects of this drug and the varied biologic process regulated by α1A-ARs.

10. Lithological influence of aggregate in the alkali-carbonate reaction

SciTech Connect

Lopez-Buendia, A.M. . E-mail: angel.lopez@aidico.es; Climent, V. . E-mail: vcliment@grupogla.com; Verdu, P.

2006-08-15

The reactivity of carbonate rock with the alkali content of cement, commonly called alkali-carbonate reaction (ACR), has been investigated. Alkali-silica reaction (ASR) can also contribute in the alkali-aggregate reaction (AAR) in carbonate rock, mainly due to micro- and crypto-crystalline quartz or clay content in carbonate aggregate. Both ACR and ASR can occur in the same system, as has been also evidenced on this paper. Carbonate aggregate samples were selected using lithological reactivity criteria, taking into account the presence of dedolomitization, partial dolomitization, micro- and crypto-crystalline quartz. Selected rocks include calcitic dolostone with chert (CDX), calcitic dolostone with dedolomitization (CDD), limestone with chert (LX), marly calcitic dolostone with partial dolomitization (CD), high-porosity ferric dolostone with clays (FD). To evaluate the reactivity, aggregates were studied using expansion tests following RILEM AAR-2, AAR-5, a modification using LiOH AAR-5Li was also tested. A complementary study was done using petrographic monitoring with polarised light microscopy on aggregates immersed in NaOH and LiOH solutions after different ages. SEM-EDAX has been used to identify the presence of brucite as a product of dedolomitization. An ACR reaction showed shrinkage of the mortar bars in alkaline solutions explained by induced dedolomitization, while an ASR process typically displayed expansion. Neither shrinkage nor expansion was observed when mortar bars were immersed in solutions of lithium hydroxide. Carbonate aggregate classification with AAR pathology risk has been elaborated based on mechanical behaviours by expansion and shrinkage. It is proposed to be used as a petrographic method for AAR diagnosis to complement the RILEM AAR1 specifically for carbonate aggregate. Aggregate materials can be classified as I (non-reactive), II (potentially reactive), and III (probably reactive), considering induced dedolomitization ACR

11. Potential Involvement of the Stem Cell Factor Receptor c-kit in Alopecia Areata and Androgenetic Alopecia: Histopathological, Immunohistochemical, and Semiquantitative Investigations

PubMed Central

Ashrafuzzaman, Md.; Yamamoto, Tomoko; Shibata, Noriyuki; Hirayama, Takeshi Thomas; Kobayashi, Makio

2010-01-01

Alopecia areata (AAR) and androgenetic alopecia (AGA) are two major forms of alopecia based on altered hair growth condition. In general, the cell cycle is regulated by several mechanisms including the stem cell factor/c-kit signaling. To assess a role for stem cell activity in alopecia, we performed histopathological, immunohistochemical, and semiquantitative analyses of c-kit as well as Ki-67 in scalp biopsy specimens obtained from 14 patients with AAR, 18 patients with AGA, and 6 age-matched control subjects, using the specific antibodies. Formalin-fixed, paraffin-embedded skin sections were examined. Immunoreactivities for Ki-67 and c-kit were localized in keratinocytes and melanocytes in the outermost layer of hair follicles. The mean length of hair follicles was significantly shorter in the AAR and AGA groups than in the control group. The mean number of Ki-67-immunoreactive cells per follicle was significantly reduced in the AAR and AGA groups as compared with the control group. The mean number of c-kit-immunoreactive cells per follicle was significantly increased in the AAR and AGA groups as compared with the control group. Our results indicate that c-kit is upregulated in the hair follicle cells in these forms of alopecia, and suggest that the upregulation reflects a negative feedback mechanism in response to possible downregulation of the ligand stem cell factor. PMID:20300219

12. A Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase (MEK)-dependent Transcriptional Program Controls Activation of the Early Growth Response 1 (EGR1) Gene during Amino Acid Limitation*

PubMed Central

Shan, Jixiu; Balasubramanian, Mukundh N.; Donelan, William; Fu, Lingchen; Hayner, Jaclyn; Lopez, Maria-Cecilia; Baker, Henry V.; Kilberg, Michael S.

2014-01-01

Amino acid (AA) limitation in mammalian cells triggers a collection of signaling cascades jointly referred to as the AA response (AAR). In human HepG2 hepatocellular carcinoma, the early growth response 1 (EGR1) gene was induced by either AA deprivation or endoplasmic reticulum stress. AAR-dependent EGR1 activation was discovered to be independent of the well characterized GCN2-ATF4 pathway and instead dependent on MEK-ERK signaling, one of the MAPK pathways. ChIP showed that constitutively bound ELK1 at the EGR1 proximal promoter region was phosphorylated after AAR activation. Increased p-ELK1 binding was associated with increased de novo recruitment of RNA polymerase II to the EGR1 promoter. EGR1 transcription was not induced in HEK293T cells lacking endogenous MEK activity, but overexpression of exogenous constitutively active MEK in HEK293T cells resulted in increased basal and AAR-induced EGR1 expression. ChIP analysis of the human vascular endothelial growth factor A (VEGF-A) gene, a known EGR1-responsive gene, revealed moderate increases in AAR-induced EGR1 binding within the proximal promoter and highly inducible binding to a site within the first intron. Collectively, these data document a novel AA-activated MEK-ERK-ELK1 signaling mechanism. PMID:25028509

13. Alkali-aggregate reactivity of typical siliceious glass and carbonate rocks in alkali-activated fly ash based geopolymers

NASA Astrophysics Data System (ADS)

Lu, Duyou; Liu, Yongdao; Zheng, Yanzeng; Xu, Zhongzi; Shen, Xiaodong

2013-08-01

For exploring the behaviour of alkali-aggregate reactivity (AAR) in alkali-activated geopolymeric materials and assessing the procedures for testing AAR in geopolymers, the expansion behaviour of fly ash based geopolymer mortars with pure silica glass and typical carbonate rocks were studied respectively by curing at various conditions, i.e. 23°C and 38°C with relative humidity over 95%, immersed in 1M NaOH solution at 80°C. Results show that, at various curing conditions, neither harmful ASR nor harmful ACR was observed in geopolymers with the criteria specified for OPC system. However, with the change of curing conditions, the geopolymer binder and reactive aggregates may experience different reaction processes leading to quite different dimensional changes, especially with additional alkalis and elevated temperatures. It suggests that high temperature with additional alkali for accelerating AAR in traditional OPC system may not appropriate for assessing the alkali-aggregate reactivity behaviour in geopolymers designed for normal conditions. On the other hand, it is hopeful to control the dimensional change of geopolymer mortar or concrete by selecting the type of aggregates and the appropriate curing conditions, thus changing the harmful AAR in OPC into beneficial AAR in geopolymers and other alkali-activated cementitious systems.

14. The antidepressant desipramine is an arrestin-biased ligand at the α(2A)-adrenergic receptor driving receptor down-regulation in vitro and in vivo.

PubMed

Cottingham, Christopher; Chen, Yunjia; Jiao, Kai; Wang, Qin

2011-10-14

The neurobiological mechanisms of action underlying antidepressant drugs remain poorly understood. Desipramine (DMI) is an antidepressant classically characterized as an inhibitor of norepinephrine reuptake. Available evidence, however, suggests a mechanism more complex than simple reuptake inhibition. In the present study, we have characterized the direct interaction between DMI and the α(2A)-adrenergic receptor (α(2A)AR), a key regulator of noradrenergic neurotransmission with altered expression and function in depression. DMI alone was found to be sufficient to drive receptor internalization acutely and a robust down-regulation of α(2A)AR expression and signaling following prolonged stimulation in vitro. These effects are achieved through arrestin-biased regulation of the receptor, as DMI selectively induces recruitment of arrestin but not activation of heterotrimeric G proteins. Meanwhile, a physiologically relevant concentration of endogenous agonist (norepinephrine) was unable to sustain a down-regulation response. Prolonged in vivo administration of DMI resulted in significant down-regulation of synaptic α(2A)AR expression, a response that was lost in arrestin3-null animals. We contend that direct DMI-driven arrestin-mediated α(2A)AR down-regulation accounts for the therapeutically desirable but mechanistically unexplained adaptive alterations in receptor expression associated with this antidepressant. Our results provide novel insight into both the pharmacology of this antidepressant drug and the targeting of the α(2A)AR in depression.

15. Paraventricular nucleus is involved in the central pathway of adipose afferent reflex in rats.

PubMed

Shi, Zhen; Wang, Yuan-Fang; Wang, Gui-Hua; Wu, Yu-Long; Ma, Chun-Lei

2016-05-01

Increasing evidence indicates a link between sympathetic nervous system activation and obesity, but the underlying mechanisms remain elusive. The adipose afferent reflex (AAR) is a sympathoexcitatory reflex that is activated by afferent neurotransmission from the white adipose tissue (WAT). This study aimed to investigate whether the hypothalamic paraventricular nucleus (PVH) is an important component of the central neurocircuitry of the AAR. In anesthetized rats, the discharge activity of individual PVH neurons was recorded in vivo. Activation of WAT afferents was initiated by capsaicin injection, and the AAR was evaluated by monitoring renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses. The responses of PVH neurons to activation of WAT afferents were evaluated by c-fos immunoreactivity and the discharge activity of individual PVH neurons, which was recorded using extracellular single-unit recording. After activation of WAT afferents, both individual PVH neuron discharge activity and c-fos immunoreactivity increased. Bilateral selective lesions of the neurons in the PVH with kainic acid abolished the AAR. These results indicate that PVH is an important component of the central neurocircuitry of the AAR. PMID:26963333

16. Optimal hierarchies for fuzzy object models

NASA Astrophysics Data System (ADS)

Matsumoto, Monica M. S.; Udupa, Jayaram K.

2013-03-01

In radiologic clinical practice, the analysis underlying image examinations are qualitative, descriptive, and to some extent subjective. Quantitative radiology (QR) is valuable in clinical radiology. Computerized automatic anatomy recognition (AAR) is an essential step toward that goal. AAR is a body-wide organ recognition strategy. The AAR framework is based on fuzzy object models (FOMs) wherein the models for the different objects are encoded in a hierarchy. We investigated ways of optimally designing the hierarchy tree while building the models. The hierarchy among the objects is a core concept of AAR. The parent-offspring relationships have two main purposes in this context: (i) to bring into AAR more understanding and knowledge about the form, geography, and relationships among objects, and (ii) to foster guidance to object recognition and object delineation. In this approach, the relationship among objects is represented by a graph, where the vertices are the objects (organs) and the edges connect all pairs of vertices into a complete graph. Each pair of objects is assigned a weight described by the spatial distance between them, their intensity profile differences, and their correlation in size, all estimated over a population. The optimal hierarchy tree is obtained by the shortest-path algorithm as an optimal spanning tree. To evaluate the optimal hierarchies, we have performed some preliminary tests involving the subsequent recognition step. The body region used for initial investigation was the thorax.

17. Cluster multi-spacecraft observations of electron and ion holes in the Auroral Acceleration Region

NASA Astrophysics Data System (ADS)

Fazakerley, A. N.; Pickett, J. S.; Berthomier, M.; Mutel, R. L.; Masson, A.; Forsyth, C.; Owen, C. J.; Khotyaintsev, Y. V.; Andre, M.; Carr, C.

2013-12-01

In spring 2013, the Cluster spacecraft have visited the Auroral Acceleration Region (AAR) for the second and final time. The spacecraft constellation was arranged to produce very small separation magnetic field aligned conjunctions (~10s km) between C3 and C4, with C1 relatively nearby. The goal was to allow study of electron and ion holes, including their propagation between C3 and C4, and their roles in generating waves that may be observed locally and also at C1. Detailed planning work has tried to maximize the opportunities to use the Cluster payload effectively during these conjunctions, but the presence of auroral activity during the relatively few AAR passes cannot be guaranteed in advance. The dataset may also be valuable for other aspects of auroral science, as data is collected throughout the AAR crossings, not only at the conjunctions. We intend to present first results from this campaign.

18. Cluster multi-spacecraft observations of electron and ion holes in the Auroral Acceleration Region

NASA Astrophysics Data System (ADS)

Fazakerley, Andrew; Pickett, Jolene; Berthomier, Matthieu; Mutel, Robert; Masson, Arnaud; Forsyth, Colin; Owen, Christopher J.; Khotyaintsev, Yuri; Andre, Mats; Carr, Chris

2014-05-01

In spring 2013, the Cluster spacecraft visited the Auroral Acceleration Region (AAR) for the second and final time. The spacecraft constellation was arranged to produce very small separation magnetic field aligned conjunctions (~10s km) between C3 and C4, with C1 relatively nearby. The goal was to allow study of electron and ion holes, including their propagation between C3 and C4, and their roles in generating waves that may be observed locally and also at C1. Detailed planning work has tried to maximize the opportunities to use the Cluster payload effectively during these conjunctions, but the presence of auroral activity during the relatively few AAR passes could be guaranteed in advance. The dataset may also be valuable for other aspects of auroral science, as data is collected throughout the AAR crossings, not only at the conjunctions. We intend to present first results from this campaign.

19. Towards a genotype-based approach for a patient-centered pharmacologic therapy of type 2 diabetes

PubMed Central

2015-01-01

The recent data reported by Tang and colleagues in Science Translational Medicine suggest that alpha-2 adrenoceptors (α2AAR) genetic heterogeneity may explain diverging results regarding the effects of α2AAR antagonists on insulin secretion and glucose control in patients with type 2 diabetes. They first confirmed that the risk variant for rs553668 (the A allele for a single-nucleotide polymorphism in ADRA2A) is likely to cause defective insulin secretion in human pancreatic islets. Second they showed that blocking α2AAR with yohimbine dose-dependently improves the reduced insulin secretion during an oral glucose tolerance test in patients with the risk variant. The successful translation of genomic information into clinical intervention in patients with type 2 diabetes provides proof of concept for the feasibility of individualized treatment based on genotype. PMID:26046083

20. Towards a genotype-based approach for a patient-centered pharmacologic therapy of type 2 diabetes.

PubMed

Scheen, André J

2015-05-01

The recent data reported by Tang and colleagues in Science Translational Medicine suggest that alpha-2 adrenoceptors (α2AAR) genetic heterogeneity may explain diverging results regarding the effects of α2AAR antagonists on insulin secretion and glucose control in patients with type 2 diabetes. They first confirmed that the risk variant for rs553668 (the A allele for a single-nucleotide polymorphism in ADRA2A) is likely to cause defective insulin secretion in human pancreatic islets. Second they showed that blocking α2AAR with yohimbine dose-dependently improves the reduced insulin secretion during an oral glucose tolerance test in patients with the risk variant. The successful translation of genomic information into clinical intervention in patients with type 2 diabetes provides proof of concept for the feasibility of individualized treatment based on genotype.

1. Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24

SciTech Connect

Nichols, R.C.; Blinder, J.; Pai, S.I.

1996-08-15

Protein synthesis is initiated by the attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (aaRS). Five of twenty human aaRS (histidyl-RS, threonyl-RS, alanyl-RS, glycyl-RS, and isoleucyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Autoantibodies to human lysyl-RS, a sixth autoantigenic aminoacyl-RS, were recently identified. The genes for histidyl-RS and threonyl-RS have been localized to chromosome 5, and we recently reported that the genes for alanyl-RS and glycyl-RS localize to chromosomes 16 and 7, respectively. To understand the genesis of autoimmune responses to aaRS better, we have used PCR-based screening of somatic cell hybrid panels and fluorescence in situ hybridization (FISH) to assign the genes for isoleucyl-RS and lysyl-RS. 19 refs., 1 fig.

2. Excellent amino acid racemization results from Holocene sand dollars

NASA Astrophysics Data System (ADS)

Kosnik, M.; Kaufman, D. S.; Kowalewski, M.; Whitacre, K.

2015-12-01

Amino acid racemization (AAR) is widely used as a cost-effective method to date molluscs in time-averaging and taphonomic studies, but it has not been attempted for echinoderms despite their paleobiological importance. Here we demonstrate the feasibility of AAR geochronology in Holocene aged Peronella peronii (Echinodermata: Echinoidea) collected from Sydney Harbour (Australia). Using standard HPLC methods we determined the extent of AAR in 74 Peronella tests and performed replicate analyses on 18 tests. We sampled multiple areas of two individuals and identified the outer edge as a good sampling location. Multiple replicate analyses from the outer edge of 18 tests spanning the observed range of D/Ls yielded median coefficients of variation < 4% for Asp, Phe, Ala, and Glu D/L values, which overlaps with the analytical precision. Correlations between D/L values across 155 HPLC injections sampled from 74 individuals are also very high (pearson r2 > 0.95) for these four amino acids. The ages of 11 individuals spanning the observed range of D/L values were determined using 14C analyses, and Bayesian model averaging was used to determine the best AAR age model. The averaged age model was mainly composed of time-dependent reaction kinetics models (TDK, 71%) based on phenylalanine (Phe, 94%). Modelled ages ranged from 14 to 5539 yrs, and the median 95% confidence interval for the 74 analysed individuals is ±28% of the modelled age. In comparison, the median 95% confidence interval for the 11 calibrated 14C ages was ±9% of the median age estimate. Overall Peronella yields exceptionally high-quality AAR D/L values and appears to be an excellent substrate for AAR geochronology. This work opens the way for time-averaging and taphonomic studies of echinoderms similar to those in molluscs.

3. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.

PubMed

Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

2012-11-01

We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

4. Geophysical Investigation of Australian-Antarctic Ridge Using High-Resolution Gravity and Bathymetry

NASA Astrophysics Data System (ADS)

Kim, S. S.; Lin, J.; Park, S. H.; Choi, H.

2015-12-01

Much of the Australian-Antarctic Ridge (AAR) has been remained uncharted until 2011 because of its remoteness and harsh weather conditions. From 2011, the multidisciplinary ridge program initiated by the Korea Polar Research Institute (KOPRI) surveyed the little-explored eastern ends of the AAR to characterize the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. In this study, we present a detailed analysis of a 300-km-long supersegment of the AAR to quantify the spatial variations in ridge morphology and axial and off-axis volcanisms as constrained by high-resolution shipboard bathymetry and gravity. The ridge axis morphology alternates between rift valleys and axial highs within relatively short ridge segments. To obtain a geological proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for neighboring seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle in comparison to the conjugate northern flank. Furthermore, this north-south asymmetry becomes more prominent toward the KR1 supersegment of the AAR. The axial topography of the KR1 supersegment exhibits a sharp transition from axial highs at the western end to rift valleys at the eastern end, with regions of axial highs being associated with more robust magma supply as indicated by more negative RMBA. We also compare and contrast the characteristics of the AAR supersegment with that of other ridges of intermediate spreading rates, including the Juan de Fuca Ridge, Galápagos Spreading Center, and Southeast Indian Ridge west of the Australian-Antarctic Discordance, to investigate the influence of ridge-hotspot interaction on ridge magma supply and tectonics.

5. Automatic anatomy recognition in post-tonsillectomy MR images of obese children with OSAS

NASA Astrophysics Data System (ADS)

Tong, Yubing; Udupa, Jayaram K.; Odhner, Dewey; Sin, Sanghun; Arens, Raanan

2015-03-01

Automatic Anatomy Recognition (AAR) is a recently developed approach for the automatic whole body wide organ segmentation. We previously tested that methodology on image cases with some pathology where the organs were not distorted significantly. In this paper, we present an advancement of AAR to handle organs which may have been modified or resected by surgical intervention. We focus on MRI of the neck in pediatric Obstructive Sleep Apnea Syndrome (OSAS). The proposed method consists of an AAR step followed by support vector machine techniques to detect the presence/absence of organs. The AAR step employs a hierarchical organization of the organs for model building. For each organ, a fuzzy model over a population is built. The model of the body region is then described in terms of the fuzzy models and a host of other descriptors which include parent to offspring relationship estimated over the population. Organs are recognized following the organ hierarchy by using an optimal threshold based search. The SVM step subsequently checks for evidence of the presence of organs. Experimental results show that AAR techniques can be combined with machine learning strategies within the AAR recognition framework for good performance in recognizing missing organs, in our case missing tonsils in post-tonsillectomy images as well as in simulating tonsillectomy images. The previous recognition performance is maintained achieving an organ localization accuracy of within 1 voxel when the organ is actually not removed. To our knowledge, no methods have been reported to date for handling significantly deformed or missing organs, especially in neck MRI.

6. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 5: a guide on the management of rosacea.

PubMed

Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Tanghetti, Emil; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

2014-03-01

The last article in this 5-part series provides a final overview of consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. Optimal management of rosacea requires careful assessment of the patient's clinical features with integration of therapies that adequately treat the presenting signs and symptoms. The treatment consensus recommendations from the AARS are based on 2 major common clinical presentations of rosacea: (1) centrofacial erythema with papulopustular lesions, and (2) centrofacial erythema without papulopustular lesions. The recommendations provided here serve to guide clinicians in their clinical practice.

7. Data on Arc and Zif268 expression in the brain of the α-2A adrenergic receptor knockout mouse.

PubMed

Sanders, Jeff

2016-06-01

The α2-adrenergic receptor (α2-AR) is widely distributed in the brain with distinct roles for α2-AR subtypes (A, B and C). In this article, data are provided on Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 expression in the brain of the α2A-AR knockout (α2A-AR KO) mouse. These data are supplemental to an original research article examining Arc and Zif268 expression in rats injected with the α2-AR antagonist, RX821002 (http://dx.doi.org/10.1016/j.neulet.2015.12.002. [1]). PMID:26952134

8. Mode of Myosin Transportation in Living Cells Studied by Single Particle Tracking

NASA Astrophysics Data System (ADS)

Liang, Zhang-yi; Xu, Ning; Guan, Ying-hua; Zhang, You-yi; Zhao, Xin-sheng

2007-08-01

The transport of internalized α1A-adrenergic receptor (α1A-AR) by myosin protein in live cells was studied. The technique of single particle tracking by fluorescence imaging with high temporal and spatial resolution was used. The endosomes of α1A-AR were transported along actin filaments in a step-by-step mode. The average step-size in different time resolutions is consistent with the step-size of myosin assay in vitro. With the simulation of the stepwise traces in different time resolutions, we found that the kinetic process of each step is in coherence with the single myosin assay in vitro.

9. Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: role of NF-kappaB in A(2A) adenosine receptor induction.

PubMed

Murphree, Lauren J; Sullivan, Gail W; Marshall, Melissa A; Linden, Joel

2005-11-01

The A(2A) adenosine receptor (A(2A)AR) mediates anti-inflammatory actions of adenosine in a variety of cell types. LPS (lipopolysaccharide) was reported to induce a small (<2-fold) increase in the expression of A(2A)AR mRNA in human monocytes and monocytic cell lines. We investigated the effects of LPS on the expression of adenosine receptor mRNAs in primary mouse IPMPhi (intraperitoneal macrophages), human macrophages and Wehi-3 cells. Treatment with 10 ng/ml LPS for 4 h produced a >100-fold increase in A(2A)AR mRNA. LPS-induced increases in mRNA for A(2A)AR and TNFalpha (tumour necrosis factor alpha) are reduced by 90% in IPMPhi pretreated with the NF-kappaB (nuclear factor kappaB) inhibitor, BAY 11-7082 {(E)3-[(4-methylphenyl)sulphonyl]-2-propenenitrile; 10 microM}. In Wehi-3 cells exposed to LPS, A(2A)AR and A(2B)AR transcripts are elevated by 290- and 10-fold respectively, the A(1)AR transcript is unchanged and the A(3)AR transcript is decreased by 67%. The induction of A(2A)AR mRNA by LPS is detectable after 1 h, reaches a peak at 6 h at 600 times control and remains elevated beyond 24 h. The ED50 (effective dose) of LPS is 2.3 ng/ml. A(2A)AR receptor number, measured by 125I-ZM241385 binding to whole cells, is undetectable in naïve cells and increases linearly at a rate of 23 receptors x cell(-1) x min(-1) to a B(max) of 348 fmol/mg (28000 receptors/cell) in 20 h. The increase in receptor number is correlated with an increase in the potency of an A(2A) agonist (4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester; referred to as ATL146e) to stimulate cAMP in these cells. After LPS pretreatment, the potency of the A(2A) agonist, ATL146e, to reduce TNFalpha release from IPMPhi was increased by 200-fold. The results support the hypothesis that regulation of adenosine receptor expression, especially up-regulation of the A(2A)AR, is part of a delayed feedback mechanism

10. Chapter K: Progress in the Evaluation of Alkali-Aggregate Reaction in Concrete Construction in the Pacific Northwest, United States and Canada

USGS Publications Warehouse

Shrimer, Fred H.

2005-01-01

The supply of aggregates suitable for use in construction and maintenance of infrastructure in western North America is a continuing concern to the engineering and resources-management community. Steady population growth throughout the region has fueled demand for high-quality aggregates, in the face of rapid depletion of existing aggregate resources and slow and difficult permitting of new sources of traditional aggregate types. In addition to these challenges, the requirement for aggregates to meet various engineering standards continues to increase. In addition to their physical-mechanical properties, other performance characteristics of construction aggregates specifically depend on their mineralogy and texture. These properties can result in deleterious chemical reactions when aggregate is used in concrete mixes. When this chemical reaction-termed 'alkali-aggregate reaction' (AAR)-occurs, it can pose a major problem for concrete structures, reducing their service life and requiring expensive repair or even replacement of the concrete. AAR is thus to be avoided in order to promote the longevity of concrete structures and to ensure that public moneys invested in infrastructure are well spent. Because the AAR phenomenon is directly related to the mineral composition, texture, and petrogenesis of the rock particles that make up aggregates, an understanding of the relation between the geology and the performance of aggregates in concrete is important. In the Pacific Northwest, some aggregates have a moderate to high AAR potential, but many others have no or only a low AAR potential. Overall, AAR is not as widespread or serious a problem in the Pacific Northwest as in other regions of North America. The identification of reactive aggregates in the Pacific Northwest and the accurate prediction of their behavior in concrete continue to present challenges for the assessment and management of geologic resources to the owners and operators of pits and quarries and to the

11. 49 CFR 179.220-6 - Thickness of plates.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... = Inside diameter in inches; E = 0.9 welded joint efficiency; except E=1.0 for seamless heads; P = Minimum... in AAR Specifications for Tank Cars, appendix M, Table M1; t = Minimum thickness of plate in...

12. 49 CFR 179.220-6 - Thickness of plates.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... = Inside diameter in inches; E = 0.9 welded joint efficiency; except E=1.0 for seamless heads; P = Minimum... in AAR Specifications for Tank Cars, appendix M, Table M1; t = Minimum thickness of plate in...

13. 49 CFR 179.220-6 - Thickness of plates.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... = Inside diameter in inches; E = 0.9 welded joint efficiency; except E=1.0 for seamless heads; P = Minimum... in AAR Specifications for Tank Cars, appendix M, Table M1; t = Minimum thickness of plate in...

14. 49 CFR 179.100-10 - Postweld heat treatment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank...

15. 49 CFR 179.400-12 - Postweld heat treatment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7...

16. 49 CFR 179.100-10 - Postweld heat treatment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank...

17. 49 CFR 179.400-12 - Postweld heat treatment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7...

18. 49 CFR 179.400-12 - Postweld heat treatment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7...

19. 49 CFR 179.100-10 - Postweld heat treatment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank...

20. 76 FR 40701 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... AN/AVR-2B Laser Warning Sets, C406 Electronic Locator Transmitters, Traffic Collision Avoidance... Systems, 6 AAR-57(V)3 Common Missile Warning Systems, 6 AN/AVR-2B Laser Warning Sets, C406 Electronic... AN/AVR-2B Laser Warning Set is a passive laser warning system that receives, processes and...

1. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... section was approved by the Director of the Federal Register in accordance with 5 U.S.C. 552(a) and 1 CFR... Pneumatic (ECP) Braking Systems § 232.603 Design, interoperability, and configuration management... reference, include the following: (1) AAR S-4200, “Electronically Controlled Pneumatic (ECP)...

2. 49 CFR 238.5 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with traditional railroads; but does not include rapid transit operations in an urban area that are not... reference of this standard in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain a copy of... TRANSPORTATION PASSENGER EQUIPMENT SAFETY STANDARDS General § 238.5 Definitions. As used in this part— AAR...

3. A New Key to Scholarly Collaboration?

ERIC Educational Resources Information Center

Fitzmier, Jack

2012-01-01

The American Academy of Religion, in concert with the Sakai Foundation, has envisioned a scholarly use of the new Sakai Open Academic Environment open-source software. Currently working under the title "Biosphere," the program would put a rich collection of collaborative tools in the hands of AAR members, their colleagues in related scholarly…

4. 49 CFR 179.5 - Certificate of construction.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and Reports § 179.5 Certificate of construction. (a) Before a tank car is placed in service, the party... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to...

5. 49 CFR 179.5 - Certificate of construction.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and Reports § 179.5 Certificate of construction. (a) Before a tank car is placed in service, the party... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to...

6. 49 CFR 179.24 - Stamping.

Code of Federal Regulations, 2014 CFR

2014-10-01

... corners of the tank in a visible location. Tank cars built before July 25, 2012, may have the plate... the tank was built from line 7 of AAR form 4-2. (v) Tank Shell Material/Head Material (SHELL MATL/HEAD... OF MFR): The month and year of tank manufacture. If the underframe has a different built date...

7. 49 CFR 179.5 - Certificate of construction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Introduction, Approvals and Reports § 179.5 Certificate of construction. (a) Before a tank car is placed in... to the owner and the Executive Director—Tank Car Safety, AAR, certifying that the tank,...

8. 49 CFR 179.5 - Certificate of construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and Reports § 179.5 Certificate of construction. (a) Before a tank car is placed in service, the party... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to...

9. 49 CFR 179.5 - Certificate of construction.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and Reports § 179.5 Certificate of construction. (a) Before a tank car is placed in service, the party... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to...

10. 49 CFR 234.109 - Recordkeeping.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL SYSTEMS, STATE ACTION PLANS, AND... Grade Crossings § 234.109 Recordkeeping. (a) Each railroad shall keep records pertaining to compliance...) Location of crossing (by highway name and DOT/AAR Crossing Inventory Number); (2) Time and date of...

11. 49 CFR 234.109 - Recordkeeping.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL SYSTEMS, STATE ACTION PLANS, AND... Grade Crossings § 234.109 Recordkeeping. (a) Each railroad shall keep records pertaining to compliance...) Location of crossing (by highway name and DOT/AAR Crossing Inventory Number); (2) Time and date of...

12. 49 CFR 234.109 - Recordkeeping.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL SYSTEMS, STATE ACTION PLANS, AND... Grade Crossings § 234.109 Recordkeeping. (a) Each railroad shall keep records pertaining to compliance...) Location of crossing (by highway name and DOT/AAR Crossing Inventory Number); (2) Time and date of...

13. Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways.

PubMed

Kleine-Brueggeney, Maren; Gradinaru, Irina; Babaeva, Ekaterina; Schwinn, Debra A; Oganesian, Anush

2014-09-01

The role of naturally occurring human α1a-Adrenergic Receptor (α1aAR) genetic variants associated with cardiovascular disorders is poorly understood. Here, we present the novel findings that expression of human α1aAR-247R (247R) genetic variant in cardiomyoblasts leads to transition of cardiomyoblasts into a fibroblast-like phenotype, evidenced by morphology and distinct de novo expression of characteristic genes. These fibroblast-like cells exhibit constitutive, high proliferative capacity and agonist-induced hypertrophy compared with cells prior to transition. We demonstrate that constitutive, synergistic activation of EGFR, Src and ERK kinases is the potential molecular mechanism of this transition. We also demonstrate that 247R triggers two distinct EGFR transactivation-dependent signaling pathways: 1) constitutive Gq-independent β-arrestin-1/Src/MMP/EGFR/ERK-dependent hyperproliferation and 2) agonist-induced Gq- and EGFR/STAT-dependent hypertrophy. Interestingly, in cardiomyoblasts agonist-independent hyperproliferation is MMP-dependent, but in fibroblast-like cells it is MMP-independent, suggesting that expression of α1aAR genetic variant in cardiomyocytes may trigger extracellular matrix remodeling. Thus, these novel findings demonstrate that EGFR transactivation by α1aAR-247R leads to hyperproliferation, hypertrophy and alterations in cardiomyoblasts, suggesting that these unique genetically-mediated alterations in signaling pathways and cellular function may lead to myocardial fibrosis. Such extracellular matrix remodeling may contribute to the genesis of arrhythmias in certain types of heart failure.

14. 77 FR 34846 - Inspection, Repair, and Maintenance; Driver-Vehicle Inspection Report for Intermodal Equipment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... FR 3316) at http://edocket.access.gpo.gov/2008/pdf/E8-785.pdf . III. Abbreviations AAR Association of....C. 31151(d) and (e)). FMCSA published a final rule on December 17, 2008 (73 FR 76794), implementing... provider's designated agent'' (49 U.S.C. 31151(a)(3)(L)). FMCSA's December 17, 2008 rule (73 FR...

15. 76 FR 81482 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... Royce engines; 12 Electronic Warfare Self Protection Suites; 12 AAR-47A(V)2 Missile Warning Systems; 12... requested a possible sale of 10 C-27J aircraft; 23 AE2100D2 Rolls Royce engines; 12 Electronic Warfare Self... electronic warfare and avionics systems. CMDS uses threat data received over the aircraft interfaces...

16. 78 FR 46680 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-01

... Requirements of the AAR MSRP. The revisions include a revised definition for a passenger equipment car as... Regulations, Part 238.'' This definition serves to address private passenger cars, particularly those operated... does not anticipate scheduling a public hearing in connection with these proceedings since the facts...

17. 49 CFR 232.307 - Modification of the single car air brake test procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

18. 49 CFR 232.307 - Modification of the single car air brake test procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

19. Positron Emission Tomography (PET) Imaging of Prostate Cancer with a Gastrin Releasing Peptide Receptor Antagonist - from Mice to Men

PubMed Central

Wieser, Gesche; Mansi, Rosalba; Grosu, Anca L.; Schultze-Seemann, Wolfgang; Dumont-Walter, Rebecca A.; Meyer, Philipp T.; Maecke, Helmut R.; Reubi, Jean Claude; Weber, Wolfgang A.

2014-01-01

Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. Methods: Biodistribution, dosimetry and tumor uptake of the GRPr antagonist 64Cu-CB-TE2A-AR06 [(64Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG4-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH2] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). Results: No adverse events were observed after injection of 64Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time. Conclusion: 64Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating 64Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary. PMID:24578724

20. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... technology. Upon written request supported by suitable justification and submitted pursuant to the special... section was approved by the Director of the Federal Register in accordance with 5 U.S.C. 552(a) and 1 CFR... Specification,” Version 2.0 (Adopted: 1999; Revised: 2002); (4) AAR S-4230, “Intratrain Communication...

1. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... technology. Upon written request supported by suitable justification and submitted pursuant to the special... section was approved by the Director of the Federal Register in accordance with 5 U.S.C. 552(a) and 1 CFR... Specification,” Version 2.0 (Adopted: 1999; Revised: 2002); (4) AAR S-4230, “Intratrain Communication...

2. 49 CFR 179.4 - Changes in specifications for tank cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Changes in specifications for tank cars. 179.4... TANK CARS Introduction, Approvals and Reports § 179.4 Changes in specifications for tank cars. (a...—Tank Car Safety, AAR, for consideration by its Tank Car Committee. An application for construction...

3. 77 FR 53184 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

.../INS) with a Selective Availability Anti-spoofing Module (SAASM), AN/AAR-60 Infrared Missile Warning...-60 Infrared Missile Warning and AN/ALE-47 Countermeasures System, Electro-Optical Sensor, SIGINT... with an integrated electro-optical and infrared (EO/IR), Eye-safe Laser Range Finder and Laser...

4. Automatic anatomy recognition on CT images with pathology

NASA Astrophysics Data System (ADS)

Huang, Lidong; Udupa, Jayaram K.; Tong, Yubing; Odhner, Dewey; Torigian, Drew A.

2016-03-01

Body-wide anatomy recognition on CT images with pathology becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem because various diseases result in various abnormalities of objects such as shape and intensity patterns. We previously developed an automatic anatomy recognition (AAR) system [1] whose applicability was demonstrated on near normal diagnostic CT images in different body regions on 35 organs. The aim of this paper is to investigate strategies for adapting the previous AAR system to diagnostic CT images of patients with various pathologies as a first step toward automated body-wide disease quantification. The AAR approach consists of three main steps - model building, object recognition, and object delineation. In this paper, within the broader AAR framework, we describe a new strategy for object recognition to handle abnormal images. In the model building stage an optimal threshold interval is learned from near-normal training images for each object. This threshold is optimally tuned to the pathological manifestation of the object in the test image. Recognition is performed following a hierarchical representation of the objects. Experimental results for the abdominal body region based on 50 near-normal images used for model building and 20 abnormal images used for object recognition show that object localization accuracy within 2 voxels for liver and spleen and 3 voxels for kidney can be achieved with the new strategy.

5. 49 CFR 1039.14 - Boxcar transportation exemptions and rules.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (6) Freight rates applicable to boxcar traffic originating or terminating at an industry facility... 1, 1985, as published in AAR Traffic Circular No. OT-10, for any boxcar excluded under paragraph (c.... (4) No freight rate made effective after April 1, 1985, that applies to traffic moving by boxcar...

6. 49 CFR 1039.14 - Boxcar transportation exemptions and rules.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... (6) Freight rates applicable to boxcar traffic originating or terminating at an industry facility... 1, 1985, as published in AAR Traffic Circular No. OT-10, for any boxcar excluded under paragraph (c.... (4) No freight rate made effective after April 1, 1985, that applies to traffic moving by boxcar...

7. 49 CFR 232.307 - Modification of the single car air brake test procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

8. Abstractions of Awareness: Aware of What?

NASA Astrophysics Data System (ADS)

Metaxas, Georgios; Markopoulos, Panos

This chapter presents FN-AAR, an abstract model of awareness systems. The purpose of the model is to capture in a concise and abstract form essential aspects of awareness systems, many of which have been discussed in design essays or in the context of evaluating specific design solutions.

9. Early visual experience shapes the representation of auditory space in the forebrain gaze fields of the barn owl.

PubMed

Miller, G L; Knudsen, E I

1999-03-15

Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain. Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls. This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli. PMID:10066282

10. 49 CFR 179.6 - Repairs and alterations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Repairs and alterations. 179.6 Section 179.6... Introduction, Approvals and Reports § 179.6 Repairs and alterations. For procedure to be followed in making repairs or alterations, see appendix R of the AAR Specifications for Tank Cars (IBR, see § 171.7 of...

11. Effects of Synephrine and B-Phenethylamine on Human a-Adrenoceptor Subtypes

Technology Transfer Automated Retrieval System (TEKTRAN)

Synephrine and B-phenethylamine are structurally related to ephedrine. In this study, the effects of synephrine and B-phenethylamine are investigated on a-adrenoceptor (a-AR) subtypes expressed in human embroyonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-no...

12. Rocket-Based Combined Cycle Engine Concept Development

NASA Technical Reports Server (NTRS)

Ratekin, G.; Goldman, Allen; Ortwerth, P.; Weisberg, S.; McArthur, J. Craig (Technical Monitor)

2001-01-01

The development of rocket-based combined cycle (RBCC) propulsion systems is part of a 12 year effort under both company funding and contract work. The concept is a fixed geometry integrated rocket, ramjet, scramjet, which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals, seal purge gas, and closeout side attachments. Engine A5 is the current configuration for NASA Marshall Space Flight Center (MSFC) for the ART program. Engine A5 models the complete flight engine flowpath of inlet, isolator, airbreathing combustor, and nozzle. High-performance rocket thrusters are integrated into the engine enabling both low speed air-augmented rocket (AAR) and high speed pure rocket operation. Engine A5 was tested in GASL's new Flight Acceleration Simulation Test (FAST) facility in all four operating modes, AAR, RAM, SCRAM, and Rocket. Additionally, transition from AAR to RAM and RAM to SCRAM was also demonstrated. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. SCRAM and rocket mode performance was above predictions. For the first time, testing also demonstrated transition between operating modes.

13. 49 CFR 179.220-6 - Thickness of plates.

Code of Federal Regulations, 2013 CFR

2013-10-01

... required bursting pressure in psig; S = Minimum tensile strength of plate material in p.s.i. as prescribed... pressure in psig; S = Minimum tensile strength of plate material in psi as prescribed in AAR Specifications... 49 Transportation 3 2013-10-01 2013-10-01 false Thickness of plates. 179.220-6 Section...

14. 77 FR 76169 - Quarterly Rail Cost Adjustment Factor

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... Surface Transportation Board Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the AAR's proposed rebasing calculations and the rebased first quarter 2013 rail cost adjustment factor (RCAF)...

15. 78 FR 47824 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

... continue in service a car if an end of car cushioning unit is leaking clearly formed droplets. In its... droplets. AAR requests a 3-year test period during which it may be shown that end of car cushioning units... the facts do not appear to warrant a hearing. If any interested party desires an opportunity for...

16. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

PubMed Central

Fang, Pengfei; Guo, Min

2015-01-01

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. PMID:26670257

17. 75 FR 11992 - Notice of Scheduling of Public Hearing; Association of American Railroads

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... Federal Railroad Administration Notice of Scheduling of Public Hearing; Association of American Railroads... Association of American Railroads (AAR) had petitioned FRA for a waiver of compliance from certain... behalf of an association, business, labor union, etc.) You may review DOT's complete Privacy...

18. 75 FR 179 - Notice of Petition for Waiver of Compliance and Scheduling of Public Hearing Association of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-04

... Hearing Association of American Railroads In accordance with part 211 of Title 49 of the Code of Federal Regulations (CFR), this document provides notice that the Association of American Railroads (AAR) has... (or signing the comment, if submitted on behalf of an association, business, labor union, etc.)...

19. 76 FR 40448 - 2010 Tax Information for Use in the Revenue Shortfall Allocation Method

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... Surface Transportation Board 2010 Tax Information for Use in the Revenue Shortfall Allocation Method... Allocation Method (RSAM). DATES: Comments are due by August 8, 2011. If any comment opposing AAR's... Shortfall Allocation Method, EP 646 (Sub-No. 2) (STB served Nov. 21, 2008). RSAM is intended to measure...

20. 78 FR 34427 - 2012 Tax Information for Use In The Revenue Shortfall Allocation Method

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... Surface Transportation Board 2012 Tax Information for Use In The Revenue Shortfall Allocation Method... Shortfall Allocation Method (RSAM). DATES: Comments are due by July 9, 2013. If any comment opposing AAR's... Revenue Shortfall Allocation Method, EP 646 (Sub-No. 2) (STB served Nov. 21, 2008). RSAM is intended...

1. 76 FR 69709 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-09

... elements of logistics support. The estimated cost is 1.2 billion. This proposed sale will contribute to... Royce AE 2100D3 spare engines, 8 AN/AAR-47 Missile Warning Systems (two of them spares), 8 AN/ALR-56M Advanced Radar Warning Receivers (two of them spares), 8 AN/ALE-47 Counter- Measures Dispensing... 2. 78 FR 26332 - 36(b)(1) Arms Sales Notification Federal Register 2010, 2011, 2012, 2013, 2014 2013-05-06 ... Turbofan F117-PW-100 Engines, 1 AN/AAR-47 Missile Approach Warning System, 1 AN/ALE-47 Countermeasure... technical and logistics support services; and related elements of initial and follow-on logistical and... Warning System, 1 AN/ALE-47 Countermeasure Dispenser Set (CMDS), secure radios, precision... 3. LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS EPA Science Inventory 2003 AAR PM Meeting Particulate Matter: Atmospheric Sciences, Exposure and the Fourth Colloquium on PM and Human Health LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, C... 4. 49 CFR 179.102-4 - Vinyl fluoride, stabilized. Code of Federal Regulations, 2013 CFR 2013-10-01 ... weld metal and heat affected zone prepared and tested in accordance with AAR Specifications for Tank...) Insulation must be of approved material. (c) Excess flow valves must be installed under all liquid and vapor... alloy containing any of these metals may not be used in the tank construction, or in fittings in... 5. New Surgical Drapes for Observation of the Lower Extremities during Abdominal Aortic Repair PubMed Central 2010-01-01 Objective: For the early diagnosis and therapy of peripheral thromboembolism (TE) as a complication of abdominal aortic repair (AAR), we developed and evaluated the usefulness of surgical drapes that permit observation of the lower extremities during AAR. Materials and Methods: Between January 2007 and June 2009, the handling, durability, and usefulness of new surgical drapes were evaluated during AAR in 157 patients with abdominal aortic aneurysms and 9 patients with peripheral arterial disease. The drapes are manufactured by Hogy Medical Co. Ltd. and made of a water-repellent, spun lace, non-woven fabric, including a transparent polyethylene film that covers the patients' legs. This transparent film enables inspection and palpation of the lower extremities during surgery for early diagnosis and therapy of peripheral TE. Results: As a peripheral complication, 1 patient had right lower extremity TE. This was diagnosed immediately after anastomosis, thrombectomy was performed, and the remaining clinical course was uneventful. In all patients, the drapes permitted observation of the lower extremities , and the dorsal arteries were palpable. There were no problems with durability. Conclusions: New surgical drapes permit observation of the lower extremities during AAR for early diagnosis and treatment of peripheral TE. PMID:23555399 6. Reproducibility of area at risk assessment in acute myocardial infarction by T1- and T2-mapping sequences in cardiac magnetic resonance imaging in comparison to Tc99m-sestamibi SPECT. PubMed Langhans, Birgit; Nadjiri, Jonathan; Jähnichen, Christin; Kastrati, Adnan; Martinoff, Stefan; Hadamitzky, Martin 2014-10-01 Area at risk (AAR) is an important parameter for the assessment of the salvage area after revascularization in acute myocardial infarction (AMI). By combining AAR assessment by T2-weighted imaging and scar quantification by late gadolinium enhancement imaging cardiovascular magnetic resonance (CMR) offers a promising alternative to the "classical" modality of Tc99m-sestamibi single photon emission tomography (SPECT). Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury, particularly the T1-mapping and T2-mapping, have attracted rising attention. But no direct comparison between the different sequences in the setting of AMI or a validation against SPECT has been reported so far. We analyzed 14 patients undergoing primary coronary revascularization in AMI in whom both a pre-intervention Tc99m-sestamibi-SPECT and CMR imaging at a median of 3.4 (interquartile range 3.3-3.6) days after the acute event were performed. Size of AAR was measured by three different non-contrast CMR techniques on corresponding short axis slices: T2-weighted, fat-suppressed turbospin echo sequence (TSE), T2-mapping from T2-prepared balanced steady state free precession sequences (T2-MAP) and T1-mapping from modified look locker inversion recovery (MOLLI) sequences. For each CMR sequence, the AAR was quantified by appropriate methods (absolute values for mapping sequences, comparison with remote myocardium for other sequences) and correlated with Tc99m-sestamibi-SPECT. All measurements were performed on a 1.5 Tesla scanner. The size of the AAR assessed by CMR was 28.7 ± 20.9 % of left ventricular myocardial volume (%LV) for TSE, 45.8 ± 16.6 %LV for T2-MAP, and 40.1 ± 14.4 %LV for MOLLI. AAR assessed by SPECT measured 41.6 ± 20.7 %LV. Correlation analysis revealed best correlation with SPECT for T2-MAP at a T2-threshold of 60 ms 7. Perikaryal and synaptic localization of alpha 2A-adrenergic receptor-like immunoreactivity. PubMed Aoki, C; Go, C G; Venkatesan, C; Kurose, H 1994-07-11 Through molecular cloning, the existence of three distinct subtypes of alpha 2-adrenergic receptors (alpha 2AR)--A, B and C--has been established and are referred to as alpha 2A AR, alpha 2B AR and alpha 2CAR. Due to limitations in pharmacological tools, it has been difficult to ascribe the role of each subtype to the central functions of alpha 2AR. In situ hybridization studies have provided valuable information regarding their distribution within brain. However, little is known about their subcellular distribution, and in particular, their pre- versus postsynaptic localization or their relation to noradrenergic neurons in the CNS. We used an antiserum that selectively recognizes the A-subtype of alpha 2AR to determine: (1) the regional distribution of the receptor within brains of rat and monkey; (2) the subcellular distribution of the receptor in locus coeruleus (LC) of rats and prefrontal cortex of monkeys; and (3) the ultrastructural relation of the receptor to noradrenergic processes in LC. Light microscopic immunocytochemistry revealed prominent immunoreactivity in LC, the brainstem regions modulating the baroreflex, the granule cell layer of the cerebellar cortex, the paraventricular and supraoptic nuclei of the hypothalamus (PVN, SON), the basal ganglia, all thalamic nuclei, the hippocampal formation and throughout cerebral cortical areas. Comparison of results obtained from rat and monkey brains revealed no apparent interspecies-differences in the regional distribution of immunoreactivity. Immunoreactivity occurred as small puncta, less than 1 micron in diameter, that cluster over neuronal perikarya. Besides these puncta, cell bodies, proximal dendrites and fine varicose processes--most likely to be axonal--of the PVN and SON and the hippocampal granule cells also exhibited homogeneously intense distribution of immunoreactivity. Subcellularly, alpha 2AAR-ir in LC and prefrontal cortex were associated with synaptic and non-synaptic plasma membrane of 8. Alfvén: magnetosphere—ionosphere connection explorers NASA Astrophysics Data System (ADS) Berthomier, M.; Fazakerley, A. N.; Forsyth, C.; Pottelette, R.; Alexandrova, O.; Anastasiadis, A.; Aruliah, A.; Blelly, P.-L.; Briand, C.; Bruno, R.; Canu, P.; Cecconi, B.; Chust, T.; Daglis, I.; Davies, J.; Dunlop, M.; Fontaine, D.; Génot, V.; Gustavsson, B.; Haerendel, G.; Hamrin, M.; Hapgood, M.; Hess, S.; Kataria, D.; Kauristie, K.; Kemble, S.; Khotyaintsev, Y.; Koskinen, H.; Lamy, L.; Lanchester, B.; Louarn, P.; Lucek, E.; Lundin, R.; Maksimovic, M.; Manninen, J.; Marchaudon, A.; Marghitu, O.; Marklund, G.; Milan, S.; Moen, J.; Mottez, F.; Nilsson, H.; Ostgaard, N.; Owen, C. J.; Parrot, M.; Pedersen, A.; Perry, C.; Pinçon, J.-L.; Pitout, F.; Pulkkinen, T.; Rae, I. J.; Rezeau, L.; Roux, A.; Sandahl, I.; Sandberg, I.; Turunen, E.; Vogt, J.; Walsh, A.; Watt, C. E. J.; Wild, J. A.; Yamauchi, M.; Zarka, P.; Zouganelis, I. 2012-04-01 The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfvén concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets. 9. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase. PubMed Murphy, Jesse R; Mullins, Elwood A; Kappock, T Joseph 2016-01-01 Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. 10. α2A-Adrenergic Receptors Filter Parabrachial Inputs to the Bed Nucleus of the Stria Terminalis PubMed Central Flavin, Stephanie A.; Matthews, Robert T.; Wang, Qin; Muly, E. Chris 2014-01-01 α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress–reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α2A-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α2A-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α2A-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α2A-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α2A-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. PMID:25009265 11. Tricyclic antidepressants exhibit variable pharmacological profiles at the α(2A) adrenergic receptor. PubMed Cottingham, Christopher; Percival, Stefanie; Birky, Tana; Wang, Qin 2014-08-29 Antidepressant mechanisms of action remain shrouded in mystery, greatly hindering our ability to develop therapeutics which can fully treat patients suffering from depressive disorders. In an attempt to shed new light on this topic, we have undertaken a series of studies investigating actions of tricyclic antidepressant drugs (TCAs) at the α2A adrenergic receptor (AR), a centrally important receptor, dysregulation of which has been linked to depression. Our previous work established a particular TCA, desipramine, as an arrestin-biased α2AAR ligand driving receptor endocytosis and downregulation but not canonical heterotrimeric G protein-mediated signaling. The present work is aimed at broadening our understanding of how members of the TCA drug class act at the α2AAR, as we have selected the closely related but subtly different TCAs imipramine and amitriptyline for evaluation. Our data demonstrate that these drugs do also function as direct arrestin-biased α2AAR ligands. However, these data reveal differences in receptor affinity and in the extent/nature of arrestin recruitment to and endocytosis of α2AARs. Specifically, amitriptyline exhibits an approximately 14-fold stronger interaction with the receptor, is a weaker driver of arrestin recruitment, and preferentially recruits a different arrestin subtype. Extent of endocytosis is similar for all TCAs studied so far, and occurs in an arrestin-dependent manner, although imipramine uniquely retains a slight ability to drive α2AAR endocytosis in arrestin-null cells. These findings signify an important expansion of our mechanistic understanding of antidepressant pharmacology, and provide useful insights for future medicinal chemistry efforts. 12. Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase NASA Astrophysics Data System (ADS) Murphy, Jesse; Mullins, Elwood; Kappock, T. 2016-05-01 Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates less than 3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analogue dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analogue of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. 13. α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis. PubMed Flavin, Stephanie A; Matthews, Robert T; Wang, Qin; Muly, E Chris; Winder, Danny G 2014-07-01 α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α(2A)-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α(2A)-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α(2A)-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. 14. Automatic localization of IASLC-defined mediastinal lymph node stations on CT images using fuzzy models NASA Astrophysics Data System (ADS) Matsumoto, Monica M. S.; Beig, Niha G.; Udupa, Jayaram K.; Archer, Steven; Torigian, Drew A. 2014-03-01 Lung cancer is associated with the highest cancer mortality rates among men and women in the United States. The accurate and precise identification of the lymph node stations on computed tomography (CT) images is important for staging disease and potentially for prognosticating outcome in patients with lung cancer, as well as for pretreatment planning and response assessment purposes. To facilitate a standard means of referring to lymph nodes, the International Association for the Study of Lung Cancer (IASLC) has recently proposed a definition of the different lymph node stations and zones in the thorax. However, nodal station identification is typically performed manually by visual assessment in clinical radiology. This approach leaves room for error due to the subjective and potentially ambiguous nature of visual interpretation, and is labor intensive. We present a method of automatically recognizing the mediastinal IASLC-defined lymph node stations by modifying a hierarchical fuzzy modeling approach previously developed for body-wide automatic anatomy recognition (AAR) in medical imagery. Our AAR-lymph node (AAR-LN) system follows the AAR methodology and consists of two steps. In the first step, the various lymph node stations are manually delineated on a set of CT images following the IASLC definitions. These delineations are then used to build a fuzzy hierarchical model of the nodal stations which are considered as 3D objects. In the second step, the stations are automatically located on any given CT image of the thorax by using the hierarchical fuzzy model and object recognition algorithms. Based on 23 data sets used for model building, 22 independent data sets for testing, and 10 lymph node stations, a mean localization accuracy of within 1-6 voxels has been achieved by the AAR-LN system. 15. α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis. PubMed Flavin, Stephanie A; Matthews, Robert T; Wang, Qin; Muly, E Chris; Winder, Danny G 2014-07-01 α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α(2A)-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α(2A)-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α(2A)-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. PMID:25009265 16. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase PubMed Central Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph 2016-01-01 Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. PMID:27242998 17. A lack of α1A-adrenergic receptor-mediated antidepressant-like effects of S-(+)-niguldipine and B8805-033 in the forced swim test. PubMed Kreiner, Grzegorz; Roman, Adam; Zelek-Molik, Agnieszka; Kowalska, Marta; Nalepa, Irena 2016-06-01 The α1-adrenergic receptors (α1-ARs), which belong to a G protein-coupled receptor family, consist of three highly homologous subtypes known as α1A-ARs, α1B-ARs, and α1D-ARs. Our previous findings suggested that α1A-ARs are an important target for imipramine and electroconvulsive therapy. The current study sought to evaluate whether S-(+)-niguldipine and B8805-033, two selective antagonists of α1A-ARs, can evoke antidepressant-like effects in the forced swim test in rats. Both compounds were administered at three time points (24, 5, and 1 h before testing), and the effects of three doses (2, 5, and 10 mg/kg) of each compound were investigated. S-(+)-Niguldipine produced no antidepressant-like effects other than a 14% reduction in immobility time at the highest dose. Although B8805-033 at a dose of 2 mg/kg did not influence the rats' behavior, higher B8805-033 doses (5 and 10 mg/kg) produced significant reductions in immobility time (approximately 42 and 44% vs. controls, respectively; P<0.01). However, this effect was abolished by the concomitant administration of WAY100135, a serotonin receptor antagonist, suggesting that the observed antidepressant-like effects of B8805-033 are unrelated to α1A-ARs. Nevertheless, given the current dearth of selective α1A-AR agonists, the question of whether this particular subtype could be involved in antidepressant therapy mechanisms remains unresolved. 18. Bifunctional staining for ex vivo determination of area at risk in rabbits with reperfused myocardial infarction PubMed Central Feng, Yuanbo; Ma, Zhan-Long; Chen, Feng; Yu, Jie; Cona, Marlein Miranda; Xie, Yi; Li, Yue; Ni, Yicheng 2013-01-01 AIM: To develop a method for studying myocardial area at risk (AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging (cMRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery (LCx) to induce myocardial infarction (MI). ECG-triggered cMRI with delayed enhancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil (RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography (DR). The perfusion density rate (PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement (iDE) and ex vivo delayed enhancement (eDE) cMRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni’s multiple comparison, and paired t tests were applied for statistics. RESULTS: All rabbits tolerated well the surgical procedure and subsequent cMRI sessions. The open-chest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally (n = 6) and by slice (n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on iDE, and 35.41% ± 12.25% and 32.40% ± 12.34% on eDE. There were no significant differences for MI determination with excellent linear regression correspondence (rglobal = 0.89; rslice = 0.9) between iDE and eDE. The percentage AAR volumes globally (n = 6) and by slice (n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis (rglobal = 0.99; rslice 19. Body-Wide Hierarchical Fuzzy Modeling, Recognition, and Delineation of Anatomy in Medical Images PubMed Central Udupa, Jayaram K.; Odhner, Dewey; Zhao, Liming; Tong, Yubing; Matsumoto, Monica M.S.; Ciesielski, Krzysztof C.; Falcao, Alexandre X.; Vaideeswaran, Pavithra; Ciesielski, Victoria; Saboury, Babak; Mohammadianrasanani, Syedmehrdad; Sin, Sanghun; Arens, Raanan; Torigian, Drew A. 2014-01-01 To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide automatic anatomy recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions – thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) – involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and 20. Random tag insertions by Transposon Integration mediated Mutagenesis (TIM). PubMed Hoeller, Brigitte M; Reiter, Birgit; Abad, Sandra; Graze, Ina; Glieder, Anton 2008-10-01 Transposon Integration mediated Mutagenesis (TIM) is a broadly applicable tool for protein engineering. This method combines random integration of modified bacteriophage Mu transposons with their subsequent defined excision employing type IIS restriction endonuclease AarI. TIM enables deletion or insertion of an arbitrary number of bases at random positions, insertion of functional sequence tags at random positions, replacing randomly selected triplets by a specific codon (e.g. scanning) and site-saturation mutagenesis. As a proof of concept a transposon named GeneOpenerAarIKan was designed and employed to introduce 6xHis tags randomly into the esterase EstC from Burkholderia gladioli. A TIM library was screened with colony based assays for clones with an integrated 6xHis tag and for clones exhibiting esterase activity. The employed strategy enables the isolation of randomly tagged active enzymes in single mutagenesis experiments. 1. Aminoacyl-tRNA synthetase inhibitors as potential antibiotics. PubMed Vondenhoff, Gaston H M; Van Aerschot, Arthur 2011-11-01 Increasing resistance to antibiotics is a major problem worldwide and provides the stimulus for development of new bacterial inhibitors with preferably different modes of action. In search for new leads, several new bacterial targets are being exploited beside the use of traditional screening methods. Hereto, inhibition of bacterial protein synthesis is a long-standing validated target. Aminoacyl-tRNA synthetases (aaRSs) play an indispensable role in protein synthesis and their structures proved quite conserved in prokaryotes and eukaryotes. However, some divergence has occurred allowing the development of selective aaRS inhibitors. Following an outline on the action mechanism of aaRSs, an overview will be given of already existing aaRS inhibitors, which are largely based on mimics of the aminoacyl-adenylates, the natural reaction intermediates. This is followed by a discussion on more recent developments in the field and the bioavailability problem. 2. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications NASA Astrophysics Data System (ADS) Hendy, Erica J.; Tomiak, Peter J.; Collins, Matthew J.; Hellstrom, John; Tudhope, Alexander W.; Lough, Janice M.; Penkman, Kirsty E. H. 2012-06-01 Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed from 3. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications. PubMed Hendy, Erica J; Tomiak, Peter J; Collins, Matthew J; Hellstrom, John; Tudhope, Alexander W; Lough, Janice M; Penkman, Kirsty E H 2012-06-01 Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed 4. Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images. PubMed Udupa, Jayaram K; Odhner, Dewey; Zhao, Liming; Tong, Yubing; Matsumoto, Monica M S; Ciesielski, Krzysztof C; Falcao, Alexandre X; Vaideeswaran, Pavithra; Ciesielski, Victoria; Saboury, Babak; Mohammadianrasanani, Syedmehrdad; Sin, Sanghun; Arens, Raanan; Torigian, Drew A 2014-07-01 To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and 5. Life in the slow lane: making hospitals safer, slowly but surely PubMed Central Walker, Judy; Andrews, Steve; Grewcock, Dave; Halligan, Aidan 2012-01-01 Recognition that serious deficiencies in mutual respect and team work were hampering safe and effective patient care led to the creation of the cultural change initiative described here. We feel this has widespread applicability to other healthcare settings. The After Action Review (AAR) concept was adapted for use in the NHS for the first time as it provides a deceptively simple vehicle to structure healthy blame free team interactions with the aim of improving practice and team behaviours. The organizational and psychological barriers to being able to do this in multi-professional teams are accentuated by the hierarchical nature of the clinical context, but this project has begun to make lasting change so that AAR is an approach that is now widely understood and frequently used. PMID:22843646 6. A 9,000-year-old caribou hunting structure beneath Lake Huron. PubMed O'Shea, John M; Lemke, Ashley K; Sonnenburg, Elizabeth P; Reynolds, Robert G; Abbott, Brian D 2014-05-13 Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. PMID:24778246 7. Embedded prediction in feature extraction: application to single-trial EEG discrimination. PubMed Hsu, Wei-Yen 2013-01-01 In this study, an analysis system embedding neuron-fuzzy prediction in feature extraction is proposed for brain-computer interface (BCI) applications. Wavelet-fractal features combined with neuro-fuzzy predictions are applied for feature extraction in motor imagery (MI) discrimination. The features are extracted from the electroencephalography (EEG) signals recorded from participants performing left and right MI. Time-series predictions are performed by training 2 adaptive neuro-fuzzy inference systems (ANFIS) for respective left and right MI data. Features are then calculated from the difference in multi-resolution fractal feature vector (MFFV) between the predicted and actual signals through a window of EEG signals. Finally, the support vector machine is used for classification. The proposed method estimates its performance in comparison with the linear adaptive autoregressive (AAR) model and the AAR time-series prediction of 6 participants from 2 data sets. The results indicate that the proposed method is promising in MI classification. PMID:23248335 8. Cluster Observations of the Auroral Acceleration Region NASA Astrophysics Data System (ADS) Sadeghi, S.; Marklund, G.; Karlsson, R.; Lindqvist, P.; Li, B.; Nilsson, H.; Marghitu, O.; Fazakerley, A. N.; Lucek, E. A. 2011-12-01 We present results from Cluster satellite multi-point event studies from the auroral acceleration region (AAR). Electric potential structures associated with inverted-V aurora are investigated using electric field, magnetic field, ion and electron data from the Cluster spacecraft, crossing the auroral acceleration region (AAR) at different altitudes above the auroral oval. The spatial and temporal development of the acceleration structures is studied, given the magnetic conjunction opportunity and the short time-difference between the Cluster spacecraft crossings. The configuration allowed for estimating the characteristic times of development for the structures and estimating the parallel electric field and potential drop. For one of the negative potential structures, a growth time of 40 s and stability for more than one minute was observed and an average parallel electric field was estimated (~ 0.56 mV/m, between 1.13 and 1.3 RE of altitude). 9. Detection, monitoring and modelling of alkali-aggregate reaction in Kouga Dam (South Africa) SciTech Connect Elges, H.; Lecocq, P.; Oosthuizen, C.; Geertsema, A. 1995-12-31 Kouga Dam (formerly Paul Sauer Dam) is a double curvature arch dam completed in 1969. The aggregates and the cement used for the construction have subsequently been proven to be alkali reactive. The results of the monitoring programme and the alkali-aggregate reaction (AAR) tests as well as the methodology developed to standardise the logging of cores for these investigations are presented. A brief description of the Finite Element Model used to approximate the AAR process in order to determine positions for in-situ stress measurements is also given. The aim with these tests is to refine the model for prediction of the long-term behaviour of the dam and to make an assessment of the possibility of raising the dam. 10. A 9,000-year-old caribou hunting structure beneath Lake Huron PubMed Central O’Shea, John M.; Lemke, Ashley K.; Sonnenburg, Elizabeth P.; Reynolds, Robert G.; Abbott, Brian D. 2014-01-01 Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. PMID:24778246 11. A 9,000-year-old caribou hunting structure beneath Lake Huron. PubMed O'Shea, John M; Lemke, Ashley K; Sonnenburg, Elizabeth P; Reynolds, Robert G; Abbott, Brian D 2014-05-13 Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. 12. Improvements of a Brain-Computer Interface Applied to a Robotic Wheelchair NASA Astrophysics Data System (ADS) Ferreira, André; Bastos-Filho, Teodiano Freire; Sarcinelli-Filho, Mário; Sánchez, José Luis Martín; García, Juan Carlos García; Quintas, Manuel Mazo Two distinct signal features suitable to be used as input to a Support-Vector Machine (SVM) classifier in an application involving hands motor imagery and the correspondent EEG signal are evaluated in this paper. Such features are the Power Spectral Density (PSD) components and the Adaptive Autoregressive (AAR) parameters. The best result (an accuracy of 97.1%) is obtained when using PSD components, while the AAR parameters generated an accuracy of 91.4%. The results also demonstrate that it is possible to use only two EEG channels (bipolar configuration around C 3 and C 4), discarding the bipolar configuration around C z . The algorithms were tested with a proprietary EEG data set involving 4 individuals and with a data set provided by the University of Graz (Austria) as well. The resulting classification system is now being implemented in a Brain-Computer Interface (BCI) used to guide a robotic wheelchair. 13. Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images. PubMed Udupa, Jayaram K; Odhner, Dewey; Zhao, Liming; Tong, Yubing; Matsumoto, Monica M S; Ciesielski, Krzysztof C; Falcao, Alexandre X; Vaideeswaran, Pavithra; Ciesielski, Victoria; Saboury, Babak; Mohammadianrasanani, Syedmehrdad; Sin, Sanghun; Arens, Raanan; Torigian, Drew A 2014-07-01 To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and 14. Modern and Little Ice Age equilibrium-line altitudes on Outlet Valley glaciers from Jostedalsbreen, western Norway: An evaluation of different approaches to their calculation SciTech Connect Torsnes, I.; Rye, N. ); Nesje, A. ) 1993-05-01 The modern and Little Ice Age (LIA) equilibrium-line altitude (ELA) of 20 outlet valley glacier from Jostedalsbreen, western Norway, has been calculated using different approaches. Using an accumulation area ratio (AAR) of 0.6 [+-] 0.05 gave a mean little Ice Age ELA depression of 70 m. A method developed by M. Kuhle, taking the influence by topography into account gave a mean ELA depression of 35-255 m, the median elevation of glaciers 115 m, and the toe-to-headwall altitude ration 140 m. Differences in the ELA estimates can be attributed to the differences in topography and morphology of the glaciers. The AAR method appears to provide the most reliable results. This will aid in determining mean global temperatures during the LIA. 34 refs., 9 figs., 5 tabs. 15. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid PubMed Central Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao 2016-01-01 This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128 16. Alpha1a-Adrenoceptor Genetic Variant Triggers Vascular Smooth Muscle Cell Hyperproliferation and Agonist Induced Hypertrophy via EGFR Transactivation Pathway. PubMed Gradinaru, Irina; Babaeva, Ekaterina; Schwinn, Debra A; Oganesian, Anush 2015-01-01 α1a Adrenergic receptors (α1aARs) are the predominant AR subtype in human vascular smooth muscle cells (SMCs). α1aARs in resistance vessels are crucial in the control of blood pressure, yet the impact of naturally occurring human α1aAR genetic variants in cardiovascular disorders remains poorly understood. To this end, we present novel findings demonstrating that 3D cultures of vascular SMCs expressing human α1aAR-247R (247R) genetic variant demonstrate significantly increased SMC contractility compared with cells expressing the α1aAR-WT (WT) receptor. Stable expression of 247R genetic variant also triggers MMP/EGFR-transactivation dependent serum- and agonist-independent (constitutive) hyperproliferation and agonist-dependent hypertrophy of SMCs. Agonist stimulation reduces contractility Using pathway-specific inhibitors we determined that the observed hyperproliferation of 247R-expressing cells is triggered via β-arrestin1/Src/MMP-2/EGFR/ERK-dependent mechanism. MMP-2-specific siRNA inhibited 247R-triggered hyperproliferation indicating MMP-2 involvement in 247R-triggered hyperproliferation in SMCs. β-arrestin1-specific shRNA also inhibited 247R-triggered hyperproliferation but did not affect hypertrophy in 247R-expressing SMCs, indicating that agonist-dependent hypertrophy is independent of β-arrestin1. Our data reveal that in different cardiovascular cells the same human receptor genetic variant can activate alternative modulators of the same signaling pathway. Thus, our findings in SMCs demonstrate that depending on the type of cells expressing the same receptor (or receptor variant), different target-specific inhibitors could be used to modulate aberrant hyperproliferative or hypertrophic pathways in order to restore normal phenotype. 17. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid. PubMed Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao 2016-01-01 This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128 18. Low-Torque Seal Development NASA Technical Reports Server (NTRS) Lattime, Scott B.; Borowski, Richard 2009-01-01 The EcoTurn Class K production prototypes have passed all AAR qualification tests and received conditional approval. The accelerated life test on the second set of seals is in progress. Due to the performance of the first set, no problems are expected.The seal has demonstrated superior performance over the HDL seal in the test lab with virtually zero torque and excellent contamination exclusion and grease retention. 19. Body-wide anatomy recognition in PET/CT images NASA Astrophysics Data System (ADS) Wang, Huiqian; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Zhao, Liming; Torigian, Drew A. 2015-03-01 With the rapid growth of positron emission tomography/computed tomography (PET/CT)-based medical applications, body-wide anatomy recognition on whole-body PET/CT images becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem and seldom studied due to unclear anatomy reference frame and low spatial resolution of PET images as well as low contrast and spatial resolution of the associated low-dose CT images. We previously developed an automatic anatomy recognition (AAR) system [15] whose applicability was demonstrated on diagnostic computed tomography (CT) and magnetic resonance (MR) images in different body regions on 35 objects. The aim of the present work is to investigate strategies for adapting the previous AAR system to low-dose CT and PET images toward automated body-wide disease quantification. Our adaptation of the previous AAR methodology to PET/CT images in this paper focuses on 16 objects in three body regions - thorax, abdomen, and pelvis - and consists of the following steps: collecting whole-body PET/CT images from existing patient image databases, delineating all objects in these images, modifying the previous hierarchical models built from diagnostic CT images to account for differences in appearance in low-dose CT and PET images, automatically locating objects in these images following object hierarchy, and evaluating performance. Our preliminary evaluations indicate that the performance of the AAR approach on low-dose CT images achieves object localization accuracy within about 2 voxels, which is comparable to the accuracies achieved on diagnostic contrast-enhanced CT images. Object recognition on low-dose CT images from PET/CT examinations without requiring diagnostic contrast-enhanced CT seems feasible. 20. 49 CFR 179.16 - Tank-head puncture-resistance systems. Code of Federal Regulations, 2010 CFR 2010-10-01 ... the impact test requirements in Section 5.3 of the AAR Specifications for Tank Cars (IBR, see § 171.7..., the system shall be capable of sustaining, without any loss of lading, coupler-to-tank-head impacts at relative car speeds of 29 km/hour (18 mph) when: (1) The weight of the impact car is at least 119,295... 1. Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery. PubMed Labazi, Hicham; Tilley, Stephen L; Ledent, Catherine; Mustafa, S Jamal 2016-03-01 Activation of adenosine receptors (ARs) has been implicated in the modulation of renal and cardiovascular systems, as well as erectile functions. Recent studies suggest that adenosine-mediated regulation of erectile function is mainly mediated through A2BAR activation. However, no studies have been conducted to determine the contribution of AR subtype in the regulation of the vascular tone of the pudendal artery (PA), the major artery supplying and controlling blood flow to the penis. Our aim was to characterize the contribution of AR subtypes and identify signaling mechanisms involved in adenosine-mediated vascular tone regulation in the PA. We used a DMT wire myograph for muscle tension measurements in isolated PAs from wild-type, A2AAR knockout, A2BAR knockout, and A2A/A2BAR double-knockout mice. Real-time reverse transcription-polymerase chain reaction was used to determine the expression of the AR subtypes. Data from our pharmacologic and genetic approaches suggest that AR activation-mediated vasodilation in the PA is mediated by both the A2AAR and A2BAR, whereas neither the A1AR nor A3AR play a role in vascular tone regulation of the PA. In addition, we showed that A2AAR- and A2BAR-mediated vasorelaxation requires activation of nitric oxide and potassium channels; however, only the A2AAR-mediated response requires protein kinase A activation. Our data are complemented by mRNA expression showing the expression of all AR subtypes with the exception of the A3AR. AR signaling in the PA may play an important role in mediating erection and represent a promising therapeutic option for the treatment of erectile dysfunction. PMID:26718241 2. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid PubMed Central Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao 2016-01-01 This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. 3. Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways. PubMed Kleine-Brueggeney, Maren; Gradinaru, Irina; Babaeva, Ekaterina; Schwinn, Debra A; Oganesian, Anush 2014-09-01 The role of naturally occurring human α1a-Adrenergic Receptor (α1aAR) genetic variants associated with cardiovascular disorders is poorly understood. Here, we present the novel findings that expression of human α1aAR-247R (247R) genetic variant in cardiomyoblasts leads to transition of cardiomyoblasts into a fibroblast-like phenotype, evidenced by morphology and distinct de novo expression of characteristic genes. These fibroblast-like cells exhibit constitutive, high proliferative capacity and agonist-induced hypertrophy compared with cells prior to transition. We demonstrate that constitutive, synergistic activation of EGFR, Src and ERK kinases is the potential molecular mechanism of this transition. We also demonstrate that 247R triggers two distinct EGFR transactivation-dependent signaling pathways: 1) constitutive Gq-independent β-arrestin-1/Src/MMP/EGFR/ERK-dependent hyperproliferation and 2) agonist-induced Gq- and EGFR/STAT-dependent hypertrophy. Interestingly, in cardiomyoblasts agonist-independent hyperproliferation is MMP-dependent, but in fibroblast-like cells it is MMP-independent, suggesting that expression of α1aAR genetic variant in cardiomyocytes may trigger extracellular matrix remodeling. Thus, these novel findings demonstrate that EGFR transactivation by α1aAR-247R leads to hyperproliferation, hypertrophy and alterations in cardiomyoblasts, suggesting that these unique genetically-mediated alterations in signaling pathways and cellular function may lead to myocardial fibrosis. Such extracellular matrix remodeling may contribute to the genesis of arrhythmias in certain types of heart failure. PMID:24835978 4. Novel Alexa Fluor-488 labeled antagonist of the A(2A) adenosine receptor: Application to a fluorescence polarization-based receptor binding assay. PubMed Kecskés, Miklós; Kumar, T Santhosh; Yoo, Lena; Gao, Zhan-Guo; Jacobson, Kenneth A 2010-08-15 Fluorescence polarization (FP) assay has many advantages over the traditional radioreceptor binding studies. We developed an A(2A) adenosine receptor (AR) FP assay using a newly synthesized fluorescent antagonist of the A(2A)AR (MRS5346), a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivative conjugated to the fluorescent dye Alexa Fluor-488. MRS5346 displayed a K(i) value of 111+/-16nM in radioligand binding using [(3)H]CGS21680 and membranes prepared from HEK293 cells stably expressing the human A(2A)AR. In a cyclic AMP functional assay, MRS5346 was shown to be an A(2A)AR antagonist. MRS5346 did not show any effect on A(1) and A(3) ARs in binding or the A(2B)AR in a cyclic AMP assay at 10microM. Its suitability as a fluorescent tracer was indicated in an initial observation of an FP signal following A(2A)AR binding. The FP signal was optimal with 20nM MRS5346 and 150microg protein/mL HEK293 membranes. The association and dissociation kinetic parameters were readily determined using this FP assay. The K(d) value of MRS5346 calculated from kinetic parameters was 16.5+/-4.7nM. In FP competition binding experiments using MRS5346 as a tracer, K(i) values of known AR agonists and antagonists consistently agreed with K(i) values from radioligand binding. Thus, this FP assay, which eliminates using radioisotopes, appears to be appropriate for both routine receptor binding and high-throughput screening with respect to speed of analysis, displaceable signal and precision. The approach used in the present study could be generally applicable to other GPCRs. 5. 5'-Substituted Amiloride Derivatives as Allosteric Modulators Binding in the Sodium Ion Pocket of the Adenosine A2A Receptor. PubMed Massink, Arnault; Louvel, Julien; Adlere, Ilze; van Veen, Corine; Huisman, Berend J H; Dijksteel, Gabrielle S; Guo, Dong; Lenselink, Eelke B; Buckley, Benjamin J; Matthews, Hayden; Ranson, Marie; Kelso, Michael; IJzerman, Adriaan P 2016-05-26 The sodium ion site is an allosteric site conserved among many G protein-coupled receptors (GPCRs). Amiloride 1 and 5-(N,N-hexamethylene)amiloride 2 (HMA) supposedly bind in this sodium ion site and can influence orthosteric ligand binding. The availability of a high-resolution X-ray crystal structure of the human adenosine A2A receptor (hA2AAR), in which the allosteric sodium ion site was elucidated, makes it an appropriate model receptor for investigating the allosteric site. In this study, we report the synthesis and evaluation of novel 5'-substituted amiloride derivatives as hA2AAR allosteric antagonists. The potency of the amiloride derivatives was assessed by their ability to displace orthosteric radioligand [(3)H]4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol ([(3)H]ZM-241,385) from both the wild-type and sodium ion site W246A mutant hA2AAR. 4-Ethoxyphenethyl-substituted amiloride 12l was found to be more potent than both amiloride and HMA, and the shift in potency between the wild-type and mutated receptor confirmed its likely binding to the sodium ion site. PMID:27124340 6. A Modified Johnson-Cook Constitutive Equation to Predict Hot Deformation Behavior of Ti-6Al-4V Alloy NASA Astrophysics Data System (ADS) Cai, Jun; Wang, Kuaishe; Zhai, Peng; Li, Fuguo; Yang, Jie 2014-09-01 A modified Johnson-Cook constitutive equation of Ti-6Al-4V alloy is proposed based on hot compression tests performed in the temperature range of 1073-1323 K and strain rate 0.001-1 s-1. The experimental stress-strain data were employed to develop the modified Johnson-Cook constitutive equation of different phase regimes (α + β and β phase). The predicted flow stresses using the developed equation were compared with experimental data. Correlation coefficient (R) and average absolute relative error (AARE) were introduced to verify the validity of the constitutive equation. The values of R and AARE for α + β phase were 0.990 and 7.81%, respectively. And in β phase region, the values of R and AARE were 0.985 and 10.36%, respectively. Meanwhile, the accuracy, the number of material constants involved, and the computational time required of the constitutive equation were evaluated by comparing with a strain-compensated Arrhenius-type constitutive equation. The results indicate that accuracy of modified Johnson-Cook constitutive equation is higher than that of compensated Arrhenius-type model at α + β phase, while lower at single β phase region. Meanwhile, the time required for evaluating the material constants of modified Johnson-Cook constitutive equation is much shorter than that of the strain-compensated Arrhenius type ones. 7. The aminoacyl-tRNA synthetases of Drosophila melanogaster. PubMed Lu, Jiongming; Marygold, Steven J; Gharib, Walid H; Suter, Beat 2015-01-01 Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. Drosophila has become a preferred system to model human diseases caused by mutations in aaRS genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of aaRS genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on Drosophila aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field. PMID:26761199 8. Automated Aerial Refueling Hitches a Ride on AFF NASA Technical Reports Server (NTRS) Hansen, Jennifer L.; Murray, James E.; Bever, Glenn; Campos, Norma V.; Schkolnik, Gerard 2007-01-01 The recent introduction of uninhabited aerial vehicles [UAVs (basically, remotely piloted or autonomous aircraft)] has spawned new developments in autonomous operation and posed new challenges. Automated aerial refueling (AAR) is a capability that will enable UAVs to travel greater distances and loiter longer over targets. NASA Dryden Flight Research Center, in cooperation with the Defense Advanced Research Projects Agency (DARPA), the Naval Air Systems Command (NAVAIR), the Naval Air Force Pacific Fleet, and the Air Force Research Laboratory, rapidly conceived and accomplished an AAR flight research project focused on collecting a unique, high-quality database on the dynamics of the hose and drogue of an aerial refueling system. This flight-derived database would be used to validate mathematical models of the dynamics in support of design and analysis of AAR systems for future UAVs. The project involved the use of two Dryden F/A-18 airplanes and an S-3 hose-drogue refueling store on loan from the Navy. In this year-long project, which was started on October 1, 2002, 583 research maneuvers were completed during 23 flights. 9. Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria. PubMed Haen, Karri M; Pett, Walker; Lavrov, Dennis V 2010-10-01 Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa. 10. Segmentation of cytoplasm and nuclei of abnormal cells in cervical cytology using global and local graph cuts. PubMed Zhang, Ling; Kong, Hui; Chin, Chien Ting; Liu, Shaoxiong; Chen, Zhi; Wang, Tianfu; Chen, Siping 2014-07-01 Automation-assisted reading (AAR) techniques have the potential to reduce errors and increase productivity in cervical cancer screening. The sensitivity of AAR relies heavily on automated segmentation of abnormal cervical cells, which is handled poorly by current segmentation algorithms. In this paper, a global and local scheme based on graph cut approach is proposed to segment cervical cells in images with a mix of healthy and abnormal cells. For cytoplasm segmentation, the multi-way graph cut is performed globally on the a* channel enhanced image, which can be effective when the image histogram presents a non-bimodal distribution. For segmentation of nuclei, especially when they are abnormal, we propose to use graph cut adaptively and locally, which allows the combination of intensity, texture, boundary and region information. Two concave points-based approaches are integrated to split the touching-nuclei. As part of an ongoing clinical trial, preliminary validation results obtained from 21 cervical cell images with non-ideal imaging condition and pathology show that our segmentation method achieved 93% accuracy for cytoplasm, and 88.4% F-measure for abnormal nuclei, outperforming state of the art methods in terms of accuracy. Our method has the potential to improve the sensitivity of AAR in screening for cervical cancer. 11. Influence of steel fibers on the development of alkali-aggregate reaction SciTech Connect Pires de Carvalho, Maria Rita; Pagan Hasparyk, Nicole 2010-04-15 This work presents the results of an experimental research concerning the use of fibers in mortar specimens subjected to alkali-aggregate reaction (AAR). Two types of steel fibers (0.16 mm diameter and 6.0 mm length, and 0.20 mm diameter and 13.0 mm length) were used with fiber volume contents of 1% and 2%. Besides the expansion accelerated tests, compressive tests and flexural tests have also been carried out to display the main mechanical characteristics of the fiber-reinforced mortars after being subjected to AAR. Moreover, the microstructure of the specimens was analyzed by scanning electron microscopy and energy dispersive X-ray. The results shown that the addition of steel fibers reduced the expansion due to AAR for the experimental conditions studied in this paper. The most expressive benefit corresponded to the addition of 13.0 mm fibers in the mixture containing 2% fiber content. This fiber volume content also corresponded to the maximum increment in the mechanical properties compared to the reference mortar, mainly for the post-cracking strength and for the toughness in bending. It was observed that the fibers have a beneficial effect on the material, without compromising its main mechanical properties. 12. Hazmat on the rails: A closer look SciTech Connect Larson, K.M. 1996-10-01 Despite what appears to be a rash of railroad incidents involving hazardous materials, the Association of American Railroads (AAR; Washington, DC) maintains that 1995 was the safest year in railroad history, even though rail freight traffic was at an all-time high. AAR says railroads have an especially good record when it comes to moving hazardous waste. Railroads in 1994 moved more than 1.6 million carloads of hazardous materials, yet only 43 cars released hazardous contents--fewer than one for every 37,000 cars moved, AAR notes. Preliminary figures indicate another 43 cars released hazardous materials in 1995. Not all rail car releases occur as a result of an accident or derailment. Nonaccident releases (NARs) can result from such problems as tank car overfilling, chemical reactions during temperature changes, or loose tank closures. The top 10 hazardous commodities are: sulfuric acid, hydrochloric acid solution, anhydrous ammonia, liquefied petroleum gases, sodium hydroxide solution, flammable liquids not otherwise specified, corrosive liquids not otherwise specified, phosphoric acid, methyl tertiary butyl ether, and methanol. 13. The aminoacyl-tRNA synthetases of Drosophila melanogaster PubMed Central Lu, Jiongming; Marygold, Steven J; Gharib, Walid H; Suter, Beat 2015-01-01 Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. Drosophila has become a preferred system to model human diseases caused by mutations in aaRS genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of aaRS genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on Drosophila aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field. PMID:26761199 14. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology. PubMed Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng 2015-10-01 Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility. 15. Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life NASA Astrophysics Data System (ADS) Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter 2011-12-01 Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed. 16. A Modified Johnson-Cook Constitutive Equation to Predict Hot Deformation Behavior of Ti-6Al-4V Alloy NASA Astrophysics Data System (ADS) Cai, Jun; Wang, Kuaishe; Zhai, Peng; Li, Fuguo; Yang, Jie 2015-01-01 A modified Johnson-Cook constitutive equation of Ti-6Al-4V alloy is proposed based on hot compression tests performed in the temperature range of 1073-1323 K and strain rate 0.001-1 s-1. The experimental stress-strain data were employed to develop the modified Johnson-Cook constitutive equation of different phase regimes (α + β and β phase). The predicted flow stresses using the developed equation were compared with experimental data. Correlation coefficient ( R) and average absolute relative error (AARE) were introduced to verify the validity of the constitutive equation. The values of R and AARE for α + β phase were 0.990 and 7.81%, respectively. And in β phase region, the values of R and AARE were 0.985 and 10.36%, respectively. Meanwhile, the accuracy, the number of material constants involved, and the computational time required of the constitutive equation were evaluated by comparing with a strain-compensated Arrhenius-type constitutive equation. The results indicate that accuracy of modified Johnson-Cook constitutive equation is higher than that of compensated Arrhenius-type model at α + β phase, while lower at single β phase region. Meanwhile, the time required for evaluating the material constants of modified Johnson-Cook constitutive equation is much shorter than that of the strain-compensated Arrhenius type ones. 17. Structural Basis of Brr2-Prp8 Interactions and Implications for U5 snRNP Biogenesis and the Spliceosome Active Site PubMed Central Nguyen, Thi Hoang Duong; Li, Jade; Galej, Wojciech P.; Oshikane, Hiroyuki; Newman, Andrew J.; Nagai, Kiyoshi 2013-01-01 Summary The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Sm proteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP. PMID:23727230 18. Fluorescence Tomography of Rapamycin-Induced Autophagy and Cardioprotection In Vivo PubMed Central Chen, Howard H.; Mekkaoui, Choukri; Cho, Hoonsung; Ngoy, Soeun; Marinelli, Brett; Waterman, Peter; Nahrendorf, Matthias; Liao, Ronglih; Josephson, Lee; Sosnovik, David E. 2013-01-01 Background Autophagy is a biological process during which cells digest organelles in their cytoplasm and recycle the constituents. The impact of autophagy in the heart, however, remains unclear in part due to the inability to noninvasively image this process in living animals. Methods and Results Here, we report the use of fluorescence molecular tomography (FMT) and a cathepsin activatable fluorochrome to image autophagy in the heart in vivo following ischemia-reperfusion and rapamycin therapy. We show that cathepsin-B activity in the lysosome is upregulated by rapamycin and that this allows the expanded lysosomal compartment in autophagy to be imaged in vivo with FMT. We further demonstrate that the delivery of diagnostic nanoparticles to the lysosome by endocytosis is enhanced during autophagy. The upregulation of autophagy by rapamycin was associated with a 23% reduction (p<0.05) of apoptosis in the area-at-risk (AAR), and a 45% reduction in final infarct size (19.6 +/− 5.6% of AAR with rapamycin versus 35.9 +/− 9.1% of AAR without rapamycin, p<0.05). Conclusions The ability to perform noninvasive tomographic imaging of autophagy in the heart has the potential to provide valuable insights into the pathophysiology of autophagy, particularly its role in cardiomyocyte salvage. While additional data are needed, our study supports the investigation of rapamycin therapy in patients with acute coronary syndromes. PMID:23537953 19. Alkane production by the marine cyanobacterium Synechococcus sp. NKBG15041c possessing the α-olefin biosynthesis pathway. PubMed Yoshino, Tomoko; Liang, Yue; Arai, Daichi; Maeda, Yoshiaki; Honda, Toru; Muto, Masaki; Kakunaka, Natsumi; Tanaka, Tsuyoshi 2015-02-01 The production of alkanes in a marine cyanobacterium possessing the α-olefin biosynthesis pathway was achieved by introducing an exogenous alkane biosynthesis pathway. Cyanobacterial hydrocarbons are synthesized via two separate pathways: the acyl-acyl carrier protein (ACP) reductase/aldehyde-deformylating oxygenase (AAR/ADO) pathway for the alkane biosynthesis and the α-olefin synthase (OLS) pathway for the α-olefin biosynthesis. Coexistence of these pathways has not yet been reported. In this study, the marine cyanobacterium Synechococcus sp. NKBG15041c was shown to produce α-olefins similar to those of Synechococcus sp. PCC7002 via the α-olefin biosynthesis pathway. The production of heptadecane in Synechococcus sp. NKBG15041c was achieved by expressing the AAR/ADO pathway genes from Synechococcus elongatus PCC 7942. The production yields of heptadecane in Synechococcus sp. NKBG15041c varied with the expression level of the aar and ado genes. The maximal yield of heptadecane was 4.2 ± 1.2 μg/g of dried cell weight in the transformant carrying a homologous promoter. Our results also suggested that the effective activation of ADO may be more important for the enhancement of alkane production by cyanobacteria. 20. Unusual cause of acute low-back pain: sudden annulus fibrosus rupture PubMed Central Ozer, Ali Fahir; Oktenoglu, Tunc; Sasani, Mehdi; Kaner, Tuncay; Ercelen, Omur; Canbulat, Nazan 2012-01-01 Low-back pain is a common problem in neu-rosurgery practice, and an algorithm has been developed for assessing these cases. However, one subgroup of these patients shares several clinical features and these individuals are not easy to categorize and diagnose. We present our observations for 8 of these patients, individuals with low-back pain caused by atypical annulus fibrosus rupture (AAR). The aim of this study is to show the consequences of overlooked annular tears on acute onset of low back pain. Eight patients with acute-onset severe low-back pain were admitted. Physical examinations were normal and each individual was examined neurologically and assessed with neuroradiologic studies [plain x-rays, magnetic resonance imaging (MRI), discography and computed tomography (CT) discography]. AAR was ultimately diagnosed with provocative discography. In all cases, MRI showed a healthy disc or mild degeneration, whereas discography and CT discography demonstrated disc disease. Anterior interbody cage implantation was performed in 3 of the 8 cases and posterior dynamic stabilization was carried out in 3 cases. The other 2 individuals refused surgery, and we were informed that one of them developed disc herniation at the affected level 1 year after our diagnosis. Clinical and radiological outcomes were evaluated. In cases where AAR is suspected, MRI, discography, and CT discography should be performed in addition to routine neuroradiologic studies. PMID:22802990 1. Unusual cause of acute low-back pain: sudden annulus fibrosus rupture. PubMed Ozer, Ali Fahir; Oktenoglu, Tunc; Sasani, Mehdi; Kaner, Tuncay; Ercelen, Omur; Canbulat, Nazan 2012-05-01 Low-back pain is a common problem in neu-rosurgery practice, and an algorithm has been developed for assessing these cases. However, one subgroup of these patients shares several clinical features and these individuals are not easy to categorize and diagnose. We present our observations for 8 of these patients, individuals with low-back pain caused by atypical annulus fibrosus rupture (AAR). The aim of this study is to show the consequences of overlooked annular tears on acute onset of low back pain. Eight patients with acute-onset severe low-back pain were admitted. Physical examinations were normal and each individual was examined neurologically and assessed with neuroradiologic studies [plain x-rays, magnetic resonance imaging (MRI), discography and computed tomography (CT) discography]. AAR was ultimately diagnosed with provocative discography. In all cases, MRI showed a healthy disc or mild degeneration, whereas discography and CT discography demonstrated disc disease. Anterior interbody cage implantation was performed in 3 of the 8 cases and posterior dynamic stabilization was carried out in 3 cases. The other 2 individuals refused surgery, and we were informed that one of them developed disc herniation at the affected level 1 year after our diagnosis. Clinical and radiological outcomes were evaluated. In cases where AAR is suspected, MRI, discography, and CT discography should be performed in addition to routine neuroradiologic studies. PMID:22802990 2. Does a Superswell Exist Between Antarctica and Australia? NASA Astrophysics Data System (ADS) Park, S. H.; Langmuir, C. H.; Scott, S. R.; Sims, K. W. W.; Lin, J.; Kim, S.; Michael, P. J.; Hahm, D. 2015-12-01 The Australian-Antarctic Ridge (AAR) is located between the Australian-Antarctic Discordance (AAD) of the Southeast Indian ridge (SEIR) in the west and Pacific-Antarctic Ridge (PAR) in the east. The AAR has intermediate spreading rate (~70 mm/yr) and consists of a series of 1st order segments bounded by parallel transform faults. KR1, a southernmost segment (63°S) of the AAR, is a 300-km-long super-segment with shallow axial depth (~2000 m). KR1 is bounded by the Macquarie transform fault in the east and the Balleney transform fault in the west, which connects KR1 with KR2 at ~ 200 km north. KR2 is 180 km long with axial depth (~2300 m) deeper than KR1. Both KR1 and KR2 are shallow relative to global mid-ocean ridges. Most of the basaltic rocks from the two segments show enriched geochemical characteristics that differ from both the AAD (Southeast Indian Ridge) and the PAR. La/Sm ratios vary from N-MORB to T-MORB; however, K2O/Nb ratios of all samples are consistently low like OIB. Their Pb isotopes are mostly more radiogenic than the N-MORB samples from PAR (and EPR) and SEIR, with 206Pb/204Pb mostly >18.6. At a given 206Pb/204Pb, their 87Sr/86Sr are higher than the PAR, but lower than the SEIR. The basalts from the two segments are geochemically similar to Cenozoic volcanoes erupted on southeast Australia, Zealandia and northwest Antarctica, suggesting a genetic relationship. According to tectonic reconstruction models, these three continents were originally joined, but separated from each other after ~80 Ma. Notably, the KR1 and KR2 segments are located at the boundary of this continental separation. The ages of Cenozoic volcanoes span from ~ 60 Ma to the recent, and the volcanoes might be related to a plume head that caused the breakup of the continents. Seismic tomography studies show that there is a low velocity zone (LVZ) in the shallow mantle (> 250 km) between Antarctica and Australia where the AAR is located. The AAR would be sampling this LVZ, and this 3. GPS navigation algorithms for Autonomous Airborne Refueling of Unmanned Air Vehicles NASA Astrophysics Data System (ADS) Khanafseh, Samer Mahmoud Unmanned Air Vehicles (UAVs) have recently generated great interest because of their potential to perform hazardous missions without risking loss of life. If autonomous airborne refueling is possible for UAVs, mission range and endurance will be greatly enhanced. However, concerns about UAV-tanker proximity, dynamic mobility and safety demand that the relative navigation system meets stringent requirements on accuracy, integrity, and continuity. In response, this research focuses on developing high-performance GPS-based navigation architectures for Autonomous Airborne Refueling (AAR) of UAVs. The AAR mission is unique because of the potentially severe sky blockage introduced by the tanker. To address this issue, a high-fidelity dynamic sky blockage model was developed and experimentally validated. In addition, robust carrier phase differential GPS navigation algorithms were derived, including a new method for high-integrity reacquisition of carrier cycle ambiguities for recently-blocked satellites. In order to evaluate navigation performance, world-wide global availability and sensitivity covariance analyses were conducted. The new navigation algorithms were shown to be sufficient for turn-free scenarios, but improvement in performance was necessary to meet the difficult requirements for a general refueling mission with banked turns. Therefore, several innovative methods were pursued to enhance navigation performance. First, a new theoretical approach was developed to quantify the position-domain integrity risk in cycle ambiguity resolution problems. A mechanism to implement this method with partially-fixed cycle ambiguity vectors was derived, and it was used to define tight upper bounds on AAR navigation integrity risk. A second method, where a new algorithm for optimal fusion of measurements from multiple antennas was developed, was used to improve satellite coverage in poor visibility environments such as in AAR. Finally, methods for using data-link extracted 4. A comparison of the toxinological characteristics of two Cassiopea and Aurelia species. PubMed Radwan, F F; Burnett, J W; Bloom, D A; Coliano, T; Eldefrawi, M E; Erderly, H; Aurelian, L; Torres, M; Heimer-de la Cotera, E P 2001-01-01 A comparison of the toxinological properties of nematocyst venoms from Old and New World Cassiopea and Aurelia species was undertaken. The cnidom of venomous Cassiopea andromeda (Ca) and Aurelia (Aa(RS)) from the Red Sea was identical to that of nonvenomous Bahamian Cassiopea xamancha (Cx) and Chesapeake Bay Aurelia aurita (Aa(CB)), respectively. A clean nematocyst preparation of Ca and both Aurelias could be obtained but algal particles could not be separated completely from the Cx nematocysts. Further purification of all four nematocyst preparations showed significant differences in the action of their protein. Only the Cassiopea had coexisting dermonecrotic and vasopermeability producing properties and Ca's hemolytic activity was associated with mouse lethality. The protein, hemolysin and phospholipase gel filtration eluant curves of Ca venom were similar. Venomous Aa(RS) actively stung lips and contained more potent mouse lethal, demonecrotic, vasopermeability plus hemolytic factors than Aa(CB). Cross reactivity of convalescent human serum obtained from patients stung by Ca and venomous Cx collected in Central America occurred. This was also observed between sera of bathers stung by Aa(RS) and stinging Aurelia which appeared in Florida during the recent El Niño year. IgG was stimulated by several nematocyst proteins since many venom subfractions tested positive at high titers against convalescent sera. T-cell proliferation of mice primed with either Aurelia venom was positive against the homologous preparation with cross reactivity to the heterologous venom. Crude venoms of both Red Sea jellyfish metabolically stimulated cultured human hepatocytes more than their New World counterparts. This data shows that considerable similarities and differences exist in the venoms of these Old and New World Cassiopea and Aurelia medusae with the Eastern species being more potent. PMID:10978742 5. Estimation of glacier mass balance: An approach based on satellite-derived transient snowlines and a temperature index driven by meteorological observations NASA Astrophysics Data System (ADS) Tawde, S. A.; Kulkarni, A. V.; Bala, G. 2015-12-01 In the Himalaya, large area is comprised of glaciers and seasonal snow, mainly due to its high elevated mountain ranges. Long term and continuous assessment of glaciers in this region is important for climatological and hydrological applications. However, rugged terrains and severe weather conditions in the Himalaya lead to paucity in field observations. Therefore, in recent decades, glacier dynamics are extensively monitored using remote sensing in inaccessible terrain like Himalaya. Estimation of glacier mass balance using empirical relationship between mass balance and area accumulation ratio (AAR) requires an accurate estimate of equilibrium-line altitude (ELA). ELA is defined as the snowline at the end of the hydrological year. However, identification of ELA, using remote sensing is difficult because of temporal gaps, cloud cover and intermediate snowfall on glaciers. This leads to large uncertainty in glacier mass-balance estimates by the conventional AAR method that uses satellite-derived highest snowline in ablation season as an ELA. The present study suggests a new approach to improve estimates of ELA location. First, positions of modelled snowlines are optimized using satellite-derived snowlines in the early melt season. Secondly, ELA at the end of the glaciological year is estimated by the melt and accumulation models driven using in situ temperature and precipitation records. From the modelled ELA, mass balance is estimated using the empirical relationship between AAR and mass balance. The modelled mass balance is validated using field measurements on Chhota Shigri and Hamtah glaciers, Himachal Pradesh, India. The new approach shows a substantial improvement in glacier mass-balance estimation, reducing bias by 46% and 108% for Chhota Shigiri and Hamtah glaciers respectively. The cumulative mass loss reconstructed from our approach is 0.85 Gt for nine glaciers in the Chandra basin from 2001 to 2009. The result of the present study is in agreement with 6. New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle PubMed Central Evans, Ann E.; Tripathi, Abhishek; LaPorte, Heather M.; Brueggemann, Lioubov I.; Singh, Abhay Kumar; Albee, Lauren J.; Byron, Kenneth L.; Tarasova, Nadya I.; Volkman, Brian F.; Cho, Thomas Yoonsang; Gaponenko, Vadim; Majetschak, Matthias 2016-01-01 Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α1A/B-AR heteromers are important for α1-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca2+-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α1A-AR heteromers are important for intrinsic α1-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC. PMID:27331810 7. The Roles of Compensatory Evolution and Constraint in Aminoacyl tRNA Synthetase Evolution. PubMed Adrion, Jeffrey R; White, P Signe; Montooth, Kristi L 2016-01-01 Mitochondrial protein translation requires interactions between transfer RNAs encoded by the mitochondrial genome (mt-tRNAs) and mitochondrial aminoacyl tRNA synthetase proteins (mt-aaRS) encoded by the nuclear genome. It has been argued that animal mt-tRNAs have higher deleterious substitution rates relative to their nuclear-encoded counterparts, the cytoplasmic tRNAs (cyt-tRNAs). This dynamic predicts elevated rates of compensatory evolution of mt-aaRS that interact with mt-tRNAs, relative to aaRS that interact with cyt-tRNAs (cyt-aaRS). We find that mt-aaRS do evolve at significantly higher rates (exemplified by higher dN and dN/dS) relative to cyt-aaRS, across mammals, birds, and Drosophila. While this pattern supports a model of compensatory evolution, the level at which a gene is expressed is a more general predictor of protein evolutionary rate. We find that gene expression level explains 10-56% of the variance in aaRS dN/dS, and that cyt-aaRS are more highly expressed in addition to having lower dN/dS values relative to mt-aaRS, consistent with more highly expressed genes being more evolutionarily constrained. Furthermore, we find no evidence of positive selection acting on either class of aaRS protein, as would be expected under a model of compensatory evolution. Nevertheless, the signature of faster mt-aaRS evolution persists in mammalian, but not bird or Drosophila, lineages after controlling for gene expression, suggesting some additional effect of compensatory evolution for mammalian mt-aaRS. We conclude that gene expression is the strongest factor governing differential amino acid substitution rates in proteins interacting with mitochondrial versus cytoplasmic factors, with important differences in mt-aaRS molecular evolution among taxonomic groups. 8. A large family of anti‐activators accompanying XylS/AraC family regulatory proteins PubMed Central Yan, Michael B.; Tran, Minh; Wright, Nathan; Luzader, Deborah H.; Kendall, Melissa M.; Ruiz‐Perez, Fernando; Nataro, James P. 2016-01-01 Summary AraC Negative Regulators (ANR) suppress virulence genes by directly down‐regulating AraC/XylS members in Gram‐negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR‐activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC‐like member AggR. ANR‐AggR binding disrupted AggR dimerization and prevented AggR‐DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α‐helices. Site‐directed mutagenesis studies suggest that at least predicted α‐helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners. PMID:27038276 9. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis PubMed Central Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan 2015-01-01 Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine 10. Command Center Training Tool (C2T2) NASA Technical Reports Server (NTRS) Jones, Phillip; Drucker, Nich; Mathews, Reejo; Stanton, Laura; Merkle, Ed 2012-01-01 This abstract presents the training approach taken to create a management-centered, experiential learning solution for the Virginia Port Authority's Port Command Center. The resultant tool, called the Command Center Training Tool (C2T2), follows a holistic approach integrated across the training management cycle and within a single environment. The approach allows a single training manager to progress from training design through execution and AAR. The approach starts with modeling the training organization, identifying the organizational elements and their individual and collective performance requirements, including organizational-specific performance scoring ontologies. Next, the developer specifies conditions, the problems, and constructs that compose exercises and drive experiential learning. These conditions are defined by incidents, which denote a single, multi-media datum, and scenarios, which are stories told by incidents. To these layered, modular components, previously developed meta-data is attached, including associated performance requirements. The components are then stored in a searchable library An event developer can create a training event by searching the library based on metadata and then selecting and loading the resultant modular pieces. This loading process brings into the training event all the previously associated task and teamwork material as well as AAR preparation materials. The approach includes tools within an integrated management environment that places these materials at the fingertips of the event facilitator such that, in real time, the facilitator can track training audience performance and resultantly modify the training event. The approach also supports the concentrated knowledge management requirements for rapid preparation of an extensive AAR. This approach supports the integrated training cycle and allows a management-based perspective and advanced tools, through which a complex, thorough training event can be developed. 11. Aminoacylating Urzymes Challenge the RNA World Hypothesis*♦ PubMed Central Li, Li; Francklyn, Christopher; Carter, Charles W. 2013-01-01 We describe experimental evidence that ancestral peptide catalysts substantially accelerated development of genetic coding. Structurally invariant 120–130-residue Urzymes (Ur = primitive plus enzyme) derived from Class I and Class II aminoacyl-tRNA synthetases (aaRSs) acylate tRNA far faster than the uncatalyzed rate of nonribosomal peptide bond formation from activated amino acids. These new data allow us to demonstrate statistically indistinguishable catalytic profiles for Class I and II aaRSs in both amino acid activation and tRNA acylation, over a time period extending to well before the assembly of full-length enzymes and even further before the Last Universal Common Ancestor. Both Urzymes also exhibit ∼60% of the contemporary catalytic proficiencies. Moreover, they are linked by ancestral sense/antisense genetic coding, and their evident modularities suggest descent from even simpler ancestral pairs also coded by opposite strands of the same gene. Thus, aaRS Urzymes substantially pre-date modern aaRS but are, nevertheless, highly evolved. Their unexpectedly advanced catalytic repertoires, sense/antisense coding, and ancestral modularities imply considerable prior protein-tRNA co-evolution. Further, unlike ribozymes that motivated the RNA World hypothesis, Class I and II Urzyme·tRNA pairs represent consensus ancestral forms sufficient for codon-directed synthesis of nonrandom peptides. By tracing aaRS catalytic activities back to simpler ancestral peptides, we demonstrate key steps for a simpler and hence more probable peptide·RNA development of rapid coding systems matching amino acids with anticodon trinucleotides. PMID:23867455 12. Understanding and identifying amino acid repeats. PubMed Luo, Hong; Nijveen, Harm 2014-07-01 Amino acid repeats (AARs) are abundant in protein sequences. They have particular roles in protein function and evolution. Simple repeat patterns generated by DNA slippage tend to introduce length variations and point mutations in repeat regions. Loss of normal and gain of abnormal function owing to their variable length are potential risks leading to diseases. Repeats with complex patterns mostly refer to the functional domain repeats, such as the well-known leucine-rich repeat and WD repeat, which are frequently involved in protein–protein interaction. They are mainly derived from internal gene duplication events and stabilized by ‘gate-keeper’ residues, which play crucial roles in preventing inter-domain aggregation. AARs are widely distributed in different proteomes across a variety of taxonomic ranges, and especially abundant in eukaryotic proteins. However, their specific evolutionary and functional scenarios are still poorly understood. Identifying AARs in protein sequences is the first step for the further investigation of their biological function and evolutionary mechanism. In principle, this is an NP-hard problem, as most of the repeat fragments are shaped by a series of sophisticated evolutionary events and become latent periodical patterns. It is not possible to define a uniform criterion for detecting and verifying various repeat patterns. Instead, different algorithms based on different strategies have been developed to cope with different repeat patterns. In this review, we attempt to describe the amino acid repeat-detection algorithms currently available and compare their strategies based on an in-depth analysis of the biological significance of protein repeats. PMID:23418055 13. Early auditory experience induces frequency-specific, adaptive plasticity in the forebrain gaze fields of the barn owl. PubMed Miller, G L; Knudsen, E I 2001-05-01 Binaural acoustic cues such as interaural time and level differences (ITDs and ILDs) are used by many species to determine the locations of sound sources. The relationship between cue values and locations in space is frequency dependent and varies from individual to individual. In the current study, we tested the capacity of neurons in the forebrain localization pathway of the barn owl to adjust their tuning for binaural cues in a frequency-dependent manner in response to auditory experience. Auditory experience was altered by raising young owls with a passive acoustic filtering device that caused frequency-dependent changes in ITD and ILD. Extracellular recordings were made in normal and device-reared owls to characterize frequency-specific ITD and ILD tuning in the auditory archistriatum (AAr), an output structure of the forebrain localization pathway. In device-reared owls, individual sites in the AAr exhibited highly abnormal, frequency-dependent variations in ITD tuning, and across the population of sampled sites, there were frequency-dependent shifts in the representation of ITD. These changes were in a direction that compensated for the acoustic effects of the device on ITD and therefore tended to restore a normal representation of auditory space. Although ILD tuning was degraded relative to normal at many sites in the AAr of device-reared owls, the representation of frequency-specific ILDs across the population of sampled sites was shifted in the adaptive direction. These results demonstrate that early auditory experience shapes the representation of binaural cues in the forebrain localization pathway in an adaptive, frequency-dependent manner. PMID:11353033 14. Distribution within the barn owl's inferior colliculus of neurons projecting to the optic tectum and thalamus. PubMed Arthur, Ben J 2005-11-01 Behavioral studies in barn owls indicate that both the optic tectum (OT) and the auditory arcopallium (AAr) mediate sound localization through the presence of neurons that respond only when sound comes from a circumscribed direction in space. The early stages of the computations leading to these so-called space-specific neurons are shared in a common brainstem pathway, which then splits at the level of the inferior colliculus (IC) such that the last computational stage is thought to be duplicated. The study presented here addresses whether the space-specific neurons in OT and AAr are indeed partially independent of each other by using anatomical methods more precise than those used in previous studies. Specifically, projection neurons in IC were retrogradely labelled with injections of fluorescein- and rhodamine-conjugated dextran amines into OT and nucleus ovoidalis (OV), the thalamic nucleus leading to AAr. By labelling the OT-projecting and OV-projecting neurons in the same owl, it was confirmed that neurons in IC project to either OV or OT but not both. However, although a segregation was generally observed between the medially positioned OV-projecting neurons and the laterally positioned OT-projecting neurons, there was also a slight overlap between the two populations. Moreover, electrolytic lesions demarcating physiological tuning properties indicate that many OV-projecting neurons are within the area containing space-specific neurons. These results highlight the need for more detailed studies elucidating the microcircuitry and corresponding physiology of IC, such as have been done in the cortices of the mammalian cerebellum and cerebrum. PMID:16175562 15. Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process PubMed Central Woese, Carl R.; Olsen, Gary J.; Ibba, Michael; Söll, Dieter 2000-01-01 The aminoacyl-tRNA synthetases (AARSs) and their relationship to the genetic code are examined from the evolutionary perspective. Despite a loose correlation between codon assignments and AARS evolutionary relationships, the code is far too highly structured to have been ordered merely through the evolutionary wanderings of these enzymes. Nevertheless, the AARSs are very informative about the evolutionary process. Examination of the phylogenetic trees for each of the AARSs reveals the following. (i) Their evolutionary relationships mostly conform to established organismal phylogeny: a strong distinction exists between bacterial- and archaeal-type AARSs. (ii) Although the evolutionary profiles of the individual AARSs might be expected to be similar in general respects, they are not. It is argued that these differences in profiles reflect the stages in the evolutionary process when the taxonomic distributions of the individual AARSs became fixed, not the nature of the individual enzymes. (iii) Horizontal transfer of AARS genes between Bacteria and Archaea is asymmetric: transfer of archaeal AARSs to the Bacteria is more prevalent than the reverse, which is seen only for the “gemini group.” (iv) The most far-ranging transfers of AARS genes have tended to occur in the distant evolutionary past, before or during formation of the primary organismal domains. These findings are also used to refine the theory that at the evolutionary stage represented by the root of the universal phylogenetic tree, cells were far more primitive than their modern counterparts and thus exchanged genetic material in far less restricted ways, in effect evolving in a communal sense. PMID:10704480 16. 8-NH2-boldine, an antagonist of alpha1A and alpha1B adrenoceptors without affinity for the alpha1D subtype: structural requirements for aporphines at alpha1-adrenoceptor subtypes. PubMed Ivorra, M Dolores; Valiente, Miguel; Martínez, Sonia; Madrero, Yolanda; Noguera, M Antonia; Cassels, Bruce K; Sobarzo, Eduardo M; D'Ocon, Pilar 2005-10-01 Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human alpha (1A), alpha (1B) and alpha (1D) adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each alpha (1)-AR subtype. All the compounds tested competed for [ (125)I]-HEAT binding with steep and monophasic curves. The most interesting compound was 8-NH (2)-boldine, which retains the selective affinity for alpha(1A)-AR (pKi = 6.37 +/- 0.21) vs. alpha(1B)-AR (pKi = 5.53 +/- 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for alpha(1D)-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cortex confirms the results obtained for human cloned alpha (1)-AR subtypes. The compounds selective for the alpha (1A) subtype discriminate two binding sites in rat cerebral cortex confirming a mixed population of alpha (1A)- and alpha (1B)-AR in this tissue. All compounds are more selective as inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. A close relationship was found between affinities obtained for cloned alpha (1A)-AR and inhibitory potencies on noradrenaline-induced contraction or inositol phosphate accumulation in tail artery, confirming that there is a homogeneous functional population of alpha(1A)-AR in this vessel. On the contrary, a poor correlation seems to exist between the affinity of 8-NH (2)-boldine for cloned alpha (1D)-AR and its potency as an inhibitor of noradrenaline-induced contraction or inositol phosphate accumulation in rat aorta, which confirms that a heterogeneous population of alpha (1)-AR mediates the adrenergic response in this vessel. 17. Determinants for tRNA-Dependent Pretransfer Editing in the Synthetic Site of Isoleucyl-tRNA Synthetase PubMed Central 2015-01-01 The accurate expression of genetic information relies on the fidelity of amino acid–tRNA coupling by aminoacyl-tRNA synthetases (aaRS). When the specificity against structurally similar noncognate amino acids in the synthetic reaction does not support a threshold fidelity level for translation, the aaRS employ intrinsic hydrolytic editing to correct errors in aminoacylation. Escherichia coli isoleucyl-tRNA synthetase (EcIleRS) is a class I aaRS that is notable for its use of tRNA-dependent pretransfer editing to hydrolyze noncognate valyl-adenylate prior to aminoacyl-tRNA formation. On the basis of the finding that IleRS possessing an inactivated post-transfer editing domain is still capable of robust tRNA-dependent editing, we have recently proposed that the pretransfer editing activity resides within the synthetic site. Here we apply an improved methodology that allows quantitation of the AMP fraction that arises particularly from tRNA-dependent aa-AMP hydrolysis. By this approach, we demonstrate that tRNA-dependent pretransfer editing accounts for nearly one-third of the total proofreading by EcIleRS and that a highly conserved tyrosine within the synthetic site modulates both editing and aminoacylation. Therefore, synthesis of aminoacyl-tRNA and hydrolysis of aminoacyl-adenylates employ overlapping amino acid determinants. We suggest that this overlap hindered the evolution of synthetic site-based pretransfer editing as the predominant proofreading pathway, because that activity is difficult to accommodate in the context of efficient aminoacyl-tRNA synthesis. Instead, the acquisition of a spatially separate domain dedicated to post-transfer editing alone allowed for the development of a powerful deacylation machinery that effectively competes with dissociation of misacylated tRNAs. PMID:25207837 18. α1A-Adrenergic receptor prevents cardiac ischemic damage through PKCδ/GLUT1/4-mediated glucose uptake. PubMed Shi, Ting; Papay, Robert S; Perez, Dianne M 2016-01-01 While α(1)-adrenergic receptors (ARs) have been previously shown to limit ischemic cardiac damage, the mechanisms remain unclear. Most previous studies utilized low oxygen conditions in addition to ischemic buffers with glucose deficiencies, but we discovered profound differences if the two conditions are separated. We assessed both mouse neonatal and adult myocytes and HL-1 cells in a series of assays assessing ischemic damage under hypoxic or low glucose conditions. We found that α(1)-AR stimulation protected against increased lactate dehydrogenase release or Annexin V(+) apoptosis under conditions that were due to low glucose concentration not to hypoxia. The α(1)-AR antagonist prazosin or nonselective protein kinase C (PKC) inhibitors blocked the protective effect. α(1)-AR stimulation increased (3)H-deoxyglucose uptake that was blocked with either an inhibitor to glucose transporter 1 or 4 (GLUT1 or GLUT4) or small interfering RNA (siRNA) against PKCδ. GLUT1/4 inhibition also blocked α(1)-AR-mediated protection from apoptosis. The PKC inhibitor rottlerin or siRNA against PKCδ blocked α(1)-AR stimulated GLUT1 or GLUT4 plasma membrane translocation. α(1)-AR stimulation increased plasma membrane concentration of either GLUT1 or GLUT4 in a time-dependent fashion. Transgenic mice overexpressing the α(1A)-AR but not α(1B)-AR mice displayed increased glucose uptake and increased GLUT1 and GLUT4 plasma membrane translocation in the adult heart while α(1A)-AR but not α(1B)-AR knockout mice displayed lowered glucose uptake and GLUT translocation. Our results suggest that α(1)-AR activation is anti-apoptotic and protective during cardiac ischemia due to glucose deprivation and not hypoxia by enhancing glucose uptake into the heart via PKCδ-mediated GLUT translocation that may be specific to the α(1A)-AR subtype. 19. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis. PubMed Tang, Xiaohu; Keenan, Melissa M; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J Will; Freedland, Stephen J; Murphy, Susan K; Chi, Jen-Tsan 2015-04-01 Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine 20. Proteomic-coupled-network analysis of T877A-androgen receptor interactomes can predict clinical prostate cancer outcomes between White (non-Hispanic) and African-American groups. PubMed Zaman, Naif; Giannopoulos, Paresa N; Chowdhury, Shafinaz; Bonneil, Eric; Thibault, Pierre; Wang, Edwin; Trifiro, Mark; Paliouras, Miltiadis 2014-01-01 The androgen receptor (AR) remains an important contributor to the neoplastic evolution of prostate cancer (CaP). CaP progression is linked to several somatic AR mutational changes that endow upon the AR dramatic gain-of-function properties. One of the most common somatic mutations identified is Thr877-to-Ala (T877A), located in the ligand-binding domain, that results in a receptor capable of promiscuous binding and activation by a variety of steroid hormones and ligands including estrogens, progestins, glucocorticoids, and several anti-androgens. In an attempt to further define somatic mutated AR gain-of-function properties, as a consequence of its promiscuous ligand binding, we undertook a proteomic/network analysis approach to characterize the protein interactome of the mutant T877A-AR in LNCaP cells under eight different ligand-specific treatments (dihydrotestosterone, mibolerone, R1881, testosterone, estradiol, progesterone, dexamethasone, and cyproterone acetate). In extending the analysis of our multi-ligand complexes of the mutant T877A-AR we observed significant enrichment of specific complexes between normal and primary prostatic tumors, which were furthermore correlated with known clinical outcomes. Further analysis of certain mutant T877A-AR complexes showed specific population preferences distinguishing primary prostatic disease between white (non-Hispanic) vs. African-American males. Moreover, these cancer-related AR-protein complexes demonstrated predictive survival outcomes specific to CaP, and not for breast, lung, lymphoma or medulloblastoma cancers. Our study, by coupling data generated by our proteomics to network analysis of clinical samples, has helped to define real and novel biological pathways in complicated gain-of-function AR complex systems. 1. Proteomic-Coupled-Network Analysis of T877A-Androgen Receptor Interactomes Can Predict Clinical Prostate Cancer Outcomes between White (Non-Hispanic) and African-American Groups PubMed Central Zaman, Naif; Giannopoulos, Paresa N.; Chowdhury, Shafinaz; Bonneil, Eric; Thibault, Pierre; Wang, Edwin; Trifiro, Mark; Paliouras, Miltiadis 2014-01-01 The androgen receptor (AR) remains an important contributor to the neoplastic evolution of prostate cancer (CaP). CaP progression is linked to several somatic AR mutational changes that endow upon the AR dramatic gain-of-function properties. One of the most common somatic mutations identified is Thr877-to-Ala (T877A), located in the ligand-binding domain, that results in a receptor capable of promiscuous binding and activation by a variety of steroid hormones and ligands including estrogens, progestins, glucocorticoids, and several anti-androgens. In an attempt to further define somatic mutated AR gain-of-function properties, as a consequence of its promiscuous ligand binding, we undertook a proteomic/network analysis approach to characterize the protein interactome of the mutant T877A-AR in LNCaP cells under eight different ligand-specific treatments (dihydrotestosterone, mibolerone, R1881, testosterone, estradiol, progesterone, dexamethasone, and cyproterone acetate). In extending the analysis of our multi-ligand complexes of the mutant T877A-AR we observed significant enrichment of specific complexes between normal and primary prostatic tumors, which were furthermore correlated with known clinical outcomes. Further analysis of certain mutant T877A-AR complexes showed specific population preferences distinguishing primary prostatic disease between white (non-Hispanic) vs. African-American males. Moreover, these cancer-related AR-protein complexes demonstrated predictive survival outcomes specific to CaP, and not for breast, lung, lymphoma or medulloblastoma cancers. Our study, by coupling data generated by our proteomics to network analysis of clinical samples, has helped to define real and novel biological pathways in complicated gain-of-function AR complex systems. PMID:25409505 2. Assessment of soil nitrogen and related enzymes as influenced by the incorporation time of field pea cultivated as a catch crop in Alfisol. PubMed Piotrowska-Długosz, Anna; Wilczewski, Edward 2014-12-01 The effect of the time of catch crop (field pea) incorporation [catch crop incorporated in the autumn (A) or in the spring (B) versus plots without a catch crop (C)] on the soil enzymes related to N transformation (urease - UR, protease - PRO, nitrate reductase - NR, arginine ammonification rate - AAR), the total N and mineral N as well as microbial biomass N (MBN) contents were investigated in a 3-year experiment. The catch crop was sown at the beginning of August and plowed in the autumn in 2008, 2009 and 2010 or left as mulch during the winter. Soil samples for microbial activity were taken from spring barley plots that were grown in 2009, 2010 and 2011 before sowing (March), during the tillering phase (May), shooting (June) and after the harvesting of spring barley (August). The use of catch crop significantly increased the soil mineral and MBN contents as well as the activities of PRO and NR as compared to the control soil. The spring incorporation of the field pea significantly increased the MBN content in contrast to the autumn application, while the activity of N-cycle enzymes were clearly unaffected (UR and AAR) regardless of the time of the incorporation of field pea or else the results were inconsistent (PRO and NR). When the catch crop was incorporated in the spring, a significantly higher content of mineral N as compared to autumn incorporation was noted on only two of the four sampling dates. The enzymatic activity (PRO and AAR) was about 1.3-2.8 times higher in May and June as compared with March and August. Both spring or autumn incorporation of catch crop can be a useful management practice to increase the soil mineral N content and enhance the soil biological activity. 3. Mutual design: Overhead transmission lines and railroad facilities: Susceptibility program: Final report SciTech Connect Frazier, M.J.; Little, D.R. 1989-07-01 The sharing of common corridors by electric power transmission lines and railroad facilities can result in the coupling of unwanted electromagnetic energy from the power lines into nearby railroad systems. The coupling can result in voltage being induced onto the railroad system conductors that may compromise the inherent safety and reliability of the railroad signalling system. This broad-scoped research program, which is co-sponsored by EPRI and the AAR, is addressing the problem from two directions. This two volume report describes a Phase 1 effort to develop the methods and techniques for quantifying the signal system response to interference. 54 figs., 7 tabs. 4. Equilibrium Line Altitude fluctuations at HualcaHualca volcano (southern Peru). NASA Astrophysics Data System (ADS) Alcalá, Jesus; Palacios, David; Juan Zamorano, Jose 2015-04-01 Interest in Andean glaciers has substantially increased during the last decades, due to its high sensitivity to climate fluctuations. In this sense, Equilibrium Line Altitude (ELA) is a reliable indicator of climate variability that has been frequently used to reconstruct palaeoenvironmental conditions at different temporal and spatial scales. However, the number of sites with ELA reconstructions is still insufficient to determine patterns in tropical climate or estimations of atmospheric cooling since the Last Glacial Maximum. The main purpose of this study is to contribute in resolving tropical climate evolution through ELA calculations on HualcaHualca (15° 43' S; 71° 52' W; 6,025 masl), a large andesitic stratovolcano located in the south-western Peruvian Andes approximately 70 km north-west of Arequipa. We applied Terminus Headwall Altitude Ratio (THAR) with 0.2; 0.4; 0.5; 0.57 ratios, Accumulation Area Ratio (AAR) and Accumulation Area Balance Ratio (AABR) methods in four valleys of HualcaHualca volcano: Huayuray (north side), Pujro Huayjo (southwest side), Mollebaya (east side) and Mucurca (west side). To estimate ELA depression, we calculated the difference between the ELA on 1955 with its position in the Maximum Glacier Extent (MGE), Tardiglacial phases, little Ice Age (LIA) and 2000. Paleotemperature reconstructions derived from vertical temperature gradient 6.5° C / 1 km, based on GODDARD global observation system considered the most appropriate model for arid Andes. During MGE, the ELA was located between 5,005 (AABR) and 5,215 (AAR 0.67) masl. But in 1955, ELA rose to 5,685 (AABR) - 5,775 (AAR 0.67) masl. The ELA depression between those two phases is 560 - 680 m that implies a temperature decrease of 3.5° - 4.4° C. The experimental process based in the use and contrast of different ELA reconstruction techniques applied in this study suggests that THAR (0.57), AAR (0.67) or AABR are the most consistent procedures for HualcaHualca glaciers, while 5. Spatial and temporal modelling of fluvial aggradation in the Hasli Valley (Swiss Alps) during the last 1300 years NASA Astrophysics Data System (ADS) Llorca, Jaime; Schulte, Lothar; Carvalho, Filipe 2016-04-01 The Haslital delta (upper Aare River catchment, Bernese Alps) progradated into the Lake Brienz after the retreat of the Aare Glacier (post-LGM). Present delta plain geomorphology and spatial distribution of sedimentary facies result from historical fluvial dynamics and aggradation. Over centuries, local communities have struggled to control the Aare floods and to mitigate their effects on the floodplain (by means of raising artificial levees, channelizing the course, creating an underground drainage network, constructing dams at the basin headwaters). This study focuses on the spatial and temporal evolution of sediment dynamics of the floodplain by analyzing fluvial sedimentary records . The internal variability of lithostratigraphic sequences is a key issue to understand hydrological processes in the basin under the effect of environmental and anthropogenic changes of the past. The floodplain lithostratigraphy was reconstructed by coring alongside four cross-sections; each one is composed of more than 25 shallow boreholes (2 m deep) and two long drillings (variable depth, up to 9 m). The chronostratigraphical models were obtained by AMS 14C dating, and information of paleofloods and channel migration were reconstructed from historical sources (Schulte et al., 2015). The identification of different sedimentary facies, associated with the fluvial architecture structures, provides information on variations of vertical and lateral accretion processes (Houben, 2007). The location and geometry of buried channel-levee facies (gravel and coarse sand layers) indicate a significant mobility of the riverbed of the Hasli-Aare river, following an oscillatory pattern during the last millennia. Furthermore, fine sedimentary deposits and peat layers represent the existence of stable areas where floods have a low incidence. Once the different types of deposits were identified, aggradation rates were estimated in order to determine the spatial variability of the accumulation 6. Intracellular transactivation of epidermal growth factor receptor by α1A-adrenoceptor is mediated by phosphatidylinositol 3-kinase independently of activation of extracellular signal regulated kinases 1/2 and serine-threonine kinases in Chinese hamster ovary cells. PubMed Ulu, Nadir; Henning, Robert H; Guner, Sahika; Zoto, Teuta; Duman-Dalkilic, Basak; Duin, Marry; Gurdal, Hakan 2013-10-01 Transactivation of epidermal growth factor receptor (EGFR) by α1-adrenoceptor (α1-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all α1-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster ovary (CHO) cells stably expressing one subtype of α1-AR were transiently transfected with EGFR. The transactivation mechanism was examined both by coexpression of a chimeric erythropoietin (EPO)-EGFR with an extracellular EPO and intracellular EGFR domain, and by pharmacologic inhibition of external and internal signaling routes. All three α1-AR subtypes transactivated EGFR, which was dependent on the increase in intracellular calcium. The EGFR kinase inhibitor AG1478 [4-(3'-chloroanilino)-6,7-dimethoxyquinazoline] abrogated α1A-AR and α1D-AR induced phosphorylation of EGFR, but both the inhibition of matrix metalloproteinases by GM6001 [(R)-N4-hydroxy-N(1)-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide] or blockade of EGFR by cetuximab did not. Stimulation of α1A-AR and α1D-AR also induced phosphorylation of EPO-EGFR chimeric receptors. Moreover, α1A-AR stimulation enhanced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 and serine-threonine kinases (Akt), which were both unaffected by AG1478, indicating that ERK1/2 and Akt phosphorylation is independent of EGFR transactivation. Accordingly, inhibitors of ERK1/2 or Akt did not influence the α1A-AR-mediated EGFR transactivation. Inhibition of calcium/calmodulin-dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by α1A-AR and α1D-AR. These findings demonstrate that all α1-AR subtypes transactivate EGFR, which is dependent on an intracellular signaling route involving an increase in calcium and activation of CaMKII, PI3K, and Src, but not the of ERK1/2 and Akt pathways. 7. Direction finding with an array of antennas having diverse polarizations NASA Astrophysics Data System (ADS) Ferrara, E. R., Jr.; Parks, T. M. 1983-03-01 The advantages of using diversely polarized antennas to determine bearings of multiple cochannel narrow-band signals are shown. Three bearing estimation algorithms - maximum likelihood (ML), adapted angular response (AAR), and Music (multiple signal classification) - are extended to handle antenna arrays with diverse polarizations; the maximum entropy method does not readily extend. The proposed algorithms are applicable to arbitrary antenna locations and directional characteristics and arbitrary noise correlations between the antenna outputs. The algorithms are compared on the basis of multiple signal resolution and bearing accuracy in the presence of noise. The Music algorithm exhibits superior performance at moderate to low signal-to-noise ratio (SNR). 8. ADCK4 “reenergizes” nephrotic syndrome PubMed Central Malaga-Dieguez, Laura; Susztak, Katalin 2013-01-01 Steroid-resistant nephrotic syndrome has a poor prognosis and often leads to end-stage renal disease development. In this issue of the JCI, Ashraf and colleagues used exome sequencing to identify mutations in the aarF domain containing kinase 4 (ADCK4) gene that cause steroid-resistant nephrotic syndrome. Patients with ADCK4 mutations had lower coenzyme Q10 levels, and coenzyme Q10 supplementation ameliorated renal disease in a patient with this particular mutation, suggesting a potential therapy for patients with steroid-resistant nephrotic syndrome with ADCK4 mutations. PMID:24270414 9. Genomic architecture of alpha-amylase activity in mature rye grain relative to that of preharvest sprouting. PubMed Masojć, Piotr; Wiśniewska, Magdalena; Łań, Anna; Milczarski, Paweł; Berdzik, Marcin; Pędziwiatr, Daniel; Pol-Szyszko, Magdalena; Gałęza, Monika; Owsianicki, Radosław 2011-05-01 Bi-directional selective genotyping (BSG) carried out on two opposite groups of F(9)(541 × Ot1-3) recombinant inbred lines (RILs) with extremely low and extremely high alpha-amylase activities in mature (dry) grain of rye, followed by molecular mapping, revealed a complex system of selection-responsive loci. Three classes of loci controlling alpha-amylase activity were discerned, including four major AAD loci on chromosomes 3R (three loci) and 6RL (one locus) responding to both directions of the disruptive selection, 20 AAR loci on chromosomes 2RL (three loci), 3R (three loci), 4RS (two loci), 5RL (three loci), 6R (two loci) and 7R (seven loci) responding to selection for low alpha-amylase activity and 17 AAE loci on chromosomes 1RL (seven loci), 2RS (two loci), 3R (two loci), 5R (two loci) and 6RL (four loci) affected by selection for high alpha-amylase activity. The majority of the discerned AA loci also showed responsiveness to selection for preharvest sprouting (PHS). Two AAD loci on chromosome arm 3RL coincided with PHSD loci. The AAD locus on chromosome arm 3RS was independent from PHS, whereas that on chromosome 6RL belonged to the PHSR class. AAR-PHSR loci were found on chromosomes 4RS (one locus) and 5R (two loci) and AAE-PHSE loci were identified on chromosomes 1RL (one locus) and 5RL (one locus). Some PHSD loci represented the AAE (chromosomes 1RL, 3RS and 3RL) or AAR classes (chromosome 5RL). AAR and AAE loci not related to PHS were found on chromosomes 1RL, 2R, 3RS, 4R, 6RL and 7RL. On the other hand, several PHS loci (1RL, 3RS, 5RL, 6RS and 7RS) had no effect on alpha-amylase activity. Allele originating from the parental line 541 mapped in six AA loci on chromosomes 2R (two loci), 5R (three loci) and 7R (one locus) exerted opposite effects on PHS and alpha-amylase activity. Differences between the AA and PHS systems of loci may explain the weak correlation between these two traits observed among recombinant inbred lines. Strategies for the 10. Testing of the Strutjet RBCC Engine NASA Technical Reports Server (NTRS) Bulman, Mel; Neill, Todd; Yam, Clement 1999-01-01 The testing of the Strutjet Rocket-Based Combined Cycle (RBCC) engine is described in this presentation. Since 1996 Aerojet has conducted thousands of tests on its Strutjet RBCC Engine. The Strutjet is specifically designed as an RBCC engine. The tests included: (1) Inlet, (2) Rocket Checkouts, (3) Direct Connect Mach 6 and 8, and (4) Freejet M = 0, 2.4, 4.1. The modes tested include: (1) Air Augmented Rocket (AAR), (2) Ramjet (3) Scramjet (4) Scram/Rocket (5) Ascent/Rocket. The Strutjet RBCC engine has been tested across the complete airbreathing trajectory. The presentation shows the results of the tests, through diagrams, charts and pictures. 11. Overdeepened glacigenic landforms in Lake Thun (Switzerland) revealed by a multichannel reflection seismic survey NASA Astrophysics Data System (ADS) Fabbri, Stefano; Herwegh, Marco; Schlunegger, Fritz; Hübscher, Christian; Weiss, Benedikt J.; Schmelzbach, Cédric; Horstmeyer, Heinrich; Buechi, Marius W.; Anselmetti, Flavio S. 2016-04-01 Recently acquired high-resolution multibeam bathymetry, in combination with a 2D multichannel reflection seismic campaign on perialpine Lake Thun (Switzerland) reveals new insights into the diverse geometry of the lake basin and a so far unknown subaquatic moraine crest with unprecedented clarity. These new data will improve our comprehension concerning the retreat phases of the Aare glacier, the morphology of its proximal deposits and the facies architecture of the subglacial units. The overdeepened basin of Lake Thun was formed by a combination of tectonically predefined weak zones and glacial erosion during the last glacial periods. The new data indicate that below the outermost edge of a morphologically distinct platform in the south eastern part of the lake basin, a ridge structure marked by strong reflection amplitudes occurs. This structure is interpreted as a subaquatic terminal moraine crest, most likely created by a slightly advancing or stagnant grounded Aare glacier during its major retreating phase. The terminal moraine smoothly transforms downstream into well distinguishable foresets with internally recognisable layering, which dip steeply towards the deepest part of the basin, eventually transforming into bottomsets. This depositional sequence formed by the fore- and bottomsets represents ˜50% of the overall sediment volume that fills the basin and was deposited while the glacier was stagnant, interpreted to represent a rather short period of time of a few hundreds of years. This sequence is overlain by lacustrine deposits formed by late-glacial and Holocene laminated muds comprising intercalated turbidites (Wirth et al. 2011). Little is known about the exact timing and behaviour of retreating glaciers between their recessional phase from the Alpine foreland to the deglaciation of the inner-Alpine ice cap, mostly due to the lack of well-developed moraines that indicate glacial stabilization or slight readvance. Findings from pollen analyses by 12. Amelie: A Recombinant Computing Framework for Ambient Awareness NASA Astrophysics Data System (ADS) Metaxas, Georgios; Markopoulos, Panos; Aarts, Emile This paper presents Amelie, a service oriented framework that supports the implementation of awareness systems. Amelie adopts the tenets of Recombinant computing to address an important non-functional requirement for Ambient Intelligence software, namely the heterogeneous combination of services and components. Amelie is founded upon FN-AAR an abstract model of Awareness Systems which enables the immediate expression and implementation of socially salient requirements, such as symmetry and social translucence. We discuss the framework and show how system behaviours can be specified using the Awareness Mark-up Language AML. 13. Crystal structures of the A2A adenosine receptor and their use in medicinal chemistry. PubMed Jacobson, Kenneth A 2013-12-20 New insights into drug design are derived from the X-ray crystallographic structures of G protein-coupled receptors (GPCRs), and the adenosine receptors (ARs) are at the forefront of this effort. The 3D knowledge of receptor binding and activation promises to enable drug discovery for GPCRs in general, and specifically for the ARs. The predictability of modeling based on the X-ray structures of the A2AAR has been well demonstrated in the identification, design and modification of both known and novel AR agonists and antagonists. It is expected that structure-based design of drugs acting through ARs will provide new avenues to clinically useful agents. 14. Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin, Pyk2, and Src kinase. PubMed Della Rocca, G J; van Biesen, T; Daaka, Y; Luttrell, D K; Luttrell, L M; Lefkowitz, R J 1997-08-01 Many receptors that couple to heterotrimeric guanine-nucleotide binding proteins (G proteins) have been shown to mediate rapid activation of the mitogen-activated protein kinases Erk1 and Erk2. In different cell types, the signaling pathways employed appear to be a function of the available repertoire of receptors, G proteins, and effectors. In HEK-293 cells, stimulation of either alpha1B- or alpha2A-adrenergic receptors (ARs) leads to rapid 5-10-fold increases in Erk1/2 phosphorylation. Phosphorylation of Erk1/2 in response to stimulation of the alpha2A-AR is effectively attenuated by pretreatment with pertussis toxin or by coexpression of a Gbetagamma subunit complex sequestrant peptide (betaARK1ct) and dominant-negative mutants of Ras (N17-Ras), mSOS1 (SOS-Pro), and Raf (DeltaN-Raf). Erk1/2 phosphorylation in response to alpha1B-AR stimulation is also attenuated by coexpression of N17-Ras, SOS-Pro, or DeltaN-Raf, but not by coexpression of betaARK1ct or by pretreatment with pertussis toxin. The alpha1B- and alpha2A-AR signals are both blocked by phospholipase C inhibition, intracellular Ca2+ chelation, and inhibitors of protein-tyrosine kinases. Overexpression of a dominant-negative mutant of c-Src or of the negative regulator of c-Src function, Csk, results in attenuation of the alpha1B-AR- and alpha2A-AR-mediated Erk1/2 signals. Chemical inhibitors of calmodulin, but not of PKC, and overexpression of a dominant-negative mutant of the protein-tyrosine kinase Pyk2 also attenuate mitogen-activated protein kinase phosphorylation after both alpha1B- and alpha2A-AR stimulation. Erk1/2 activation, then, proceeds via a common Ras-, calcium-, and tyrosine kinase-dependent pathway for both Gi- and Gq/11-coupled receptors. These results indicate that in HEK-293 cells, the Gbetagamma subunit-mediated alpha2A-AR- and the Galphaq/11-mediated alpha1B-AR-coupled Erk1/2 activation pathways converge at the level of phospholipase C. These data suggest that calcium 15. Surface electric properties of emulsions of apolar reagents SciTech Connect Baichenko, A.A.; Baran, A.A. 1986-09-01 This article presents the results of studies of surface electric properties of kerosene and AAR-2 (apolar aromatized reagent) emulsons in water, which can be used in coal slime flotation, in presence of various salts and high-molecular flocculants. The data obtained were compared with the effect of electrolytes on the surface electric properties of a model emulsion of heptane in water stabilized by sodium hapthenate. The studies indicate that similarity of changes in the electrokinetic properties of various emulsions in presence of electrolytes and flocculants. 16. Towards Stratifying Ischemic Components by Cardiac MRI and Multifunctional Stainings in a Rabbit Model of Myocardial Infarction PubMed Central Feng, Yuanbo; Chen, Feng; Ma, Zhanlong; Dekeyzer, Frederik; Yu, Jie; Xie, Yi; Cona, Marlein Miranda; Oyen, Raymond; Ni, Yicheng 2014-01-01 Objectives: We sought to identify critical components of myocardial infarction (MI) including area at risk (AAR), MI-core and salvageable zone (SZ) by using cardiac magnetic resonance imaging (cMRI) and multifunctional stainings in rabbits. Materials and Methods: Fifteen rabbits received 90-min coronary artery (CA) ligation and reopening to induce reperfused MI. First-pass perfusion weighted imaging (PWI90') was performed immediately before CA reperfusion. Necrosis avid dye Evans blue (EB) was intravenously injected for later MI-core detection. One-day later, cMRI with T2-weighted imaging (T2WI), PWI24h and delayed enhancement (DE) T1WI was performed at a 3.0T clinical scanner. The heart was excised and CA was re-ligated with aorta infused by red-iodized-oil (RIO). The heart was sliced into 3-mm sections for digital radiography (DR), histology and planimetry with myocardial salvage index (MSI) and perfusion density rate (PDR) calculated. Results: There was no significant difference between MI-cores defined by DE-T1WI and EB-staining (31.13±8.55% vs 29.80±7.97%; p=0.74). The AAR was defined similarly by PWI90' (39.93±9.51%), RIO (38.82±14.41%) and DR (38.17±15.98%), underestimated by PWI24h (36.44±5.31%), but overestimated (p<0.01) by T2WI (56.93±8.87%). Corresponding MSI turned out to be 24.17±9.5% (PWI90'), 21.97±9.41% (DR) and 22.68±9.65% (RIO), which were significantly (p<0.01) higher and lower than that with PWI24h (15.15±7.34%) and T2WI (45.52±7.5%) respectively. The PDR differed significantly (p<0.001) between normal myocardium (350.6±33.1%) and the AAR (31.2±15%), suggesting 11-times greater blood perfusion in normal myocardium over the AAR. Conclusion: The introduced rabbit platform and new staining techniques together with the use of a 3.0T clinical scanner for cMRI enabled visualization of MI components and may contribute to translational cardiac imaging research for improved theranostic management of ischemic heart disease. PMID:24396513 17. Quantifying the Area-at-Risk in Reperfused STEMI Patients Using Hybrid Cardiac PET-MR Imaging PubMed Central Bulluck, Heerajnarain; White, Steven K.; Fröhlich, Georg M.; Casson, Steven G.; O’Meara, Celia; Newton, Ayla; Nicholas, Jennifer; Weale, Peter; Wan, Simon M.Y.; Sirker, Alex; Moon, James C.; Yellon, Derek M.; Groves, Ashley; Menezes, Leon; Hausenloy, Derek J 2016-01-01 Background Hybrid Positron Emission Tomography and Magnetic Resonance (PET-MR) allows the advantages of MR in tissue characterizing the myocardium to be combined with the unique metabolic insights of PET. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area-at-risk (AAR) delineated by T2-mapping in ST-segment elevation myocardial infarction (STEMI) patients. Methods and Results Hybrid PET-MR using 18F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 STEMI patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (LGE) (37.2±11.6% versus 22.3±11.7%; P<0.001), and closely matched the AAR by T2-mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R 0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared to the acute scans (19.5 [6.3-31.8]% versus 44.0 [21.3-55.3]%, P=0.002), and closely correlated with the areas of LGE (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of LGE and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. Conclusions Hybrid PET-MR in the reperfused STEMI patient showed reduced myocardial glucose uptake within the AAR and closely matched the AAR delineated by T2-mapping. FDG uptake, as well as transmural extent of LGE acutely can identify viable myocardial segments. PMID:26926269 18. Direct dating of human fossils. PubMed Grün, Rainer 2006-01-01 The methods that can be used for the direct dating of human remains comprise of radiocarbon, U-series, electron spin resonance (ESR), and amino acid racemization (AAR). This review gives an introduction to these methods in the context of dating human bones and teeth. Recent advances in ultrafiltration techniques have expanded the dating range of radiocarbon. It now seems feasible to reliably date bones up to 55,000 years. New developments in laser ablation mass spectrometry permit the in situ analysis of U-series isotopes, thus providing a rapid and virtually non-destructive dating method back to about 300,000 years. This is of particular importance when used in conjunction with non-destructive ESR analysis. New approaches in AAR analysis may lead to a renaissance of this method. The potential and present limitations of these direct dating techniques are discussed for sites relevant to the reconstruction of modern human evolution, including Florisbad, Border Cave, Tabun, Skhul, Qafzeh, Vindija, Banyoles, and Lake Mungo. 19. Bicalutamide Activated Oncolytic Adenovirus for the Adjuvant Therapy of High Risk Prostate Cancer PubMed Central Johnson, Tamara Jane; Hoti, Naser Uddin; Liu, Chunyan; Chowdhury, Wasim H.; Li, Ying; Zhang, Yonggang; Lupold, Shawn E.; DeWeese, Theodore; Rodriguez, Ronald 2013-01-01 Conditionally replicating adenoviruses (CRAds) utilize tissue specific promoters to control the expression of the early genes, E1A and E1B, to preferentially replicate and lyse tumor cells (oncolysis). Previous CRAds used in prostate cancer gene therapy require androgens to activate prostate specific promoters and induce viral replication. Unfortunately, these CRAds have reduced activity in patients on androgen suppressive therapy. We describe a novel prostate specific CRAd generated by fusing the E1A gene to the androgen receptor (AR) cDNA with a point mutation in codon 685 (C685Y). The E1A-AR fusion neutralizes the previously described mutual inhibition of E1A & AR, and the C685Y point mutation alters specificity of steroid ligand binding to the AR, such that both androgens and non-steroidal anti-androgens can activate viral replication. We demonstrate that the mutated E1A-AR retained the ability to function in regulating AR responsive genes and E1A responsive viral genes. In combination therapy of virus, bicalutamide (anti-androgen) and radiation, a profound impact on cell death by viral oncolysis was seen both in vitro and tumor xenografts. To our knowledge, this is the first gene therapy engineered to be enhanced by anti-androgens, and a particularly attractive adjuvant strategy for intensity modulated radiation therapy (IMRT) of high-risk prostate cancers. PMID:23764901 20. Measurement of track strength using nondestructive evaluation techniques NASA Astrophysics Data System (ADS) Kalay, Semih F. 1995-06-01 As a direct result of the industry's goal to improve the quality and safety of service to its customers, the Association of American Railroads (AAR) has embarked on a major research project to develop and implement automated inspection methods to effectively measure the available track stength, and to identify and repair the weak spots before further track degradation and increased maintenance are needed. The AAR has designed and constructed a track loading vehicle (TLV) which was used extensively in testing of track lateral restraint. This new vehicle is capable of applying computer controlled loads over a range of track conditions and measure the dynamic response of the track. The TLV is built on the underframe of a diesel-electric locomotive and features a retractable load bogie mounted underneath the center for applying computer controlled loads to the track and measuring the response while stationary or moving. The TLV was successfuly tested over 3,500 miles of revenue track to identify wide gage and weaker tie/fastener conditions. The test results have shown that it is feasible to implement automated inspection methods to effectively measure the available track strength, and to identify and repair the weak spots before further degradation and increased maintenance is needed. Substantial savings could be realized by the industry if positive identification of defective ties can be improved using test devices like the TLV. 1. Descriptive Epidemiology of Musculoskeletal Injuries and Concussions in the National Football League, 2012-2014 PubMed Central Lawrence, David W.; Hutchison, Michael G.; Comper, Paul 2015-01-01 Background: The risk of all-cause injury and concussion associated with football is significant. The National Football League (NFL) has implemented changes to increase player safety warranting investigation into the incidence and patterns of injury. Purpose: To document the incidence and patterns of all-cause injury and concussions in the NFL. Study Design: Descriptive epidemiology study. Methods: Injury data were collected prospectively from official NFL injury reports over 2 regular seasons from 2012 to 2014, with identification of injury incidence rates and patterns. Concussion rate ratios were calculated using previously reported NFL rates. Results: A total of 4284 injuries were identified, including 301 concussions. The all-cause injury rate was 395.8 per 1000 athletes at risk (AAR) and concussion incidence was 27.8 per 1000 AAR. Only 2.3% of team games were injury free. Wide receivers, tight ends, and defensive backs had the highest incidence of injury and concussion. Concussion incidence was 1.61-fold higher in 2012 to 2014 compared with 2002 to 2007. The knee was injured most frequently, followed by the ankle, hamstring, shoulder, and head. Conclusion: The incidence of all-cause injury and concussion in the NFL is significant. Concussion injury rates are higher than previous reports, potentially reflecting an improvement in recognition and awareness. Injury prevention efforts should continue to reduce the prevalence of injury associated with football. PMID:26675321 2. An enhanced system for unnatural amino acid mutagenesis in E. coli. PubMed Young, Travis S; Ahmad, Insha; Yin, Jun A; Schultz, Peter G 2010-01-15 We report a new vector, pEVOL, for the incorporation of unnatural amino acids into proteins in Escherichia coli using evolved Methanocaldococcus jannaschii aminoacyl-tRNA synthetase(s) (aaRS)/suppressor tRNA pairs. This new system affords higher yields of mutant proteins through the use of both constitutive and inducible promoters to drive the transcription of two copies of the M. jannaschii aaRS gene. Yields were further increased by coupling the dual-aaRS promoter system with a newly optimized suppressor tRNA(CUA)(opt) in a single-vector construct. The optimized suppressor tRNA(CUA)(opt) afforded increased plasmid stability compared with previously reported vectors for unnatural amino acid mutagenesis. To demonstrate the utility of this new system, we introduced 14 mutant aaRS into pEVOL and compared their ability to insert unnatural amino acids in response to three independent amber nonsense codons in sperm whale myoglobin or green fluorescent protein. When cultured in rich media in shake flasks, pEVOL was capable of producing more than 100 mg/L mutant GroEL protein. The versatility, increased yields, and increased stability of the pEVOL vector will further facilitate the expression of proteins with unnatural amino acids. PMID:19852970 3. Sediment accumulation, stratigraphic order, and the extent of time-averaging in lagoonal sediments: a comparison of 210Pb and 14C/amino acid racemization chronologies NASA Astrophysics Data System (ADS) Kosnik, Matthew A.; Hua, Quan; Kaufman, Darrell S.; Zawadzki, Atun 2015-03-01 Carbon-14 calibrated amino acid racemization (14C/AAR) data and lead-210 (210Pb) data are used to examine sediment accumulation rates, stratigraphic order, and the extent of time-averaging in sediments collected from the One Tree Reef lagoon (southern Great Barrier Reef, Australia). The top meter of lagoonal sediment preserves a stratigraphically ordered deposit spanning the last 600 yrs. Despite different assumptions, the 210Pb and 14C/AAR chronologies are remarkably similar indicating consistency in sedimentary processes across sediment grain sizes spanning more than three orders of magnitude (0.1-10 mm). Estimates of long-term sediment accumulation rates range from 2.2 to 1.2 mm yr-1. Molluscan time-averaging in the taphonomically active zone is 19 yrs, whereas below the depth of final burial (~15 cm), it is ~110 yrs/5 cm layer. While not a high-resolution paleontological record, this reef lagoon sediment is suitable for paleoecological studies spanning the period of Western colonization and development. This sedimentary deposit, and others like it, should be useful, albeit not ideal, for quantifying anthropogenic impacts on coral reef systems. 4. A Comparative Study on Improved Arrhenius-Type and Artificial Neural Network Models to Predict High-Temperature Flow Behaviors in 20MnNiMo Alloy PubMed Central Yu, Chun-tang; Liu, Ying-ying; Xia, Yu-feng 2014-01-01 The stress-strain data of 20MnNiMo alloy were collected from a series of hot compressions on Gleeble-1500 thermal-mechanical simulator in the temperature range of 1173∼1473 K and strain rate range of 0.01∼10 s−1. Based on the experimental data, the improved Arrhenius-type constitutive model and the artificial neural network (ANN) model were established to predict the high temperature flow stress of as-cast 20MnNiMo alloy. The accuracy and reliability of the improved Arrhenius-type model and the trained ANN model were further evaluated in terms of the correlation coefficient (R), the average absolute relative error (AARE), and the relative error (η). For the former, R and AARE were found to be 0.9954 and 5.26%, respectively, while, for the latter, 0.9997 and 1.02%, respectively. The relative errors (η) of the improved Arrhenius-type model and the ANN model were, respectively, in the range of −39.99%∼35.05% and −3.77%∼16.74%. As for the former, only 16.3% of the test data set possesses η-values within ±1%, while, as for the latter, more than 79% possesses. The results indicate that the ANN model presents a higher predictable ability than the improved Arrhenius-type constitutive model. PMID:24688358 5. Representative rainfall thresholds for flash floods in the Cali river watershed, Colombia NASA Astrophysics Data System (ADS) Ávila, A. D.; Carvajal, Y. E.; Justino, F. 2015-06-01 In the 21st century, societies face a significant increase in the number of extreme hydrometeorological events associated with climate variability (CV) and/or climate change (CC). Research has recently focused on establishing adaptation and mitigation measures to counteract the effects of CV and CC, especially those associated with precipitation, such as flash floods and flooding. In this study, 27 floods, listed in the historical database of natural disasters (DesInventar), occurring between 1980 and 2012, were analyzed. Using the daily hydrometeorological data, representative rainfall thresholds were defined to predict flash floods in the hydrographic basin of the Cali River, Colombia. Antecedent rainfall (AR), or short-term rain (1, 3, 5 and 7 days), and accumulated antecedent rainfall (AAR), or long-term rain (5, 7, 10, 15, 20, 25, 30, 60 and 90 days), levels were defined. The analysis showed that the greatest determinant for the occurrence of floods is AAR, with thresholds greater than 73, 95, 124, 170, 218 and 273 mm, for 5, 7, 10, 15, 20 and 25 days, respectively. Additionally, the data showed that, historically, the greatest number of flash floods (81.7 %) occurred in the Cali River basin in the months of April, May, and June. 6. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins SciTech Connect Sung, Uhna; Jennings, Jennifer L.; Link, Andrew J.; Blakely, Randy D.; E-mail: andy.blakely@vanderbilt.edu 2005-08-05 The norepinephrine transporter (NET) terminates noradrenergic signals by clearing released NE at synapses. NET regulation by receptors and intracellular signaling pathways is supported by a growing list of associated proteins including syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and Hic-5. In the present study, we sought evidence for additional partnerships by mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our initial proteomic analyses reveal multiple peptides derived from hNET, peptides arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from 14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co-immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via a fusion pull-down approach, implicating specifically the hNET NH{sub 2}-terminus for interactions. The transporter complexes described likely support mechanisms regulating transporter activity, localization, and trafficking. 7. A Characterization of Hot Flow Behaviors Involving Different Softening Mechanisms by ANN for As-Forged Ti-10V-2Fe-3Al Alloy NASA Astrophysics Data System (ADS) Quan, Guo-zheng; Zou, Zhen-yu; Wen, Hai-rong; Pu, Shi-ao; Lv, Wen-quan 2015-11-01 The isothermal compressions of as-forged Ti-10V-2Fe-3Al alloy at the deformation temperature range of 948-1,123 K and the strain rates in the range of 0.001-10 s-1 with a height reduction of 60% were conducted on a Gleeble-3500 thermo-mechanical simulator. The flow behaviors show nonlinear sensitivity to strain, strain rate and temperature. Based on the experimental data, an artificial neural network (ANN) with back-propagation algorithm was developed to deal with the complex deformation behavior characteristics. In the present ANN model, strain, strain rate and temperature were taken as inputs, and flow stress as output. A comparative study on the constitutive relationships based on regression and ANN methods was conducted. According to the predicted and experimental results, the predictabilities of the two models have been evaluated in terms of correlation coefficient (R) and average absolute relative error (AARE). The R-value and the AARE-value at strain of 0.5 from the ANN model is 0.9998 and 0.572%, respectively, better than 0.9902 and 6.583% from the regression model. The predicted strain-stress curves outside of experimental conditions indicate similar characteristics with experimental curves. The results have sufficiently articulated that the well-trained ANN model with back-propagation algorithm has excellent capability to deal with the complex flow behaviors of as-forged Ti-10V-2Fe-3Al alloy. 8. Hot compression deformation behavior and a modified physically-based constitutive model of Cu-6 %Ag alloy NASA Astrophysics Data System (ADS) Meng, Lie; Wang, Menghan; Liu, Xiao; Wang, Fenglin 2016-04-01 In order to reveal the flow characteristics of Cu-6 %Ag alloy on the condition of hot deformation, the isothermal compression experiments are carried out at the temperatures of 973-1123 K under strain rates of 0.01-10 s-1. The effects of deformation condition on the hot compression deformation behavior are investigated. The low instability strain (ɛ i) behavior at high strain rate (10 s-1) is discussed in this paper. According to the experiment results and analyses, the deformation twinning and inhomogeneous grains are thought to be the possible reasons for low strain cracking. Then, a modified physically based constitutive model is established. The strain for maximum softening rate (\\varepsilon_{ *} ) is quoted in the constitutive equation which is proved that there is a nearly linear relationship between { ln }\\varepsilon_{ *} and { ln }Z . What's more, the correlation coefficient (R) and the average absolute relative error (AARE) are used to evaluate the accuracy of the established constitutive model. The values of R and AARE are 0.99612 and 3.47 %, respectively, which show that the modified constitutive model can exactly reveal the flow stress of Cu-6 %Ag alloy. 9. A Constitutive Model of 6111-T4 Aluminum Alloy Sheet Based on the Warm Tensile Test NASA Astrophysics Data System (ADS) Hua, Lin; Meng, Fanzhi; Song, Yanli; Liu, Jianing; Qin, Xunpeng; Suo, Lianbing 2014-03-01 As main light-weight material, aluminum alloy sheets have been widely applied to produce auto body panels. In order to predict the formability and springback of aluminum alloy sheets, a precise constitutive model is a necessity. In this article, a series of warm tensile tests were conducted on Gleeble-1500D thermal mechanical simulator for 6111-T4 aluminum alloy sheets. The corresponding strain rate ranged from 0.015 to 1.5 s-1, and the temperature ranged from 25 to 350 °C. The relationship between the temperature, the strain rate, and the flow stress were discussed. A constitutive model based on the updated Fields-Backofen equation was established to describe the flow behavior of 6111-T4 aluminum alloy during the warm tensile tests. Subsequently, the average absolute relative error (AARE) was introduced to verify the predictability of the constitutive model. The value of AARE at the uniform plastic deformation stage was calculated to be 1.677%, which demonstrates that the predicted flow stress values were in accordance with the experimental ones. The constitutive model was validated by the fact that the simulated results of the warm tensile tests coincided with the experimental ones. 10. The crystal structure of yeast mitochondrial ThrRS in complex with the canonical threonine tRNA PubMed Central Holman, Kaitlyn M.; Wu, Jiang; Ling, Jiqiang; Simonović, Miljan 2016-01-01 In mitochondria of Saccharomyces cerevisiae, a single aminoacyl-tRNA synthetase (aaRS), MST1, aminoacylates two isoacceptor tRNAs, tRNA1Thr and tRNA2Thr, that harbor anticodon loops of different size and sequence. As a result of this promiscuity, reassignment of the CUN codon box from leucine to threonine is facilitated. However, the mechanism by which a single aaRS binds distinct anticodon loops with high specificity is not well understood. Herein, we present the crystal structure of MST1 in complex with the canonical tRNA2Thr and non-hydrolyzable analog of threonyl adenylate. Our structure reveals that the dimeric arrangement of MST1 is essential for binding the 5′-phosphate, the second base pair of the acceptor stem, the first two base pairs of the anticodon stem and the first nucleotide of the variable arm. Further, in contrast to the bacterial ortholog that ‘reads’ the entire anticodon sequence, MST1 recognizes bases in the second and third position and the nucleotide upstream of the anticodon sequence. We speculate that a flexible loop linking strands β4 and β5 may be allosteric regulator that establishes cross-subunit communication between the aminoacylation and tRNA-binding sites. We also propose that structural features of the anticodon-binding domain in MST1 permit binding of the enlarged anticodon loop of tRNA1Thr. PMID:26704982 11. Novel proteins associated with human dilated cardiomyopathy: selective reduction in α(1A)-adrenergic receptors and increased desensitization proteins. PubMed Shi, Ting; Moravec, Christine S; Perez, Dianne M 2013-04-01 Abstract Therapeutics to treat human heart failure (HF) and the identification of proteins associated with HF are still limited. We analyzed α(1)-adrenergic receptor (AR) subtypes in human HF and performed proteomic analysis on more uniform samples to identify novel proteins associated with human HF. Six failing hearts with end-stage dilated cardiomyopathy (DCM) and four non-failing heart controls were subjected to proteomic analysis. Out of 48 identified proteins, 26 proteins were redundant between samples. Ten of these 26 proteins were previously reported to be associated with HF. Of the newly identified proteins, we found several muscle proteins and mitochondrial/electron transport proteins, while novel were functionally similar to previous reports. However, we also found novel proteins involved in functional classes such as β-oxidation and G-protein coupled receptor signaling and desensitization not previously associated with HF. We also performed radioligand-binding studies on the heart samples and not only confirmed a large loss of β(1)-ARs in end-stage DCM, but also found a selective decrease in the α(1A)-AR subtype not previously reported. We have identified new proteins and functional categories associated with end-stage DCM. We also report that similar to the previously characterized loss of β(1)-AR in HF, there is also a concomitant loss of α(1A)-ARs, which are considered cardioprotective proteins. 12. Alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora arose from duplication of a dual-functional predecessor of mitochondrial origin. PubMed Chang, Chia-Pei; Tseng, Yi-Kuan; Ko, Chou-Yuan; Wang, Chien-Chia 2012-01-01 In eukaryotes, the cytoplasmic and mitochondrial forms of a given aminoacyl-tRNA synthetase (aaRS) are typically encoded by two orthologous nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. We herein report a novel scenario of aaRS evolution in yeast. While all other yeast species studied possess a single nuclear gene encoding both forms of alanyl-tRNA synthetase (AlaRS), Vanderwaltozyma polyspora, a yeast species descended from the same whole-genome duplication event as Saccharomyces cerevisiae, contains two distinct nuclear AlaRS genes, one specifying the cytoplasmic form and the other its mitochondrial counterpart. The protein sequences of these two isoforms are very similar to each other. The isoforms are actively expressed in vivo and are exclusively localized in their respective cellular compartments. Despite the presence of a promising AUG initiator candidate, the gene encoding the mitochondrial form is actually initiated from upstream non-AUG codons. A phylogenetic analysis further revealed that all yeast AlaRS genes, including those in V. polyspora, are of mitochondrial origin. These findings underscore the possibility that contemporary AlaRS genes in V. polyspora arose relatively recently from duplication of a dual-functional predecessor of mitochondrial origin. 13. SMALL ACIDIC PROTEIN1 acts with RUB modification components, the COP9 signalosome, and AXR1 to regulate growth and development of Arabidopsis. PubMed Nakasone, Akari; Fujiwara, Masayuki; Fukao, Yoichiro; Biswas, Kamal Kanti; Rahman, Abidur; Kawai-Yamada, Maki; Narumi, Issay; Uchimiya, Hirofumi; Oono, Yutaka 2012-09-01 Previously, a dysfunction of the SMALL ACIDIC PROTEIN1 (SMAP1) gene was identified as the cause of the anti-auxin resistant1 (aar1) mutant of Arabidopsis (Arabidopsis thaliana). SMAP1 is involved in the response pathway of synthetic auxin, 2,4-dichlorophenoxyacetic acid, and functions upstream of the auxin/indole-3-acetic acid protein degradation step in auxin signaling. However, the exact mechanism by which SMAP1 functions in auxin signaling remains unknown. Here, we demonstrate that SMAP1 is required for normal plant growth and development and the root response to indole-3-acetic acid or methyl jasmonate in the auxin resistant1 (axr1) mutation background. Deletion analysis and green fluorescent protein/glutathione S-transferase pull-down assays showed that SMAP1 physically interacts with the CONSTITUTIVE PHOTOMORPHOGENIC9 SIGNALOSOME (CSN) via the SMAP1 F/D region. The extremely dwarf phenotype of the aar1-1 csn5a-1 double mutant confirms the functional role of SMAP1 in plant growth and development under limiting CSN functionality. Our findings suggest that SMAP1 is involved in the auxin response and possibly in other cullin-RING ubiquitin ligase-regulated signaling processes via its interaction with components associated with RELATED TO UBIQUITIN modification. 14. Battlefield Documentation of Tactical Combat Casualty Care in Afghanistan. PubMed Robinson, John B; Smith, Michael P; Gross, Kirby R; Sauer, Samual W; Geracci, James J; Day, Charlie D; Kotwal, Russ S 2016-01-01 Performance improvement is reliant on information and data, as you cannot improve what you do not measure. The US military went to war in 2001 without an integrated trauma care system to collect and analyze combat casualty care data. By 2006, the conflict in Afghanistan began appreciating the capture and consolidation of hospital care documentation into the Department of Defense Trauma Registry. In contrast, a paucity of documentation has existed for prehospital or tactical combat casualty care (TCCC). Using the 75th Ranger casualty documentation model established in 2005, the Joint Trauma System developed a casualty data collection system for prehospital care using the TCCC Card, the TCCC After Action Report (AAR), and the Prehospital Trauma Registry. In 2013, this system was mandated for use by US forces in Afghanistan. The Joint Trauma System also created and deployed a prehospital team to be an integral part of the Joint Theater Trauma System in Afghanistan. This prehospital team provided prehospital training and facilitated prehospital data capture. Described and analyzed in this report are prehospital data captured in Afghanistan from 2013 to 2014 using the TCCC Card and the TCCC AAR. PMID:27215873 15. Constitutive Equations and Flow Behavior of an As-Extruded AZ31 Magnesium Alloy Under Large Strain Condition NASA Astrophysics Data System (ADS) Dong, Yuanyuan; Zhang, Cunsheng; Lu, Xing; Wang, Cuixue; Zhao, Guoqun 2016-06-01 A reasonable constitutive model is the key to achieving the accurate numerical simulation of magnesium alloy extrusion process. Based on the hot compression tests of the as-extruded AZ31 magnesium alloy, the strain-compensated Arrhenius equation, the constitutive equation taking into account dynamic recovery (DRV) and dynamic recrystallization (DRX), and the modified Fields-Backofen equation (FB) are established to describe the deformation behavior of this alloy under large strain condition (strain level greater than 1.0) and wide strain rate range (0.01 to 10 s-1), respectively. Then material parameters in each constitutive model are determined by linear fitting method. The comparison of these three kinds of equations shows that the strain-compensated Arrhenius model provides the best prediction of flow stress, and the calculated value of correlation coefficient ( R) is the highest as 0.9945 and the average absolute relative error (AARE) is the lowest as 3.11%. The constitutive equation with DRV + DRX can also predict flow stress accurately, and its values of R and AARE are 0.9920 and 4.41%, respectively. However, compared to the other two constitutive equations, the modified FB equation does not give good description of hot deformation behavior for this magnesium alloy. Finally, the advantages and drawbacks of these three kinds of constitutive models are discussed and compared. Therefore, this work could provide theoretical guidelines for investigating hot deformation behavior of wrought magnesium alloys and determining the appropriate extrusion process parameters under large strain condition. 16. Cardiorespiratory responses and reduced apneic time to cold-water face immersion after high intensity exercise. PubMed Konstantinidou, Sylvia; Soultanakis, Helen 2016-01-01 Apnea after exercise may evoke a neurally mediated conflict that may affect apneic time and create a cardiovascular strain. The physiological responses, induced by apnea with face immersion in cold water (10 °C), after a 3-min exercise bout, at 85% of VO2max,were examined in 10 swimmers. A pre-selected 40-s apnea, completed after rest (AAR), could not be met after exercise (AAE), and was terminated with an agonal gasp reflex, and a reduction of apneic time, by 75%. Bradycardia was evident with immersion after both, 40-s of AAR and after AAE (P<0.05). The dramatic elevation of, systolic pressure and pulse pressure, after AAE, were indicative of cardiovascular stress. Blood pressure after exercise without apnea was not equally elevated. The activation of neurally opposing functions as those elicited by the diving reflex after high intensity exercise may create an autonomic conflict possibly related to oxygen-conserving reflexes stimulated by the trigeminal nerve, and those elicited by exercise. PMID:26343750 17. Amino acid racemization dating of marine shells: A mound of possibilities PubMed Central Demarchi, Beatrice; Williams, Matt G.; Milner, Nicky; Russell, Nicola; Bailey, Geoff; Penkman, Kirsty 2011-01-01 Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization (AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscan species. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins (by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea. Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world. PMID:21776187 18. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification NASA Astrophysics Data System (ADS) Kadir, K.; Gao, H.; Payne, A.; Soraghan, J.; Berry, C. 2012-10-01 In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm2 between individual investigator one (IV1) and LSM, and -122 mm2 between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients. 19. Difference of intensity and disparity in impact of climate on several vascular diseases. PubMed Ishikawa, Kiyotake; Niwa, Manabu; Tanaka, Toshikazu 2012-01-01 Several studies have reported the correlation between regional weather patterns and various vascular diseases. However, each vascular disease has inherent characteristics, and the difference of meteorological correlation between these diseases is not well known. This study was aimed at investigating the disparity and intensity of the relationship between meteorological factors and various vascular diseases. A total of 1113 events within 2 years were included in this study. Daily meteorological parameters with and without events were, respectively, compared in acute coronary syndrome (ACS), cerebral infarction (CI), cerebral embolism (CE), cerebral hemorrhage (CH), subarachnoid hemorrhage (SAH), aortic dissection (AD), and aortic aneurysm rupture (AAR). Days with CI onset correlated with fewer sunshine hours, fewer solar radiation factors, greater amounts of precipitation factors, and more humidity factors, whereas CH and CE only showed lower correlation in temperature factors. However, there was no relation seen between ACS, SAH, AD, AAR, and climatic parameters. Our findings suggest that climate affects various cardiovascular and cerebrovascular diseases differently. This finding may help in understanding the mechanism of how vascular events are triggered. 20. Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine Dependence, Elicit an Antidepressant-like Effect PubMed Central 2012-01-01 This study demonstrated that cyclomethyline (2) and the corresponding enantiomers (R)-(−)-2 and (S)-(+)-2, displaying α2C-adrenoreceptor (AR) agonism/α2A-AR antagonism, similarly to allyphenyline (1) and its enantiomers, significantly decreased the naloxone-precipitated withdrawal symptoms in mice at very low doses. It also highlighted that such positive effects on morphine dependence can even be improved by additional serotoninergic 5-HT1A receptor (5-HT1A-R) activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all behaving as α2C-AR agonists/α2A-AR antagonists/5-HT1A-R agonists, alone and at the same low dose, improved morphine withdrawal syndrome and exerted a potent antidepressant-like effect. Therefore, considering the elevated comorbidity between opiate abuse and depressed mood and the benefit of these multifunctional compounds to both disorders, it is possible that they prove more efficacious and less toxic than a cocktail of drugs in managing opioid addiction. PMID:24900506 1. Structure-based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates. PubMed Jacobson, Kenneth A 2013-05-23 Adenosine receptor (ARs) and P2Y receptors (P2YRs) that respond to extracellular nucleosides/nucleotides are associated with new directions for therapeutics. The X-ray structures of the A2AAR complexes with agonists and antagonists are examined in relationship to the G-protein-coupled receptor (GPCR) superfamily and applied to drug discovery. Much of the data on AR ligand structure from early SAR studies now are explainable from the A2AAR X-ray crystallography. The ligand-receptor interactions in related GPCR complexes can be identified by means of modeling approaches, e.g., molecular docking. Thus, molecular recognition in binding and activation processes has been studied effectively using homology modeling and applied to ligand design. Virtual screening has yielded new nonnucleoside AR antagonists, and existing ligands have been improved with knowledge of the receptor interactions. New agonists are being explored for central nervous system and peripheral therapeutics based on in vivo activity, such as chronic neuropathic pain. Ligands for receptors more distantly related to the X-ray template, i.e., P2YRs, have been introduced and are mainly used as pharmacological tools for elucidating the physiological role of extracellular nucleotides. Other ligand tools for drug discovery include fluorescent probes, radioactive probes, multivalent probes, and functionalized nanoparticles. 2. Seemingly irrational driving behavior model: The effect of habit strength and anticipated affective reactions. PubMed Chung, Yi-Shih 2015-09-01 An increasing amount of evidence suggests that aberrant driving behaviors are not entirely rational. On the basis of the dual-process theory, this study postulates that drivers may learn to perform irrational aberrant driving behaviors, and these behaviors could be derived either from a deliberate or an intuitive decision-making approach. Accordingly, a seemingly irrational driving behavior model is proposed; in this model, the theory of planned behavior (TPB) was adopted to represent the deliberate decision-making mechanism, and habit strength was incorporated to reflect the intuitive decision process. A multiple trivariate mediation structure was designed to reflect the process through which driving behaviors are learned. Anticipated affective reactions (AARs) were further included to examine the effect of affect on aberrant driving behaviors. Considering the example of speeding behaviors, this study developed scales and conducted a two-wave survey of students in two departments at a university in Northern Taiwan. The analysis results show that habit strength consists of multiple aspects, and frequency of past behavior cannot be a complete repository for accumulating habit strength. Habit strength appeared to be a crucial mediator between intention antecedents (e.g., attitude) and the intention itself. Including habit strength in the TPB model enhanced the explained variance of speeding intention by 26.7%. In addition, AARs were different from attitudes; particularly, young drivers tended to perform speeding behaviors to reduce negative feelings such as regret. The proposed model provides an effective alternative approach for investigating aberrant driving behaviors; corresponding countermeasures are discussed. 3. Adding intelligent services to an object oriented system NASA Technical Reports Server (NTRS) Robideaux, Bret R.; Metzler, Theodore A. 1994-01-01 As today's software becomes increasingly complex, the need grows for intelligence of one sort or another to becomes part of the application, often an intelligence that does not readily fit the paradigm of one's software development. There are many methods of developing software, but at this time, the most promising is the object oriented (OO) method. This method involves an analysis to abstract the problem into separate 'objects' that are unique in the data that describe them and the behavior that they exhibit, and eventually to convert this analysis into computer code using a programming language that was designed (or retrofitted) for OO implementation. This paper discusses the creation of three different applications that are analyzed, designed, and programmed using the Shlaer/Mellor method of OO development and C++ as the programming language. All three, however, require the use of an expert system to provide an intelligence that C++ (or any other 'traditional' language) is not directly suited to supply. The flexibility of CLIPS permitted us to make modifications to it that allow seamless integration with any of our applications that require an expert system. We illustrate this integration with the following applications: (1) an after action review (AAR) station that assists a reviewer in watching a simulated tank battle and developing an AAR to critique the performance of the participants in the battle; (2) an embedded training system and over-the-shoulder coach for howitzer crewmen; and (3) a system to identify various chemical compounds from their infrared absorption spectra. 4. The physiological target for LeuRS translational quality control is norvaline PubMed Central Cvetesic, Nevena; Palencia, Andrés; Halasz, Ivan; Cusack, Stephen; Gruic-Sovulj, Ita 2014-01-01 The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNAs. Here, we show that the editing activity of Escherichia coli leucyl-tRNA synthetase (EcLeuRS) is not required to prevent incorrect isoleucine incorporation. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline. This conclusion follows from a reassessment of the discriminatory power of LeuRS against isoleucine and the demonstration that a LeuRS editing-deficient E. coli strain grows normally in high concentrations of isoleucine but not under oxygen deprivation conditions when norvaline accumulates to substantial levels. Thus, AARS-based translational quality control is a key feature for bacterial adaptive response to oxygen deprivation. The non-essential role for editing under normal bacterial growth has important implications for the development of resistance to antimicrobial agents targeting the LeuRS editing site. PMID:24935946 5. Recent Updates on DTD (D-Tyr-tRNATyr Deacylase): An Enzyme Essential for Fidelity and Quality of Protein Synthesis PubMed Central Bhatt, Tarun K.; Soni, Rani; Sharma, Drista 2016-01-01 During protein synthesis, there are several checkpoints in the cell to ensure that the information encoded within genetic material is decoded correctly. Charging of tRNA with its cognate amino acid is one of the important steps in protein synthesis and is carried out by aminoacyl-tRNA synthetase (aaRS) with great accuracy. However, due to presence of D-amino acids in the cell, sometimes aaRS charges tRNA with D-amino acids resulting in the hampering of protein translational process, which is lethal to the cell. Every species has some mechanism in order to prevent the formation of D-amino acid-tRNA complex, for instance DTD (D-Tyr-tRNA deacylase) is an enzyme responsible for the cleavage of ester bond formed between D-amino acid and tRNA leading to error free translation process. In this review, structure, function, and enzymatic mechanism of DTD are discussed. The role of DTD as a drug target is also considered. PMID:27200345 6. Cardiorespiratory responses and reduced apneic time to cold-water face immersion after high intensity exercise. PubMed Konstantinidou, Sylvia; Soultanakis, Helen 2016-01-01 Apnea after exercise may evoke a neurally mediated conflict that may affect apneic time and create a cardiovascular strain. The physiological responses, induced by apnea with face immersion in cold water (10 °C), after a 3-min exercise bout, at 85% of VO2max,were examined in 10 swimmers. A pre-selected 40-s apnea, completed after rest (AAR), could not be met after exercise (AAE), and was terminated with an agonal gasp reflex, and a reduction of apneic time, by 75%. Bradycardia was evident with immersion after both, 40-s of AAR and after AAE (P<0.05). The dramatic elevation of, systolic pressure and pulse pressure, after AAE, were indicative of cardiovascular stress. Blood pressure after exercise without apnea was not equally elevated. The activation of neurally opposing functions as those elicited by the diving reflex after high intensity exercise may create an autonomic conflict possibly related to oxygen-conserving reflexes stimulated by the trigeminal nerve, and those elicited by exercise. 7. Learning to smell danger: acquired associative representation of threat in the olfactory cortex PubMed Central Li, Wen 2014-01-01 Neuroscience research over the past few decades has reached a strong consensus that the amygdala plays a key role in emotion processing. However, many questions remain unanswered, especially concerning emotion perception. Based on mnemonic theories of olfactory perception and in light of the highly associative nature of olfactory cortical processing, here I propose a sensory cortical model of olfactory threat perception (i.e., sensory-cortex-based threat perception): the olfactory cortex stores threat codes as acquired associative representations (AARs) formed via aversive life experiences, thereby enabling encoding of threat cues during sensory processing. Rodent and human research in olfactory aversive conditioning was reviewed, indicating learning-induced plasticity in the amygdala and the olfactory piriform cortex. In addition, as aversive learning becomes consolidated in the amygdala, the associative olfactory (piriform) cortex may undergo (long-term) plastic changes, resulting in modified neural response patterns that underpin threat AARs. This proposal thus brings forward a sensory cortical pathway to threat processing (in addition to amygdala-based processes), potentially accounting for an alternative mechanism underlying the pathophysiology of anxiety and depression. PMID:24778610 8. Niemeyer Virus: A New Mimivirus Group A Isolate Harboring a Set of Duplicated Aminoacyl-tRNA Synthetase Genes PubMed Central Boratto, Paulo V. M.; Arantes, Thalita S.; Silva, Lorena C. F.; Assis, Felipe L.; Kroon, Erna G.; La Scola, Bernard; Abrahão, Jônatas S. 2015-01-01 It is well recognized that gene duplication/acquisition is a key factor for molecular evolution, being directly related to the emergence of new genetic variants. The importance of such phenomena can also be expanded to the viral world, with impacts on viral fitness and environmental adaptations. In this work we describe the isolation and characterization of Niemeyer virus, a new mimivirus isolate obtained from water samples of an urban lake in Brazil. Genomic data showed that Niemeyer harbors duplicated copies of three of its four aminoacyl-tRNA synthetase genes (cysteinyl, methionyl, and tyrosyl RS). Gene expression analysis showed that such duplications allowed significantly increased expression of methionyl and tyrosyl aaRS mRNA by Niemeyer in comparison to APMV. Remarkably, phylogenetic data revealed that Niemeyer duplicated gene pairs are different, each one clustering with a different group of mimivirus strains. Taken together, our results raise new questions about the origins and selective pressures involving events of aaRS gain and loss among mimiviruses. PMID:26635738 9. Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs. PubMed Godinic-Mikulcic, Vlatka; Jaric, Jelena; Greber, Basil J; Franke, Vedran; Hodnik, Vesna; Anderluh, Gregor; Ban, Nenad; Weygand-Durasevic, Ivana 2014-04-01 Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal protein synthesis. Previous studies have suggested a link between tRNA aminoacylation and high-molecular-weight cellular complexes such as the cytoskeleton or ribosomes. However, the structural basis of these interactions and potential mechanistic implications are not well understood. To biochemically characterize these interactions we have used a system of two interacting archaeal aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS. More specifically, we have shown by thermophoresis and surface plasmon resonance that these two aaRSs bind to the large ribosomal subunit with micromolar affinities. We have identified the L7/L12 stalk and the proteins located near the stalk base as the main sites for aaRS binding. Finally, we have performed a bioinformatics analysis of synonymous codons in the Methanothermobacter thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs may be recharged by aaRSs bound to the ribosome and reused at the next occurrence of a codon encoding the same amino acid. These results suggest a mechanism of tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture the tRNAs released from the preceding ribosome in polysomes. 10. Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa, Mojave Desert, California: A comparison of the applicability of radiocarbon, luminescence, terrestrial cosmogenic nuclide, electron spin resonance, U-series and amino acid racemization methods USGS Publications Warehouse Owen, L.A.; Bright, Jordon; Finkel, R.C.; Jaiswal, M.K.; Kaufman, D.S.; Mahan, S.; Radtke, U.; Schneider, J.S.; Sharp, W.; Singhvi, A.K.; Warren, C.N. 2007-01-01 A Late Quaternary spit-shoreline complex on the northern shore of Pleistocene Lake Mojave of southeastern California, USA was studied with the goal of comparing accelerator mass spectrometry (AMS) radiocarbon, luminescence, electron spin resonance (ESR), terrestrial cosmogenic radionuclide (TCN) surface exposure, amino acid racemization (AAR) and U-series dating methods. The pattern of ages obtained by the different methods illustrates the complexity of processes acting in the lakeshore environment and highlights the utility of a multi-method approach. TCN surface exposure ages (mostly ???20-30 ka) record the initial erosion of shoreline benches, whereas radiocarbon ages on shells (determined in this and previous studies) within the spit, supported by AAR data, record its construction at fluctuating lake levels from ???16 to 10 ka. Luminescence ages on spit sediment (???6-7 ka) and ESR ages on spit shells (???4 ka) are anomalously young relative to radiocarbon ages of shells within the same deposits. The significance of the surprisingly young luminescence ages is not clear. The younger ESR ages could be a consequence of post-mortem enrichment of U in the shells. High concentrations of detrital thorium in tufa coating spit gravels inhibited the use of single-sample U-series dating. Detailed comparisons such as this provide one of the few means of assessing the accuracy of Quaternary dating techniques. More such comparisons are needed. ?? 2007 Elsevier Ltd and INQUA. 11. Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials NASA Astrophysics Data System (ADS) Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe 2004-09-01 We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity. 12. Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs PubMed Central Godinic-Mikulcic, Vlatka; Jaric, Jelena; Greber, Basil J.; Franke, Vedran; Hodnik, Vesna; Anderluh, Gregor; Ban, Nenad; Weygand-Durasevic, Ivana 2014-01-01 Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal protein synthesis. Previous studies have suggested a link between tRNA aminoacylation and high-molecular-weight cellular complexes such as the cytoskeleton or ribosomes. However, the structural basis of these interactions and potential mechanistic implications are not well understood. To biochemically characterize these interactions we have used a system of two interacting archaeal aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS. More specifically, we have shown by thermophoresis and surface plasmon resonance that these two aaRSs bind to the large ribosomal subunit with micromolar affinities. We have identified the L7/L12 stalk and the proteins located near the stalk base as the main sites for aaRS binding. Finally, we have performed a bioinformatics analysis of synonymous codons in the Methanothermobacter thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs may be recharged by aaRSs bound to the ribosome and reused at the next occurrence of a codon encoding the same amino acid. These results suggest a mechanism of tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture the tRNAs released from the preceding ribosome in polysomes. PMID:24569352 13. Fabrics of migmatites and relationships between partial melting and deformation in high-grade transpressional shear zones: the Patos anatexite (Borborema Province, NE Brazil) NASA Astrophysics Data System (ADS) Viegas, L. G. F.; Archanjo, C. J.; Vauchez, A. 2012-04-01 Migmatites are heterogeneous rocks that record flow processes in the middle crust of actively deforming orogens. The Patos anatexite is located within a transpressional, high-temperature shear zone in which mylonites are associated with partial melting at different scales. The relationships between melting and deformation inside continental ductile shear zones can be hindered due to the apparent structural complexity of migmatites, which encompass shear zone-parallel syntectonic leucosome veins, randomly-oriented nebulites and isotropic leucogranite accumulations of various sizes. A comprehensive petrostructural study was carried out in these rocks in order to test the compatibility of field, magnetic and crystallographic fabrics with the kinematics of melt deformation within high-grade shear zones. Magnetic fabrics of partially molten rocks were investigated using the anisotropy of magnetic susceptibility (AMS) and anisotropy of anhysteretic remanence (AAR). Crystallographic preferred orientations (CPOs) were measured using Electron Backscatter Diffraction (EBSD). Bulk AMS results indicate that ferromagnetic minerals dominate the overall susceptibility of the Patos anatexite, while a subset of samples shows composite ferro- and paramagnetic susceptibilities. AAR in the paramagnetic subfabrics reveals coaxiality between ferro- and paramagnetic fabric ellipsoids, suggesting formation of the magnetic fabric in the Patos anatexite as resulting from a single viscous flow process. AMS lineations display a well-oriented pattern in which magnetic foliations rotate consistently with a dextral simple shear sense, while AAR subfabrics are broadly parallel to the main AMS axes. The CPO of biotite crystals shows a good correlation of <001> axes with the k3 direction of the magnetic susceptibility ellipsoid in samples displaying orientations consistent with the shear-zone fabric and dominantly ferromagnetic behavior. In sites where the nebulitic fabric displays complex patterns 14. Modified spleen stiffness measurement by transient elastography is associated with presence of large oesophageal varices in patients with compensated hepatitis C virus cirrhosis. PubMed Calvaruso, V; Bronte, F; Conte, E; Simone, F; Craxì, A; Di Marco, V 2013-12-01 To evaluate the accuracy of liver transient elastography (TE), spleen TE and other noninvasive tests (AAR, APRI score, platelet count, platelet/spleen ratio) in predicting the presence and the size of oesophageal varices in compensated hepatitis C virus (HCV) cirrhosis, we studied 112 consecutive patients with compensated HCV cirrhosis who underwent biochemical tests, gastrointestinal endoscopy, liver TE and spleen TE by Fibroscan(®) (Echosens, Paris, France) using a modified software version with a range between 1.5 and 150 kPa. Spleen TE was not reliable in 16 patients (14.3%). Among the 96 patients with a valid measurement (69.8% men, mean age: 63.2 ± 9.5 years), 43.7% had no oesophageal varices, 29.2% had grade 1% and 27.1% had grade 2 or grade 3 oesophageal varices. Patients with values of 75 kPa by standard spleen TE had mean values of modified spleen TE of 117 kPa (range: 81.7-149.5). Linear regression revealed a significant correlation between modified spleen TE and oesophageal varix size (r = 0.501; beta: 0.763, SE: 0.144; P < 0.001). On univariate analysis, the variables associated with grade 2/grade 3 oesophageal varices were AAR score, APRI score, platelet/spleen ratio, liver TE and modified spleen TE. On multivariate analysis, only modified spleen TE (OR: 1.026; 95% CI: 1.007-1.046; P = 0.006) and AAR (OR: 14.725; 95% CI: 1.928-112.459; P = 0.010) remained independently associated with grade 2/grade 3 oesophageal varices. Platelet/spleen ratio was the best predictor of oesophageal varices area under the ROC curve (AUROC: 0.763, cut-off: 800, sensitivity: 74%, specificity: 70%), while modified spleen TE was more accurate in predicting grade 2/grade 3 oesophageal varices (AUROC: 0.82, cut-off: 54.0 kPa, sensitivity: 80%, specificity: 70%). Portal hypertension increases spleen stiffness, and the measurement of modified spleen TE is an accurate, noninvasive tool for predicting the presence of large oesophageal varices in patients with compensated HCV 15. Sensitivity of annual mass balance gradient and Hypsometry to the changing climate: the case of Dokriani Glacier, central Himalaya, India NASA Astrophysics Data System (ADS) Pratap, B. 2015-12-01 The glacier mass balance is undelayed, unfiltered and direct method to assess the impact of climate change on the glaciers. Many studies suggest that some of the Himalayan glaciers have lost their mass at an increased rate during the past few decades. Furthermore, the mass balance gradient and hypsometric analysis are important to understand the glacier response towards climatic perturbations. Our long term in-situ monitoring on the Dokriani Glacier provides great insights to understand the variability in central Himalayan glaciers. We report the relationship between glacier hypsometry and annual mass balance gradient (12 years) to understand the glacier's response towards climate change. Dokriani Glacier in the Bhagirathi basin is a small (7 km2) NNW exposed glacier in the western part of central Himalaya, India. The study analysed the annual balance, mass balance gradient and length changes observed during first decade of 21st century (2007-2013) and compare with the previous observations of 1990s (1992-2000). A large spatial variability in the mass balance gradients of two different periods has been observed. The equilibrium-line altitude (ELA) was fluctuated between 5000 and 5100 m a.s.l. and the derived time averaged ELA (ELAn) and balance budget ELA (ELA0) were 5075 and 4965 m a.s.l respectively during 1992-2013. The observed time-averaged accumulation-area ratio (AARn) and balance budget AAR (AAR0) were 0.67 and 0.72 respectively during 1992-2013. The higher value of AAR comprises due to flat and broader accumulation area (4.50 km2) of the glacier. Although, having larger accumulation area, the glacier has faced strong mass wasting with average annual ablation of -1.82 m w.e. a-1 in the ablation zone as compare to residual average annual accumulation of 0.41 m w.e. a-1. Based on the annual mass balance series (12 years) Dokriani Glacier has continuous negative annual balances with monotonically negative cumulative mass loss of -3.86 m w.e with the average 16. Alpha2A adrenergic receptor activation inhibits epileptiform activity in the rat hippocampal CA3 region. PubMed Jurgens, Chris W D; Hammad, Hana M; Lichter, Jessica A; Boese, Sarah J; Nelson, Brian W; Goldenstein, Brianna L; Davis, Kylie L; Xu, Ke; Hillman, Kristin L; Porter, James E; Doze, Van A 2007-06-01 Norepinephrine has potent antiepileptic properties, the pharmacology of which is unclear. Under conditions in which GABAergic inhibition is blocked, norepinephrine reduces hippocampal cornu ammonis 3 (CA3) epileptiform activity through alpha(2) adrenergic receptor (AR) activation on pyramidal cells. In this study, we investigated which alpha(2)AR subtype(s) mediates this effect. First, alpha(2)AR genomic expression patterns of 25 rat CA3 pyramidal cells were determined using real-time single-cell reverse transcription-polymerase chain reaction, demonstrating that 12 cells expressed alpha(2A)AR transcript; 3 of the 12 cells additionally expressed mRNA for alpha(2C)AR subtype and no cells possessing alpha(2B)AR mRNA. Hippocampal CA3 epileptiform activity was then examined using field potential recordings in brain slices. The selective alphaAR agonist 6-fluoronorepinephrine caused a reduction of CA3 epileptiform activity, as measured by decreased frequency of spontaneous epileptiform bursts. In the presence of betaAR blockade, concentration-response curves for AR agonists suggest that an alpha(2)AR mediates this response, as the rank order of potency was 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK-14304) >or= epinephrine >6-fluoronorepinephrine > norepinephrine > phenylephrine. Finally, equilibrium dissociation constants (K(b)) of selective alphaAR antagonists were functionally determined to confirm the specific alpha(2)AR subtype inhibiting CA3 epileptiform activity. Apparent K(b) values calculated for atipamezole (1.7 nM), MK-912 (4.8 nM), BRL-44408 (15 nM), yohimbine (63 nM), ARC-239 (540 nM), prazosin (4900 nM), and terazosin (5000 nM) correlated best with affinities previously determined for the alpha(2A)AR subtype (r = 0.99, slope = 1.0). These results suggest that, under conditions of impaired GABAergic inhibition, activation of alpha(2A)ARs is primarily responsible for the antiepileptic actions of norepinephrine in the rat hippocampal CA3 17. Aminoacyl-tRNA Synthetases in the Bacterial World. PubMed Giegé, Richard; Springer, Mathias 2016-05-01 Aminoacyl-tRNA synthetases (aaRSs) are modular enzymes globally conserved in the three kingdoms of life. All catalyze the same two-step reaction, i.e., the attachment of a proteinogenic amino acid on their cognate tRNAs, thereby mediating the correct expression of the genetic code. In addition, some aaRSs acquired other functions beyond this key role in translation. Genomics and X-ray crystallography have revealed great structural diversity in aaRSs (e.g., in oligomery and modularity, in ranking into two distinct groups each subdivided in 3 subgroups, by additional domains appended on the catalytic modules). AaRSs show huge structural plasticity related to function and limited idiosyncrasies that are kingdom or even species specific (e.g., the presence in many Bacteria of non discriminating aaRSs compensating for the absence of one or two specific aaRSs, notably AsnRS and/or GlnRS). Diversity, as well, occurs in the mechanisms of aaRS gene regulation that are not conserved in evolution, notably between distant groups such as Gram-positive and Gram-negative Bacteria. The review focuses on bacterial aaRSs (and their paralogs) and covers their structure, function, regulation, and evolution. Structure/function relationships are emphasized, notably the enzymology of tRNA aminoacylation and the editing mechanisms for correction of activation and charging errors. The huge amount of genomic and structural data that accumulated in last two decades is reviewed, showing how the field moved from essentially reductionist biology towards more global and integrated approaches. Likewise, the alternative functions of aaRSs and those of aaRS paralogs (e.g., during cell wall biogenesis and other metabolic processes in or outside protein synthesis) are reviewed. Since aaRS phylogenies present promiscuous bacterial, archaeal, and eukaryal features, similarities and differences in the properties of aaRSs from the three kingdoms of life are pinpointed throughout the review and 18. D-Dimer Levels Predict Myocardial Injury in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study PubMed Central Song, Young Bin; Lima, Joao A. C.; Guallar, Eliseo; Choe, Yeon Hyeon; Hwang, Jin Kyung; Kim, Eun Kyoung; Yang, Jeong Hoon; Hahn, Joo-Yong; Choi, Seung-Hyuk; Lee, Sang-Chol; Lee, Sang Hoon; Gwon, Hyeon-Cheol 2016-01-01 Objectives Elevated D-dimer levels on admission predict prognosis in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but the association of D-dimer levels with structural markers of myocardial injury in these patients is unknown. Methods We performed cardiac magnetic resonance (CMR) imaging in 208 patients treated with primary PCI for STEMI. CMR was performed a median of 3 days after the index procedure. Of the 208 patients studied, 75 patients had D-dimer levels above the normal range on admission (>0.5 μg/mL; high D-dimer group) while 133 had normal levels (≤0.5 μg/mL; low D-dimer group). The primary outcome was myocardial infarct size assessed by CMR. Secondary outcomes included area at risk (AAR), microvascular obstruction (MVO) area, and myocardial salvage index (MSI). Results In CMR analysis, myocardial infarct size was larger in the high D-dimer group than in the low D-dimer group (22.3% [16.2–30.5] versus 18.8% [10.7–26.7]; p = 0.02). Compared to the low D-dimer group, the high D-dimer group also had a larger AAR (38.1% [31.7–46.9] versus 35.8% [24.2–45.3]; p = 0.04) and a smaller MSI (37.7 [28.2–46.9] versus 47.1 [33.2–57.0]; p = 0.01). In multivariate analysis, high D-dimer levels were significantly associated with larger myocardial infarct (OR 2.59; 95% CI 1.37–4.87; p<0.01) and lower MSI (OR 2.62; 95% CI 1.44–4.78; p<0.01). Conclusions In STEMI patients undergoing primary PCI, high D-dimer levels on admission were associated with a larger myocardial infarct size, a greater extent of AAR, and lower MSI, as assessed by CMR data. Elevated initial D-dimer level may be a marker of advanced myocardial injury in patients treated with primary PCI for STEMI. PMID:27513758 19. The Diagnostic Accuracy and Clinical Utility of Three Noninvasive Models for Predicting Liver Fibrosis in Patients with HBV Infection PubMed Central Zhang, Zhiqiao; Wang, Gongsui; Kang, Kaifu; Wu, Guobiao; Wang, Peng 2016-01-01 Aim To evaluate the diagnostic accuracy and clinical utility of the fibrosis index based on the four factors (FIB-4), aspartate aminotransferase -to-platelet ratio index (APRI), and aspartate aminotransferase–alanine aminotransferase ratio index (AAR) for predicting liver fibrosis in patients with HBV infection. Methods From January 2006 to December 2010,a total of 1543 consecutive chronic hepatitis B(CHB) patients who underwent liver biopsies were enrolled. FIB-4,APRI, and AAR were calculated.The areas under the receiver-operating characteristic curves (AUROCs) were calculated to assess the diagnostic accuracy of these models.The AUROCs of these models were compared by DeLong’s test.For further comparisons in different studies,the AUROCs were adjusted to conduct Adjusted AUROCs(ADjAUROCs) according to the prevalence of fibrosis stages using the difference between advanced and nonadvanced fibrosis (DANA). Results For prediction of significant fibrosis,severe fibrosis,and cirrhosis,the AUROCs of FIB-4 were 0.646(ADjAUROC 0.717),0.670(ADjAUROC 0.741), and 0.715(ADjAUROC 0.786) respectively;whereas it were 0.656(ADjAUROC 0.727),0.653(ADjAUROC 0.724) and 0.639(ADjAUROC 0.710) for APRI, 0.498(ADjAUROC 0.569),0.548(ADjAUROC 0.619) and 0.573(ADjAUROC 0.644) for AAR. The further comparisons demonstrated that there were no significant differences of AUROCs between FIB-4 and APRI in predicting significant and severe fibrosis(P > 0.05),while FIB-4 was superior to APRI in predicting cirrhosis(P < 0.001). Further subgroup analysis demonstrated that the diagnostic accuracy of FIB-4 and APRI in patients with normal alanine aminotransferase(ALT) were higher than that in patients with elevated ALT. Conclusions The results demonstrated that FIB-4 and APRI are useful for diagnosis of fibrosis. FIB-4 and APRI have similar diagnostic accuracy in predicting significant and severe fibrosis,while FIB-4 is superior to APRI in predicting cirrhosis. The clinical utility of FIB-4 and APRI 20. High Temperature Calcination - MACT Upgrade Equipment Pilot Plant Test SciTech Connect Richard D. Boardman; B. H. O'Brien; N. R. Soelberg; S. O. Bates; R. A. Wood; C. St. Michel 2004-02-01 About one million gallons of acidic, hazardous, and radioactive sodium-bearing waste are stored in stainless steel tanks at the Idaho Nuclear Technology and Engineering Center (INTEC), which is a major operating facility of the Idaho National Engineering and Environmental Laboratory. Calcination at high-temperature conditions (600 C, with alumina nitrate and calcium nitrate chemical addition to the feed) is one of four options currently being considered by the Department of Energy for treatment of the remaining tank wastes. If calcination is selected for future processing of the sodium-bearing waste, it will be necessary to install new off-gas control equipment in the New Waste Calcining Facility (NWCF) to comply with the Maximum Achievable Control Technology (MACT) standards for hazardous waste combustors and incinerators. This will require, as a minimum, installing a carbon bed to reduce mercury emissions from their current level of up to 7,500 to <45 {micro}g/dscm, and a staged combustor to reduce unburned kerosene fuel in the off-gas discharge to <100 ppm CO and <10 ppm hydrocarbons. The staged combustor will also reduce NOx concentrations of about 35,000 ppm by 90-95%. A pilot-plant calcination test was completed in a newly constructed 15-cm diameter calciner vessel. The pilot-plant facility was equipped with a prototype MACT off-gas control system, including a highly efficient cyclone separator and off-gas quench/venturi scrubber for particulate removal, a staged combustor for unburned hydrocarbon and NOx destruction, and a packed activated carbon bed for mercury removal and residual chloride capture. Pilot-plant testing was performed during a 50-hour system operability test January 14-16, followed by a 100-hour high-temperature calcination pilot-plant calcination run January 19-23. Two flowsheet blends were tested: a 50-hour test with an aluminum-to-alkali metal molar ratio (AAR) of 2.25, and a 50-hour test with an AAR of 1.75. Results of the testing 1. How logical reasoning ability and empirical knowledge interact in the process of solving problems about light and vision among Taiwanese secondary school students NASA Astrophysics Data System (ADS) Liao, Shih-Chieh Piagetian scholars argue that the effect of problem content, e.g., empirical knowledge, should decrease with age. Indeed, they believe that the empirical knowledge cannot affect human problem-solving after individuals approach the formal operation stage. In arguing this point, this study uses an A-AR model to address how empirical knowledge affects the problem-solving process among Taiwanese secondary students. The A-AR model is borrowed from mathematics and the symbols, A, A, and R, represent Assumption, Answering, and Reasoning, respectively. Similar to solving mathematics problems, the A-AR model problems require participants to use the given assumptions by logical reasoning in order to respond to the problems. In this situation, the effect of empirical knowledge on problem-solving is easy to detect. There are three results about human problem-solving found in this study. First, the empirical knowledge still affects human problem-solving at the formal operation stage. Not like the Piagetian scholars' assumption: the effect of empirical knowledge is decreasing with age, this study finds that the effect of empirical knowledge is S-shape. The S-shape is a result of academic training. Second, the academic training, major, shapes human problem-solving strategies. For instance, the 12th grade science students' problem-solving strategy is based on logical reasoning ability by the given assumptions and the same grade social science students' strategy is according of their empirical knowledge. Third, the interference of logical reasoning ability and empirical knowledge is a predictor of the empirical knowledge effect on human problem-solving. The relation between the empirical knowledge and interference can be characterized as: the more negative interference the participants have, the more of the empirical knowledge effect they will have in the next year. This study does not agree with the Piagetian theory about human problem-solving: the effect of empirical knowledge 2. A 2600 year history of floods in the Bernese Alps, Switzerland: frequencies, mechanisms and climate forcing NASA Astrophysics Data System (ADS) Schulte, L.; Peña, J. C.; Carvalho, F.; Schmidt, T.; Julià, R.; Llorca, J.; Veit, H. 2015-03-01 A 2600 yr long composite palaeoflood record is reconstructed from high-resolution delta plain sediments of the Hasli-Aare floodplain on the northern slope of the Swiss Alps. Natural proxies compiled from sedimentary, geochemical and geomorphological data were calibrated by textual and factual sources and instrumental data. No fewer than 12 of the 14 historically recorded extreme events between 1480 and the termination of the Hasli-Aare Correction in 1875 were also identified by coarse-grained flood layers, log(Zr/Ti) peaks and Factor 1 anomalies. Geomorphological, historical and instrumental data provide evidence for flood damage intensities and discharge estimations of severe and catastrophic historical floods. Spectral analysis of the geochemical and documentary flood series and several climate proxies (TSI, δ18O, tree-rings, NAO, SNAO) identify similar periodicities of around 60, 80, 100, 120 and 200 years during the last millennia, indicating the influence of the North Atlantic circulation and solar forcing on alpine flood dynamics. The composite floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (from the medium high catchment area) match those of Total Solar Irradiance maxima, suggesting reduced flood activity during warmer climate pulses. Aggradation of clusters of flood layers with increased contribution of siliciclasts from the highest catchment area (plutonic bedrock) (e.g., 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) occurred predominantly during periods with reduced solar irradiance, lower δ18O anomalies, cooler summer temperatures and phases of drier spring climate in the Alps. Increased water storage by glaciers, snow cover and snow patches susceptible to melting processes associated with rainfall episodes and abrupt rises in temperature substantially increased surface run-off on slopes and discharges of alpine rivers. This interpretation is in agreement with the findings 3. A 2600-year history of floods in the Bernese Alps, Switzerland: frequencies, mechanisms and climate forcing NASA Astrophysics Data System (ADS) Schulte, L.; Peña, J. C.; Carvalho, F.; Schmidt, T.; Julià, R.; Llorca, J.; Veit, H. 2015-07-01 A 2600-year long composite palaeoflood record is reconstructed from high-resolution delta plain sediments of the Hasli-Aare floodplain on the northern slope of the Swiss Alps. Natural proxies compiled from sedimentary, geochemical and geomorphological data were calibrated by textual and factual sources and instrumental data. No fewer than 12 of the 14 historically recorded extreme events between 1480 and the termination of the Hasli-Aare river channel correction in 1875 were also identified by coarse-grained flood layers, log(Zr / Ti) peaks and factor 1 anomalies. Geomorphological, historical and instrumental data provide evidence for flood damage intensities and discharge estimations of severe and catastrophic historical floods. Spectral analysis of the geochemical and documentary flood series and several climate proxies (TSI, δ18O, tree-rings, NAO, SNAO) identify similar periodicities of around 60, 80, 100, 120 and 200 years during the last millennia, indicating the influence of the North Atlantic circulation and solar forcing on alpine flood dynamics. The composite floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (from the medium high catchment area) match those of total solar irradiance maxima, suggesting reduced flood activity during warmer climate pulses. Aggradation with multiple sets of flood layers with increased contribution of siliciclasts from the highest catchment area (plutonic bedrock) (e.g. 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) occurred predominantly during periods with reduced solar irradiance, lower δ18O anomalies, cooler summer temperatures and phases of drier spring climate in the Alps. Increased water storage by glaciers, snow cover and snow patches susceptible to melting processes associated with rainfall episodes and abrupt rises in temperature substantially increased surface runoff on slopes and discharges of alpine rivers. This interpretation is in 4. Mass spectrometry-based ligand binding assays on adenosine A1 and A2A receptors. PubMed Massink, A; Holzheimer, M; Hölscher, A; Louvel, J; Guo, D; Spijksma, G; Hankemeier, T; IJzerman, A P 2015-12-01 Conventional methods to measure ligand-receptor binding parameters typically require radiolabeled ligands as probes. Despite the robustness of radioligand binding assays, they carry inherent disadvantages in terms of safety precautions, expensive synthesis, special lab requirements, and waste disposal. Mass spectrometry (MS) is a method that can selectively detect ligands without the need of a label. The sensitivity of MS equipment increases progressively, and currently, it is possible to detect low ligand quantities that are usually found in ligand binding assays. We developed a label-free MS ligand binding (MS binding) assay on the adenosine A(1) and A(2A) receptors (A(1)AR and A(2A)AR), which are well-characterized members of the class A G protein-coupled receptor (GPCR) family. Radioligand binding assays for both receptors are well established, and ample data is available to compare and evaluate the performance of an MS binding assay. 1,3-Dipropyl-8-cyclopentyl-xanthine (DPCPX) and 4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol (ZM-241,385) are high-affinity ligands selective for the A(1)AR and A(2A)AR, respectively. To proof the feasibility of MS binding on the A(1)AR and A(2A)AR, we first developed an MS detection method for unlabeled DPCPX and ZM-241,385. To serve as internal standards, both compounds were also deuterium-labeled. Subsequently, we investigated whether the two unlabeled compounds could substitute for their radiolabeled counterparts as marker ligands in binding experiments, including saturation, displacement, dissociation, and competition association assays. Furthermore, we investigated the accuracy of these assays if the use of internal standards was excluded. The results demonstrate the feasibility of the MS binding assay, even in the absence of a deuterium-labeled internal standard, and provide great promise for the further development of label-free assays based on MS for other GPCRs. PMID 5. The glaciers of Sierra Segundera (Zamora, NW Spain) during their Maximum Ice Extent: area, volume, Glacial Equilibrium Line Altitude and paleo-climatic implications NASA Astrophysics Data System (ADS) María Fernández, Jose; Ubeda, Jose; Palacios, David 2015-04-01 The aim of this paper is to reconstruct the Quaternary glaciers which formed the eastern sector of the Sierra Segundera ice-cap (NW Iberian Peninsula) during its Maximum Ice Extent (MIE) local phase (33 ka) in a surface area of 165 km2, to estimate the ice volumes and Equilibrium Line Altitudes (ELAs). The study area presents a wide altimetric range of approx. 1200 m, from the Tera glacier front to the Peña Trevinca (42°14'33'' N, 6°47'46'' W; 2127 m) and Peña Negra (42°14'58'' N, 6°47'39'' W; 2121 m) horns, covering a wide plateau at an altitude of over 1700 m. The reconstruction of the MIE paleoglaciers used a combination of various tools: a rheological numerical model which describes the ice flow, GIS and geomorphological field work to validate the results. The model used here allowed the reconstruction of the surface topography of the paleoglacial ice, even though there is no existing geomorphologic evidence to reveal the thickness of the ice at that time. The GIS enabled the creation of Digital Elevation Models (DEMs) and the estimation of thicknesses and volumes. The reconstructed topography and the delimitation of the geomorphologic features were used to estimate the ELA using the following methods: Area x Altitude Balance Ratio (AABR), Accumulation Area Ratio (AAR), Terminus Headwall Altitude Ratio (THAR) and Maximum Elevation of Lateral Moraines (MELM). The DEM reconstructed for the surface of the paleoglaciers obtained an estimated maximum ice thickness of over 450 m during the MIE, and a total ice volume of 2.63 x 10(10)m3 for the eastern half of the ice-cap. When estimating the paleo-ELAs, the AABR and AAR methods obtain more logical values. The AABR method obtains BR=1, which questions the BR=2 assumed as representative for medium latitude glaciers with oceanic influence; the paleo-ELA AABR was 1739 m. Applying the AAR method with the ratio 0.65 gives the result 1735 m. The THAR and MELM methods give values of 1637 m and 1651 m respectively for 6. Transfer Relations Between Landscape Functions - The Hydrological Point of View NASA Astrophysics Data System (ADS) Fohrer, N.; Lenhart, T.; Eckhardt, K.; Frede, H.-G. EC market policies and regional subsidy programs have an enormous impact on local land use. This has far reaching consequences on various landscape functions. In the joint research project SFB299 at the Giessen University the effect of land use options on economic, ecological and hydrological landscape functions are under investigation. The continuous time step model SWAT-G (Eckhardt et al., 2000; Arnold et al., 1998) is employed to characterize the influence of land use patterns on hydrological processes. The model was calibrated and validated employing a split sample approach. For two mesoscale watersheds (Aar, 60 km2; Dietzhölze, 81 km2) located in the Lahn-Dill- Bergland, Germany, different land use scenarios were analyzed with regard to their hydrological impact. Additionally the effect of land use change was analyzed with an ecological and an agro-economic model. The impact of the stepwise changing land use was expressed as trade off relations between different landscape functions. 7. Independent component analysis and multiresolution asymmetry ratio for brain-computer interface. PubMed Hsu, Wei-Yen 2013-04-01 This study proposes a brain-computer interface (BCI) system for the recognition of single-trial electroencephalogram (EEG) data. With the combination of independent component analysis (ICA) and multiresolution asymmetry ratio, a support vector machine (SVM) is used to classify left and right finger lifting or motor imagery. First, ICA and similarity measures are proposed to eliminate the electrooculography (EOG) artifacts automatically. The features are then extracted from the wavelet data by means of an asymmetry ratio. Finally, the SVM classifier is used to discriminate between the features. Compared to the EEG data without EOG artifact removal, band power, and adoptive autoregressive (AAR) parameter features, the proposed system achieves promising results in BCI applications. 8. Fuzzy object modeling NASA Astrophysics Data System (ADS) Udupa, Jayaram K.; Odhner, Dewey; Falcao, Alexandre X.; Ciesielski, Krzysztof C.; Miranda, Paulo A. V.; Vaideeswaran, Pavithra; Mishra, Shipra; Grevera, George J.; Saboury, Babak; Torigian, Drew A. 2011-03-01 To make Quantitative Radiology (QR) a reality in routine clinical practice, computerized automatic anatomy recognition (AAR) becomes essential. As part of this larger goal, we present in this paper a novel fuzzy strategy for building bodywide group-wise anatomic models. They have the potential to handle uncertainties and variability in anatomy naturally and to be integrated with the fuzzy connectedness framework for image segmentation. Our approach is to build a family of models, called the Virtual Quantitative Human, representing normal adult subjects at a chosen resolution of the population variables (gender, age). Models are represented hierarchically, the descendents representing organs contained in parent organs. Based on an index of fuzziness of the models, 32 thorax data sets, and 10 organs defined in them, we found that the hierarchical approach to modeling can effectively handle the non-linear relationships in position, scale, and orientation that exist among organs in different patients. 9. How to predict Italy L'Aquila M6.3 earthquake NASA Astrophysics Data System (ADS) Guo, Guangmeng 2016-04-01 According to the satellite cloud anomaly appeared over eastern Italy on 21-23 April 2012, we predicted the M6.0 quake occurred in north Italy successfully. Here checked the satellite images in 2011-2013 in Italy, and 21 cloud anomalies were found. Their possible correlation with earthquakes bigger than M4.7 which located in Italy main fault systems was statistically examined by assuming various lead times. The result shows that when the leading time interval is set to 23≤ΔT≤45 days, 8 of the 10 quakes were preceded by cloud anomalies. Poisson random test shows that AAR (anomaly appearance rate) and EOR (EQ occurrence rate) is much higher than the values by chance. This study proved the relation between cloud anomaly and earthquake in Italy. With this method, we found that L'Aquila earthquake can also be predicted according to cloud anomaly. 10. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 3: a status report on systemic therapies. PubMed Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Tanghetti, Emil; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea 2014-01-01 The third article in this 5-part series reviews systemic therapies used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The consensus recommendations are based on current understanding of research that describes pathophysiologic mechanisms that appear to be operative in rosacea, correlation of these underlying pathophysiologic mechanisms with specific clinical manifestations of rosacea, and outcomes from clinical trials that evaluate therapies for rosacea both as monotherapy and in combination with other agents. Systemic agents used for treatment of rosacea have been administered as oral formulations (ie, tablets, capsules). The only oral agent for rosacea approved by the US Food and Drug Administration (FDA) is a modified-release doxycycline 40-mg capsule. Other non-FDA-approved oral agents also are discussed including other tetracyclines, macrolides, metronidazole, and isotretinoin. 11. Consensus recommendations from the American acne & rosacea society on the management of rosacea, part 4: a status report on physical modalities and devices. PubMed Tanghetti, Emil; Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea 2014-02-01 The fourth article in this 5-part series reviews physical modalities and devices used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The major therapeutic uses of physical modalities and devices, especially laser and light-based systems, are for treatment of telangiectases and persistent facial erythema (background erythema). Phymas, especially rhinophyma, also are treated with physical modalities such as ablative lasers or surgical devices (eg, electrosurgical loop). Appropriately selected and properly used lasers and intense pulsed light (IPL) devices can successfully address specific clinical manifestations of rosacea that exhibit limited or no response to available medical therapies, such as telangiectases and background centrofacial erythema. Rosacea-associated symptoms also may improve. In most cases, treatment will need to be repeated intermittently to sustain improvement. 12. Contest of Web-Based Geospatial Applications for Students and Young Scientists NASA Astrophysics Data System (ADS) Tsai, F.; Cho, K. 2016-06-01 The Asian Association on Remote Sensing (AARS) organizes a web contest (WEBCON) of photogrammetry, remote sensing and spatial information sciences in the annual meeting of Asian Conference on Remote Sensing (ACRS) every year. The purpose of WEBCON is to promote the development of web and other forms of internet services of the internet related to geo-information sciences and to attract more students and young scientists participating in the related fields of study and applications. Since 2011, WEBCON has become one of the major events in ACRS and successfully increased the interest in the research, development and applications of photogrammetry, remote sensing and spatial information sciences among students and young scientist. The success of WEBCON is an excellent example of promoting the profession of spatial information to young people. 13. Anal carcinoma and HIV infection: is it time for screening? PubMed Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M 2014-03-01 A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented? 14. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. PubMed Mirando, Adam C; Fang, Pengfei; Williams, Tamara F; Baldor, Linda C; Howe, Alan K; Ebert, Alicia M; Wilkinson, Barrie; Lounsbury, Karen M; Guo, Min; Francklyn, Christopher S 2015-08-14 Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans. 15. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor PubMed Central Mirando, Adam C.; Fang, Pengfei; Williams, Tamara F.; Baldor, Linda C.; Howe, Alan K.; Ebert, Alicia M.; Wilkinson, Barrie; Lounsbury, Karen M.; Guo, Min; Francklyn, Christopher S. 2015-01-01 Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans. PMID:26271225 16. Prediction of Weather Impacted Airport Capacity using Ensemble Learning NASA Technical Reports Server (NTRS) Wang, Yao Xun 2011-01-01 Ensemble learning with the Bagging Decision Tree (BDT) model was used to assess the impact of weather on airport capacities at selected high-demand airports in the United States. The ensemble bagging decision tree models were developed and validated using the Federal Aviation Administration (FAA) Aviation System Performance Metrics (ASPM) data and weather forecast at these airports. The study examines the performance of BDT, along with traditional single Support Vector Machines (SVM), for airport runway configuration selection and airport arrival rates (AAR) prediction during weather impacts. Testing of these models was accomplished using observed weather, weather forecast, and airport operation information at the chosen airports. The experimental results show that ensemble methods are more accurate than a single SVM classifier. The airport capacity ensemble method presented here can be used as a decision support model that supports air traffic flow management to meet the weather impacted airport capacity in order to reduce costs and increase safety. 17. Strutjet RBCC Engine Performance NASA Technical Reports Server (NTRS) Bulman, Mel; Neill, Todd; Yam, Clement 1999-01-01 In the past two years Strutjet Rocket Based Combined Cycle (RBCC) engine has been tested extensively under the Advanced Reusable Technology (ART) contract from NASA MSFC. RBCC Engines combine the high thrust to weight of the rocket with the high efficiency of the ramjet engine. This propulsion system has the potential to reduce the cost of launching payloads to orbit by up to a factor of 100. In the ART program we have conducted over 100 hot fire tests. The propellants have been hydrogen and oxygen. The Modes tested have included the Air Augmented Rocket (AAR) from M = 0 to 2.4, the Ramjet at M = 2.4 & 6, Scramjet at M = 6 & 8, Scram/Rocket at Mach 8 and Ascent Rocket in Vacuum. This invited paper will present an overview of these test results and plans for future development of this propulsion cycle. 18. Synthesis and structure-activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor. PubMed Silva, Renata Oliveira; de Oliveira, Andressa Souza; Nunes Lemes, Laís Flávia; de Camargo Nascente, Luciana; Coelho do Nascimento Nogueira, Patrícia; Silveira, Edilberto R; Brand, Guilherme D; Vistoli, Giulio; Cilia, Antonio; Poggesi, Elena; Buccioni, Michela; Marucci, Gabriella; Bolognesi, Maria Laura; Romeiro, Luiz Antonio Soares 2016-10-21 Arylpiperazines 2-11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Modifications at the 1,3-benzodioxole and phenyl phamacophoric units resulted in the identification of a number of potent compounds (moderately selective with respect to the α1b-AR), in binding experiments. Notably, compound 7 (LDT451) showed a subnanomolar pKi of 9.41 towards α1a-AR. An encouragingly lower α1B-potency was a general trend for all the series of compounds, which showed α1A/D over α1B selectivity in functional assays. If adequately optimized, such peculiar selectivity could have relevance for a potential LUTS/BPH therapeutic application. PMID:27448917 19. ERP and Adaptive Autoregressive identification with spectral power decomposition to study rapid auditory processing in infants. PubMed Piazza, C; Cantiani, C; Tacchino, G; Molteni, M; Reni, G; Bianchi, A M 2014-01-01 The ability to process rapidly-occurring auditory stimuli plays an important role in the mechanisms of language acquisition. For this reason, the research community has begun to investigate infant auditory processing, particularly using the Event Related Potentials (ERP) technique. In this paper we approach this issue by means of time domain and time-frequency domain analysis. For the latter, we propose the use of Adaptive Autoregressive (AAR) identification with spectral power decomposition. Results show EEG delta-theta oscillation enhancement related to the processing of acoustic frequency and duration changes, suggesting that, as expected, power modulation encodes rapid auditory processing (RAP) in infants and that the time-frequency analysis method proposed is able to identify this modulation. 20. Mantle Heterogeneity and Mixing Beneath the Bouvet Triple Junction Region: Hf Isotope Constraints from the Westernmost Southwest Indian Ridge (0-11deg.E) NASA Astrophysics Data System (ADS) Janney, P. E.; le Roex, A. P. 2013-12-01 SWIR (0-26E) appears to be fairly similar to that sampled by the American Antarctic Ridge (AAR) and southernmost Mid-Atlantic Ridge (MAR; 49-54°S) in the BTJ region. The most depleted MORB from these areas have similar maximum ɛHf values of +13 to +14 (Andres et al., G-cubed, 2002; Barry et al., EPSL, 2006). The southern MAR extends to slightly higher ɛNd and lower 206Pb/204Pb values than SWIR or AAR MORB, but it is possible that this reflects the greater density of analyzed samples from the southern MAR. Mixing trends between depleted and variably enriched compositions displayed on 206Pb/204Pb-ɛHf, -ɛNd and -87Sr/86Sr diagrams for southern MAR and AAR MORB are not consistent with significant addition of Bouvet hot spot material to the mantle beneath these ridges. Rather, they are more consistent with mixing between a depleted end-member and enriched material from the Shona anomaly (which lies between the MAR and AAR, ≈300 km northwest of the BTJ), which has similar Sr, Nd and Hf isotopic characteristics to Bouvet, but less radiogenic 206Pb/204Pb ratios (Douglass et al., JGR, 1995; Andres et al, G-cubed, 2002). 1. Encapsulation of Arn complexes by Calix[4]arene: Endo- vs. exo-complexes SciTech Connect Ebata, Takayuki; Hontama, Naoya; Inokuchi, Yoshiya; Haino, Takeharu; Apra, Edoardo; Xantheas, Sotiris S. 2010-05-14 The structure of the calix[4]arene(C4A)-Arn complexes has been investigated by laser induced fluorescence spectroscopy, mass-selected resonant two-color two-photon ionization (2C-R2PI) spectroscopy, fragment detected IR photodissociation (FDIRPD) spectroscopy, and high level first principles electronic structure calculations at the MP2 and CCSD(T) levels of theory. C4A has a very high ability of forming van der Waals complexes with rare gas atoms. For the C4A-Ar dimer two isomers are observed. A major species shows a 45 cm-1 red-shift of its band origin with respect to the monomer, while that of a minor species is 60 cm-1. The binding energy of the major species is determined to be in the range of 350 - 2250 cm-1 from 2C-R2PI spectroscopy and FDIRPD spectroscopy. Two isomers are also identified in the quantum chemical calculations, depending on whether the Ar atom resides inside (endo) or outside (exo) the C4A. We propose a scheme to derive CCSD(T)-quality binding energies for the C4A-Ar complex based on the ratio of CCSD(T)/MP2 energies for the smaller model systems Benzene-Ar and Phenol-Ar, for which the CCSD(T) level of theory converges to the experimentally determined binding energies. Our best computed estimates for the binding energies of the C4A-Ar endo- and endo-complexes at the CCSD(T)/Complete Basis Set (CBS) level of theory are 1560 cm-1 and 510 cm-1, respectively. For the C4A-Ar2 trimer the calculations support the existence of two nearly isoenergetic isomers: one is the {2:0} endo-complex, in which the Ar2 dimer is encapsulated inside the C4A cavity, and the other is the {1:1} endo-exo-complex, in which one Ar resides inside and the other outside the C4A cavity. However, the experimental evidence 3 strongly suggests that the observed species is the {2:0} endo-complex. The endo structural motif is also suggested for the larger C4A-Arn complexes because of the systematic red-shifts of the complexes with the number of bound Ar atoms suggesting that the 2. Preparation and characterization of human ADCK3, a putative atypical kinase. PubMed Wheeler, Brody; Jia, Zongchao 2015-04-01 AarF domain containing kinase 3 (ADCK3) is a mitochondrial protein known to have a role in the electron transport chain. Despite being required for the biosynthesis of coenzyme Q10, a lipid-soluble electron transporter found to be essential for aerobic cellular respiration, the precise biological function of ADCK3 remains unknown. Patients with mutations in ADCK3 experience an onset of neurological disorders from childhood, including cerebellar ataxia and exercise intolerance. After extensive screening for soluble recombinant protein expression, an N-terminal fusion of maltose-binding protein was found to facilitate the overexpression of the human ADCK3 kinase domain in Escherichia coli as a soluble and biologically active entity. For the first time our work reveals Mg(2+)-dependent ATPase activity of ADCK3, providing strong support for the theoretical prediction of this protein being a functional atypical kinase. 3. Origanum species native to the island of Crete: in vitro antioxidant characteristics and liquid chromatography-mass spectrometry identification of major polyphenolic components. PubMed Tair, Asma; Weiss, Erika-Krisztina; Palade, Laurentiu Mihai; Loupassaki, Sofia; Makris, Dimitris P; Ioannou, Efstathia; Roussis, Vassilios; Kefalas, Panagiotis 2014-01-01 Extracts from three Origanum species, including Origanum microphyllum, Origanum dictamnus and Origanum vulgare subsp. hirtum, native to the island of Crete (southern Greece), were partly fractionated through successive partition with ethyl acetate and n-butanol. All the fractions obtained were profiled with regard to their major polyphenolic constituents, using liquid chromatography-diode array-mass spectrometry. Furthermore, the antioxidant potency of each fraction was assessed by estimating the antiradical activity (A(AR)) and the hydroxyl free radical scavenging activity (SA(HFR)). The chromatographic analyses revealed a rich profile mainly for the ethyl acetate fractions, composed principally by flavones, which were accompanied by a limited number of phenylpropanoids, flavanones and dihydroflavonols. The highest values of antioxidant activity were displayed by the ethyl acetate extract of O. dictamnus, which also possessed the richest polyphenolic composition. 4. Determination of Constitutive Equation for Thermo-mechanical Processing of INCONEL 718 Through Double Multivariate Nonlinear Regression Analysis NASA Astrophysics Data System (ADS) Hussain, Mirza Zahid; Li, Fuguo; Wang, Jing; Yuan, Zhanwei; Li, Pan; Wu, Tao 2015-07-01 The present study comprises the determination of constitutive relationship for thermo-mechanical processing of INCONEL 718 through double multivariate nonlinear regression, a newly developed approach which not only considers the effect of strain, strain rate, and temperature on flow stress but also explains the interaction effect of these thermo-mechanical parameters on flow behavior of the alloy. Hot isothermal compression experiments were performed on Gleeble-3500 thermo-mechanical testing machine in the temperature range of 1153 to 1333 K within the strain rate range of 0.001 to 10 s-1. The deformation behavior of INCONEL 718 is analyzed and summarized by establishing the high temperature deformation constitutive equation. The calculated correlation coefficient ( R) and average absolute relative error ( AARE) underline the precision of proposed constitutive model. 5. Dating and biogeographical patterns in the sea slug genus Acanthodoris Gray, 1850 (Mollusca, Gastropoda, Nudibranchia). PubMed Hallas, Joshua M; Simison, W Brian; Gosliner, Terrence M 2016-04-01 Recent studies investigating vicariance and dispersal have been focused on correlating major geological events with instances of taxonomic expansion by incorporating the fossil record with molecular clock analyses. However, this approach becomes problematic for soft-bodied organisms that are poorly represented in the fossil record. Here, we estimate the phylogenetic relationships of the nudibranch genus Acanthodoris Gray, 1850 using three molecular markers (16S, COI, H3), and then test two alternative geologically calibrated molecular clock scenarios in BEAST and their effect on ancestral area reconstruction (AAR) estimates employed in LAGRANGE. The global temperate distribution of Acanthodoris spans multiple geological barriers, including the Bering Strait (∼5.32 Mya) and the Baja Peninsula (∼5.5 Mya), both of which are used in our dating estimates. The expansion of the Atlantic Ocean (∼95-105 Mya) is also used to calibrate the relationship between A. falklandica Eliot, 1905 and A. planca Fahey and Valdés, 2005, which are distributed in southern Chile and South Africa respectively. Phylogenetic analyses recovered strong biogeographical signal and recovered two major clades representing northern and southern hemispheric distributions of Acanthodoris. When all three geological events are applied to the calibration analyses, the age for Acanthodoris is estimated to be mid-Cretaceous. When the expansion of the Atlantic Ocean is excluded from our analyses, however, Acanthodoris is estimated to be much younger, with a divergence time estimate during the Miocene. Regardless of divergence estimates, our AAR suggests that Acanthodoris may have origins in the Atlantic Ocean with the Atlantic acting as a dispersal point to the northeastern Pacific. These results suggest that Acanthodoris exhibits a rare instance of western trans-arctic expansion. This study also shows that northeast Pacific specimens of A. pilosa should be regarded as A. atrogriseata and that A 6. Dating and biogeographical patterns in the sea slug genus Acanthodoris Gray, 1850 (Mollusca, Gastropoda, Nudibranchia). PubMed Hallas, Joshua M; Simison, W Brian; Gosliner, Terrence M 2016-04-01 Recent studies investigating vicariance and dispersal have been focused on correlating major geological events with instances of taxonomic expansion by incorporating the fossil record with molecular clock analyses. However, this approach becomes problematic for soft-bodied organisms that are poorly represented in the fossil record. Here, we estimate the phylogenetic relationships of the nudibranch genus Acanthodoris Gray, 1850 using three molecular markers (16S, COI, H3), and then test two alternative geologically calibrated molecular clock scenarios in BEAST and their effect on ancestral area reconstruction (AAR) estimates employed in LAGRANGE. The global temperate distribution of Acanthodoris spans multiple geological barriers, including the Bering Strait (∼5.32 Mya) and the Baja Peninsula (∼5.5 Mya), both of which are used in our dating estimates. The expansion of the Atlantic Ocean (∼95-105 Mya) is also used to calibrate the relationship between A. falklandica Eliot, 1905 and A. planca Fahey and Valdés, 2005, which are distributed in southern Chile and South Africa respectively. Phylogenetic analyses recovered strong biogeographical signal and recovered two major clades representing northern and southern hemispheric distributions of Acanthodoris. When all three geological events are applied to the calibration analyses, the age for Acanthodoris is estimated to be mid-Cretaceous. When the expansion of the Atlantic Ocean is excluded from our analyses, however, Acanthodoris is estimated to be much younger, with a divergence time estimate during the Miocene. Regardless of divergence estimates, our AAR suggests that Acanthodoris may have origins in the Atlantic Ocean with the Atlantic acting as a dispersal point to the northeastern Pacific. These results suggest that Acanthodoris exhibits a rare instance of western trans-arctic expansion. This study also shows that northeast Pacific specimens of A. pilosa should be regarded as A. atrogriseata and that A 7. Fuzzylot: a novel self-organising fuzzy-neural rule-based pilot system for automated vehicles. PubMed Pasquier, M; Quek, C; Toh, M 2001-10-01 This paper presents part of our research work concerned with the realisation of an Intelligent Vehicle and the technologies required for its routing, navigation, and control. An automated driver prototype has been developed using a self-organising fuzzy rule-based system (POPFNN-CRI(S)) to model and subsequently emulate human driving expertise. The ability of fuzzy logic to represent vague information using linguistic variables makes it a powerful tool to develop rule-based control systems when an exact working model is not available, as is the case of any vehicle-driving task. Designing a fuzzy system, however, is a complex endeavour, due to the need to define the variables and their associated fuzzy sets, and determine a suitable rule base. Many efforts have thus been devoted to automating this process, yielding the development of learning and optimisation techniques. One of them is the family of POP-FNNs, or Pseudo-Outer Product Fuzzy Neural Networks (TVR, AARS(S), AARS(NS), CRI, Yager). These generic self-organising neural networks developed at the Intelligent Systems Laboratory (ISL/NTU) are based on formal fuzzy mathematical theory and are able to objectively extract a fuzzy rule base from training data. In this application, a driving simulator has been developed, that integrates a detailed model of the car dynamics, complete with engine characteristics and environmental parameters, and an OpenGL-based 3D-simulation interface coupled with driving wheel and accelerator/ brake pedals. The simulator has been used on various road scenarios to record from a human pilot driving data consisting of steering and speed control actions associated to road features. Specifically, the POPFNN-CRI(S) system is used to cluster the data and extract a fuzzy rule base modelling the human driving behaviour. Finally, the effectiveness of the generated rule base has been validated using the simulator in autopilot mode. PMID:11681754 8. L-arginine recognition by yeast arginyl-tRNA synthetase. PubMed Central Cavarelli, J; Delagoutte, B; Eriani, G; Gangloff, J; Moras, D 1998-01-01 The crystal structure of arginyl-tRNA synthetase (ArgRS) from Saccharomyces cerevisiae, a class I aminoacyl-tRNA synthetase (aaRS), with L-arginine bound to the active site has been solved at 2.75 A resolution and refined to a crystallographic R-factor of 19.7%. ArgRS is composed predominantly of alpha-helices and can be divided into five domains, including the class I-specific active site. The N-terminal domain shows striking similarity to some completely unrelated proteins and defines a module which should participate in specific tRNA recognition. The C-terminal domain, which is the putative anticodon-binding module, displays an all-alpha-helix fold highly similar to that of Escherichia coli methionyl-tRNA synthetase. While ArgRS requires tRNAArg for the first step of the aminoacylation reaction, the results show that its presence is not a prerequisite for L-arginine binding. All H-bond-forming capability of L-arginine is used by the protein for the specific recognition. The guanidinium group forms two salt bridge interactions with two acidic residues, and one H-bond with a tyrosine residue; these three residues are strictly conserved in all ArgRS sequences. This tyrosine is also conserved in other class I aaRS active sites but plays several functional roles. The ArgRS structure allows the definition of a new framework for sequence alignments and subclass definition in class I aaRSs. PMID:9736621 9. Fuzzylot: a novel self-organising fuzzy-neural rule-based pilot system for automated vehicles. PubMed Pasquier, M; Quek, C; Toh, M 2001-10-01 This paper presents part of our research work concerned with the realisation of an Intelligent Vehicle and the technologies required for its routing, navigation, and control. An automated driver prototype has been developed using a self-organising fuzzy rule-based system (POPFNN-CRI(S)) to model and subsequently emulate human driving expertise. The ability of fuzzy logic to represent vague information using linguistic variables makes it a powerful tool to develop rule-based control systems when an exact working model is not available, as is the case of any vehicle-driving task. Designing a fuzzy system, however, is a complex endeavour, due to the need to define the variables and their associated fuzzy sets, and determine a suitable rule base. Many efforts have thus been devoted to automating this process, yielding the development of learning and optimisation techniques. One of them is the family of POP-FNNs, or Pseudo-Outer Product Fuzzy Neural Networks (TVR, AARS(S), AARS(NS), CRI, Yager). These generic self-organising neural networks developed at the Intelligent Systems Laboratory (ISL/NTU) are based on formal fuzzy mathematical theory and are able to objectively extract a fuzzy rule base from training data. In this application, a driving simulator has been developed, that integrates a detailed model of the car dynamics, complete with engine characteristics and environmental parameters, and an OpenGL-based 3D-simulation interface coupled with driving wheel and accelerator/ brake pedals. The simulator has been used on various road scenarios to record from a human pilot driving data consisting of steering and speed control actions associated to road features. Specifically, the POPFNN-CRI(S) system is used to cluster the data and extract a fuzzy rule base modelling the human driving behaviour. Finally, the effectiveness of the generated rule base has been validated using the simulator in autopilot mode. 10. North Cascade Glacier Annual Mass Balance Record Analysis 1984-2013 NASA Astrophysics Data System (ADS) Pelto, M. S. 2014-12-01 The North Cascade Glacier Climate Project (NCGCP) was founded in 1983 to monitor 10 glaciers throughout the range and identify their response to climate change. The annual observations include mass balance, terminus behavior, glacier surface area and accumulation area ratio (AAR). Annual mass balance (Ba) measurements have been continued on the 8 original glaciers that still exist. Two glaciers have disappeared: the Lewis Glacier and Spider Glacier. In 1990, Easton Glacier and Sholes Glacier were added to the annual balance program to offset the loss. One other glacier Foss Glacier has declined to the extent that continued measurement will likely not be possible. Here we examine the 30 year long Ba time series from this project. All of the data have been reported to the World Glacier Monitoring Service (WGMS). This comparatively long record from glaciers in one region conducted by the same research program using the same methods offers some useful comparative data. Degree day factors for melt of 4.3 mm w.e.°C-1d-1 for snow and 6.6 mm w.e.°C-1d-1 for ice has been determined from 412 days of ablation observation. The variation in the AAR for equilibrium Ba is small ranging from 60 to 67. The mean annual balance of the glaciers from 1984-2013 is -0.45 ma-1, ranging from -0.31 to -0.57 ma-1 for individual glacier's. The correlation coefficient of Ba is above 0.80 between all glaciers including the USGS benchmark glacier, South Cascade Glacier. This indicates that the response is to regional climate change, not local factors. The mean annual balance of -0.45 ma-1 is close to the WGMS global average for this period -0.50 ma-1. The cumulative loss of 13.5 m w.e. and 15 m of ice thickness represents more than 20% of the volume of the glaciers. 11. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats. PubMed Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi 2013-01-01 This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes. 12. Fluid regimes during late stages of a continental collision: Physical, chemical, and stable isotope measurements of fluid inclusions in fissure quartz from a geotraverse through the Central Alps, Switzerland SciTech Connect Mullis, J. ); Dubessy, J.; Poty, B. ); O'Neil, J. ) 1994-05-01 Fluid evolution during neo-alpine metamorphism during late stages of the continental collision between Europe and Africa was studied by analyzing fluid inclusions in alpine fissure quartz collected in forty-nine localities along a geotraverse through the Central Alps, Switzerland. The methods employed include microthermometry, micro-Raman spectroscopy, K/Na thermometry, and stable isotope analysis. Early fluid inclusions provide evidence of close to peak metamorphic temperatures of the late Tertiary or neo-alpine metamorphic event. Fluid composition evolved along the geotraverse from north to south as follows: higher hydrocarbons were dominant in the low- and medium-grade diagenetic zones, methane was the main volatile in the high-grade diagenetic and low-grade anchizone, water dominated in the high-grade anchizone and low-grade epizone, with CO[sub 2] > 10 mol% in the high-grade epizone and in the mesozone. Higher hydrocarbons and CH[sub 4] were the products of kerogen maturation and cracking of preexisting petroleum. Large water supplies originated from the dehydration of cooler metasedimentary rocks that were overthrust by crystalline basements of the Lepontines, Aar, and Gotthard massifs. Carbon isotope analyses suggest that the CO[sub 2] component was derived from oxidation of graphitic matter, especially in the vicinity of sulfate-bearing metasediments and from decarbonation reactions. In the Aar and Gotthard massifs as well as in the Helvetic Axen nappe and its underlying North Helvetic flysch, high fluid pressures prevailed and favored nappe transport. By contrast, in the southern Lepontine area, very low early fluid pressures were probably related to dry rocks and scarce metasediments, and to high geothermal gradients that resulted from intense uplift and erosion between 26 and 18 Ma. 13. Crystal structures of Acetobacter aceti succinyl-coenzyme A (CoA):acetate CoA-transferase reveal specificity determinants and illustrate the mechanism used by class I CoA-transferases. PubMed Mullins, Elwood A; Kappock, T Joseph 2012-10-23 Coenzyme A (CoA)-transferases catalyze transthioesterification reactions involving acyl-CoA substrates, using an active-site carboxylate to form covalent acyl anhydride and CoA thioester adducts. Mechanistic studies of class I CoA-transferases suggested that acyl-CoA binding energy is used to accelerate rate-limiting acyl transfers by compressing the substrate thioester tightly against the catalytic glutamate [White, H., and Jencks, W. P. (1976) J. Biol. Chem. 251, 1688-1699]. The class I CoA-transferase succinyl-CoA:acetate CoA-transferase is an acetic acid resistance factor (AarC) with a role in a variant citric acid cycle in Acetobacter aceti. In an effort to identify residues involved in substrate recognition, X-ray crystal structures of a C-terminally His(6)-tagged form (AarCH6) were determined for several wild-type and mutant complexes, including freeze-trapped acetylglutamyl anhydride and glutamyl-CoA thioester adducts. The latter shows the acetate product bound to an auxiliary site that is required for efficient carboxylate substrate recognition. A mutant in which the catalytic glutamate was changed to an alanine crystallized in a closed complex containing dethiaacetyl-CoA, which adopts an unusual curled conformation. A model of the acetyl-CoA Michaelis complex demonstrates the compression anticipated four decades ago by Jencks and reveals that the nucleophilic glutamate is held at a near-ideal angle for attack as the thioester oxygen is forced into an oxyanion hole composed of Gly388 NH and CoA N2″. CoA is nearly immobile along its entire length during all stages of the enzyme reaction. Spatial and sequence conservation of key residues indicates that this mechanism is general among class I CoA-transferases. 14. Simulated performance of biomass gasification based combined power and refrigeration plant for community scale application NASA Astrophysics Data System (ADS) Chattopadhyay, S.; Mondal, P.; Ghosh, S. 2016-07-01 Thermal performance analysis and sizing of a biomass gasification based combined power and refrigeration plant (CPR) is reported in this study. The plant is capable of producing 100 kWe of electrical output while simultaneously producing a refrigeration effect, varying from 28-68 ton of refrigeration (TR). The topping gas turbine cycle is an indirectly heated all-air cycle. A combustor heat exchanger duplex (CHX) unit burns producer gas and transfer heat to air. This arrangement avoids complex gas cleaning requirements for the biomass-derived producer gas. The exhaust air of the topping GT is utilized to run a bottoming ammonia absorption refrigeration (AAR) cycle via a heat recovery steam generator (HRSG), steam produced in the HRSG supplying heat to the generator of the refrigeration cycle. Effects of major operating parameters like topping cycle pressure ratio (rp) and turbine inlet temperature (TIT) on the energetic performance of the plant are studied. Energetic performance of the plant is evaluated via energy efficiency, required biomass consumption and fuel energy savings ratio (FESR). The FESR calculation method is significant for indicating the savings in fuel of a combined power and process heat plant instead of separate plants for power and process heat. The study reveals that, topping cycle attains maximum power efficiency of 30%in pressure ratio range of 8-10. Up to a certain value of pressure ratio the required air flow rate through the GT unit decreases with increase in pressure ratio and then increases with further increase in pressure ratio. The capacity of refrigeration of the AAR unit initially decreases up to a certain value of topping GT cycle pressure ratio and then increases with further increase in pressure ratio. The FESR is found to be maximized at a pressure ratio of 9 (when TIT=1100°C), the maximum value being 53%. The FESR is higher for higher TIT. The heat exchanger sizing is also influenced by the topping cycle pressure ratio and GT-TIT. 15. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats. PubMed Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi 2013-01-01 This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes. PMID:23936589 16. Sedimentary records of trace elements from large European lakes (Switzerland) document historic to recent freshwater pollution and climate-induced runoff variations NASA Astrophysics Data System (ADS) Thevenon, F.; Wirth, S. B.; Fujak, M.; Poté, J.; Thierry, A.; Chiaradia, M.; Girardclos, S. 2011-12-01 Continuous sedimentary records of anthropogenic and natural trace elements determined by ICPMS, from 5 large and deep perialpine lakes from Central Europe (Switzerland), evidence the environmental impacts of industrial fossil fuel pollution. In fact, the greatest increase in heavy metal pollution was registered at all the studied sites following the European industrial revolution of ca. AD 1800; with the highest values during the middle part of the 20th century. On a regional scale, anthropogenic heavy metal input subsequently stopped increasing thanks to remediation strategies such as the implementation of wastewater treatment plants (WWTPs). On the other hand, the discharge of industrial treated wastewaters into Vidy Bay of Lake Geneva during the second part of the 20th century involved the sedimentation of highly contaminated sediments in the area surrounding the WWTP outlet pipe discharge; less than 4 km from the main supply of drinking water of Lausanne (127'000 hab.). Microbial analyses furthermore reveal i) high increase in bacterial densities following the lake eutrophication in the 1970s, and that ii) the related sediments can be considered as a reservoir of antibiotic resistant bacteria/genes (of human origin). We finally compare instrumental hydrological data over the last century with variations of lithogenic trace elements (e.g., titanium) as registered in three large lakes (Brienz, Thun and Bienne) connected by the River Aar. This task allows to better constraining the runoff variations on a regional scale over the last decades for the the River Aar, and its possible increase under warming climate conditions in the European Alps. 17. A New Species of the Genus Kiwa (Decapoda: Anomura) from the Hydrothermal Vent of the Australia-Antarctic Ridge NASA Astrophysics Data System (ADS) Won, Y. J.; Lee, S. H.; Lee, W. K. 2014-12-01 Due to extreme weather conditions and remoteness to access, the great part of the Southern Ocean remains to be explored. Therefore, little is known about the Circum-Antarctic Ridge (CAR) system and its hydrothermal vent ecosystem underlying the Southern Ocean. We report the first discovery of a new deep-sea hydrothermal vent field and a new anomuran species from the Australia-Antarctic Ridge (AAR), the highest latitude (62°S; 158°E) explored in the Southern Ocean up to date. At this site, a new anomuran species which belongs to the genus Kiwa known as 'yeti crabs' was found. Morphologically, this species has characteristics of the genus Kiwa, including fifth pereopod inserted below sterna plastron, third sternite strongly produced anteriorly, and eyes extremely reduced. However, the new species differs from the other known species of Kiwa, K. hirsuta and K. puravida, showing relatively short rostrum and slender dactylus on second to fourth pereopods. Phylogenetic analysis using DNA sequences of eight genetic loci also supported the result of morphological analysis, confirming this species as a new Kiwa species, Kiwa n. sp. In addition, phylogenetic tree revealed the evolutionary relationship among the Kiwa species, presenting the Kiwa n. sp. as the sister species to K. puravida which inhabits the methane cold seep on the Pacific continental slope off Costa Rica. Considering the geography and the physicochemical environment, this unlikely result casts a mystery to be solved through further taxon sampling particularly from as-yet-unexplored vents and seeps. Discovery of the hydrothermal vent and Kiwa n. sp. from the AAR segment is significant because this site is located in the high latitude of the southern hemisphere and it is the region affected by the Antarctic Circumpolar Current (ACC). Future research on the relation of Kiwa n. sp. and the other Kiwa species affected by the ACC will provide an idea about the biogeography and the evolutionary connections of the 18. Multi-point Analysis of Electrostatic Solitary Waves and Field Aligned Electrons Observed by Cluster in and Near the Auroral Current Regions NASA Astrophysics Data System (ADS) Pickett, J. S.; Forsyth, C.; Christopher, I.; Fazakerley, A. N.; Masson, A.; Marklund, G. T.; Georgescu, E. 2011-12-01 The four Cluster spacecraft have been transiting Earth's mid and upper auroral acceleration region (AAR) during parts of the year since late 2008. The Wideband Data (WBD) plasma wave receiver mounted on all four spacecraft obtains high time resolution, band-limited waveforms over a wide frequency range (100 Hz to 577 kHz). We present observations of Electrostatic Solitary Waves (ESWs) made by the WBD instrument simultaneously on more than one Cluster spacecraft in and near the auroral downward current region in the following two frequency bands: 100 Hz to 9.5 kHz and 700 Hz to 77 kHz. We examine and analyze these ESWs for similarities on different spacecraft, and investigate the conclusion, based on single spacecraft FAST satellite data, that fast ESWs (~1 ms duration) in this region are observed in conjunction with modulations in both upgoing and downgoing electrons, suggesting a current instability as the mechanism for generation of these ESWs. We also analyze and discuss the very short time duration ESWs (~20-30 microseconds) observed in the upward current region by the Cluster spacecraft. Such short time duration ESWs have not been previously reported in this region, although fast ESWs of ~300 microseconds duration have been reported using data from the FAST satellite. The Cluster PEACE electron data in this upward current region are examined to determine if there is a correlation of ESW detection with narrow, field-aligned downgoing beams as shown by the FAST results, suggesting ESW generation through a beam instability. The electron density and electric field data are also presented for some events in order to place the wave measurements into context with relation to the auroral density cavity and electric field configuration in and near the AAR. 19. The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation. PubMed Perez-Aso, M; Segura, V; Montó, F; Barettino, D; Noguera, M A; Milligan, G; D'Ocon, P 2013-10-01 We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation and internalization-dependent ERK1/2 activation. The different pathways of phenylephrine induced ERK phosphorylation were determined by western blot, using the PKC inhibitor Ro 31-8425, the receptor internalization inhibitor concanavalin A and the siRNA targeting β-arrestin 2. Receptor internalization properties were studied using CypHer5 technology and VSV-G epitope-tagged receptors. Activation of α1A- and α1B-ARs by phenylephrine elicited rapid ERK1/2 phosphorylation that was directed to the nucleus and inhibited by Ro 31-8425. Concomitant with phenylephrine induced receptor internalization α1A-AR, but not α1B-AR, produced a maintained and PKC-independent ERK phosphorylation, which was restricted to the cytosol and inhibited by β-arrestin 2 knockdown or concanavalin A treatment. α1D-AR displayed constitutive ERK phosphorylation, which was reduced by incubation with prazosin or the selective α1D antagonist BMY7378. Following activation by phenylephrine, α1D-AR elicited rapid, transient ERK1/2 phosphorylation that was restricted to the cytosol and not inhibited by Ro 31-8425. Internalization of the α1D-AR subtype was not observed via CypHer5 technology. The three α1-AR subtypes present different spatio-temporal patterns of receptor internalization, and only α1A-AR stimulation translates to a late, sustained ERK1/2 phosphorylation that is restricted to the cytosol and dependent on β-arrestin 2 mediated internalization. 20. Spinophilin Is Indispensable for the α2B Adrenergic Receptor-Elicited Hypertensive Response. PubMed Che, Pulin; Chen, Yunjia; Lu, Roujian; Peng, Ning; Gannon, Mary; Wyss, J Michael; Jiao, Kai; Wang, Qin 2015-01-01 The α2 adrenergic receptor (AR) subtypes are important for blood pressure control. When activated, the α2A subtype elicits a hypotensive response whereas the α2B subtype mediates a hypertensive effect that counteracts the hypotensive response by the α2A subtype. We have previously shown that spinophilin attenuates the α2AAR-dependent hypotensive response; in spinophilin null mice, this response is highly potentiated. In this study, we demonstrate that spinophilin impedes arrestin-dependent phosphorylation and desensitization of the α2BAR subtype by competing against arrestin binding to this receptor subtype. The Del301-303 α2BAR, a human variation that shows impaired phosphorylation and desensitization and is linked to hypertension in certain populations, exhibits preferential interaction with spinophilin over arrestin. Furthermore, Del301-303 α2BAR-induced ERK signaling is quickly desensitized in cells without spinophilin expression, showing a profile similar to that induced by the wild type receptor in these cells. Together, these data suggest a critical role of spinophilin in sustaining α2BAR signaling. Consistent with this notion, our in vivo study reveals that the α2BAR-elicited hypertensive response is diminished in spinophilin deficient mice. In arrestin 3 deficient mice, where the receptor has a stronger binding to spinophilin, the same hypertensive response is enhanced. These data suggest that interaction with spinophilin is indispensable for the α2BAR to elicit the hypertensive response. This is opposite of the negative role of spinophilin in regulating α2AAR-mediated hypotensive response, suggesting that spinophilin regulation of these closely related receptor subtypes can result in distinct functional outcomes in vivo. Thus, spinophilin may represent a useful therapeutic target for treatment of hypertension. 1. Structure of Leishmania major Methionyl-tRNA Synthetase in Complex with Intermediate Products Methionyladenylate and Pyrophosphate PubMed Central Larson, Eric T.; Kim, Jessica E.; Zucker, Frank H.; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J.; Verlinde, Christophe L.M.J.; Fan, Erkang; Buckner, Frederick S.; Van Voorhis, Wesley C.; Merritt, Ethan A.; Hol, Wim G.J. 2011-01-01 Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg2+ ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of E. coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNAMet complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme. PMID:21144880 2. Gαi2-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart PubMed Central Waterson, Rachael E.; Thompson, Corbin G.; Mabe, Nathaniel W.; Kaur, Kuljeet; Talbot, Jeffery N.; Neubig, Richard R.; Rorabaugh, Boyd R. 2011-01-01 Aims Regulator of G protein signalling (RGS) proteins act as molecular ‘off switches’ that terminate G protein signalling by catalyzing the hydrolysis of Gα-bound GTP to GDP. Many different Gαi-coupled receptors have been implicated in the cardioprotective effects of ischaemic preconditioning. However, the role of RGS proteins in modulating cardioprotection has not been previously investigated. We used mice that were homozygous (GS/GS) or heterozygous (GS/+) for a mutation in Gαi2 rendering it RGS-insensitive (G184S) to determine whether interactions between endogenous RGS proteins and Gαi2 modulate Gαi-mediated protection from ischaemic injury. Methods and results Langendorff-perfused mouse hearts were subjected to 30 min global ischaemia and 2 h reperfusion. Infarcts in GS/GS (14.5% of area at risk) and GS/+ (22.6% of AAR) hearts were significantly smaller than those of +/+ hearts (37.2% of AAR) and recovery of contractile function was significantly enhanced in GS/GS and GS/+ hearts compared with +/+ hearts. The cardioprotective phenotype was not reversed by wortmannin or U0126 but was reversed by 5-hydroxydecanoic acid and HMR 1098, indicating that RGS-insensitive Gαi2 protects the heart through a mechanism that requires functional ATP-dependent potassium channels but does not require acute activation of extracellular-regulated kinase or Akt signalling pathways. Conclusions This is the first study to demonstrate that Gαi2-mediated cardioprotection is suppressed by RGS proteins. These data suggest that RGS proteins may provide novel therapeutic targets to protect the heart from ischaemic injury. PMID:21349876 3. Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements NASA Astrophysics Data System (ADS) Forsyth, C.; Fazakerley, A. N.; Walsh, A. P.; Watt, C. E.; Garza, K.; Owen, C. J.; Constantinescu, D. O.; Dandouras, I. S.; Fornacon, K.; Lucek, E. A.; Marklund, G. T.; Sadeghi, S. S.; Khotyaintsev, Y. V.; Masson, A.; Doss, N. 2013-12-01 Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modelling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations. 4. Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements NASA Astrophysics Data System (ADS) Forsyth, C.; Fazakerley, A. N.; Walsh, A. P.; Watt, C. E. J.; Garza, K. J.; Owen, C. J.; Constantinescu, D.; Dandouras, I.; FornaçOn, K.-H.; Lucek, E.; Marklund, G. T.; Sadeghi, S. S.; Khotyaintsev, Y.; Masson, A.; Doss, N. 2012-12-01 Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modeling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations. 5. Fat segmentation on chest CT images via fuzzy models NASA Astrophysics Data System (ADS) Tong, Yubing; Udupa, Jayaram K.; Wu, Caiyun; Pednekar, Gargi; Subramanian, Janani Rajan; Lederer, David J.; Christie, Jason; Torigian, Drew A. 2016-03-01 Quantification of fat throughout the body is vital for the study of many diseases. In the thorax, it is important for lung transplant candidates since obesity and being underweight are contraindications to lung transplantation given their associations with increased mortality. Common approaches for thoracic fat segmentation are all interactive in nature, requiring significant manual effort to draw the interfaces between fat and muscle with low efficiency and questionable repeatability. The goal of this paper is to explore a practical way for the segmentation of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) components of chest fat based on a recently developed body-wide automatic anatomy recognition (AAR) methodology. The AAR approach involves 3 main steps: building a fuzzy anatomy model of the body region involving all its major representative objects, recognizing objects in any given test image, and delineating the objects. We made several modifications to these steps to develop an effective solution to delineate SAT/VAT components of fat. Two new objects representing interfaces of SAT and VAT regions with other tissues, SatIn and VatIn are defined, rather than using directly the SAT and VAT components as objects for constructing the models. A hierarchical arrangement of these new and other reference objects is built to facilitate their recognition in the hierarchical order. Subsequently, accurate delineations of the SAT/VAT components are derived from these objects. Unenhanced CT images from 40 lung transplant candidates were utilized in experimentally evaluating this new strategy. Mean object location error achieved was about 2 voxels and delineation error in terms of false positive and false negative volume fractions were, respectively, 0.07 and 0.1 for SAT and 0.04 and 0.2 for VAT. 6. Chemistry of Hydrothermal Plumes at 159°E on the Australian-Antarctic Ridge NASA Astrophysics Data System (ADS) Hahm, D.; Baker, E. T.; Rhee, T. S.; Lupton, J. E.; Resing, J. A.; Park, S. H. 2014-12-01 The Australian-Antarctic Ridge (AAR) is one of the largest unexplored regions of the global mid-ocean ridge system. In the present contribution, we present the geochemistry of the hydrothermal plumes over the KR1, an AAR segment at 159ºE and 62ºS. In 2011, we collected 48 Miniature Autonomous Plume Recorder profiles, measuring optical back scatter and oxidation-reduction potential, and identified the area between 158.5 and 159ºE as the densest concentration of active hydrothermal sites. In order to further characterize the chemistry of the hydrothermal plumes over the area, named 'Mujin', we conducted intensive vertical and tow-yo CTD casts in 2013. The maximum concentrations of the chemical tracers 3He, CH4, H2, and dissolved Mn, were 7.47 fmol/kg, 19.6 nmol/kg, 8.8 nmol/kg, 94.3 nmol/L, respectively. The CH4/3He (1 -10) and CH4/Mn (0.01 - 0.2) ratios were significantly lower than many ultra-mafic hosted systems, which are often found in slow spreading ridges. The lower ratios are consistent with a basaltic-hosted system, typical of the intermediate spreading rate of 6.8 cm/yr of KR1. Additionally, some of the plume samples collected around 158.6 and 158.8ºE exhibited slightly higher ratios of H2/3He than the others. Assuming that H2 is produced from the reduction of water by reduced iron compounds in the rock, the higher ratios suggest that those plumes are supported by a younger hydrothermal system, which may have experienced a recent eruption. 7. Intraventricular and interventricular cellular heterogeneity of inotropic responses to α(1)-adrenergic stimulation. PubMed Chu, Charles; Thai, Kevin; Park, Ki Wan; Wang, Paul; Makwana, Om; Lovett, David H; Simpson, Paul C; Baker, Anthony J 2013-04-01 α1-Adrenergic receptors (α1-ARs) elicit a negative inotropic effect (NIE) in the mouse right ventricular (RV) myocardium but a positive inotropic effect (PIE) in the left ventricular (LV) myocardium. Effects on myofilament Ca(2+) sensitivity play a role, but effects on Ca(2+) handling could also contribute. We monitored the effects of α1-AR stimulation on contraction and Ca(2+) transients using single myocytes isolated from the RV or LV. Interestingly, for both the RV and LV, we found heterogeneous myocyte inotropic responses. α1-ARs mediated either a PIE or NIE, although RV myocytes had a greater proportion of cells manifesting a NIE (68%) compared with LV myocytes (36%). Stimulation of a single α1-AR subtype (α1A-ARs) with a subtype-selective agonist also elicited heterogeneous inotropic responses, suggesting that the heterogeneity arose from events downstream of the α1A-AR subtype. For RV and LV myocytes, an α1-AR-mediated PIE was associated with an increased Ca(2+) transient and a NIE was associated with a decreased Ca(2+) transient, suggesting a key role for Ca(2+) handling. For RV and LV myocytes, α1-AR-mediated decreases in the Ca(2+) transient were associated with increased Ca(2+) export from the cell and decreased Ca(2+) content of the sarcoplasmic reticulum. In contrast, for myocytes with α1-AR-induced increased Ca(2+) transients, sarcoplasmic reticulum Ca(2+) content was not increased, suggesting that other mechanisms contributed to the increased Ca(2+) transients. This study demonstrates the marked heterogeneity of LV and RV cellular inotropic responses to stimulation of α1-ARs and reveals a new aspect of biological heterogeneity among myocytes in the regulation of contraction. 8. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification. PubMed Kadir, K; Gao, H; Payne, A; Soraghan, J; Berry, C 2012-10-01 In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm(2) between individual investigator one (IV1) and LSM, and -122 mm(2) between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients. 9. GPCR Ligand Dendrimer (GLiDe) Conjugates: Adenosine Receptor Interactions of a Series of Multivalent Xanthine Antagonists PubMed Central Kecskés, Angela; Tosh, Dilip K.; Wei, Qiang; Gao, Zhan-Guo; Jacobson, Kenneth A. 2011-01-01 Previously, G protein–coupled receptor (GPCR) agonists were tethered from polyamidoamine (PAMAM) dendrimers to provide high receptor affinity and selectivity. Here we prepared GPCR Ligand Dendrimer (GLiDe) conjugates from a potent adenosine receptor (AR) antagonist; such agents are of interest for treating Parkinson’s disease, asthma, and other conditions. Xanthine amine congener (XAC) was appended with an alkyne group on an extended C8 substituent for coupling by Cu(I)-catalyzed click chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. These conjugates also contained triazole-linked PEG groups (8 or 22 moieties per 64 terminal positions) for increasing water-solubility and optionally prosthetic groups for spectroscopic characterization and affinity labeling. Human AR binding affinity increased progressively with the degree of xanthine substitution to reach Ki values in the nM range. The order of affinity of each conjugate was hA2AAR > hA3AR > hA1AR, while the corresponding monomer was ranked hA2AAR > hA1AR ≥ hA3AR. The antagonist activity of the most potent conjugate 14 (34 xanthines per dendrimer) was examined at the Gi-coupled A1AR. Conjugate 14 at 100 nM right-shifted the AR agonist concentration-response curve in a cyclic AMP functional assay in a parallel manner, but at 10 nM (lower than its Ki value) it significantly suppressed the maximal agonist effect in calcium mobilization. This is the first systematic probing of a potent AR antagonist tethered on a dendrimer and its activity as a function of variable loading. PMID:21539392 10. Optimal Duration of Coronary Ligation and Reperfusion for Reperfusion Injury Study in a Rat Model PubMed Central Chang, Shih-Tai; Chu, Chi-Ming; Yang, Teng-Yao; Hung, Li-Man; Pan, Kuo-Li; Cherng, Wen-Jin 2016-01-01 Background Reperfusion injury (RI) has an important impact on the clinical prognosis for patients with acute myocardial injury who had their coronary blood flow reestablished. However, no studies to date have investigated the timeframe of coronary occlusion and reperfusion effects on RI. Methods A total of 100 rats were divided into 4 groups based on the coronary ligation period: 30, 60, 120, and 180 min, and each group was further divided into 5 subgroups with different reperfusion periods: 0, 30, 60, 120, and 180 min. R0 was the baseline of each subgroup. All animals received the same protocols for designed ligation and reperfusion periods. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to distinguish different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The differences of the ratios of the necrotic area to AAR between each subgroup and baseline were further averaged to calculate an overall value of each heart. Results The relative RI percentages showed significant differences (0.8 ± 2.3%, 4.9 ± 3.3%, 10.8 ± 3.1%, and 20.3 ± 3.6% respectively, p < 0.001) at different time points of reperfusion but not at different time points of ligation (p = 0.593). The effects of different time courses in RI showed that the L120R180 group (43.4 ± 2.3%) had the highest RI difference with the baseline group. Conclusions Maximal RI occurred at the timeframe of L120R180 in our animal model. This result may be utilized to assess the substantial benefits of RI therapies in an experimental rat model setting. PMID:27471363 11. Mapping the Putative G Protein-coupled Receptor (GPCR) Docking Site on GPCR Kinase 2 PubMed Central Beautrait, Alexandre; Michalski, Kevin R.; Lopez, Thomas S.; Mannix, Katelynn M.; McDonald, Devin J.; Cutter, Amber R.; Medina, Christopher B.; Hebert, Aaron M.; Francis, Charnelle J.; Bouvier, Michel; Tesmer, John J. G.; Sterne-Marr, Rachel 2014-01-01 G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied receptors initiating the processes of desensitization and β-arrestin-dependent signaling. Interaction of GRKs with activated receptors serves to stimulate their kinase activity. The extreme N-terminal helix (αN), the kinase small lobe, and the active site tether (AST) of the AGC kinase domain have previously been implicated in mediating the allosteric activation. Expanded mutagenesis of the αN and AST allowed us to further assess the role of these two regions in kinase activation and receptor phosphorylation in vitro and in intact cells. We also developed a bioluminescence resonance energy transfer-based assay to monitor the recruitment of GRK2 to activated α2A-adrenergic receptors (α2AARs) in living cells. The bioluminescence resonance energy transfer signal exhibited a biphasic response to norepinephrine concentration, suggesting that GRK2 is recruited to Gβγ and α2AAR with EC50 values of 15 nm and 8 μm, respectively. We show that mutations in αN (L4A, V7E, L8E, V11A, S12A, Y13A, and M17A) and AST (G475I, V477D, and I485A) regions impair or potentiate receptor phosphorylation and/or recruitment. We suggest that a surface of GRK2, including Leu4, Val7, Leu8, Val11, and Ser12, directly interacts with receptors, whereas residues such as Asp10, Tyr13, Ala16, Met17, Gly475, Val477, and Ile485 are more important for kinase domain closure and activation. Taken together with data on GRK1 and GRK6, our data suggest that all three GRK subfamilies make conserved interactions with G protein-coupled receptors, but there may be unique interactions that influence selectivity. PMID:25049229 12. First hydrothermal discoveries on the Australian-Antarctic Ridge: Discharge sites, plume chemistry, and vent organisms NASA Astrophysics Data System (ADS) Hahm, Doshik; Baker, Edward T.; Siek Rhee, Tae; Won, Yong-Jin; Resing, Joseph A.; Lupton, John E.; Lee, Won-Kyung; Kim, Minjeong; Park, Sung-Hyun 2015-09-01 The Australian-Antarctic Ridge (AAR) is one of the largest unexplored regions of the global mid-ocean ridge system. Here, we report a multiyear effort to locate and characterize hydrothermal activity on two first-order segments of the AAR: KR1 and KR2. To locate vent sites on each segment, we used profiles collected by Miniature Autonomous Plume Recorders on rock corers during R/V Araon cruises in March and December of 2011. Optical and oxidation-reduction-potential anomalies indicate multiple active sites on both segments. Seven profiles on KR2 found 3 sites, each separated by ˜25 km. Forty profiles on KR1 identified 17 sites, some within a few kilometer of each other. The spatial density of hydrothermal activity along KR1 and KR2 (plume incidence of 0.34) is consistent with the global trend for a spreading rate of ˜70 mm/yr. The densest area of hydrothermal activity, named "Mujin," occurred along the 20 km-long inflated section near the segment center of KR1. Continuous plume surveys conducted in January-February of 2013 on R/V Araon found CH4/3He (1 - 15 × 106) and CH4/Mn (0.01-0.5) ratios in the plume samples, consistent with a basaltic-hosted system and typical of ridges with intermediate spreading rates. Additionally, some of the plume samples exhibited slightly higher ratios of H2/3He and Fe/Mn than others, suggesting that those plumes are supported by a younger hydrothermal system that may have experienced a recent eruption. The Mujin-field was populated by Kiwa crabs and seven-armed Paulasterias starfish previously recorded on the East Scotia Ridge, raising the possibility of circum-Antarctic biogeographic connections of vent fauna. 13. Effects of a Mask on Breathing Impairment During a Fencing Assault: A Case Series Study PubMed Central Passali, Desiderio; Cambi, Jacopo; Salerni, Lorenzo; Stortini, Giancarlo; Bellussi, Luisa Maria; Passali, Francesco Maria 2015-01-01 Background: Fencers often complain of progressive difficulty in breathing during matches, which is generally attributed to restricted air, light and heat circulation from wearing a mask. Physiologically, the nasal structure generates airflow resistance that can reach -50% of the total respiratory resistance. Objectives: This study aims to investigate the presence of nasal obstruction in fencers and the relationship with the use of mask. Materials and Methods: An observational study on 40 fencers (18 males, 22 females) was conducted. Fencers perform a usual assault, wearing the mask and standardized physical exercises (running, sprints and obstacles) without the mask. ENT examination with a nasal flexible fiberscope, Anterior Active Rhinomanometry (AAR) and Peak Nasal Inspiratory Flow (PNIF) measurement before and after physical activity with or without the mask was recorded. Results: Before physical exercise, the total nasal airway resistance mean value for AAR was 0.33 ± 0.17 Pa/cm3/s at 150 Pa. After a match with the mask, the mean value was 0.28 ± 0.16 Pa/cm3/s. After normal physical exercises without mask, the mean value was 0.24 ± 0.15 Pa/cm3/s. Using t tests, statistically significant difference between nasal resistance before and after physical activity (P < 0.05) was observed, but no significant difference in nasal resistance between the basal value and that taken after a match wearing the masks (P = 0.1265). PNIF values significantly increase with exercise (P < 0.05). Conclusions: Our study shows that wearing the mask causes increased breathing impairment in fencers, when compared with similar physical activity without the mask. PMID:26448845 14. The Alfvén Mission for the ESA M5 Call: Mission Concept NASA Astrophysics Data System (ADS) Fazakerley, Andrew; Berthomier, Matthieu; Pottelette, Raymond; Forsyth, Colin 2016-04-01 This poster will present the proposed Alfvén mission concept and is complemented by a presentation of the mission scientific goals planned for the ST1.5 session. The Alfvén mission has the scientific objective of studying particle acceleration and other forms of electromagnetic energy conversion in a collisionless low beta plasma. The mission is proposed to operate in the Earth's Auroral Acceleration Region (AAR), the most accessible laboratory for investigating plasmas at an interface where ideal magneto-hydrodynamics does not apply. Alfvén is designed to answer questions about where and how the particles that create the aurorae are accelerated, how and why they emit auroral kilometric radiation, what creates and maintains large scale electric fields aligned with the magnetic field, and to elucidate the ion outflow processes which are slowly removing the Earth's atmosphere. The mission will provide the required coordinated two-spacecraft observations within the AAR several times a day. From well designed separations along or across the magnetic field lines, using a comprehensive suite of inter-calibrated particles and field instruments, it will measure the parallel electric fields, variations in particle flux, and wave energy that will answer open questions on energy conversion. It will use onboard auroral imagers to determine how this energy conversion occurs in the regional context and, together with its orbit design, this makes the mission ideally suited to resolving spatio-temporal ambiguities that have plagued previous auroral satellite studies. The spacecraft observations will be complemented by coordinated observations with the existing dense network of ground based observatories, for more detailed ionospheric and auroral information when Alfvén overflights occur. 15. Influence of granitoid textural parameters on sediment composition: Implications for sediment generation NASA Astrophysics Data System (ADS) Caracciolo, L.; Tolosana-Delgado, R.; Le Pera, E.; von Eynatten, H.; Arribas, J.; Tarquini, S. 2012-12-01 The aim of this study is to determine and characterise the control exerted by parent rock texture on sand composition as a function of grain size. The sands investigated were generated from granitoid parent rocks by the Rhone, Damma and Sidelen glaciers, which drain the Aar Massif in the Central Alps (Switzerland), and were deposited in glacial and fluvio-glacial settings. Mechanical erosion, comminution (crystal breakdown and abrasion) and hydraulic sorting are the most important processes controlling the generation of sediments in this environment, whereas chemical and/or biochemical weathering plays a negligible role. By using a GIS-based Microscopic Information System (MIS), five samples from the glacier-drained portions of the Aar basement have been analysed to determine textural parameters such as modal composition, crystal size distribution and mineral interfaces (types and lengths). Petrographic data of analysed sands include traditional point counts (Gazzi-Dickinson method, minimum of 300 points) as well as textural counts to determine interface types, frequency, and polycrystallinity in phaneritic rock fragments. According to Pettijohn's classification, grain-size dependent compositions vary from feldspathic litharenite (0φ fraction) via lithic arkose (1φ and 2φ) to arkose (3φ and 4φ). Compositional differences among our data set were compared to modern plutoniclastic sands from the Iberian Massif (Spain) and the St. Gabriel Mts. (California, USA), which allowed us to assess the role exerted by glaciers in generating sediments. By combining data from the MIS with those from petrographic analysis, we outlined the evolution of mineral interfaces from the parent rocks to the sediments. 16. Exome Sequencing Identifies Mitochondrial Alanyl-tRNA Synthetase Mutations in Infantile Mitochondrial Cardiomyopathy PubMed Central Götz, Alexandra; Tyynismaa, Henna; Euro, Liliya; Ellonen, Pekka; Hyötyläinen, Tuulia; Ojala, Tiina; Hämäläinen, Riikka H.; Tommiska, Johanna; Raivio, Taneli; Oresic, Matej; Karikoski, Riitta; Tammela, Outi; Simola, Kalle O.J.; Paetau, Anders; Tyni, Tiina; Suomalainen, Anu 2011-01-01 Infantile cardiomyopathies are devastating fatal disorders of the neonatal period or the first year of life. Mitochondrial dysfunction is a common cause of this group of diseases, but the underlying gene defects have been characterized in only a minority of cases, because tissue specificity of the manifestation hampers functional cloning and the heterogeneity of causative factors hinders collection of informative family materials. We sequenced the exome of a patient who died at the age of 10 months of hypertrophic mitochondrial cardiomyopathy with combined cardiac respiratory chain complex I and IV deficiency. Rigorous data analysis allowed us to identify a homozygous missense mutation in AARS2, which we showed to encode the mitochondrial alanyl-tRNA synthetase (mtAlaRS). Two siblings from another family, both of whom died perinatally of hypertrophic cardiomyopathy, had the same mutation, compound heterozygous with another missense mutation. Protein structure modeling of mtAlaRS suggested that one of the mutations affected a unique tRNA recognition site in the editing domain, leading to incorrect tRNA aminoacylation, whereas the second mutation severely disturbed the catalytic function, preventing tRNA aminoacylation. We show here that mutations in AARS2 cause perinatal or infantile cardiomyopathy with near-total combined mitochondrial respiratory chain deficiency in the heart. Our results indicate that exome sequencing is a powerful tool for identifying mutations in single patients and allows recognition of the genetic background in single-gene disorders of variable clinical manifestation and tissue-specific disease. Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure. PMID:21549344 17. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment SciTech Connect Ling, Jiqiang; Peterson, Kaitlyn M.; Simonovic, Ivana; Cho, Chris; Soll, Dieter; Simonovic, Miljan 2014-03-12 Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular ?? with a threonine (Thr) anticodon, MST1 also recognizes an unusual ??, which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employs distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for ?? recognition, whereas the anticodon sequence is essential for aminoacylation of ??. The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate ??, reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix {alpha}11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria. 18. T3 enhances Ang2 in rat aorta in myocardial I/R: comparison with left ventricle. PubMed Sabatino, Laura; Kusmic, Claudia; Nicolini, Giuseppina; Amato, Rosario; Casini, Giovanni; Iervasi, Giorgio; Balzan, Silvana 2016-10-01 Angiogenesis is important for recovery after tissue damage in myocardial ischemia/reperfusion, and tri-iodothyronine (T3) has documented effects on angiogenesis. The angiopoietins 1/2 and tyrosine kinase receptor represent an essential system in angiogenesis controlling endothelial cell survival and vascular maturation. Recently, in a 3-day ischemia/reperfusion rat model, the infusion of a low dose of T3 improved the post-ischemic recovery of cardiac function.Adopting this model, our study aimed to investigate the effects of T3 on the capillary index and the expression of angiogenic genes as the angiopoietins 1/2 and tyrosine kinase receptor system, in the thoracic aorta and in the left ventricle. In the thoracic aorta, T3 infusion significantly improved the angiogenic sprouting and angiopoietin 2 expression. Instead, Sham-T3 group did not show any significant increment of capillary density and angiopoietin 2 expression. In the area at risk (AAR) of the left ventricle, T3 infusion did not increase capillary density but restored levels of angiopoietin 1, which were reduced in I/R group. Angiopoietin 2 levels were similar to Sham group and unchanged by T3 administration. In the remote zone, T3 induced a significant increment of both angiopoietin 1/2. In conclusion, T3 infusion induced a different response of angiopoietin 1/2 between the ventricle (the AAR and the remote zone) and the thoracic aorta, probably reflecting the different action of angiopoietin 1/2 in cardiomyocytes and endothelial cells. Overall, these data suggest a new aspect of T3-mediated cardioprotection through angiogenesis. PMID:27444191 19. Abdominal Surgical Incision Induces Remote Preconditioning of Trauma (RPCT) via Activation of Bradykinin Receptors (BK2R) and the Cytochrome P450 Epoxygenase Pathway in Canine Hearts PubMed Central Gross, Garrett J.; Baker, John E.; Moore, Jeannine; Falck, John R.; Nithipatikom, Kasem 2012-01-01 Recently, a novel observation was made in which nonischemic trauma at a site remote from the heart produced by a transverse abdominal incision resulted in a marked reduction of infarct size (IS) in the mouse heart via activation of sensory nerve fibers in the skin and subsequent activation of bradykinin 2 receptors (BK2R). This phenomenon was termed remote preconditioning of trauma (RPCT). Since RPCT may have potential clinical implications we attempted to confirm these findings in a large animal model, the dog. The epoxyeicosatrienoic acids (EETs) have also recently been shown to be antinociceptive and have been shown to mimic ischemic preconditioning (IPC) and postconditioning (POC) in dogs, therefore, we tested the role of the EETs in RPCT. Anesthetized adult mongrel dogs of either sex were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion followed by 3 h of reperfusion. In all groups except the controls (no slit), a transverse slit (9 cm) was applied to the abdominal wall of the dog being careful to only slit the skin. Subsequently, 15 min after the slit the heart was subjected to the ischemia/reperfusion protocol. In the control dogs, the IS as a percent of the area at risk (AAR) was 22.5 ± 2.4%, whereas in the dogs subjected to the slit alone the IS/AAR was reduced to 9.2 ± 1.2% (*P<0.01). The BR2R blocker, HOE 140 (50 ug/kg, iv) given 10 min prior to the slit, completely abolished the protective effects of RCPT as did pretreatment with 14,15-EEZE, a putative EET receptor blocker or pretreatment with the selective EET synthesis inhibitor, MSPPOH. These results suggest that BK and the EETs share cardioprotective properties in a large animal model of RPCT. PMID:21786213 20. Mechanisms Underlying Activation of α1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions PubMed Central Bragiel, Aneta M.; Wang, Di; Pieczonka, Tomasz D.; Shono, Masayuki; Ishikawa, Yasuko 2016-01-01 Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α1-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La3+, implying the participation of store-operated Ca2+ channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La3+, suggesting the involvement of extracellular Ca2+ entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca2+/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca2+ entry. PMID:27367668 1. Modeling debris-covered glaciers: response to steady debris deposition NASA Astrophysics Data System (ADS) Anderson, Leif S.; Anderson, Robert S. 2016-05-01 Debris-covered glaciers are common in rapidly eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. If continuous debris cover is present, ablation rates can be significantly reduced leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2-D long-valley numerical glacier model that includes englacial and supraglacial debris advection. We ran 120 simulations on a linear bed profile in which a hypothetical steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier terminus. Our model and parameter selections can produce 2-fold increases in glacier length. Debris flux onto the glacier and the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris-related variables are held constant. Debris deposited near the equilibrium-line altitude re-emerges high in the ablation zone and therefore impacts melt rate over a greater fraction of the glacier surface. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to initial debris-free glaciers. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). Our simulations reproduce the "general trends" between debris cover, AARs, and glacier surface velocity patterns from modern debris-covered glaciers. We provide a quantitative, theoretical foundation to interpret the effect of debris cover on the moraine record, and to assess the effects of climate change on debris-covered glaciers. 2. Localization of two human autoantigen genes by PCR screening and in situ hybridization-glycyl-tRNA synthetase locates to 7p15 and Alanyl-tRNA synthetase locates to 16q22 SciTech Connect Nichols, R.C.; Pai, S.I.; Liu, P.; Ge, Q.; Targoff, I.N. 1995-11-01 Aminoacyl-tRNA synthetases (aminoacyl-RS) catalyze the attachment of an amino acid to its cognate tRNA. Five of 20 human aminoacyl-RS (histidyl-RS, threonyl-RS, isoleucyl-RS, glycyl-RS, and alanyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis (PM/DM; 9). A sixth autoantigenic amino-acyl-RS, lysyl-RS, was recently reported. The genes for histidyl-RS and threonyl-RS have been assigned to chromosome 5, as have the genes for leucyl-RS and arginyl-RS. Six other aminoacyl-RS (glutamyl-prolyl-RS, valyl-RS, cysteinyl-RS, methionyl-RS, tryptophanyl-RS, and asparaginyl-RS) were assigned to chromosomes 1, 6, 11, 12, 14, and 18, respectively. The reason for a preponderance of aminoacyl-RS genes on chromosome 5 is unknown, but it has been suggested that regulatory relatedness might be a factor. Recently the entire or partial cDNA sequences for two autoantigenic aminoacyl-RS genes, glycyl-RS (gene symbol GARS; 4) and alanyl-RS (gene symbol AARS; 1), were reported. To understand further the genesis of autoimmune responses to aminoacyl-RS and to determine whether genes for autoantigenic aminoacyl-RS colocalize to chromosome 5, we have determined the chromosomal site of the GARS and AARS genes by PCR-based screening of somatic cell hybrid panels and by fluorescence in situ hybridization (FISH) analysis. 10 refs., 1 fig. 3. Hot Deformation Behavior and Flow Stress Prediction of TC4-DT Alloy in Single-Phase Region and Dual-Phase Regions NASA Astrophysics Data System (ADS) Liu, Jianglin; Zeng, Weidong; Zhu, Yanchun; Yu, Hanqing; Zhao, Yongqing 2015-05-01 Isothermal compression tests of TC4-DT titanium alloy at the deformation temperature ranging from 1181 to 1341 K covering α + β phase field and β-phase field, the strain rate ranging from 0.01 to 10.0 s-1 and the height reduction of 70% were conducted on a Gleeble-3500 thermo-mechanical simulator. The experimental true stress-true strain data were employed to develop the strain-compensated Arrhenius-type flow stress model and artificial neural network (ANN) model; the predictability of two models was quantified in terms of correlation coefficient ( R) and average absolute relative error (AARE). The R and AARE for the Arrhenius-type flow stress model were 0.9952 and 5.78%, which were poorer linear relation and more deviation than 0.9997 and 1.04% for the feed-forward back-propagation ANN model, respectively. The results indicated that the trained ANN model was more efficient and accurate in predicting the flow behavior for TC4-DT titanium alloy at elevated temperature deformation than the strain-compensated Arrhenius-type constitutive equations. The constitutive relationship compensating strain could track the experimental data across the whole hot working domain other than that at high strain rates (≥1 s-1). The microstructure analysis illustrated that the deformation mechanisms existed at low strain rates (≤0.1 s-1), where dynamic recrystallization occurred, were far different from that at high strain rates (≥1 s-1) that presented bands of flow localization and cracking along grain boundary. 4. Neural network classification of autoregressive features from electroencephalogram signals for brain computer interface design NASA Astrophysics Data System (ADS) Huan, Nai-Jen; Palaniappan, Ramaswamy 2004-09-01 In this paper, we have designed a two-state brain-computer interface (BCI) using neural network (NN) classification of autoregressive (AR) features from electroencephalogram (EEG) signals extracted during mental tasks. The main purpose of the study is to use Keirn and Aunon's data to investigate the performance of different mental task combinations and different AR features for BCI design for individual subjects. In the experimental study, EEG signals from five mental tasks were recorded from four subjects. Different combinations of two mental tasks were studied for each subject. Six different feature extraction methods were used to extract the features from the EEG signals: AR coefficients computed with Burg's algorithm, AR coefficients computed with a least-squares (LS) algorithm and adaptive autoregressive (AAR) coefficients computed with a least-mean-square (LMS) algorithm. All the methods used order six applied to 125 data points and these three methods were repeated with the same data but with segmentation into five segments in increments of 25 data points. The multilayer perceptron NN trained by the back-propagation algorithm (MLP-BP) and linear discriminant analysis (LDA) were used to classify the computed features into different categories that represent the mental tasks. We compared the classification performances among the six different feature extraction methods. The results showed that sixth-order AR coefficients with the LS algorithm without segmentation gave the best performance (93.10%) using MLP-BP and (97.00%) using LDA. The results also showed that the segmentation and AAR methods are not suitable for this set of EEG signals. We conclude that, for different subjects, the best mental task combinations are different and proper selection of mental tasks and feature extraction methods are essential for the BCI design. 5. Upregulation of Phosphodiesterase type 5 in the Hyperplastic Prostate PubMed Central Zhang, Wenhao; Zang, Ning; Jiang, Yaoming; Chen, Ping; Wang, Xinghuan; Zhang, Xinhua 2015-01-01 Both erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) are common in the aging male. Numerous clinical trials have demonstrated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5-Is) for treating LUTS/BPH with/without ED. However, the influence of BPH on prostatic PDE5 expression has never been studied. A testosterone-induced rat model of BPH was developed and human hyperplastic prostate specimens were harvested during cystoprostatectomy. PDE5, nNOS, eNOS and α1-adrenoreceptor subtypes (α1aARs, α1bARs and α1dARs) were determined with real-time RT-PCR for rat tissues whilst PDE5 and α1-adrenoreceptor subtypes were determined in human samples. PDE5 was further analyzed with Western-blot and histological examination. Serum testosterone was measured with ELISA. The rat BPH model was validated as having a significantly enlarged prostate. PDE5 localized mainly in fibromuscular stroma in prostate. Our data showed a significant and previously undocumented upregulation of PDE5 in both rat and human BPH, along with increased expression of nNOS and α1dARs for rat tissues and α1aARs for human BPH. The upregulation of PDE5 in the hyperplastic prostate could explain the mechanism and contribute to the high effectiveness of PDE5-Is for treating LUTS/BPH. Fibromuscular stroma could be the main target for PDE5-Is within prostate. PMID:26657792 6. Hypsometric control on glacier mass balance sensitivity in Alaska NASA Astrophysics Data System (ADS) McGrath, D.; Sass, L.; Arendt, A. A.; O'Neel, S.; Kienholz, C.; Larsen, C.; Burgess, E. W. 2015-12-01 Mass loss from glaciers in Alaska is dominated by strongly negative surface balances, particularly on small, continental glaciers but can be highly variable from glacier to glacier. Glacier hypsometry can exert significant control on mass balance sensitivity, particularly if the equilibrium line altitude (ELA) is in a broad area of low surface slope. In this study, we explore the spatial variability in glacier response to future climate forcings on the basis of hypsometry. We first derive mass balance sensitivities (30-70 m ELA / 1° C and 40-90 m ELA / 50% decrease in snow accumulation) from the ~50-year USGS Benchmark glaciers mass balance record. We subsequently assess mean climate fields in 2090-2100 derived from the IPCC AR5/CMIP5 RCP 6.0 5-model mean. Over glaciers in Alaska, we find 2-4° C warming and 10-20% increase in precipitation relative to 2006-2015, but a corresponding 0-50% decrease in snow accumulation due to rising temperatures. We assess changes in accumulation area ratios (AAR) to a rising ELA using binned individual glacier hypsometries. For an ELA increase of 150 m, the mean statewide AAR drops by 0.45, representing a 70% reduction in accumulation area on an individual glacier basis. Small, interior glaciers are the primary drivers of this reduction and for nearly 25% of all glaciers, the new ELA exceeds the glacier's maximum elevation, portending eventual loss. The loss of small glaciers, particularly in the drier interior of Alaska will significantly modify streamflow properties (flashy hydrographs, earlier and reduced peak flows, increased interannual variability, warmer temperatures) with poorly understood downstream ecosystem and oceanographic impacts. 7. Optimisation of a system for the co-translational incorporation of a keto amino acid and its application to a tumour-specific Anticalin. PubMed Reichert, Andreas J; Poxleitner, Gabriele; Dauner, Martin; Skerra, Arne 2015-12-01 The bioorthogonal keto group has attracted interest for the site-specific chemical conjugation of recombinant proteins under mild conditions, e.g. with aminooxy-functionalised fluorescent probes, radiometal chelates, toxins or polymers. However, the cotranslational incorporation of the corresponding non-canonical amino acid p-acetyl-L-phenylalanine (Apa) into proteins expressed in Escherichia coli by means of amber suppression using a previously described system with a mutated tRNA and an engineered tyrosyl-tRNA synthetase from Methanococcus jannaschii shows limited efficiency and considerable promiscuity towards endogenous amino acids. Employing a one-plasmid system that encodes all three components required for selection, i.e. the modified aminoacyl-tRNA synthetase (aaRS), the cognate amber suppressor tRNA and the enhanced green fluorescent protein equipped with an amber stop codon and serving as reporter, we have generated an Apa-specific aaRS&tRNA pair with considerably improved efficiency (17-fold increased expression) and also fidelity (6-fold). To this end, both the aaRS and the tRNA were subjected to doped random mutagenesis and selection in altogether four evolutionary cycles using fluorescence-activated bacterial cell sorting as well as automated screening of microcultures. The resulting aaRS&tRNA pair was applied to the functionalisation of an Anticalin with specificity towards oncofetal fibronectin by introducing a keto group at a permissible site for subsequent conjugation with a fluorescent dye, thus allowing visualisation of this tumour target under the microscope. 8. Effect of Hypercholesterolemia on Myocardial Necrosis and Apoptosis in the Setting of Ischemia-Reperfusion PubMed Central Osipov, Robert M.; Bianchi, Cesario; Feng, Jun; Clements, Richard T.; Liu, Yuhong; Robich, Michael P.; Glazer, Hilary P.; Sodha, Neel R.; Sellke, Frank W. 2009-01-01 Background Hypercholesterolemia is prevalent in patients who experience myocardial ischemia-reperfusion injury (IR). We investigate the impact of dietary induced hypercholesterolemia on the myocardium in the setting of acute IR. Methods and Results In normocholesterolemic (NC,n=7) and hypercholesterolemic (HC,n=7) Yucatan male pigs, the left anterior descending coronary artery was occluded for 60 min, followed by reperfusion for 120 min. Hemodynamic values were recorded and TTC staining was used to assess necrosis. Oxidative stress was measured. Specific cell death and survival signaling pathways were assessed by Western blot and TUNEL staining. Infarct size was 45% greater in HC vs. NC (42% vs. 61%,p<.05), whereas the area at risk (AAR) was similar in both groups (p=0.61). While global LV function (+dP/dt,p<.05) was higher during entire period of IR in HC vs. NC, regional function deteriorated more following reperfusion in HC (p<.05). Ischemia increased indices of myocardial oxidative stress such as protein oxidation (p<.05), lipid peroxidation (p<.05), and nitrotyrosylation in HC vs. NC, as well as the expression of phospho-eNOS (p<.05). The expression of myeloperoxidase, p38 MAPK, and phospho-p38 MAPK was higher in HC vs. NC (all p<05). Ischemia caused higher expression of the pro-apoptotic protein PARP (p<.05), and lower expression of the pro-survival proteins Bcl2 (p<.05), phospho-Akt, (p<.05), and phospho-PKCε (p<.05) in the HC vs. NC. TUNEL positive cell count was 3.8 fold (p<.05) higher in the AAR of HC vs. NC. Conclusions This study demonstrates that experimental hypercholesterolemia is associated with increased myocardial oxidative stress and inflammation, attenuation of cell survival pathways and induction of apoptosis in the ischemic territory, which together may account for the expansion of myocardial necrosis in the setting of acute IR. PMID:19752371 9. A Transform-Based Feature Extraction Approach for Motor Imagery Tasks Classification PubMed Central Khorshidtalab, Aida; Mesbah, Mostefa; Salami, Momoh J. E. 2015-01-01 In this paper, we present a new motor imagery classification method in the context of electroencephalography (EEG)-based brain–computer interface (BCI). This method uses a signal-dependent orthogonal transform, referred to as linear prediction singular value decomposition (LP-SVD), for feature extraction. The transform defines the mapping as the left singular vectors of the LP coefficient filter impulse response matrix. Using a logistic tree-based model classifier; the extracted features are classified into one of four motor imagery movements. The proposed approach was first benchmarked against two related state-of-the-art feature extraction approaches, namely, discrete cosine transform (DCT) and adaptive autoregressive (AAR)-based methods. By achieving an accuracy of 67.35%, the LP-SVD approach outperformed the other approaches by large margins (25% compared with DCT and 6 % compared with AAR-based methods). To further improve the discriminatory capability of the extracted features and reduce the computational complexity, we enlarged the extracted feature subset by incorporating two extra features, namely, Q- and the Hotelling’s \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}T^{2}\$ \\end{document} statistics of the transformed EEG and introduced a new EEG channel selection method. The performance of the EEG classification based on the expanded feature set and channel selection method was compared with that of a number of the state-of-the-art classification methods previously reported with the BCI IIIa competition data set. Our method came second with an average accuracy of 81.38%. PMID:27170898

10. Seemingly irrational driving behavior model: The effect of habit strength and anticipated affective reactions.

PubMed

Chung, Yi-Shih

2015-09-01

An increasing amount of evidence suggests that aberrant driving behaviors are not entirely rational. On the basis of the dual-process theory, this study postulates that drivers may learn to perform irrational aberrant driving behaviors, and these behaviors could be derived either from a deliberate or an intuitive decision-making approach. Accordingly, a seemingly irrational driving behavior model is proposed; in this model, the theory of planned behavior (TPB) was adopted to represent the deliberate decision-making mechanism, and habit strength was incorporated to reflect the intuitive decision process. A multiple trivariate mediation structure was designed to reflect the process through which driving behaviors are learned. Anticipated affective reactions (AARs) were further included to examine the effect of affect on aberrant driving behaviors. Considering the example of speeding behaviors, this study developed scales and conducted a two-wave survey of students in two departments at a university in Northern Taiwan. The analysis results show that habit strength consists of multiple aspects, and frequency of past behavior cannot be a complete repository for accumulating habit strength. Habit strength appeared to be a crucial mediator between intention antecedents (e.g., attitude) and the intention itself. Including habit strength in the TPB model enhanced the explained variance of speeding intention by 26.7%. In addition, AARs were different from attitudes; particularly, young drivers tended to perform speeding behaviors to reduce negative feelings such as regret. The proposed model provides an effective alternative approach for investigating aberrant driving behaviors; corresponding countermeasures are discussed. PMID:26056969

11. Sustained augmentation of cardiac alpha1A-adrenergic drive results in pathological remodeling with contractile dysfunction, progressive fibrosis and reactivation of matricellular protein genes.

PubMed

Chaulet, H; Lin, F; Guo, J; Owens, W A; Michalicek, J; Kesteven, S H; Guan, Z; Prall, O W; Mearns, B M; Feneley, M P; Steinberg, S F; Graham, R M

2006-04-01

We previously reported that transgenic (TG) mice with cardiac-restricted alpha(1A)-adrenergic receptor (alpha(1A)-AR)-overexpression showed enhanced contractility, but no hypertrophy. Since chronic inotropic enhancement may be deleterious, we investigated if long-term, cardiac function and longevity are compromised. alpha(1A)-TG mice, but not their non-TG littermates (NTLs), showed progressive loss of left ventricular (LV) hypercontractility (dP/dt(max): 14,567+/-603 to 11,610+/-915 mmHg/s, P<0.05, A1A1 line: 170-fold overexpression; and 13,625+/-826 to 8322+/-682 mmHg/s, respectively, P<0.05, A1A4 line: 112-fold overexpression, at 2 and 6 months, respectively). Both TG lines developed LV fibrosis, but not LV dilatation or hypertrophy, despite activation of hypertrophic signaling pathways. Microarray and real time RT-PCR analyses revealed activation of matricellular protein genes, including those for thrombospondin 1, connective tissue growth factor and tenascin C, but not transforming growth factor beta1. Life-span was markedly shortened (mean age at death: 155 days, A1A1 line; 224 days, A1A4 line compared with NTLs: >300 days). Telemetric electrocardiography revealed that death in the alpha(1A)-AR TG mice was due to cardiac standstill preceded by a progressive diminution in QRS amplitude, but not by arrhythmias. The QRS changes and sudden death could be mimicked by alpha(1)-AR activation, and reversed preterminally by alpha(1)-AR blockade, suggesting a relationship to stress- or activity-associated catecholamine release. Thus, long-term augmentation of cardiac alpha(1A)-adrenergic drive leads to premature death and progressive LV fibrosis with reactivation of matricellular protein genes. To our knowledge this is the first evidence in vivo for a role of the alpha(1A)-AR in ventricular fibrosis and in pathological cardiac remodeling.

12. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart

PubMed Central

Thomas, R. Croft; Singh, Abhishek; Cowley, Patrick; Myagmar, Bat-Erdene; Montgomery, Megan D.; Swigart, Philip M.; De Marco, Teresa; Baker, Anthony J.; Simpson, Paul C.

2016-01-01

Background Translation of preclinical findings could benefit from a simple, reproducible, high throughput human model to study myocardial signaling. Alpha-1A-adrenergic receptors (ARs) are expressed at very low levels in the human heart, and it is unknown if they function. Objectives To develop a high throughput human myocardial slice culture model, and to test the hypothesis that alpha-1A- ARs are functional in the human heart. Methods Cores of LV free wall 8 mm diameter were taken from 52 hearts (18 failing and 34 nonfailing). Slices 250 μm thick were cut with a Krumdieck apparatus and cultured using a rotating incubation unit. Results About 60 slices were cut from each LV core, and a typical study could use 96 slices. Myocyte morphology was maintained, and diffusion into the slice center was rapid. Slice viability was stable for at least 3 days in culture by ATP and MTT assays. The beta-AR agonist isoproterenol stimulated phospholamban phosphorylation, and the alpha-1A-AR agonist A61603 stimulated ERK phosphorylation, with nanomolar EC50 values in slices from both failing and nonfailing hearts. Strips cut from the slices were used to quantify activation of contraction by isoproterenol, A61603, and phenylephrine. The slices supported transduction by adenovirus. Conclusions We have developed a simple, high throughput LV myocardial slice culture model to study signaling in the human heart. This model can be useful for translational studies, and we show for the first time that the alpha-1A-AR is functional in signaling and contraction in the human heart. PMID:27453955

13. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

USGS Publications Warehouse

Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffery S.; Nekola, Jeffery C.; Wiles, Gregory C.

2013-01-01

Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this ‘limestone problem’ and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

14. Recognition of upper airway and surrounding structures at MRI in pediatric PCOS and OSAS

NASA Astrophysics Data System (ADS)

Tong, Yubing; Udupa, J. K.; Odhner, D.; Sin, Sanghun; Arens, Raanan

2013-03-01

Obstructive Sleep Apnea Syndrome (OSAS) is common in obese children with risk being 4.5 fold compared to normal control subjects. Polycystic Ovary Syndrome (PCOS) has recently been shown to be associated with OSAS that may further lead to significant cardiovascular and neuro-cognitive deficits. We are investigating image-based biomarkers to understand the architectural and dynamic changes in the upper airway and the surrounding hard and soft tissue structures via MRI in obese teenage children to study OSAS. At the previous SPIE conferences, we presented methods underlying Fuzzy Object Models (FOMs) for Automatic Anatomy Recognition (AAR) based on CT images of the thorax and the abdomen. The purpose of this paper is to demonstrate that the AAR approach is applicable to a different body region and image modality combination, namely in the study of upper airway structures via MRI. FOMs were built hierarchically, the smaller sub-objects forming the offspring of larger parent objects. FOMs encode the uncertainty and variability present in the form and relationships among the objects over a study population. Totally 11 basic objects (17 including composite) were modeled. Automatic recognition for the best pose of FOMs in a given image was implemented by using four methods - a one-shot method that does not require search, another three searching methods that include Fisher Linear Discriminate (FLD), a b-scale energy optimization strategy, and optimum threshold recognition method. In all, 30 multi-fold cross validation experiments based on 15 patient MRI data sets were carried out to assess the accuracy of recognition. The results indicate that the objects can be recognized with an average location error of less than 5 mm or 2-3 voxels. Then the iterative relative fuzzy connectedness (IRFC) algorithm was adopted for delineation of the target organs based on the recognized results. The delineation results showed an overall FP and TP volume fraction of 0.02 and 0.93.

15. The effects of automated artifact removal algorithms on electroencephalography-based Alzheimer's disease diagnosis

PubMed Central

Cassani, Raymundo; Falk, Tiago H.; Fraga, Francisco J.; Kanda, Paulo A. M.; Anghinah, Renato

2014-01-01

Over the last decade, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG signals, however, are susceptible to several artifacts, such as ocular, muscular, movement, and environmental. To overcome this limitation, existing diagnostic systems commonly depend on experienced clinicians to manually select artifact-free epochs from the collected multi-channel EEG data. Manual selection, however, is a tedious and time-consuming process, rendering the diagnostic system “semi-automated.” Notwithstanding, a number of EEG artifact removal algorithms have been proposed in the literature. The (dis)advantages of using such algorithms in automated AD diagnostic systems, however, have not been documented; this paper aims to fill this gap. Here, we investigate the effects of three state-of-the-art automated artifact removal (AAR) algorithms (both alone and in combination with each other) on AD diagnostic systems based on four different classes of EEG features, namely, spectral, amplitude modulation rate of change, coherence, and phase. The three AAR algorithms tested are statistical artifact rejection (SAR), blind source separation based on second order blind identification and canonical correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component analysis (wICA). Experimental results based on 20-channel resting-awake EEG data collected from 59 participants (20 patients with mild AD, 15 with moderate-to-severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone outperforming other enhancement algorithm combinations across three tasks: diagnosis (control vs. mild vs. moderate), early detection (control vs. mild), and disease progression (mild vs. moderate), thus opening the doors for fully-automated systems that can assist clinicians with early detection of AD, as well as disease severity progression assessment. PMID:24723886

16. Metasomatism in the Chain of Ponds K-feldspars: Reassessing Discrete Domain 39Ar-40Ar Modelling

NASA Astrophysics Data System (ADS)

Villa, I. M.; Chafe, A. N.; Hanchar, J. M.; Wirth, R.

2012-12-01

The post-crystallization petrology of K-feldspar (Kfs) is mostly controlled by fluids. Accordingly, [1] documented that successive mineral generations in Kfs grains of the Aar metagranite can be concordantly identified by both cathodoluminescence (CL) and back-scattered electron (BSE) imaging, elemental, and multi-isotope techniques. Imaging microstructures is a particularly powerful tool appreciated by many U-Pb geochronologists, and its use in 39Ar-40Ar dating is beginning to show beneficial progress [2]. However, a dissenting reviewer of [1] argued that the Aar sample was not typical of "orthodox" Kfs and the results could not be generalized to all Kfs [3]. On a different front, [4] demonstrated that the mathematical modeling that assumed Fickian diffusion in discrete domains, defined once and for all by [5], lacked internal consistency on several counts. As Chain of Ponds Pluton (CPP) Kfs sample MH-10 played a foundational role in the development of the mathematical model by [5], we decided to obtain direct evidence whether the numerous internal inconsistencies of the model are due to the previously undescribed petrological history of MH-10. We collected sample JH-02-01 on the same CPP outcrop as MH-10 [6]. All age spectra of different sieve fractions of the Kfs separate, both handpicked and unpicked, show a staircase shape. The Arrhenius diagram of apparent diffusivity agrees with the original MH-10 [5] and shows the same apparent r/r0 behavior. However, Arrhenius trajectories for all size fractions are parallel to each other and self-similar, as predicted by [4], instead of being joined at low temperature ("small domains") and diverging only at high T ("largest domain"), as would be implicit in the model by [5]. The CL and BSE images demonstrate several successive Kfs generations of diverse luminescence and chemical and isotopic properties. Microchemical analyses document patchy Ba enrichment, a tell-tale fingerprint of deuteric fluid interaction and

17. Suitability of alkaline leaching and etching experiments in the quantification of ASR potential of quartz-rich rocks

NASA Astrophysics Data System (ADS)

Kuchařová, Aneta; Šachlová, Šárka; Pertold, Zdeněk; Přikryl, Richard

2015-04-01

Three groups of methods are conventionally applied in the assessment of the susceptibility of aggregates used in concrete to be affected by alkali-silica reaction (ASR). The most frequently employed expansion tests (accelerated mortar bar test and concrete prism test, e.g. ASTM C1260, RILEM AAR2, RILEM AAR4.1) quantify ASR potential of aggregates according to the expansion values of mortar bars (resp. concrete prisms) measured after certain testing time period. Petrographic methods are based on the quantification of alkali-reactive phases by polarizing microscopy (e.g. RILEM AAR1). Chemical methods quantify ASR potential according to the amount of Si4+ dissolved into alkaline solution combined with the reduction of alkalinity of the solution (e.g. ASTM C289). The current study focused on the comparison of three approaches: the alkaline etching of polished rock sections and standard chemical method (following ASTM C289) with the measuring of expansion values of mortar bars (following ASTM C1260). Various types of quartz and amorphous SiO2 used for the experiments were separated from rock samples of orthoquartzite, quartz meta-greywacke, pegmatite, phyllite, chert, and flint. Polished rock sections (resp. crushed fraction 0.125/0.250) were used and subjected to leaching in 1M NaOH solution at 80°C for 14 days (resp. 24 hours). After alkaline etching in alkaline solution, the rock sections were analyzed by scanning electron microscopy combined with energy dispersive spectrometer. Representative areas were documented in back scattered electron images and quantified using fully-automatic petrographic image analysis. ASR potential of the polished rock sections was evaluated by the vol. % of area affected by alkaline etching. ASR potential of crushed aggregate was estimated by measurements of Si4+ dissolved into the solution versus the reduction of alkalinity of the solution (following ASTM C289). Classification according to the ASTM C289 indicated three of investigated

18. The history of Cesium-137 liquid emissions by Mühleberg Nuclear Power Plant (Switzerland) is recorded in Lake Biel sediments

NASA Astrophysics Data System (ADS)

Girardclos, Stéphanie; Faessler, Jérôme; Loizeau, Jean-Luc; Zehringer, Markus

2014-05-01

Lake sediments record changes happening in their upstream river catchment and regional environment which includes traces of artificial radionuclides emissions deriving from human activities. 137Cs emissions started worldwide in the early 1950's and peaked in 1963-64 due to nuclear bomb tests in the high atmosphere. A second 137Cs activity peak, due to the 1986 Chernobyl catastrophe is recorded in sediment archives from central Europe. These two events (1963/64 and 1986) serve routinely as time markers for recent lake records. Nuclear Power Plants (NPPs) are often constructed along river course for cooling purposes. Since 1972, Mühleberg NPP (central Switzerland) lies 18 km upstream Lake Biel and releases radioactive liquid emissions into the Aare river which adds to the diffuse - above mentioned - radioactive pollution, as revealed by Albrecht et al. (1995; 1998) and recently confirmed by Thevenon et al. (2013) from Lake Biel sediments. The water of Lake Biel is used as drinking water for ca. 60'000 inhabitants and its outflowing water is further used by downstream cities lying on the Aare-Rhine course such as Basel (200'000 inhab.) In this study, the 137Cs activity curve of a 90-cm-long sediment core (BIE10-8), retrieved in April 2010 from the central Lake Biel basin at ca. 50 m depth, and measured by gamma ray spectrometry using high resolution germanium detectors, confirms previous work and reveals a new peak for the year 1998-2000, as observed by Thevenon et al. (2013). This peak is most certainly due to Mühleberg NPP as shown by the good correlation with declared 137Cs liquid emissions indicating a significant increase in 1998-99. Decay corrected activity data, converted into 137Cs fluxes, point to water pollution by Mühleberg NPP in 1975-1985 as being similar to those linked to the catastrophic events in 1963-64 and 1986 (about 75%). As former study showed that Lake Biel sediments scavenge only a portion of the total radionuclide in water, i.e. 30-55% for

19. Rock Magnetic Fabrics, Paleomagnetic Vectors, and Rock Magnetic Cyclostratigraphy of the Marcellus FM, Sunbury PA

NASA Astrophysics Data System (ADS)

Minguez, D. A.; Kodama, K. P.

2013-12-01

We present the preliminary results of a multi-faceted rock magnetic study conducted on 195 samples from the Oatka Creek member of the Marcellus formation, where it has been extracted from the subsurface as a drill core near Sunbury, PA. Samples were oriented based on bedding attitude observed within the core and were removed from the core at a spacing of ≈0.25 meters starting from the base (depth ≈ 500 meters) and spanning 51 meters of stratigraphic section. The results of measurements of the anisotropy of magnetic susceptibility (AMS) consistently demonstrate a nearly triaxial fabric with maximum principal axes clustering east-west and horizontal in geographic coordinates, nearly parallel to the direction of bedding strike. AMS minimum principal axes cluster near the pole to the bedding plane. Anisotropy of anhysteretic remanence (AAR) applied with a 100 mT peak field and a 97 μT bias field in 9 orientations demonstrates a markedly different fabric, with maximum principal axis clustering north-south and horizontal in geographic coordinates. Minimum principal axes of AAR cluster steeply (~60-70 degrees) to the west. The discrepancy between AAR and AMS fabrics likely indicates the AMS is dominated by paramagnetic clays, and thus may be interpreted as an east-west intersection lineation of clay particles dipping gently north or south. Paleomagnetic directions obtained using Alternating Field (AF) demagnetization in 5 mT steps up to 110 mT demonstrates a high coercivity remanence (>35 mT) with a south and shallow direction (D= 183.4 I=-14.7). This result is consistent with previous studies of the Marcellus formation and the Devonian Catskill red beds. Thermal demagnetization experiments demonstrate a similar magnetization removed by temperatures between 250 and 350 degrees Celsius, however, continued heating results in the acquisition of strong, inconsistent magnetizations likely the result of oxidizing iron sulfides. Thermal demagnetization of orthogonal partial

20. Frequencies, mechanisms and climate forcing of paleofloods in the Bernese Alps (Switzerland) inferred from natural, historical, and instrumental time series

NASA Astrophysics Data System (ADS)

Schulte, Lothar; Peña, Juan Carlos; Carvalho, Filipe; Julià, Ramon; Gómez-Bolea, Antonio; Burjachs, Francesc; Llorca, Jaime; Rubio, Patricio; Veit, Heinz

2015-04-01

The aim of this contribution is the reconstruction of a 2600-yr long flood series generated from high-resolution deltaplain sediments of the Hasli-Aare and Lütschine delta, which reproduces the fluvial dynamic and related mechanisms, including trends, clusters and gaps of floods in alpine catchments. Paleofloods frequencies were reconstructed from geoarchives particularly by sedimentary, geochemical (XRF-core scan, conventional XRF, LOI and grain size), mineralogical, geomorphological, pollen and lichenometric records. An important issue is the question if these paleofloods can be calibrated (exact dating) by data series from historical sources (textual and factual) and by instrumental data. Not less than 12 of 14 severe and catastrophic events before the termination of the River Aare Correction in 1867, are detected during the last 700 years also by coarse-grained flood layers, ln(Zr/Ti) peaks and Factor 1 scores. Spectral analysis of the geochemical and pollen time series and climate proxies (δ14C, TSI, δ18O isotopes from the Greenland ice, temperatures and precipitation reconstruction from tree-rings, NAO, SNAO) evidence similar periodicities of 60, 85, 105, 120 and 200 yrs during the two last Millennia. Thus, the mechanisms of the flood processes are strongly influenced by the North Atlantic dynamics and solar forcing. The composite 2600-yr sedimentary floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (medium high catchment area) match very clearly to maxima of Total Solar Irradiance (Steinhilber et al., 2009) pointing to reduced flood activity during warmer climate pulses. The aggradation of the paleoflood clusters (e.g. 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) with contribution of siliciclasts from highest catchment area (plutonic bedrock) occurred predominantly during periods with cooler summer temperature, reduced solar irradiance and phases of drier spring climate (B

1. Annual and seasonal mass balances of Chhota Shigri Glacier (benchmark glacier, Western Himalaya), India

NASA Astrophysics Data System (ADS)

Mandal, Arindan; Ramanathan, Alagappan; Farooq Azam, Mohd; Wagnon, Patrick; Vincent, Christian; Linda, Anurag; Sharma, Parmanand; Angchuk, Thupstan; Bahadur Singh, Virendra; Pottakkal, Jose George; Kumar, Naveen; Soheb, Mohd

2015-04-01

Several studies on Himalayan glaciers have been recently initiated as they are of particular interest in terms of future water supply, regional climate change and sea-level rise. In 2002, a long-term monitoring program was initiated on Chhota Shigri Glacier (15.7 square km, 9 km long, 6263-4050 m a.s.l.) located in Lahaul and Spiti Valley, Himachal Pradesh, India. This glacier lies in the monsoon-arid transition zone (western Himalaya) and is a representative glacier in Lahaul and Spiti Valley. While annual mass balances have been measured continuously since 2002 using the glaciological method, seasonal scale observations began in 2009. The annual and seasonal mass balances were then analyzed along with meteorological conditions in order to understand the role of winter and summer balances on annual glacier-wide mass balance of Chhota Shigri glacier. During the period 2002-2013, the glacier experienced a negative glacier-wide mass balance of -0.59±0.40 m w.e. a-1 with a cumulative glaciological mass balance of -6.45 m w.e. Annual glacier-wide mass balances were negative except for four years (2004/05, 2008/09, 2009/10 and 2010/11) where it was generally close to balanced conditions. Equilibrium line altitude (ELA) for steady state condition is calculated as 4950 m a.s.l. corresponding to an accumulation area ratio (AAR) of 62% using annual glacier-wide mass balance, ELA and AAR data between 2002 and 2013. The winter glacier-wide mass balance between 2009 and 2013 ranges from a maximum value of 1.38 m w.e. in 2009/10 to a minimum value of 0.89 in 2012/13 year whereas the summer glacier-wide mass balance varies from the highest value of -0.95 m w.e. in 2010/11 to the lowest value of -1.72 m w.e. in 2011/12 year. The mean vertical mass balance gradient between 2002 and 2013 was 0.66 m w.e. (100 m)-1 quite similar to Alps, Nepalese Himalayas etc. Over debris covered area, the gradients are highly variable with a negative mean value of -2.15 m w.e. (100 m)-1 over 2002

2. Reconstructed glacier geometry and inferred Equilibrium Line Altitude changes during the Late Pleistocene deglaciation in the Retezat Mountains, Southern Carpathians

NASA Astrophysics Data System (ADS)

Madarász, Balázs; Ruszkiczay-Rüdiger, Zsófia; Kern, Zoltán; Urdea, Petru

2016-04-01

Quaternary glaciations had a major imprint on the landscape and topography of the Southern Carpathians. Their transitional position between continental and Mediterranean climate zones arouses special interest concerning the timing and pattern of glaciations in this area. Probably the Retezat Mts hosted the most extended glaciation during the Late Pleistocene within this range. The peak elevations of the study area reach 2500 m asl, and the most extended glaciers descended to 1040 m in the northern and to 1130 m on the southern valleys. Major cirque floors are typically situated at 2000-2100 m asl. Glacial landforms have been mapped in order to reconstruct the past ice bodies and the elevation shifts of the paleo equilibrium line altitudes (ELA) during several deglaciation phases of the Last Glacial Maximum (LGM) and Lateglacial in the Retezat Mts. On the basis of published 10Be exposure age data on the northern valleys of the study area, deglaciation of the Retezat Mts occurred at least in five phases between ~21.0 ka and 13.5 ka [1]. Various methods (THAR, AAR, AABR) have been tested using a GIS tool to estimate the ELA of the reconstructed paleoglaciers [2] and paleo ELAs were calculated for each of the deglaciation phases. Preliminary estimates of regional LGM paleoELA employing the simplest THAR method (with a ratio of 0.5) ranged from ~1670 m during the LGM to ~2210 m for the smallest cirque glacier at 13.5 ka, respectively. The AAR and AABR methods provide somewhat higher ELAs for each phase. The obtained paleoELAs were compared to ELA reconstructions available from other Carpathian ranges and also to the Alps and Dinarides. Our data will contribute to a more accurate ELA distribution during the LGM, which may be indicative of the past state of the climate system (moisture gradient, circulation regimes). Thanks to OTKA PD83610, PD104899; NKM-96/2014, NKM-31/2015; OMAA 90öu17; LP2012-27/2012. References: [1] Ruszkiczay-Rüdiger et al. 2016 Quat. Int. (in

3. Caspase-dependent and serine protease-dependent DNA fragmentation of myocytes in the ischemia-reperfused rabbit heart: these inhibitors do not reduce infarct size.

PubMed

Minatoguchi, S; Kariya, T; Uno, Y; Arai, M; Nishida, Y; Hashimoto, K; Wang, N; Aoyama, T; Takemura, G; Fujiwara, T; Fujiwara, H

2001-10-01

Some infarcted myocytes undergo caspase-dependent DNA fragmentation, but serine protease-dependent DNA fragmentation may also be involved. There is controversy regarding whether caspase inhibitors can reduce infarct size, so the present study investigated whether serine protease inhibitor can reduce the DNA fragmentation of infarcted myocytes and whether serine protease or caspase inhibitors attenuates myocardial infarct size in Japanese white rabbits without collateral circulation. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. A vehicle (dimethylsulfoxide, control group, n=8) or Z-Val-Ala-Asp(Ome)-CH2F (ZVAD-fmk, a caspase inhibitor, ZVAD group, 0.8 mg/kg iv at 20 min before coronary occlusion and 0.8 mg/kg at 90 min after reperfusion, n=8) or 3,4-dichloroisocoumarin (DCI, a serine protease inhibitor, 2 mg/kg iv at 20 min before coronary occlusion, DCI group, n=8) was administered. Animals were killed at 48h after reperfusion for the detection of myocardial infarct size and at 4h after reperfusion for the detection of dUTP nick end-labeling (TUNEL)-positive myocytes, the electrophoretic pattern of DNA fragmentation and ultrastructural analysis. The left ventricle (LV) was excised and sliced. The myocardial infarct size as a percentage of the area at risk was assessed by triphenyltetrazolium chloride staining. DNA fragmentation was assessed by in situ TUNEL at the light microscopic level. ZVAD and DCI significantly reduced the mean blood pressure during reperfusion without affecting heart rate. There was no significant difference in the % area at risk (AAR) of LV among the 3 groups (control: 26.3+/-3.0%; ZVAD: 25.6+/-2.6%; DCI: 25.6+/-2.0%). The % infarct size as a percentage of the AAR in the ZVAD group (41.3+/-4.5%) and the DCI group (50.4+/-3.8%) was not significantly different from the control group (43.5+/-4.5%). However, the percent DNA fragmentation in the infarcted area in the ZVAD (3.5+/-0.8%) and DCI groups (4

4. Zooplankton Growth, Respiration and Grazing on the Australian Margins of the Tropical Indian and Pacific Oceans.

PubMed

McKinnon, A David; Doyle, Jason; Duggan, Samantha; Logan, Murray; Lønborg, Christian; Brinkman, Richard

2015-01-01

The specific activity of aminoacyl-tRNA synthetases (spAARS), an index of growth rate, and of the electron transport system (spETS), an index of respiration, was measured in three size fractions (73-150 μm, >150 μm and >350 μm) of zooplankton during five cruises to tropical coastal waters of the Kimberley coast (North West Australia) and four cruises to waters of the Great Barrier Reef (GBR; North East Australia). The N-specific biomass of plankton was 3-4-fold higher in the Kimberley than on the GBR in all 3 size classes: Kimberley 1.27, 3.63, 1.94 mg m-3; GBR 0.36, 0.88 and 0.58 mg m-3 in the 73-150 μm, >150 μm and >350 μm size classes, respectively. Similarly, spAARS activity in the Kimberley was greater than that of the GBR: 88.4, 132.2, and 147.6 nmol PPi hr-1 mg protein -1 in the Kimberley compared with 71.7, 82.0 and 83.8 nmol PPi hr-1 mg protein -1 in the GBR, for the 73-150 μm, >150 μm and >350 μm size classes, respectively. Specific ETS activity showed similar differences in scale between the two coasts: 184.6, 148.8 and 92.2 μL O2 hr-1 mg protein-1 in the Kimberley, against 86.5, 88.3 and 71.3 μL O2 hr-1 mg protein-1 in the GBR. On the basis of these measurements, we calculated that >150 μm zooplankton grazing accounted for 7% of primary production in the Kimberley and 8% in GBR waters. Area-specific respiration by >73 μm zooplankton was 7-fold higher in the Kimberley than on the GBR and production by >150 μm zooplankton was of the order of 278 mg C m-2 d-1 in the Kimberley and 42 mg C m-2 d-1 on the GBR. We hypothesize that the much stronger physical forcing on the North West shelf is the principal driver of higher rates in the west than in the east of the continent. PMID:26469275

5. Motor unit potential morphology differences in individuals with non-specific arm pain and lateral epicondylitis

PubMed Central

Calder, Kristina M; Stashuk, Daniel W; McLean, Linda

2008-01-01

Background The pathophysiology of non-specific arm pain (NSAP) is unclear and the diagnosis is made by excluding other specific upper limb pathologies, such as lateral epicondylitis or cervical radiculopathy. The purpose of this study was to determine: (i) if the quantitative parameters related to motor unit potential morphology and/or motor unit firing patterns derived from electromyographic (EMG) signals detected from an affected muscle of patients with NSAP are different from those detected in the same muscle of individuals with lateral epicondylitis (LE) and/or control subjects and (ii) if the quantitative EMG parameters suggest that the underlying pathophysiology in NSAP is either myopathic or neuropathic in nature. Methods Sixteen subjects with NSAP, 11 subjects with LE, eight subjects deemed to be at-risk for developing a repetitive strain injury, and 37 control subjects participated. A quantitative electromyography evaluation was completed using decomposition-based quantitative electromyography (DQEMG). Needle- and surface-detected EMG signals were collected during low-level isometric contractions of the extensor carpi radialis brevis (ECRB) muscle. DQEMG was used to extract needle-detected motor unit potential trains (MUPTs), and needle-detected motor unit potential (MUP) and surface detected motor unit potential (SMUP) morphology and motor unit (MU) firing rates were compared among the four groups using one-way analysis of variance (ANOVA). Post hoc analyses were performed using Tukey's pairwise comparisons. Results Significant group differences were found for all MUP variables and for MU firing rate (p < 0.006). The post-hoc analyses revealed that patients with NSAP had smaller MUP amplitude and SMUP amplitude and area compared to the control and LE groups (p < 0.006). MUP duration and AAR values were significantly larger in the NSAP, LE and at-risk groups compared to the control group (p < 0.006); while MUP amplitude, duration and AAR values were

6. Zooplankton Growth, Respiration and Grazing on the Australian Margins of the Tropical Indian and Pacific Oceans

PubMed Central

McKinnon, A. David; Doyle, Jason; Duggan, Samantha; Logan, Murray; Lønborg, Christian; Brinkman, Richard

2015-01-01

The specific activity of aminoacyl-tRNA synthetases (spAARS), an index of growth rate, and of the electron transport system (spETS), an index of respiration, was measured in three size fractions (73–150 μm, >150 μm and >350 μm) of zooplankton during five cruises to tropical coastal waters of the Kimberley coast (North West Australia) and four cruises to waters of the Great Barrier Reef (GBR; North East Australia). The N-specific biomass of plankton was 3–4-fold higher in the Kimberley than on the GBR in all 3 size classes: Kimberley 1.27, 3.63, 1.94 mg m-3; GBR 0.36, 0.88 and 0.58 mg m-3 in the 73–150 μm, >150 μm and >350 μm size classes, respectively. Similarly, spAARS activity in the Kimberley was greater than that of the GBR: 88.4, 132.2, and 147.6 nmol PPi hr-1 mg protein -1 in the Kimberley compared with 71.7, 82.0 and 83.8 nmol PPi hr-1 mg protein -1 in the GBR, for the 73–150 μm, >150 μm and >350 μm size classes, respectively. Specific ETS activity showed similar differences in scale between the two coasts: 184.6, 148.8 and 92.2 μL O2 hr-1 mg protein-1 in the Kimberley, against 86.5, 88.3 and 71.3 μL O2 hr-1 mg protein-1 in the GBR. On the basis of these measurements, we calculated that >150 μm zooplankton grazing accounted for 7% of primary production in the Kimberley and 8% in GBR waters. Area-specific respiration by >73 μm zooplankton was 7-fold higher in the Kimberley than on the GBR and production by >150 μm zooplankton was of the order of 278 mg C m-2 d-1 in the Kimberley and 42 mg C m-2 d-1 on the GBR. We hypothesize that the much stronger physical forcing on the North West shelf is the principal driver of higher rates in the west than in the east of the continent. PMID:26469275

7. Morphological control on sedimentation rates and patterns of delta floodplains in the Swiss Alps

NASA Astrophysics Data System (ADS)

Carvalho, Filipe; Schulte, Lothar

2013-09-01

Glacially overdeepened Alpine valleys and their perialpine lakes are very effective sedimentary sinks that include landforms as alluvial fans, fan deltas, and deltas. The sedimentary archives of these landforms can provide long sedimentary records of erosion and aggradation processes in a catchment. Focusing on longer time series is vital to improve the conventional instrument-based models of sediment transfer, as longer time series record the effective low frequency sediment discharges triggered by high magnitude floods. The research reported here combines statigraphical analysis of the sedimentary records of two lake deltas in the Bernese Alps with geostatistical modeling of the sedimentation storage of delta plain deposits. From the three-dimensional sediment storage model, the sedimentary environments and aggradation dynamics of the Aare and the Lütschine Rivers were reconstructed in 500-year time slices over the last 2500 years. The spatial distributions of the aggradation rates of the two deltas show similar trends, with decreasing downstream rates from delta apex to the delta front at Lake Brienz, which is related to the adaption of the river's longitudinal profile to the Pleistocene overdeepened valley morphology. Local modification of this trend was detected at narrowing of the valley floor caused by landslides. The quantification of delta plain sediment volumes provides evidence that aggradation processes have decreased (Aare) or remained nearly stable (Lütschine) in the delta plains during the last 1500 years, despite the strong human impact in the form of land use. This decrease and the possible compensation of major human-induced catchment erosion may be attributed to a more or less efficient regulation of the river channels during the last millennium, which transferred the sediment load into Lake Brienz. The sediment volumes obtained and the historical progradation of delta lobes support the previous hypothesis of the connectivity from source

8. Intragenic homogenization and multiple copies of prey-wrapping silk genes in Argiope garden spiders

PubMed Central

2014-01-01

Background Spider silks are spectacular examples of phenotypic diversity arising from adaptive molecular evolution. An individual spider can produce an array of specialized silks, with the majority of constituent silk proteins encoded by members of the spidroin gene family. Spidroins are dominated by tandem repeats flanked by short, non-repetitive N- and C-terminal coding regions. The remarkable mechanical properties of spider silks have been largely attributed to the repeat sequences. However, the molecular evolutionary processes acting on spidroin terminal and repetitive regions remain unclear due to a paucity of complete gene sequences and sampling of genetic variation among individuals. To better understand spider silk evolution, we characterize a complete aciniform spidroin gene from an Argiope orb-weaving spider and survey aciniform gene fragments from congeneric individuals. Results We present the complete aciniform spidroin (AcSp1) gene from the silver garden spider Argiope argentata (Aar_AcSp1), and document multiple AcSp1 loci in individual genomes of A. argentata and the congeneric A. trifasciata and A. aurantia. We find that Aar_AcSp1 repeats have >98% pairwise nucleotide identity. By comparing AcSp1 repeat amino acid sequences between Argiope species and with other genera, we identify regions of conservation over vast amounts of evolutionary time. Through a PCR survey of individual A. argentata, A. trifasciata, and A. aurantia genomes, we ascertain that AcSp1 repeats show limited variation between species whereas terminal regions are more divergent. We also find that average dN/dS across codons in the N-terminal, repetitive, and C-terminal encoding regions indicate purifying selection that is strongest in the N-terminal region. Conclusions Using the complete A. argentata AcSp1 gene and spidroin genetic variation between individuals, this study clarifies some of the molecular evolutionary processes underlying the spectacular mechanical attributes of

9. The response of debris-covered glaciers to climate change: A numerical modeling approach

NASA Astrophysics Data System (ADS)

Anderson, Leif S.; Anderson, Robert S.

2016-04-01

Debris-covered glaciers are common in rapidly-eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. Continuous debris cover can therefore reduce the mass balance gradient in the ablation zone, leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2D long-valley numerical glacier model that includes deposition of debris on the glacier surface, and both englacial and supraglacial debris advection. We ran 120 simulations in which a steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to new steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier. The debris flux onto the glacier surface, and the details of the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris-related variables are held constant. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to debris-free glaciers forced by the same climate. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). The model reproduces first-order relationships between debris cover, AARs, and glacier surface velocities reported from glaciers in High Asia. We also explore the response of debris-covered glaciers to increases in the equilibrium-line altitude (climate warming). We highlight the conditions required to generate a low surface velocity 'dead' ice terminal reach during a warming climate, and the associated increase of fractional glacier surface debris. We also compare our debris-covered glacier climate response results with data from glaciers in High Asia. Our model provides a quantitative, theoretical

10. Phylogenomics reveals subfamilies of fungal nonribosomal peptide synthetases and their evolutionary relationships

PubMed Central

2010-01-01

Background Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes, found in fungi and bacteria, which biosynthesize peptides without the aid of ribosomes. Although their metabolite products have been the subject of intense investigation due to their life-saving roles as medicinals and injurious roles as mycotoxins and virulence factors, little is known of the phylogenetic relationships of the corresponding NRPSs or whether they can be ranked into subgroups of common function. We identified genes (NPS) encoding NRPS and NRPS-like proteins in 38 fungal genomes and undertook phylogenomic analyses in order to identify fungal NRPS subfamilies, assess taxonomic distribution, evaluate levels of conservation across subfamilies, and address mechanisms of evolution of multimodular NRPSs. We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including α-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi. Results Phylogenomic analysis identified nine major subfamilies of fungal NRPSs which fell into two main groups: one corresponds to NPS genes encoding primarily mono/bi-modular enzymes which grouped with bacterial NRPSs and the other includes genes encoding primarily multimodular and exclusively fungal NRPSs. AARs shared a closer phylogenetic relationship to NRPSs than to other acyl-adenylating enzymes. Phylogenetic analyses and taxonomic distribution suggest that several mono/bi-modular subfamilies arose either prior to, or early in, the evolution of fungi, while two multimodular groups appear restricted to and expanded in fungi. The older mono/bi-modular subfamilies show conserved domain architectures suggestive of functional conservation, while multimodular NRPSs, particularly those unique to euascomycetes, show a diversity of architectures and of genetic mechanisms generating this diversity. Conclusions This work is the first to characterize subfamilies of fungal

11. Metabolic hyperemia requires ATP-sensitive K+ channels and H2O2 but not adenosine in isolated mouse hearts

PubMed Central

Zhou, Xueping; Teng, Bunyen; Tilley, Stephen; Ledent, Catherine

2014-01-01

We have previously demonstrated that adenosine-mediated H2O2 production and opening of ATP-sensitive K+ (KATP) channels contributes to coronary reactive hyperemia. The present study aimed to investigate the roles of adenosine, H2O2, and KATP channels in coronary metabolic hyperemia (MH). Experiments were conducted on isolated Langendorff-perfused mouse hearts using combined pharmacological approaches with adenosine receptor (AR) knockout mice. MH was induced by electrical pacing at graded frequencies. Coronary flow increased linearly from 14.4 ± 1.2 to 20.6 ± 1.2 ml·min−1·g−1 with an increase in heart rate from 400 to 650 beats/min in wild-type mice. Neither non-selective blockade of ARs by 8-(p-sulfophenyl)theophylline (8-SPT; 50 μM) nor selective A2AAR blockade by SCH-58261 (1 μM) or deletion affected MH, although resting flow and left ventricular developed pressure were reduced. Combined A2AAR and A2BAR blockade or deletion showed similar effects as 8-SPT. Inhibition of nitric oxide synthesis by N-nitro-l-arginine methyl ester (100 μM) or combined 8-SPT administration failed to reduce MH, although resting flows were reduced (by ∼20%). However, glibenclamide (KATP channel blocker, 5 μM) decreased not only resting flow (by ∼45%) and left ventricular developed pressure (by ∼36%) but also markedly reduced MH by ∼94%, resulting in cardiac contractile dysfunction. Scavenging of H2O2 by catalase (2,500 U/min) also decreased resting flow (by ∼16%) and MH (by ∼24%) but to a lesser extent than glibenclamide. Our results suggest that while adenosine modulates coronary flow under both resting and ischemic conditions, it is not required for MH. However, H2O2 and KATP channels are important local control mechanisms responsible for both coronary ischemic and metabolic vasodilation. PMID:25108010

12. Monitoring temporal variations in water resources across the Arabian Peninsula and identification of their controlling factors

NASA Astrophysics Data System (ADS)

Ahmed, M.; Sultan, M.; Othman, A.

2015-12-01

Assessment, monitoring, and development of the fresh water resources in the Arabian Peninsula (AP) are critical for the sustenance of the AP's growing population and water consumption. Monthly (01/2003-12/2013) Gravity Recovery and Climate Experiment (GRACE) data along with other relevant climatic, geologic, hydrogeologic, and remote sensing datasets were used to monitor the spatiotemporal variability in the AP's water resources and to investigate the causes of those variations. Four regions were selected; in our selection, we tried to cover major aquifers, follow political boundaries, and exceed GRACE footprint (~0.20×106 km2) to minimize uncertainties. The selected regions are: (1) Northern Saudi Arabia and Jordan (area: 0.53×106 km2), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis (area: 0.97×106 km2), (3) Yemen (area: 0.45×106 km2), and (4) Oman (area: 0.32×106 km2). Results indicate: (1) Northern Saudi Arabia and Jordan area is experiencing large depletions (-8.76±0.94 mm/yr; -4.68±0.50 km3/yr) in GRACE-derived terrestrial water storage (TWS) that is largely related to groundwater extraction as well as decrease in rainfall rates throughout the investigated period compared to the preceding period (average annual rainfall [AAR]: 2003-2013: 58 mm; 1979-2002: 103 mm), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis area is experiencing a moderate depletion (-2.73±1.0 mm/yr; -2.63±0.96 km3/yr) in TWS that might be related to groundwater/oil extraction as well as a moderate decrease in rainfall rates (AAR: 2003-2013: 61 mm; 1979-2002: 82 mm), (3) Yemen is experiencing a slight depletion (-0.82±0.30 mm/yr; -0.36±0.13 km3/yr) in TWS that might be related groundwater extraction, and (4) Oman is experiencing slight increase (+0.78±0.30 mm/yr; +0.25±0.09 km3/yr) in TWS that might be related an increase in rainfall rates. Our preliminary results are being further examined by: (1) extracting temporal variations in groundwater storage by

13. Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dog

PubMed Central

Gross, Garrett J.; Gauthier, Kathryn M.; Moore, Jeannine; Campbell, William B.; Falck, John R.; Nithipatikom, Kasem

2009-01-01

Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce marked reductions in infarct size (IS) in canine myocardium either given before an ischemic insult or at reperfusion similar to that produced in ischemic preconditioning (IPC) and postconditioning (POC) protocols. However, no studies have addressed the possibility that EETs serve a beneficial role in IPC or POC. We tested the hypothesis that EETs may play a role in these two phenomena by preconditioning dog hearts with one 5-min period of total coronary occlusion followed by 10 min of reperfusion before 60 min of occlusion and 3 h of reperfusion or by postconditioning with three 30-s periods of reperfusion interspersed with three 30-s periods of occlusion. To test for a role of EETs in IPC and POC, the selective EET antagonists 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) or its derivative, 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester (14,15-EEZE-PEG), were administered 10 min before IPC, 5 min after IPC, or 5 min before POC. In a separate series, the selective EET synthesis inhibitor N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH) was administered 10 min before IPC. Infarct size was determined by tetrazolium staining and coronary collateral blood flow at 30 min of occlusion and reperfusion flow at 3 h by radioactive microspheres. Both IPC and POC produced nearly equivalent reductions in IS expressed as a percentage of the area at risk (AAR) [Control 21.2 ± 1.2%, IPC 8.3 ± 2.2%, POC 10.1 ± 1.8% (P < 0.001)]. 14,15-EEZE, 14,15-EEZE-PEG, and MS-PPOH markedly attenuated the cardioprotective effects of IPC and POC (14,15-EEZE and 14,15-EEZE-PEG) at doses that had no effect on IS/AAR when given alone. These results suggest a unique role for endogenous EETs in both IPC and POC. PMID:19448143

14. An Interglacial Polar Bear and an Early Weichselian Glaciation at Poolepynten, Western Svalbard

NASA Astrophysics Data System (ADS)

Ingolfsson, O.; Alexanderson, H.

2012-12-01

Recent discovery of a subfossil polar bear (Ursus maritimus) jawbone in the Poolepynten coastal cliff sequence, western Svalbard (Ingolfsson & Wiig, 2009), and its implications for the natural history of the polar bear (Lindqvist et al. 2010; Miller et al. 2012), motivated an effort to better constrain the environmental history and age envelope of the Poolepynten sediment sequence, particularly the lithostratigraphy of the coastal cliffs with emphasis on re-dating the sequence using the optically stimulated luminescence (OSL) dating technique. We report a revised lithostratigraphy and nine new OSL ages. It is concluded that the Poolepynten sequence holds evidence of four regional glaciation events, recorded in the strata as erosional unconformities and/or glacial deposits followed by shallow-marine deposition signifying transgressions and subsequent glacio-isostatic rebound and regression. Our OSL ages refine previous age determinations (14C and IRSL) and support the interpretation that the subfossil polar bear jawbone is of last interglacial (Eemian) age (Alexanderson et al. in press). References: Alexanderson, H., Ingolfsson, O., Murray, A.S. & Dudek, J. in press. An Interglacial Polar Bear and an Early Weichselian Glaciation at Poolepynten, Western Svalbard. Boreas 00, 000-000. Ingolfsson, O. & Wiig, O. 2009. Late Pleistocene fossil find in Svalbard: the oldest remains of a polar bear (Ursus maritimus Phipps, 1744) ever discovered. Polar Research 28, 455-466. Lindqvist, C., Schuster, S. C., Sun, Y., Talbot, S. L., Qi, J., Ratan, A., Tomsho, L. P., Kasson, L., Zeyl, E., Aars, J., Miller, W., Ingólfsson, Ó., Bachmann, L. & Wiig, Ø. 2010. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear. Proceedings of the National Academy of Sciences 107, 5053-5057. Miller, W., Schuster, S. C., Welch, A. J., Ratan, A., Bedoya-Reina, O. C., Zhao, F., Kim, H. L., Burhans, R.C., Drautz, D.I., Wittekindt, N.E., Tomsho, L.P., Ibarra-Laclette, E

15. Interpretation of fluid inclusions in quartz deformed by weak ductile shearing: Reconstruction of differential stress magnitudes and pre-deformation fluid properties

NASA Astrophysics Data System (ADS)

Diamond, Larryn W.; Tarantola, Alexandre

2015-05-01

A well developed theoretical framework is available in which paleofluid properties, such as chemical composition and density, can be reconstructed from fluid inclusions in minerals that have undergone no ductile deformation. The present study extends this framework to encompass fluid inclusions hosted by quartz that has undergone weak ductile deformation following fluid entrapment. Recent experiments have shown that such deformation causes inclusions to become dismembered into clusters of irregularly shaped relict inclusions surrounded by planar arrays of tiny, new-formed (neonate) inclusions. Comparison of the experimental samples with a naturally sheared quartz vein from Grimsel Pass, Aar Massif, Central Alps, Switzerland, reveals striking similarities. This strong concordance justifies applying the experimentally derived rules of fluid inclusion behaviour to nature. Thus, planar arrays of dismembered inclusions defining cleavage planes in quartz may be taken as diagnostic of small amounts of intracrystalline strain. Deformed inclusions preserve their pre-deformation concentration ratios of gases to electrolytes, but their H2O contents typically have changed. Morphologically intact inclusions, in contrast, preserve the pre-deformation composition and density of their originally trapped fluid. The orientation of the maximum principal compressive stress (σ1) at the time of shear deformation can be derived from the pole to the cleavage plane within which the dismembered inclusions are aligned. Finally, the density of neonate inclusions is commensurate with the pressure value of σ1 at the temperature and time of deformation. This last rule offers a means to estimate magnitudes of shear stresses from fluid inclusion studies. Application of this new paleopiezometer approach to the Grimsel vein yields a differential stress (σ1-σ3) of ˜ 300 MPa at 390 ± 30 °C during late Miocene NNW-SSE orogenic shortening and regional uplift of the Aar Massif. This differential

16. Formation mechanisms and near-surface stress orientations derived from fractographic markings on exfoliation joints in the Alps

NASA Astrophysics Data System (ADS)

Ziegler, M.; Loew, S.; Bahat, D.

2013-12-01

Granitic bedrock of the upper Aar valley (Grimsel area, Swiss Alps) contains four distinct exfoliation joint generations, which formed during different stages of the Pleistocene and occur in an Alpine landscape between inner trough valley bottoms and high mountain crests. Exfoliation joints of this investigation likely formed during the Middle Pleistocene (0.7-0.4 Ma; batch 1) and Upper Pleistocene to Holocene (<0.1 Ma; batch 2), subparallel to distinct glacial valley (palaeo-)topography. Mapping revealed that exfoliation joints of these batches exhibit prominent fracture surface morphologies. The bulk of exfoliation joints of batches 1 and 2 show common, characteristic fractographic features: (1) noncircular, radial plumose structures, (2) arrest marks on parent fracture planes and fringe cracks, and (3) gradually-developing fringe zones of en échelon type (Figure 1). We interpret smooth transitions from plumose structures on the parent plane to en échelon fringe cracks, combined with non-systematic stepping senses of fringe cracks, as local stress field variations (vs. temporal variations) in the vicinity of pre-existing joints and faults. Multiple arrest marks reveal that exfoliation joints in the Grimsel area formed incrementally and, together with absence of hackle fringes, suggest stable fracture conditions. Furthermore, we put special emphasis on surveying the orientations of plumose structure axes. We assume that plumose structure axes formed parallel to the maximum principal (far-field) compressive stress (σ1). This enables us to infer near-surface stress orientations within Alpine slopes. We found a correlation between the orientations of plumose structure axes and slope aspects for batches 1 and 2. Primarily low pitch angles (<~30°) of plumose structure axes suggest persistently subhorizontal to slightly inclined σ1 orientations, i.e. the orientation of σ1 changes together with change in slope aspect. We attribute this surface-near variability of

17. XCALIBUR: a Vertical Takeoff TSTO RLV Concept with a HEDM Upperstage and a Scram-Rocket Booster

NASA Astrophysics Data System (ADS)

Bradford, J.

2002-01-01

A new 3rd generation, two-stage-to-orbit (TSTO) reusable launch vehicle (RLV) has been designed. The Xcalibur concept represents a novel approach due to its integration method for the upperstage element of the system. The vertical-takeoff booster, which is powered by rocket-based combined-cycle (RBCC) engines, carries the upperstage internally in the aft section of the airframe to a Mach 15 staging condition. The upperstage is released from the booster and carries the 6,820 kg of payload to low earth orbit (LEO) using its high energy density matter (HEDM) propulsion system. The booster element is capable of returning to the original launch site in a ramjet-cruise propulsion mode. Both the booster and the upperstage utilize advanced technologies including: graphite-epoxy tanks, metal-matrix composites, UHTC TPS materials, electro- mechanical actuators (EMAs), and lightweight subsystems (avionics, power distribution, etc.). The booster system is enabled main propulsion system which utilizes four RBCC engines. These engines operate in four distinct modes: air- augmented rocket (AAR), ramjet, scram-rocket, and all-rocket. The booster operates in AAR mode from takeoff to Mach 3, with ramjet mode operation from Mach 3 to Mach 6. The rocket re-ignition for scram-rocket mode occurs at Mach 6, with all-rocket mode from Mach 14 to the staging condition. The extended utilization of the scram-rocket mode greatly improves vehicle performance by providing superior vehicle acceleration when compared to the scramjet mode performance over the same flight region. Results indicate that the specific impulse penalty due to the scram-rocket mode operation is outweighed by the reduced flight time, smaller vehicle size due to increased mixture ratio, and lower allowable maximum dynamic pressure. A complete vehicle system life-cycle analysis was performed in an automated, multi-disciplinary design environment. Automated disciplinary performance analysis tools include: trajectory (POST

18. Quaternary calcarenite stratigraphy on Lord Howe Island, southwestern Pacific Ocean and the record of coastal carbonate deposition

NASA Astrophysics Data System (ADS)

Brooke, Brendan P.; Woodroffe, Colin D.; Murray-Wallace, Colin V.; Heijnis, Hendrik; Jones, Brian G.

2003-04-01

Lord Howe Island is a small, mid-ocean volcanic and carbonate island in the southwestern Pacific Ocean. Skeletal carbonate eolianite and beach calcarenite on the island are divisible into two formations based on lithostratigraphy. The Searles Point Formation comprises eolianite units bounded by clay-rich paleosols. Pore-filling sparite and microsparite are the dominant cements in these eolianite units, and recrystallised grains are common. Outcrops exhibit karst features such as dolines, caves and subaerially exposed relict speleothems. The Neds Beach Formation overlies the Searles Point Formation and consists of dune and beach units bounded by weakly developed fossil soil horizons. These younger deposits are characterised by grain-contact and meniscus cements, with patchy pore-filling micrite and mirosparite. The calcarenite comprises several disparate successions that contain a record of up to 7 discrete phases of deposition. A chronology is constructed based on U/Th ages of speleothems and corals, TL ages of dune and paleosols, AMS 14C and amino acid racemization (AAR) dating of land snails and AAR whole-rock dating of eolianite. These data indicate dune units and paleosols of the Searles Point Formation were emplaced during oxygen isotope stage (OIS) 7 and earlier in the Middle Pleistocene. Beach units of the Neds Beach Formation were deposited during OIS 5e while dune units were deposited during two major phases, the first coeval with or shortly after the beach units, the second later during OIS 5 (e.g. OIS 5a) when the older dune and beach units were buried. Large-scale exposures and morphostratigraphical features indicate much of the carbonate was emplaced as transverse and climbing dunes, with the sediment source located seaward of and several metres below the present shoreline. The lateral extent and thickness of the eolianite deposits contrast markedly with the relatively small modern dunes. These features indicate that a slight fall (2-10 m) in sea level

19. K-Ar age data of clay fault gouges from some major Neoalpine faults

NASA Astrophysics Data System (ADS)

Pleuger, J.; Zwingmann, H.; Mancktelow, N.; Manser, M.

2012-04-01

In the Central Alps, the Insubric Phase in the sense of Argand (1916, Eclogae geol. Helv. 14, 145-191) was related to underthrusting of South Alpine units below the Penninic nappes along the Periadriatic Fault. Several other large-scale faults were active during the same, though not always the entire, Oligocene to Miocene time span. These faults form an array interpreted as to result from the partitioning of strain induced by the crustal convergence between the European and Adriatic plates (e.g. Handy et al. 2005, Geol. Soc. Spec. Publ. 243, 249-276). With ongoing Alpine convergence and deformation during exhumation there is a general progression from ductile to brittle behaviour on the Periadriatic Fault and kinematically related faults further north (e.g. the Simplon Rhone Fault and a diffuse, discontinous zone of generally dextral strike-slip movement on the southern boundary of the Aar massif). K-Ar dating of fine grained illite from clay fault gouges provides a reliable method for establishing the approximate time of faulting. New results establish that brittle faulting on the northeastern segment of the Canavese Fault (i.e. the part of the Periadriatic Fault SW of Val d'Ossola) occurred around 20 Ma, with south-side-up kinematics. An age of ca. 17 Ma for the crosscutting Giudicarie Fault in the Eastern Alps is effectively identical with an already published pseudotachylyte age and places a lower limit on major and continuous strike slip movements the Periadriatic Fault. The age of brittle faulting further north, on the southern border of the Aar massif, is from 13.6±0.3 to 8.3±1.1 Ma, consistent with the younger cooling and exhumation in this area. The dominantly dextral brittle faulting becoming younger to the north reflects the continued indentation and anticlockwise rotation of Adria as Alpine units become exhumed and progressively welded to the southern block. In contrast to the eastern Alps, there is no field evidence for (westward) lateral extrusion

20. Late Holocene climate change at Goat Lake, Kenai Mountains, south-central Alaska

NASA Astrophysics Data System (ADS)

Daigle, T. A.; Kaufman, D. S.

2006-12-01

Lake sediments, glacier extents, and tree rings were used to reconstruct late Holocene climate changes from Goat Lake in the Kenai Mountains, south-central Alaska (60° 14' N/149° 54' W). Two sediment cores (3.7 and 5.6 m long) were dated with 16 AMS 14C ages and record changes in watershed (organic- matter content) and within-lake (biogenic silica) productivity since ~9500 cal yr BP. Sediment analyses focused on the last 1000 yr; this interval includes a sharp transition from gyttja to inorganic mud at ~1660 AD, which marks the fist time since Pleistocene deglaciation that the north goat outlet glacier (NGO) of the Harding Icefield overtopped the drainage divide at 590 m asl to spill meltwater into Goat Lake. One 14C age of ~1535 AD from a subfossil log in the NGO valley requires ~125 yr for the NGO to thicken 150 m to the elevation of the drainage divide where it remained until ~1930. Since ~1930, the NGO has thinned 150 m and retreated 1.4 km. Equilibrium-line altitudes (ELA) were reconstructed for 12 cirque glaciers nearby Goat Lake based on the accumulation-area ratio (AAR) method following field mapping of ice-marginal features formed during the maximum Little Ice Age (LIA) in the 19th century. Maximum LIA ELA data (AAR = 0.58) were compared with 1950 ELA and yield an average lowering of 50 ± 20 m. Application of the local lapse rate of 0.47°C/100 m indicates an average ablation-season temperature reduction of 0.3°C during the maximum LIA compared to 1950, assuming no change in winter precipitation. A new tree-ring chronology from 27 hemlock trees in the Goat Lake watershed correlates with mean March through August temperature from Kenai airport (r = 0.35) and a 207 yr reconstruction indicates an average temperature reduction of 1.0°C from 1800-1900 compared with 1930-1950. Assuming no change in winter precipitation, then a 1°C cooling should have been associated with an ELA lowering by 200 m. This did not occur, and we suggest that some degree of

1. Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population.

PubMed

He, Yisha; Gong, Jianhang; Wang, Yanru; Qin, Zhenzhen; Jiang, Yue; Ma, Hongxia; Jin, Guangfu; Chen, Jiaping; Hu, Zhibin; Guan, Xiaoxiang; Shen, Hongbing

2015-07-01

Aminoacyl-tRNA synthetases (ARSs) are responsible for cellular protein synthesis and cell viability involving in various process of tumorigenesis. We hypothesized that genetic variants in core ARSs genes may play an important role in the development of breast cancer. Thus, we conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of 28 potentially functional polymorphisms in 12 core ARSs genes (AARS, CARS, EPRS, HARS, KARS, LARS, MARS, QARS, RARS, VARS, WARS, and YARS) with breast cancer risk. We found significant associations with the risk of breast cancer for rs34087264 in AARS [odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.01-1.31], rs801186 in HARS (OR = 1.29, 95% CI = 1.08-1.54), rs193466 in RARS (OR = 1.17, 95% CI = 1.02-1.35), and rs2273802 in WARS (OR = 1.14, 95% CI = 1.01-1.30). We further observed significant interactions between rs2273802 and age at the first live birth (P = 0.041), and between rs801186 and age on breast cancer risk (P = 0.018). Combined analysis of these four SNPs showed a significant allele-dosage association between the number of risk alleles and breast cancer risk (Ptrend  = 2.00 × 10(-4) ). Compared with individuals with "0-2" risk alleles, those carrying "3," "4," or "5 or more" risk alleles had a 1.32 (95% CI = 1.07-1.64), 1.48 (95% CI = 1.45-1.91), or 1.60 folds (95% CI = 1.06-2.41) risk of breast cancer, respectively. These findings indicate that genetic variants in core ARSs genes may modify the individual susceptibility to breast cancer in Chinese population.

2. Aminostratigraphy of surface and subsurface Quaternary sediments, North Carolina coastal plain, USA

USGS Publications Warehouse

Wehmiller, J. F.; Thieler, E.R.; Miller, D.; Pellerito, V.; Bakeman, Keeney V.; Riggs, S.R.; Culver, S.; Mallinson, D.; Farrell, K.M.; York, L.L.; Pierson, J.; Parham, P.R.

2010-01-01

The Quaternary stratigraphy and geochronology of the Albemarle Embayment of the North Carolina (NC) Coastal Plain is examined using amino acid racemization (AAR) in marine mollusks, in combination with geophysical, lithologic, and biostratigraphic analysis of 28 rotasonic cores drilled between 2002 and 2006. The Albemarle Embayment is bounded by structural highs to the north and south, and Quaternary strata thin westward toward the Suffolk paleoshoreline, frequently referred to as the Suffolk Scarp. The Quaternary section is up to ???90. m thick, consists of a variety of estuarine, shelf, back-barrier, and lagoonal deposits, and has been influenced by multiple sea-level cycles. The temporal resolution of the amino acid racemization method is tested statistically and with the stratigraphic control provided by this geologic framework, and it is then applied to the correlation and age estimation of subsurface units throughout the region. Over 500 specimens (primarily Mercenaria and Mulinia) from the subsurface section have been analyzed using either gas chromatographic (GC) or reverse-phase liquid chromatographic (RPLC) techniques. The subsurface stratigraphic data are compared with AAR results from numerous natural or excavated exposures from the surrounding region, as well as results from NC beach collections, to develop a comprehensive aminostratigraphic database for the entire Quaternary record within the NC coastal system. Age mixing, recognized in the beach collections, is also seen in subsurface sections, usually where major seismic reflections or core lithology indicate the presence of stratigraphic discontinuities. Kinetic models for racemization are tested within the regional stratigraphic framework, using either radiocarbon or U-series calibrations or comparison with regional biostratigraphy. Three major Pleistocene aminozones [AZ2, AZ3, and AZ4] are found throughout the region, all being found in superposition in several cores. Each can be subdivided

3. Ground state of bilayer hα-silica: mechanical and electronic properties

NASA Astrophysics Data System (ADS)

Han, Yang; Hu, Ming

2015-12-01

The family of two-dimensional (2D) crystals was recently joined by silica, one of the most abundant resources on earth. So far two different polymorphs of this material, namely a tetrahedra-shaped monolayer and a fully saturated bilayer structure, have been synthesized on various metal substrates and their fascinating properties enable 2D silica to hold promise in nanoelectronic device applications. In this paper a new ground state of bilayer—AAr-stacking hα-silica—has been discovered by first principles calculations. The new structure is featured with a formation of Si-Si bonds between all sp3 hybridized SiO3 triangular pyramids, lying respectively in different silica layers, with an intrinsic rotational angle of about 12.5° along the out-of-plane Si-Si bond. Due to the doubled number of Si-Si bonds in the new structure, the system energy is lowered by nearly three times more than that reported recently in literature (0.8 eV) (Özçelik et al 2014 Phys. Rev. Lett. 112 246803), when compared with the single layer hα-silica. A mechanical property investigation shows that the AAr-stacking bilayer hα-silica possesses high in-plane stiffness and a negative Poisson’s ratio, which stems from the intrinsic rotational angle of the SiO3 triangular pyramids. Strikingly, the negative Poisson’s ratio evolves into positive at a critical tensile strain ɛ ≈ 1.2%. Such negative-to-positive evolvement is associated with the adaptation of the rotational angle to the applied strain and the structure transition into the nearby valley of the energy landscape. The detailed transition process has been thoroughly analyzed. The electronic properties of the new ground state are also calculated, along with their response to the external strain. Our new ground state structure introduces a new member to the family of 2D bilayer silica materials and is expected to facilitate experimental studies identifying the related structures and exploring further physical and chemical

4. Improved ultrasonic testing of railroad rail for transverse discontinuities in the rail head using higher order Rayleigh (M{sub 21}) waves

SciTech Connect

Grewal, D.S.

1996-09-01

Railroads are a very efficient and economical way of moving bulk commodities over large distances. However, like any other mode of transportation, this mode has its fair share of problems. It can be seen from the data (AAR, 1993) that over a period of time the average carload and trainload tonnage has gone up substantially. The average length of haul has also increased. However, the amount of new rail laid has actually decreased significantly. This presents a challenging opportunity to research better and more efficient ways of keeping the current railroad rail track in service and to find better ways of testing those rails to pre-empt any causes for accidents. An important factor to be considered here is the testing of the railroad rail for the amount of cold work in the top layer and the presence of microcracks in that layer. This article describes a surface guided acoustic mode with several inherent characteristics that make it particularly useful for detecting subsurface transverse flaws in railroad rail. These flaws have been previously in the blind spot of other ultrasonic NDT techniques.

5. Autonomous Aerial Refueling Ground Test Demonstration--A Sensor-in-the-Loop, Non-Tracking Method.

PubMed

Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

2015-05-11

An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously.

6. RNA tertiary structure prediction with ModeRNA.

PubMed

Rother, Magdalena; Rother, Kristian; Puton, Tomasz; Bujnicki, Janusz M

2011-11-01

Noncoding RNAs perform important roles in the cell. As their function is tightly connected with structure, and as experimental methods are time-consuming and expensive, the field of RNA structure prediction is developing rapidly. Here, we present a detailed study on using the ModeRNA software. The tool uses the comparative modeling approach and can be applied when a structural template is available and an alignment of reasonable quality can be performed. We guide the reader through the entire process of modeling Escherichia coli tRNA(Thr) in a conformation corresponding to the complex with an aminoacyl-tRNA synthetase (aaRS). We describe the choice of a template structure, preparation of input files, and explore three possible modeling strategies. In the end, we evaluate the resulting models using six alternative benchmarks. The ModeRNA software can be freely downloaded from http://iimcb.genesilico.pl/moderna/ under the conditions of the General Public License. It runs under LINUX, Windows and Mac OS. It is also available as a server at http://iimcb.genesilico.pl/modernaserver/. The models and the script to reproduce the study from this article are available at http://www.genesilico.pl/moderna/examples/.

7. Glaciological and hydrological sensitivities in the Hindu Kush - Himalaya

NASA Astrophysics Data System (ADS)

Shea, Joseph; Immerzeel, Walter

2016-04-01

Glacier responses to future climate change will affect hydrology at subbasin-scales. The main goal of this study is to assess glaciological and hydrological sensitivities of sub-basins throughout the Hindu Kush - Himalaya (HKH) region. We use a simple geometrical analysis based on a full glacier inventory and digital elevation model (DEM) to estimate sub-basin equilibrium line altitudes (ELA) from assumptions of steady-state accumulation area ratios (AARs). The ELA response to an increase in temperature is expressed as a function of mean annual precipitation, derived from a range of high-altitude studies. Changes in glacier contributions to streamflow in response to increased temperatures are examined for scenarios of both static and adjusted glacier geometries. On average, glacier contributions to streamflow increase by approximately 50% for a +1K warming based on a static geometry. Large decreases (-60% on average) occur in all basins when glacier geometries are instantaneously adjusted to reflect the new ELA. Finally, we provide estimates of sub-basin glacier response times that suggest a majority of basins will experience declining glacier contributions by the year 2100.

8. Alkali-silica reactivity of expanded glass granules in structure of lightweight concrete

NASA Astrophysics Data System (ADS)

Bumanis, G.; Bajare, D.; Locs, J.; Korjakins, A.

2013-12-01

Main component in the lightweight concrete, which provides its properties, is aggregate. A lot of investigations on alkali silica reaction (ASR) between cement and lightweight aggregates have been done with their results published in the academic literature. Whereas expanded glass granules, which is relatively new product in the market of building materials, has not been a frequent research object. Therefore lightweight granules made from waste glass and eight types of cement with different chemical and mineralogical composition were examined in this research. Expanded glass granules used in this research is commercially available material produced by Penostek. Lightweight concrete mixtures were prepared by using commercial chemical additives to improve workability of concrete. The aim of the study is to identify effect of cement composition to the ASR reaction which occurs between expanded glass granules and binder. Expanded glass granules mechanical and physical properties were determined. In addition, properties of fresh and hardened concrete were determined. The ASR test was processed according to RILEM AAR-2 testing recommendation. Tests with scanning electron microscope and microstructural investigations were performed for expanded glass granules and hardened concrete specimens before and after exposing them in alkali solution.

9. A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in African trypanosomes.

PubMed

Cestari, Igor; Kalidas, Savitha; Monnerat, Severine; Anupama, Atashi; Phillips, Margaret A; Stuart, Kenneth

2013-12-01

The genes for all cytoplasmic and potentially all mitochondrial aminoacyl-tRNA synthetases (aaRSs) were identified, and all those tested by RNA interference were found to be essential for the growth of Trypanosoma brucei. Some of these enzymes were localized to the cytoplasm or mitochondrion, but most were dually localized to both cellular compartments. Cytoplasmic T. brucei aaRSs were organized in a multiprotein complex in both bloodstream and procyclic forms. The multiple aminoacyl-tRNA synthetase (MARS) complex contained at least six aaRS enzymes and three additional non-aaRS proteins. Steady-state kinetic studies showed that association in the MARS complex enhances tRNA-aminoacylation efficiency, which is in part dependent on a MARS complex-associated protein (MCP), named MCP2, that binds tRNAs and increases their aminoacylation by the complex. Conditional repression of MCP2 in T. brucei bloodstream forms resulted in reduced parasite growth and infectivity in mice. Thus, association in a MARS complex enhances tRNA-aminoacylation and contributes to parasite fitness. The MARS complex may be part of a cellular regulatory system and a target for drug development.

10. Design of (N)-Methanocarba Adenosine 5′-Uronamides as Species-Independent A3 Receptor-Selective Agonists

PubMed Central

Melman, Artem; Gao, Zhan-Guo; Kumar, Deepmala; Wan, Tina C.; Gizewski, Elizabeth; Auchampach, John A.; Jacobson, Kenneth A.

2008-01-01

2-Chloro-5′ -N-methylcarboxamidoadenosine analogues containing the (N)-methanocarba (bicyclo[3.1.0]hexane) ring system as a ribose substitute display increased selectivity as agonists of the human A3 adenosine receptor (AR). However, the selectivity in mouse was greatly reduced due to an increased tolerance of this ring system at the mouse A1AR. Therefore, we varied substituents at the N6 and C2 positions in search of compounds that have improved A3AR selectivity and are species independent. An N6-methyl analogue was balanced in affinity at mouse A1/A3ARs, with high selectivity in comparison to the A2AAR. Substitution of the 2-chloro atom with larger and more hydrophobic substituents, such as iodo and alkynyl groups, tended to increase the A3AR selectivity (up to 430-fold) in mouse and preserve it in human. Extended and chemically functionalized alkynyl chains attached at the C2 position of the purine moiety preserved A3AR selectivity more effectively than similar chains attached at the 3 position of the N6–benzyl group. PMID:18424135

11. Ecotoxicological effects extrapolation models

SciTech Connect

Suter, G.W. II

1996-09-01

One of the central problems of ecological risk assessment is modeling the relationship between test endpoints (numerical summaries of the results of toxicity tests) and assessment endpoints (formal expressions of the properties of the environment that are to be protected). For example, one may wish to estimate the reduction in species richness of fishes in a stream reach exposed to an effluent and have only a fathead minnow 96 hr LC50 as an effects metric. The problem is to extrapolate from what is known (the fathead minnow LC50) to what matters to the decision maker, the loss of fish species. Models used for this purpose may be termed Effects Extrapolation Models (EEMs) or Activity-Activity Relationships (AARs), by analogy to Structure-Activity Relationships (SARs). These models have been previously reviewed in Ch. 7 and 9 of and by an OECD workshop. This paper updates those reviews and attempts to further clarify the issues involved in the development and use of EEMs. Although there is some overlap, this paper does not repeat those reviews and the reader is referred to the previous reviews for a more complete historical perspective, and for treatment of additional extrapolation issues.

12. Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis.

PubMed

Cosentino, Marco; Zaffaroni, Mauro; Legnaro, Massimiliano; Bombelli, Raffaella; Schembri, Laura; Baroncini, Damiano; Bianchi, Anna; Clerici, Raffaella; Guidotti, Mario; Banfi, Paola; Bono, Giorgio; Marino, Franca

2016-09-15

Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients. No information exists so far in CIS subjects. We investigated DR and AR gene expression in peripheral blood mononuclear cells (PBMC) and in CD4+ T effector (Teff) and regulatory (Treg) cells from CIS subjects, and assessed their relationship with MS progression after 12months. Expression of several DR and AR are upregulated in PBMC, Teff and Treg from CIS subjects. DR D3 and α2A-AR mRNA in PBMC, and DR D5 mRNA in Treg correlate with the risk of MS at 12months. Results show the involvement of dopaminergic and adrenergic pathways in CIS as well as in MS pathogenesis, supporting the evaluation of dopaminergic and adrenergic agents in MS. PMID:27609280

13. ISAP: ISO Spectral Analysis Package

NASA Astrophysics Data System (ADS)

Ali, Babar; Bauer, Otto; Brauher, Jim; Buckley, Mark; Harwood, Andrew; Hur, Min; Khan, Iffat; Li, Jing; Lord, Steve; Lutz, Dieter; Mazzarella, Joe; Molinari, Sergio; Morris, Pat; Narron, Bob; Seidenschwang, Karla; Sidher, Sunil; Sturm, Eckhard; Swinyard, Bruce; Unger, Sarah; Verstraete, Laurent; Vivares, Florence; Wieprecht, Ecki

2014-03-01

ISAP, written in IDL, simplifies the process of visualizing, subsetting, shifting, rebinning, masking, combining scans with weighted means or medians, filtering, and smoothing Auto Analysis Results (AARs) from post-pipeline processing of the Infrared Space Observatory's (ISO) Short Wavelength Spectrometer (SWS) and Long Wavelength Spectrometer (LWS) data. It can also be applied to PHOT-S and CAM-CVF data, and data from practically any spectrometer. The result of a typical ISAP session is expected to be a "simple spectrum" (single-valued spectrum which may be resampled to a uniform wavelength separation if desired) that can be further analyzed and measured either with other ISAP functions, native IDL functions, or exported to other analysis package (e.g., IRAF, MIDAS) if desired. ISAP provides many tools for further analysis, line-fitting, and continuum measurements, such as routines for unit conversions, conversions from wavelength space to frequency space, line and continuum fitting, flux measurement, synthetic photometry and models such as a zodiacal light model to predict and subtract the dominant foreground at some wavelengths.

14. "Agriculture at risk: A report to the nation"--a historical review, critical analysis, and implications for future planning.

PubMed

Donham, K J; Storm, J F

2002-02-01

"Agricultural at Risk: A Report to the Nation" is a proceedings document of a three-year (1987-1990) policy development process entitled "Agricultural Occupational and Environmental Health: Policy Strategies for the Future." That process culminated in the emergence of occupational health and safety in agriculture as a public health policy issue in the U.S. Several agricultural health and safety programs evolved as direct or indirect consequences of this process, including, but not limited to, the NIOSH agricultural occupational health programs, The Kellogg Foundation agricultural health grants programs, and the prospective chronic health studies of pesticides (EPA-NlH funded). The Agriculture at Risk report resulted in 86 specific recommendations. The authors of this article reviewed each of these recommendations and rated them on a subjective scale as to their degree of attainment. They found that 44% of the recommendations had received moderate to substantial action. Most of the positive action was in the areas of research and coalition building. A noticeable lack of action was in the areas of standards and regulation, occupational health service delivery, and education categories. This article concludes with an analysis of the limitations of the AAR report, changes in exposed populations over the past decade, and specific recommendations on future actions to address the issues.

15. Aminoacyl-tRNA synthetases are multivalent suppressors of defects due to human equivalent mutations in yeast mt tRNA genes.

PubMed

Montanari, Arianna; De Luca, Cristina; Frontali, Laura; Francisci, Silvia

2010-09-01

The use of the yeast model for the study of the molecular and cellular effects of the pathogenic base substitutions in human mitochondrial tRNA genes has recently been validated by the finding that the suppressing factors identified in yeast (the mitochondrial protein elongation factor EF-Tu and the cognate aminoacyl-tRNA synthetase) have suppressing activities also in human cells. In this paper we report a detailed analysis of the cross-suppressing activities of valyl- and leucyl-tRNA synthetases on different tRNA mutants. Glycerol growth, respiration, Northern analysis consistently show that similar suppressing effects can be obtained by these two yeast synthetases and by the orthologous human enzymes. As a whole the present data indicate that the suppression by mt aa-RS is probably not related to the enzyme activities per se, and may be due to a stabilizing chaperon-like effect of the synthetase molecules on the tRNA structure altered by the mutations.

16. How to identify carbonate rock reactions in concrete

SciTech Connect

Katayama, Tetsuya . E-mail: katayamat@kge.co.jp

2004-11-15

This paper summarizes the modern petrographic techniques used to diagnose carbonate rock reactions in concrete. Concrete microbar specimens of the prototype RILEM AAR-5 test, provided by the Austrian Cement Research Institute, and typical Canadian concrete that had undergone alkali-carbonate reaction (ACR) were examined. Scanning electron microscopy, element mapping and quantitative analysis using electron-probe microanalyzer with energy-dispersive spectrometry (EPMA/EDS: around x 2000, <0.1 nA) were made of polished thin sections after completing polarizing microscopy. Dedolomitization produced a myrmekitic texture, composed of spotted brucite (<3 {mu}m) and calcite within the reaction rim, along with a carbonate halo of calcite in the surrounding cement paste. However, no evidence was detected that dedolomitization had produced the expansion cracks in the cement paste, while the classical definition of alkali-carbonate reaction postulates their development. It was found that the alkali-silica reaction (ASR) due to cryptocrystalline quartz hidden in the matrix, always associated with dedolomitization in all the carbonate aggregates tested, was responsible for the expansion of both the laboratory and field concretes, even with the Canadian dolomitic limestone from Kingston, the reference material for alkali-carbonate reaction. It is suggested that the term alkali-carbonate reaction is misleading.

17. Improving alkane synthesis in Escherichia coli via metabolic engineering.

PubMed

Song, Xuejiao; Yu, Haiying; Zhu, Kun

2016-01-01

Concerns about energy security and global petroleum supply have made the production of renewable biofuels an industrial imperative. The ideal biofuels are n-alkanes in that they are chemically and structurally identical to the fossil fuels and can "drop in" to the transportation infrastructure. In this work, an Escherichia coli strain that produces n-alkanes was constructed by heterologous expression of acyl-acyl carrier protein (ACP) reductase (AAR) and aldehyde deformylating oxygenase (ADO) from Synechococcus elongatus PCC7942. The accumulation of alkanes ranged from 3.1 to 24.0 mg/L using different expressing strategies. Deletion of yqhD, an inherent aldehyde reductase in E. coli, or overexpression of fadR, an activator for fatty acid biosynthesis, exhibited a nearly twofold increase in alkane titers, respectively. Combining yqhD deletion and fadR overexpression resulted in a production titer of 255.6 mg/L in E. coli, and heptadecene was the most abundant product. PMID:26476644

18. Biscrolling nanotube sheets and functional guests into yarns

NASA Astrophysics Data System (ADS)

Baughman, Ray

2011-03-01

Multifunctional applications of textiles have been limited by the inability to spin important materials into yarns. Generically applicable methods are demonstrated for producing weavable yarns comprising up to 95 wt % of otherwise unspinnable particulate or nanofiber powders that remain highly functional. Scrolled 50 nm thick carbon nanotube sheets confine these powders in the galleries of irregular scroll sacks, whose observed complex structures are related to twist-dependent extension of Archimedean spirals, Fermat spirals, or spiral pairs into scrolls. The strength and electronic connectivity of a small weight fraction of scrolled carbon nanotube sheet enables yarn weaving, sewing, knotting, braiding, and charge collection. This technology is used to make yarns of superconductors, Li-ion battery materials, graphene ribbons, catalytic nanofibers for fuel cells, and Ti O2 for photocatalysis. Work done in collaboration with Shaoli Fang, Xavier Lepro-Chavez, Chihye Lewis, Raquel Ovalle-Robles, Javier Carratero-Gonzalez, Elisabet Castillo-Martinez, Mikhail Kozlov, Jiyoung Oh, Neema Rawat, Carter Haines, Mohammed Haque, Vaishnavi Aare, Stephanie Stoughton, Anvar Zakhidov, and Ray Baughman, The University of Texas at Dallas / Alan G. MacDiarmid NanoTech Institute.

19. Alpine Post-Collisional Orogeny: topics of debate and possible targets for AlpArray research

NASA Astrophysics Data System (ADS)

Kissling, Edi

2016-04-01

In all aspects, the Alps are by far the best documented orogen. Within their only 1000km lengths from Nice to Vienna, the Alps exhibit an extraordinary variation in structure along strike and from surface to great depth. The modern well-accepted mountain building concept calls for a material flux carefully balanced by mantle flow, plate convergence, subduction, crustal delamination, surface topography, uplift and erosion. The Alpine data set provides a basis to relate subduction processes with Penninic nappes evolution and overthrusting of Austroalpine lid, collision and oceanic slab break-off with build-up of topography, and post-collisional slab rollback and isostatic rebound due to erosional unloading to exhumation of deep European basement structures such as Tauern and Aar massiv. Temporal and spatial variations and relative importance of these processes and their relation to the overall convergence between the Adriatic/Africa and European continental plates, however, are still poorly understood and remain matters of debate. While the AlpArray Seismic Experiment will provide new geophysical information of unprecedented resolution and reliability, discussions and interdisciplinary earth science research among AlpArray community targeted at key questions will lead to a better understanding of collisional orogeny in general and Alpine evolution in particular.

20. Activities of Asian Students and Young Scientists on Photogrammetry and Remote Sensing

NASA Astrophysics Data System (ADS)

Miyazaki, H.; Lo, C.-Y.; Cho, K.

2012-07-01

This paper reports a history and future prospects of the activities by Asian students and young scientists on photogrammetry and remote sensing. For future growths of academic fields, active communications among students and young scientists are indispensable. In some countries and regions in Asia, local communities are already established by youths and playing important roles of building networks among various schools and institutes. The networks are expected to evolve innovative cooperations after the youths achieve their professions. Although local communities are getting solid growth, Asian youths had had little opportunities to make contacts with youths of other countries and regions. To promote youth activities among Asian regions, in 2007, Asian Association on Remote Sensing (AARS) started a series of programs involving students and young scientists within the annual conferences, the Asian Conference on Remote Sensing (ACRS). The programs have provided opportunities and motivations to create networks among students and young scientists. As a result of the achievements, the number of youth interested and involved in the programs is on growing. In addition, through the events held in Asian region by ISPRS Student Consortium (ISPRSSC) and WG VI/5, the Asian youths have built friendly partnership with ISPRSSC. Currently, many Asian youth are keeping contacts with ACRS friends via internet even when they are away from ACRS. To keep and expand the network, they are planning to establish an Asian youth organization on remote sensing. This paper describes about the proposals and future prospects on the Asian youth organization.

1. GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export

PubMed Central

Zhang, Maoxiang; Davis, Jason E.; Li, Chunman; Gao, Jie; Huang, Wei; Lambert, Nevin A.; Terry, Alvin V.

2016-01-01

Molecular mechanisms governing the anterograde trafficking of nascent G protein-coupled receptors (GPCRs) are poorly understood. Here, we have studied the regulation of cell surface transport of α2-adrenergic receptors (α2-ARs) by GGA3 (Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding protein 3), a multidomain clathrin adaptor protein that sorts cargo proteins at the trans-Golgi network (TGN) to the endosome/lysosome pathway. By using an inducible system, we demonstrated that GGA3 knockdown significantly inhibited the cell surface expression of newly synthesized α2B-AR without altering overall receptor synthesis and internalization. The receptors were arrested in the TGN. Furthermore, GGA3 knockdown attenuated α2B-AR-mediated signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) activation and cyclic AMP (cAMP) inhibition. More interestingly, GGA3 physically interacted with α2B-AR, and the interaction sites were identified as the triple Arg motif in the third intracellular loop of the receptor and the acidic motif EDWE in the VHS domain of GGA3. In contrast, α2A-AR did not interact with GGA3 and its cell surface export and signaling were not affected by GGA3 knockdown. These data reveal a novel function of GGA3 in export trafficking of a GPCR that is mediated via a specific interaction with the receptor. PMID:26811329

2. Flow Behavior and Constitutive Equation of Ti-6.5Al-2Sn-4Zr-4Mo-1W-0.2Si Titanium Alloy

NASA Astrophysics Data System (ADS)

Yang, Xuemei; Guo, Hongzhen; Liang, Houquan; Yao, Zekun; Yuan, Shichong

2016-04-01

In order to get a reliable constitutive equation for the finite element simulation, flow behavior of Ti-6.5Al-2Sn-4Zr-4Mo-1W-0.2Si alloy under high temperature was investigated by carrying a series of isothermal compression tests at temperatures of 1153-1293 K and strain rates of 0.01-10.0 s-1 on the Gleeble-1500 simulator. Results showed that the true stress-strain curves exhibited peaks at small strains, after which the flow stress decreased monotonically. Ultimately, the flow curves reached steady state at the strain of 0.6, showing a dynamic flow softening phenomenon. The effects of strain rate, temperature, and strain on the flow behavior were researched by establishing a constitutive equation. The relations among stress exponent, deformation activation energy, and strain were preliminarily discussed by using strain rate sensitivity exponent and dynamic recrystallization kinetics curve. Stress values predicted by the modified constitutive equation showed a good agreement with the experimental ones. The correlation coefficient ( R) and average absolute relative error (AARE) were 98.2% and 4.88%, respectively, which confirmed that the modified constitutive equation could give an accurate estimation of the flow stress for BT25y titanium alloy.

3. Prediction of FV520B Steel Flow Stresses at High Temperature and Strain Rates

NASA Astrophysics Data System (ADS)

Han, Xiaolan; Zhao, Shengdun; Zhang, Chenyang; Fan, Shuqin; Xu, Fan

2015-10-01

In order to develop reliable constitutive equations for the simulation, the hot deformation behavior of FV520B steel was investigated through isothermal compression tests in a wide range of temperatures from 900 °C to 1100 °C at an interval of 50 °C and strain rate from 0.01 to 10 s-1 on Gleeble-1500D simulator. The effects of temperature and strain rate on deformation behavior were represented by Zener-Holloman parameter in an exponent-type equation of Arrhenius constitutive. The influence of strain was incorporated in the constitutive analysis by material constants expressed as a polynomial function of strain. The constitutive equation (considering the compensation of strain) could precisely predict the flow stress only at strain rate 0.01 s-1 except at the temperatures of 900 °C and 1000 °C, whereas the flow stress predicted by a modified equation (incorporating both the strain and strain rate) demonstrated a well agreement with the experimental data throughout the entire range of temperatures and strain rates. Correlation coefficient (R) of 0.988 and average absolute relative error (AARE) of 5.7% verified the validity of developed equation from statistical analysis, which further confirmed that the modified constitutive equation could accurately predict the flow stress of FV520B steel.

4. Sesamin protects against renal ischemia reperfusion injury by promoting CD39-adenosine-A2AR signal pathway in mice.

PubMed

Li, Ke; Gong, Xia; Kuang, Ge; Jiang, Rong; Wan, Jingyuan; Wang, Bin

2016-01-01

Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inﬂammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway. PMID:27347331

5. Enhancing Alkane Production in Cyanobacterial Lipid Droplets: A ModeFl Platform for Industrially Relevant Compound Production

PubMed Central

Peramuna, Anantha; Morton, Ray; Summers, Michael L.

2015-01-01

Cyanobacterial lipid droplets (LDs) are packed with hydrophobic energy-dense compounds and have great potential for biotechnological expression and the compartmentalization of high value compounds. Nostoc punctiforme normally accumulates LDs containing neutral lipids, and small amounts of heptadecane, during the stationary phase of growth. In this study, we further enhanced heptadecane production in N. punctiforme by introducing extrachromosomal copies of aar/adc genes, and report the discovery of a putative novel lipase encoded by Npun_F5141, which further enhanced alkane production. Extra copies of all three genes in high light conditions resulted in a 16-fold higher accumulation of heptadecane compared to the wild type strain in the exponential phase. LD accumulation during exponential phase also increased massively to accommodate the heptadecane production. A large number of small, less fluorescent LDs were observed at the cell periphery in exponential growth phase, whereas fewer number of highly fluorescent, much larger LDs were localized towards the center of the cell in the stationary phase. These advances demonstrate that cyanobacterial LDs are an ideal model platform to make industrially relevant compounds, such as alkanes, during exponential growth, and provide insight into LD formation in cyanobacteria. PMID:25821934

6. Bidirectional modulation of hippocampal gamma (20-80 Hz) frequency activity in vitro via alpha(α)- and beta(β)-adrenergic receptors (AR).

PubMed

Haggerty, D C; Glykos, V; Adams, N E; Lebeau, F E N

2013-12-01

Noradrenaline (NA) in the hippocampus plays an important role in memory function and has been shown to modulate different forms of synaptic plasticity. Oscillations in the gamma frequency (20-80 Hz) band in the hippocampus have also been proposed to play an important role in memory functions and, evidence from both in vitro and in vivo studies, has suggested this activity can be modulated by NA. However, the role of different NA receptor subtypes in the modulation of gamma frequency activity has not been fully elucidated. We have found that NA (30 μM) exerts a bidirectional control on the magnitude of kainate-evoked (50-200 nM) gamma frequency oscillations in the cornu Ammonis (CA3) region of the rat hippocampus in vitro via activation of different receptor subtypes. Activation of alpha-adrenergic receptors (α-AR) reduced the power of the gamma frequency oscillation. In contrast, activation of beta-adrenergic receptors (β-AR) caused an increase in the power of the gamma frequency oscillations. Using specific agonists and antagonists of AR receptor subtypes we demonstrated that these effects are mediated specifically via α1A-AR and β1-AR subtypes. NA activated both receptor subtypes, but the α1A-AR-mediated effect predominated, resulting in a reversible suppression of gamma frequency activity. These results suggest that NA is able to differentially modulate on-going gamma frequency oscillatory activity that could result in either increased or decreased information flow through the hippocampus.

7. Characterization of a fragment containing a putative TLP cDNA sequence.

PubMed

Tarro, G

2002-01-01

With the aim of isolating the Tumor Liberated Protein (TLP) gene, reverse transcription-polymerase chain reaction (RT-PCR) was used to isolate a approximately equal to 500 bp fragment containing a putative TLP cDNA sequence. Total RNAs were extracted from several cell lines with RNAzol B reagent (Tel-Test, Inc) and reverse transcribed using the Reverse Transcription System (Promega). PCR was carried out for 35 cycles (1 minute at 95 degrees C, 2 minutes at 40 degrees C and 1 minute at 72 degrees C) using an upstream degenerate oligonucleotide, ACN AAY AAR GAR GCN TCN ATG TG, which corresponds to the amino acid sequence T N K E A S I, and random hexamers as the downstream primer. PCR products were electrophoresed on a 1% agarose gel containing ethidium bromide. The PCR products were cloned in the pGEM-T easy vector (PROMEGA) and the resulting plasmid clones were sequenced with the chain termination method using the Applied Biosystems model 373A DNA sequencer. A putative open reading frame was deducted. The results obtained can be considered as preliminary data that will require more investigation in order to confirm them. We propose to continue the studies to verify that TLP could be a diagnostic marker in human cancer.

8. Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2).

PubMed

Vanlander, Arnaud V; Menten, Björn; Smet, Joél; De Meirleir, Linda; Sante, Tom; De Paepe, Boel; Seneca, Sara; Pearce, Sarah F; Powell, Christopher A; Vergult, Sarah; Michotte, Alex; De Latter, Elien; Vantomme, Lies; Minczuk, Michal; Van Coster, Rudy

2015-02-01

A homozygous missense mutation (c.822G>C) was found in the gene encoding the mitochondrial asparaginyl-tRNA synthetase (NARS2) in two siblings born to consanguineous parents. These siblings presented with different phenotypes: one had mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy. Biochemical analysis of the oxidative phosphorylation (OXPHOS) complexes in both siblings revealed a combined complex I and IV deficiency in skeletal muscle. In-gel activity staining after blue native-polyacrylamide gel electrophoresis confirmed the decreased activity of complex I and IV, and, in addition, showed the presence of complex V subcomplexes. Considering the consanguineous descent, homozygosity mapping and whole-exome sequencing were combined revealing the presence of one single missense mutation in the shared homozygous region. The c.822G>C variant affects the 3' splice site of exon 7, leading to skipping of the whole exon 7 and a part of exon 8 in the NARS2 mRNA. In EBV-transformed lymphoblasts, a specific decrease in the amount of charged mt-tRNA(Asn) was demonstrated as compared with controls. This confirmed the pathogenic nature of the variant. To conclude, the reported variant in NARS2 results in a combined OXPHOS complex deficiency involving complex I and IV, making NARS2 a new member of disease-associated aaRS2. PMID:25385316

9. Allosteric regulation of rhomboid intramembrane proteolysis

PubMed Central

Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

2014-01-01

Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. PMID:25009246

10. Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2).

PubMed

Vanlander, Arnaud V; Menten, Björn; Smet, Joél; De Meirleir, Linda; Sante, Tom; De Paepe, Boel; Seneca, Sara; Pearce, Sarah F; Powell, Christopher A; Vergult, Sarah; Michotte, Alex; De Latter, Elien; Vantomme, Lies; Minczuk, Michal; Van Coster, Rudy

2015-02-01

A homozygous missense mutation (c.822G>C) was found in the gene encoding the mitochondrial asparaginyl-tRNA synthetase (NARS2) in two siblings born to consanguineous parents. These siblings presented with different phenotypes: one had mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy. Biochemical analysis of the oxidative phosphorylation (OXPHOS) complexes in both siblings revealed a combined complex I and IV deficiency in skeletal muscle. In-gel activity staining after blue native-polyacrylamide gel electrophoresis confirmed the decreased activity of complex I and IV, and, in addition, showed the presence of complex V subcomplexes. Considering the consanguineous descent, homozygosity mapping and whole-exome sequencing were combined revealing the presence of one single missense mutation in the shared homozygous region. The c.822G>C variant affects the 3' splice site of exon 7, leading to skipping of the whole exon 7 and a part of exon 8 in the NARS2 mRNA. In EBV-transformed lymphoblasts, a specific decrease in the amount of charged mt-tRNA(Asn) was demonstrated as compared with controls. This confirmed the pathogenic nature of the variant. To conclude, the reported variant in NARS2 results in a combined OXPHOS complex deficiency involving complex I and IV, making NARS2 a new member of disease-associated aaRS2.

11. Synthesis and Anti-Renal Fibrosis Activity of Conformationally Locked Truncated 2-Hexynyl-N6-Substituted-(N)-Methanocarba-nucleosides as A3 Adenosine Receptor Antagonists and Partial Agonists

PubMed Central

2015-01-01

Truncated N6-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4′-thioadenosines. Hydrophobic N6 and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high hA2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N6-cycloalkyl group (4d) showed excellent binding affinity at the hA3AR and was better than an unsubstituted free amino group (4a). A3AR affinities of 3-halobenzylamine derivatives 4f–4i did not differ significantly, with Ki values of 7.8–16.0 nM. N6-Methyl derivative 4b (Ki = 4.9 nM) was a highly selective, low efficacy partial A3AR agonist. All compounds were screened for renoprotective effects in human TGF-β1-stimulated mProx tubular cells, a kidney fibrosis model. Most compounds strongly inhibited TGF-β1-induced collagen I upregulation, and their A3AR binding affinities were proportional to antifibrotic effects; 4b was most potent (IC50 = 0.83 μM), indicating its potential as a good therapeutic candidate for treating renal fibrosis. PMID:24456490

12. Entamoeba lysyl-tRNA Synthetase Contains a Cytokine-Like Domain with Chemokine Activity towards Human Endothelial Cells

PubMed Central

Han, Jung Min; Kim, Sunghoon; Celada, Antonio; Ribas de Pouplana, Lluís

2011-01-01

Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity. PMID:22140588

13. A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

PubMed

Santiago, Araceli E; Ruiz-Perez, Fernando; Jo, Noah Y; Vijayakumar, Vidhya; Gong, Mei Q; Nataro, James P

2014-05-01

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

14. Definition and automatic anatomy recognition of lymph node zones in the pelvis on CT images

NASA Astrophysics Data System (ADS)

Liu, Yu; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Guo, Shuxu; Attor, Rosemary; Reinicke, Danica; Torigian, Drew A.

2016-03-01

Currently, unlike IALSC-defined thoracic lymph node zones, no explicitly provided definitions for lymph nodes in other body regions are available. Yet, definitions are critical for standardizing the recognition, delineation, quantification, and reporting of lymphadenopathy in other body regions. Continuing from our previous work in the thorax, this paper proposes a standardized definition of the grouping of pelvic lymph nodes into 10 zones. We subsequently employ our earlier Automatic Anatomy Recognition (AAR) framework designed for body-wide organ modeling, recognition, and delineation to actually implement these zonal definitions where the zones are treated as anatomic objects. First, all 10 zones and key anatomic organs used as anchors are manually delineated under expert supervision for constructing fuzzy anatomy models of the assembly of organs together with the zones. Then, optimal hierarchical arrangement of these objects is constructed for the purpose of achieving the best zonal recognition. For actual localization of the objects, two strategies are used -- optimal thresholded search for organs and one-shot method for the zones where the known relationship of the zones to key organs is exploited. Based on 50 computed tomography (CT) image data sets for the pelvic body region and an equal division into training and test subsets, automatic zonal localization within 1-3 voxels is achieved.

15. A Comparative Investigation on the Capability of Modified Zerilli-Armstrong and Arrhenius-Type Constitutive Models to Describe Flow Behavior of BFe10-1-2 Cupronickel Alloy at Elevated Temperature

NASA Astrophysics Data System (ADS)

Cai, Jun; Lei, Ying; Wang, Kuaishe; Zhang, Xiaolu; Miao, Chengpeng; Li, Wenbing

2016-05-01

True stress and true strain data obtained from isothermal compression tests on a Gleeble-3800 thermo-mechanical simulator, in a wide range of temperatures (1073-1323 K) and strain rates (0.001-10 s-1), has been used to evaluate the material constants of two constitutive models: the modified Zerilli-Armstrong and the strain compensation Arrhenius-type models. Furthermore, a comparative study was conducted on the capabilities of the two models in order to represent the elevated temperature flow behavior of BFe10-1-2 cupronickel alloy. The suitability levels of these two models were evaluated by comparing the accuracy of their predictions of deformation behavior, correlation coefficient ( R), average absolute relative error ( AARE), relative errors of prediction, and the number of material constants. The results show that the predicted values of these two models agree well with the experimental values of BFe10-1-2 cupronickel alloy except at the temperature of 1123 K and the strain rate of 1 s-1. Meanwhile, the strain compensated Arrhenius-type model can track the deformation behavior of BFe10-1-2 cupronickel alloy more accurately throughout the entire temperature and strain rate range, while fewer material constants are involved in the modified Zerilli-Armstrong model.

16. Double-sieving-defective aminoacyl-tRNA synthetase causes protein mistranslation and affects cellular physiology and development

PubMed Central

Lu, Jiongming; Bergert, Martin; Walther, Anita; Suter, Beat

2014-01-01

Aminoacyl-tRNA synthetases (aaRSs) constitute a family of ubiquitously expressed essential enzymes that ligate amino acids to their cognate tRNAs for protein synthesis. Recently, aaRS mutations have been linked to various human diseases; however, how these mutations lead to diseases has remained unclear. In order to address the importance of aminoacylation fidelity in multicellular organisms, we generated an amino-acid double-sieving model in Drosophila melanogaster using phenylalanyl-tRNA synthetase (PheRS). Double-sieving-defective mutations dramatically misacylate non-cognate Tyr, induce protein mistranslation and cause endoplasmic reticulum stress in flies. Mutant adults exhibit many defects, including loss of neuronal cells, impaired locomotive performance, shortened lifespan and smaller organ size. At the cellular level, the mutations reduce cell proliferation and promote cell death. Our results also reveal the particular importance of the first amino-acid recognition sieve. Overall, these findings provide new mechanistic insights into how malfunctioning of aaRSs can cause diseases. PMID:25427601

17. Drogue tracking using 3D flash lidar for autonomous aerial refueling

NASA Astrophysics Data System (ADS)

Chen, Chao-I.; Stettner, Roger

2011-06-01

Autonomous aerial refueling (AAR) is an important capability for an unmanned aerial vehicle (UAV) to increase its flying range and endurance without increasing its size. This paper presents a novel tracking method that utilizes both 2D intensity and 3D point-cloud data acquired with a 3D Flash LIDAR sensor to establish relative position and orientation between the receiver vehicle and drogue during an aerial refueling process. Unlike classic, vision-based sensors, a 3D Flash LIDAR sensor can provide 3D point-cloud data in real time without motion blur, in the day or night, and is capable of imaging through fog and clouds. The proposed method segments out the drogue through 2D analysis and estimates the center of the drogue from 3D point-cloud data for flight trajectory determination. A level-set front propagation routine is first employed to identify the target of interest and establish its silhouette information. Sufficient domain knowledge, such as the size of the drogue and the expected operable distance, is integrated into our approach to quickly eliminate unlikely target candidates. A statistical analysis along with a random sample consensus (RANSAC) is performed on the target to reduce noise and estimate the center of the drogue after all 3D points on the drogue are identified. The estimated center and drogue silhouette serve as the seed points to efficiently locate the target in the next frame.

18. Autonomous Aerial Refueling Ground Test Demonstration—A Sensor-in-the-Loop, Non-Tracking Method

PubMed Central

Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

2015-01-01

An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously. PMID:25970254

19. Design Considerations of ISTAR Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

NASA Technical Reports Server (NTRS)

Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

2003-01-01

The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system that produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

20. Design Considerations of Istar Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

NASA Technical Reports Server (NTRS)

Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

2002-01-01

The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system thai: produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

1. Study of the Binding Energies between Unnatural Amino Acids and Engineered Orthogonal Tyrosyl-tRNA Synthetases

NASA Astrophysics Data System (ADS)

Ren, Wei; Truong, Tan M.; Ai, Hui-Wang

2015-07-01

We utilized several computational approaches to evaluate the binding energies of tyrosine (Tyr) and several unnatural Tyr analogs, to several orthogonal aaRSes derived from Methanocaldococcus jannaschii and Escherichia coli tyrosyl-tRNA synthetases. The present study reveals the following: (1) AutoDock Vina and ROSETTA were able to distinguish binding energy differences for individual pairs of favorable and unfavorable aaRS-amino acid complexes, but were unable to cluster together all experimentally verified favorable complexes from unfavorable aaRS-Tyr complexes; (2) MD-MM/PBSA provided the best prediction accuracy in terms of clustering favorable and unfavorable enzyme-substrate complexes, but also required the highest computational cost; and (3) MM/PBSA based on single energy-minimized structures has a significantly lower computational cost compared to MD-MM/PBSA, but still produced sufficiently accurate predictions to cluster aaRS-amino acid interactions. Although amino acid-aaRS binding is just the first step in a complex series of processes to acylate a tRNA with its corresponding amino acid, the difference in binding energy, as shown by MD-MM/PBSA, is important for a mutant orthogonal aaRS to distinguish between a favorable unnatural amino acid (unAA) substrate from unfavorable natural amino acid substrates. Our computational study should assist further designing and engineering of orthogonal aaRSes for the genetic encoding of novel unAAs.

2. Improved dual promotor-driven reverse genetics system for influenza viruses.

PubMed

Mostafa, Ahmed; Kanrai, Pumaree; Ziebuhr, John; Pleschka, Stephan

2013-11-01

Reverse genetic systems for influenza A virus (IAV) allow the generation of genetically manipulated infectious virus from a set of transfected plasmid DNAs encoding the eight genomic viral RNA segments (vRNA). For this purpose, cDNAs representing these eight vRNA segments are cloned into specific plasmid vectors that allow the generation of vRNA-like transcripts using polymerase I (Pol I). In addition, these plasmids support the transcription of viral mRNA by polymerase II (Pol II), leading to the expression of viral protein(s) encoded by the respective transcripts. In an effort to develop this system further, we constructed the bi-directional vector pMPccdB. It is based on pHW2000 (Hoffmann et al., 2000b) but contains additionally (i) the ccdB gene whose expression is lethal for most Escherichia coli strains and therefore used as a negative selection marker and (ii) more efficient AarI cloning sites that flank the ccdB gene on either side. Furthermore, we used a modified one-step restriction/ligation protocol to insert the desired cDNA into the respective pMPccdB vector DNA. Both the use of a negative selection marker and an improved cloning protocol were shown to facilitate the generation of genetically engineered IAV as illustrated in this study by the cloning and rescue of the 2009 pandemic isolate A/Giessen/6/2009 (Gi-H1N1). PMID:23886561

3. A new paleomagnetic study of the Itararé Group of Brazil: evidence for shallow paleomagnetic inclinations and implications for Pangea reconstructions

NASA Astrophysics Data System (ADS)

Bilardello, D.; Raposo, M. B.

2012-12-01

When reconstructing the paleogeography of Pangea, paleomagnetic data for the Permo-Carboniferous imposes an overlap between the two major continental blocks, Laurasia and Gondwana, in the traditional A-type assemblage. Sedimentary rocks dominate the Carboniferous apparent polar wander path (APWP) of South America, and the few igneous rocks are probably either remagnetized or have been subjected to tectonic rotations. Recent work by Bilardello and Kodama (2010) has shown how inclination shallowing corrections of Gondwana sedimentary rocks may completely eliminate the continental overlap. Estimated inclination corrections, however, lack a solid base: they are unreliable and should only be performed to verify if a full inclination correction is required. To this extent, we are performing an inclination shallowing study of the Itararé Group of Brazil. The stratigraphy of the Group has been re-interpreted in recent years, and such study will provide new key paleomagnetic poles in Gondwana's Permo-Carboniferous APWP. Anisotropy of anhysteretic remanence (AAR) and of high field isothermal remanence (hf-AIR) are used to perform inclination corrections of magnetite and hematite bearing rocks, respectively. Corrections have already been successfully applied to Carboniferous rocks from North America. Comparing inclination-corrected paleopoles from Laurasia and Gondwana will give a persuasive, quantitative and robust test of the role of inclination shallowing in the Pangea controversy. Preliminary results will be presented.

4. A Large Family of Antivirulence Regulators Modulates the Effects of Transcriptional Activators in Gram-negative Pathogenic Bacteria

PubMed Central

Santiago, Araceli E.; Ruiz-Perez, Fernando; Jo, Noah Y.; Vijayakumar, Vidhya; Gong, Mei Q.; Nataro, James P.

2014-01-01

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44–100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

5. Constitutive Modeling of Hot Deformation Behavior of High-Strength Armor Steel

NASA Astrophysics Data System (ADS)

Bobbili, Ravindranadh; Madhu, Vemuri

2016-05-01

The hot isothermal compression tests of high-strength armor steel under a wide range of deformation temperatures (1100-1250 °C) and strain rates of (0.001-1/s) were performed. Based on the experimental data, constitutive models were established using the original Johnson-Cook (JC) model, modified JC model, and strain-compensated Arrhenius model, respectively. The modified JC model considers the coupled effects of strain hardening, strain rate hardening, and thermal softening. Moreover, the prediction accuracy of these developed models was determined by estimating the correlation coefficient ( R) and average absolute relative error (AARE). The results demonstrate that the flow behavior of high-strength armor steel is considerably influenced by the strain rate and temperature. The original JC model is inadequate to provide good description on the flow stress at evaluated temperatures. The modified JC model and strain-compensated Arrhenius model significantly enhance the predictability. It is also observed from the microstructure study that at low strain rates (0.001-0.01/s) and high temperatures (1200-1250 °C), a typical dynamic recrystallization (DRX) occurs.

6. A Comparative Study on Johnson Cook, Modified Zerilli-Armstrong and Arrhenius-Type Constitutive Models to Predict High-Temperature Flow Behavior of Ti-6Al-4V Alloy in α + β Phase

NASA Astrophysics Data System (ADS)

Cai, Jun; Wang, Kuaishe; Han, Yingying

2016-03-01

True stress and true strain values obtained from isothermal compression tests over a wide temperature range from 1,073 to 1,323 K and a strain rate range from 0.001 to 1 s-1 were employed to establish the constitutive equations based on Johnson Cook, modified Zerilli-Armstrong (ZA) and strain-compensated Arrhenius-type models, respectively, to predict the high-temperature flow behavior of Ti-6Al-4V alloy in α + β phase. Furthermore, a comparative study has been made on the capability of the three models to represent the elevated temperature flow behavior of Ti-6Al-4V alloy. Suitability of the three models was evaluated by comparing both the correlation coefficient R and the average absolute relative error (AARE). The results showed that the Johnson Cook model is inadequate to provide good description of flow behavior of Ti-6Al-4V alloy in α + β phase domain, while the predicted values of modified ZA model and the strain-compensated Arrhenius-type model could agree well with the experimental values except under some deformation conditions. Meanwhile, the modified ZA model could track the deformation behavior more accurately than other model throughout the entire temperature and strain rate range.

7. Growth inhibition in Chinese cabbage (Brassica rapa var. chinensis) growth exposed to di-n-butyl phthalate.

PubMed

Liao, Chien-Sen; Yen, Jui-Hung; Wang, Yei-Shung

2009-04-30

The toxicity and effects of di-n-butyl phthalate (DBP), an endocrine disruptor, on the growth of Chinese cabbage (Brassica rapa var. chinensis) were studied. Etiolation occurred on leaves of Chinese cabbage plant treated with 50mg/L of DBP for 42 d. DBP even below 1mg/L had a significant effect on the concentration of chlorophyll in Chinese cabbage and the biomass showed a severe decrease under treatment with more than 30 mg/L of DBP. At a concentration below 1mg/L of DBP, no significant difference in accumulation was found, but treatments with concentration exceeding 10, 30, 50 and 100mg/L all resulted in significant accumulation of DBP. Six protein spots extracted from leaf tissue of DBP-treated Chinese cabbage displaying a differential expression are shown in 2-DE maps. According to proteome level studies, three protein spots were found to increase and were identified, respectively, as acyl-[acyl-carrier-protein] desaturase (acyl-ACP desaturase), root phototropism protein 3 (RPT3) and ferredoxin-nitrite reductase (Fd-NiR). The other three protein spots were found to decrease and were identified respectively as dihydroflavonol-4-reductase (DFR), aminoacyl-tRNA synthetase (aaRS) and ATP synthase subunit beta. The key finding is that the other closely related plant, Bok choy (Brassica rapa subsp. chinensis), the subspecies of Chinese cabbage, respond differently to the same chemicals.

8. Improving alkane synthesis in Escherichia coli via metabolic engineering.

PubMed

Song, Xuejiao; Yu, Haiying; Zhu, Kun

2016-01-01

Concerns about energy security and global petroleum supply have made the production of renewable biofuels an industrial imperative. The ideal biofuels are n-alkanes in that they are chemically and structurally identical to the fossil fuels and can "drop in" to the transportation infrastructure. In this work, an Escherichia coli strain that produces n-alkanes was constructed by heterologous expression of acyl-acyl carrier protein (ACP) reductase (AAR) and aldehyde deformylating oxygenase (ADO) from Synechococcus elongatus PCC7942. The accumulation of alkanes ranged from 3.1 to 24.0 mg/L using different expressing strategies. Deletion of yqhD, an inherent aldehyde reductase in E. coli, or overexpression of fadR, an activator for fatty acid biosynthesis, exhibited a nearly twofold increase in alkane titers, respectively. Combining yqhD deletion and fadR overexpression resulted in a production titer of 255.6 mg/L in E. coli, and heptadecene was the most abundant product.

9. Two-dimensional cross-section sensitivity and uncertainty analysis of the LBM (Lithium Blanket Module) experiments at LOTUS

SciTech Connect

Davidson, J.W.; Dudziak, D.J.; Pelloni, S.; Stepanek, J.

1988-01-01

In a recent common Los Alamos/PSI effort, a sensitivity and nuclear data uncertainty path for the modular code system AARE (Advanced Analysis for Reactor Engineering) was developed. This path includes the cross-section code TRAMIX, the one-dimensional finite difference S/sub N/-transport code ONEDANT, the two-dimensional finite element S/sub N/-transport code TRISM, and the one- and two-dimensional sensitivity and nuclear data uncertainty code SENSIBL. Within the framework of the present work a complete set of forward and adjoint two-dimensional TRISM calculations were performed both for the bare, as well as for the Pb- and Be-preceeded, LBM using MATXS8 libraries. Then a two-dimensional sensitivity and uncertainty analysis for all cases was performed. The goal of this analysis was the determination of the uncertainties of a calculated tritium production per source neutron from lithium along the central Li/sub 2/O rod in the LBM. Considered were the contributions from /sup 1/H, /sup 6/Li, /sup 7/Li, /sup 9/Be, /sup nat/C, /sup 14/N, /sup 16/O, /sup 23/Na, /sup 27/Al, /sup nat/Si, /sup nat/Cr, /sup nat/Fe, /sup nat/Ni, and /sup nat/Pb. 22 refs., 1 fig., 3 tabs.

10. Pharmacological Profiles of Alpha 2 Adrenergic Receptor Agonists Identified Using Genetically Altered Mice and Isobolographic Analysis

PubMed Central

Fairbanks, Carolyn A.; Stone, Laura S.; Wilcox, George L.

2009-01-01

Endogenous, descending noradrenergic fibers convey powerful analgesic control over spinal afferent circuitry mediating the rostrad transmission of pain signals. These fibers target alpha 2 adrenergic receptors (α2ARs) on both primary afferent terminals and secondary neurons, and their activation mediates substantial inhibitory control over this transmission, rivaling that of opioid receptors which share similar a similar pattern of distribution. The terminals of primary afferent nociceptive neurons and secondary spinal dorsal horn neurons express α2AAR and α2CAR subtypes, respectively. Spinal delivery of these agents serves to reduce their side effects, which are mediated largely at supraspinal sites, by concentrating the drugs at the spinal level. Targeting these spinal α2ARs with one of five selective therapeutic agonists, clonidine, dexmedetomidine, brimonidine, ST91 and moxonidine, produces significant antinociception that can work in concert with opioid agonists to yield synergistic antinociception. Application of several genetically altered mouse lines had facilitated identification of the primary receptor subtypes that likely mediate the antinociceptive effects of these agents. This review provides first an anatomical description of the localization of the three subtypes in the central nervous system, second a detailed account of the pharmacological history of each of these six primary agonists, and finally a comprehensive report of the specific interactions of other GPCR agonists with each of the six principal α2AR agonists featured. PMID:19393691

11. MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery

PubMed Central

Li, Rongzhong; Macnamara, Lindsay M.; Leuchter, Jessica D.; Alexander, Rebecca W.; Cho, Samuel S.

2015-01-01

While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes. PMID:26184179

12. Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains within translational compartments of P. falciparum.

PubMed

Khan, Sameena; Sharma, Arvind; Jamwal, Abhishek; Sharma, Vinay; Pole, Anil Kumar; Thakur, Kamal Kishor; Sharma, Amit

2011-01-01

Accuracy of aminoacylation is dependent on maintaining fidelity during attachment of amino acids to cognate tRNAs. Cis- and trans-editing protein factors impose quality control during protein translation, and 8 of 36 Plasmodium falciparum aminoacyl-tRNA synthetase (aaRS) assemblies contain canonical putative editing modules. Based on expression and localization profiles of these 8 aaRSs, we propose an asymmetric distribution between the parasite cytoplasm and its apicoplast of putative editing-domain containing aaRSs. We also show that the single copy alanyl- and threonyl-tRNA synthetases are dually targeted to parasite cytoplasm and apicoplast. This bipolar presence of two unique synthetases presents opportunity for inhibitor targeting their aminoacylation and editing activities in twin parasite compartments. We used this approach to identify specific inhibitors against the alanyl- and threonyl-tRNA synthetases. Further development of such inhibitors may lead to anti-parasitics which simultaneously block protein translation in two key parasite organelles, a strategy of wider applicability for pathogen control.

13. Unconventional gas outlook: resources, economics, and technologies

SciTech Connect

Drazga, B.

2006-08-15

The report explains the current and potential of the unconventional gas market including country profiles, major project case studies, and new technology research. It identifies the major players in the market and reports their current and forecasted projects, as well as current volume and anticipated output for specific projects. Contents are: Overview of unconventional gas; Global natural gas market; Drivers of unconventional gas sources; Forecast; Types of unconventional gas; Major producing regions Overall market trends; Production technology research; Economics of unconventional gas production; Barriers and challenges; Key regions: Australia, Canada, China, Russia, Ukraine, United Kingdom, United States; Major Projects; Industry Initiatives; Major players. Uneconomic or marginally economic resources such as tight (low permeability) sandstones, shale gas, and coalbed methane are considered unconventional. However, due to continued research and favorable gas prices, many previously uneconomic or marginally economic gas resources are now economically viable, and may not be considered unconventional by some companies. Unconventional gas resources are geologically distinct in that conventional gas resources are buoyancy-driven deposits, occurring as discrete accumulations in structural or stratigraphic traps, whereas unconventional gas resources are generally not buoyancy-driven deposits. The unconventional natural gas category (CAM, gas shales, tight sands, and landfill) is expected to continue at double-digit growth levels in the near term. Until 2008, demand for unconventional natural gas is likely to increase at an AAR corresponding to 10.7% from 2003, aided by prioritized research and development efforts. 1 app.

14. ORNL RAIL & BARGE DB. Network Database

SciTech Connect

Johnson, P.

1991-07-01

The Oak Ridge National Laboratory (ORNL) Rail and Barge Network Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database. The database consists of 96 subnetworks. Each of the subnetworks represent an individual railroad, a waterway system, or a composite group of small railroads. Two subnetworks represent waterways; one being barge/intercoastal, and the other coastal merchant marine with access through the Great Lakes/Saint Lawrence Seaway, Atlantic and Gulf Coasts, the Panama Canal, and Pacific Coast. Two other subnetworks represent small shortline railroads and terminal railroad operations. One subnetwork is maintained for the representation of Amtrak operations. The remaining 91 subnetworks represent individual or corporate groups of railroads. Coordinate locations are included as part of the database. The rail portion of the database is similar to the original FRA rail network. The waterway coordinates are greatly enhanced in the current release. Inland waterway representation was extracted from the 1:2,000,000 United States Geological Survey data. An important aspect of the database is the transfer file. This file identifies where two railroads interline traffic between their systems. Also included are locations where rail/waterway intermodal transfers could occur. Other files in the database include a translation table between Association of American Railroad (AAR) codes to the 96 subnetworks in the database, a list of names of the 96 subnetworks, and a file of names for a large proportion of the nodes in the network.

15. ORNL RAIL & BARGE DB. Network Database

SciTech Connect

Johnson, P.

1992-03-16

The Oak Ridge National Laboratory (ORNL) Rail and Barge Network Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database. The database consists of 96 subnetworks. Each of the subnetworks represent an individual railroad, a waterway system, or a composite group of small railroads. Two subnetworks represent waterways; one being barge/intercoastal, and the other coastal merchant marine with access through the Great Lakes/Saint Lawrence Seaway, Atlantic and Gulf Coasts, the Panama Canal, and Pacific Coast. Two other subnetworks represent small shortline railroads and terminal railroad operations. One subnetwork is maintained for the representation of Amtrak operations. The remaining 91 subnetworks represent individual or corporate groups of railroads. Coordinate locations are included as part of the database. The rail portion of the database is similar to the original FRA rail network. The waterway coordinates are greatly enhanced in the current release. Inland waterway representation was extracted from the 1:2,000,000 United States Geological Survey data. An important aspect of the database is the transfer file. This file identifies where two railroads interline traffic between their systems. Also included are locations where rail/waterway intermodal transfers could occur. Other files in the database include a translation table between Association of American Railroad (AAR) codes to the 96 subnetworks in the database, a list of names of the 96 subnetworks, and a file of names for a large proportion of the nodes in the network.

16. ORNL RAIL BARGE DB

SciTech Connect

Johnson, P. )

1991-07-01

The Oak Ridge National Laboratory (ORNL) Rail and Barge Network Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database. The database consists of 96 subnetworks. Each of the subnetworks represent an individual railroad, a waterway system, or a composite group of small railroads. Two subnetworks represent waterways; one being barge/intercoastal, and the other coastal merchant marine with access through the Great Lakes/Saint Lawrence Seaway, Atlantic and Gulf Coasts, the Panama Canal, and Pacific Coast. Two other subnetworks represent small shortline railroads and terminal railroad operations. One subnetwork is maintained for the representation of Amtrak operations. The remaining 91 subnetworks represent individual or corporate groups of railroads. Coordinate locations are included as part of the database. The rail portion of the database is similar to the original FRA rail network. The waterway coordinates are greatly enhanced in the current release. Inland waterway representation was extracted from the 1:2,000,000 United States Geological Survey data. An important aspect of the database is the transfer file. This file identifies where two railroads interline traffic between their systems. Also included are locations where rail/waterway intermodal transfers could occur. Other files in the database include a translation table between Association of American Railroad (AAR) codes to the 96 subnetworks in the database, a list of names of the 96 subnetworks, and a file of names for a large proportion of the nodes in the network.

17. Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis

PubMed Central

Hsu, Cheng-Lung; Liu, Jai-Shin; Wu, Po-Long; Guan, Hong-Hsiang; Chen, Yuh-Ling; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Yeh, Shauh-Der; Ma, Wen-Lung; Chen, Chung-Jung; Wu, Wen-Guey; Chang, Chawnshang

2014-01-01

Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR), including T877A (hydroxyflutamide [HF]) and W741(C/L) (bicalutamide [CDX]). Here, we found that anti-androgens bound mt-ARs (HF-T877A-AR-LBD and CDX-W741L-AR-LBD) have similar binary structure to the 5α-dihydrotestosterone (DHT) bound wild type (wt) AR (DHT-wt-AR-LBD). Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex at 2.1 Å resolution revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and Gln733 of the AR AF2 domain, suggesting that peptides with Fxx(F/H/L/W/Y)Y motifs can interact with wt or mutated ARs. Functional studies showed that BUD31-related peptides suppressed transactivation of both DHT-wt-AR and HF-T877A-AR by interrupting AR N- and C-terminal interactions, thereby inhibiting wt and mutant AR-mediated prostate cancer cell growth. Collectively, these results suggest the combination of peptide screening and X-ray structure analysis as a new strategy for developing anti-androgens that simultaneously suppress both wt and mutated AR function. PMID:25091737

18. Using gaseous emissions of a proton accelerator facility as tracer for small-scale atmospheric dispersion.

PubMed

Butterweck, G; Heese, I; Hugi, R; Züllig, J; Hödlmoser, H; Hohmann, E; Mayer, S

2015-04-01

The gaseous effluents of the proton accelerator facility located in the Western part of the Paul Scherrer Institute, Aargau, Switzerland, contain a mixture of positron emitters (50 % (15)O, 20 % (13)N and 30 % (11)C). For the experimental verification of a future upgrade of the dispersion model in the complex topography of the Aare valley, a measuring campaign using three continuous gamma-spectrometric measuring stations was launched in 2011. The concept of a modified man-made-gross-count (MMGC) ratio yields a clear signal associated with the positron emitters while minimising the influence of radon progeny rain-out events. A dependence of the measured MMGC ratios on the emitted activity and wind direction could be demonstrated using frequency distributions of the modified MMGC ratio measured in 2012 and 2013. A significant fraction of high MMGC-ratio values was found associated with dispersion directions (based on measurements of the wind direction in 70 m above ground) not towards or even against the direction between stack and measuring station.

19. Growth inhibition in Chinese cabbage (Brassica rapa var. chinensis) growth exposed to di-n-butyl phthalate.

PubMed

Liao, Chien-Sen; Yen, Jui-Hung; Wang, Yei-Shung

2009-04-30

The toxicity and effects of di-n-butyl phthalate (DBP), an endocrine disruptor, on the growth of Chinese cabbage (Brassica rapa var. chinensis) were studied. Etiolation occurred on leaves of Chinese cabbage plant treated with 50mg/L of DBP for 42 d. DBP even below 1mg/L had a significant effect on the concentration of chlorophyll in Chinese cabbage and the biomass showed a severe decrease under treatment with more than 30 mg/L of DBP. At a concentration below 1mg/L of DBP, no significant difference in accumulation was found, but treatments with concentration exceeding 10, 30, 50 and 100mg/L all resulted in significant accumulation of DBP. Six protein spots extracted from leaf tissue of DBP-treated Chinese cabbage displaying a differential expression are shown in 2-DE maps. According to proteome level studies, three protein spots were found to increase and were identified, respectively, as acyl-[acyl-carrier-protein] desaturase (acyl-ACP desaturase), root phototropism protein 3 (RPT3) and ferredoxin-nitrite reductase (Fd-NiR). The other three protein spots were found to decrease and were identified respectively as dihydroflavonol-4-reductase (DFR), aminoacyl-tRNA synthetase (aaRS) and ATP synthase subunit beta. The key finding is that the other closely related plant, Bok choy (Brassica rapa subsp. chinensis), the subspecies of Chinese cabbage, respond differently to the same chemicals. PMID:18678443

20. Short peptides from leucyl-tRNA synthetase rescue disease-causing mitochondrial tRNA point mutations.

PubMed

Perli, Elena; Fiorillo, Annarita; Giordano, Carla; Pisano, Annalinda; Montanari, Arianna; Grazioli, Paola; Campese, Antonio F; Di Micco, Patrizio; Tuppen, Helen A; Genovese, Ilaria; Poser, Elena; Preziuso, Carmela; Taylor, Robert W; Morea, Veronica; Colotti, Gianni; d'Amati, Giulia

2016-03-01

Mutations in mitochondrial (mt) genes coding for mt-tRNAs are responsible for a range of syndromes, for which no effective treatment is available. We recently showed that the carboxy-terminal domain (Cterm) of human mt-leucyl tRNA synthetase rescues the pathologic phenotype associated either with the m.3243A>G mutation in mt-tRNA(Leu(UUR)) or with mutations in the mt-tRNA(Ile), both of which are aminoacylated by Class I mt-aminoacyl-tRNA synthetases (mt-aaRSs). Here we show, by using the human transmitochondrial cybrid model, that the Cterm is also able to improve the phenotype caused by the m.8344A>G mutation in mt-tRNA(Lys), aminoacylated by a Class II aaRS. Importantly, we demonstrate that the same rescuing ability is retained by two Cterm-derived short peptides, β30_31 and β32_33, which are effective towards both the m.8344A>G and the m.3243A>G mutations. Furthermore, we provide in vitro evidence that these peptides bind with high affinity wild-type and mutant human mt-tRNA(Leu(UUR)) and mt-tRNA(Lys), and stabilize mutant mt-tRNA(Leu(UUR)). In conclusion, we demonstrate that small Cterm-derived peptides can be effective tools to rescue cellular defects caused by mutations in a wide range of mt-tRNAs.

1. Turbulent transport and production/destruction of ozone in a boundary layer over complex terrain

NASA Technical Reports Server (NTRS)

Greenhut, Gary K.; Jochum, Anne M.; Neininger, Bruno

1994-01-01

The first Intensive Observation Period (IOP) of the Swiss air pollution experiment POLLUMET took place in 1990 in the Aare River Valley between Bern and Zurich. During the IOP, fast response measurements of meteorological variables and ozone concentration were made within the boundary layer aboard a motorglider. In addition, mean values of meteorological variables and the concentrations of ozone and other trace species were measured using other aircraft, pilot balloons, tethersondes, and ground stations. Turbulent flux profiles of latent and sensible heat and ozone are calculated from the fast response data. Terms in the ozone mean concentration budget (time rate of change of mean concentration, horizontal advection, and flux divergence) are calculated for stationary time periods both before and after the passage of a cold front. The source/sink term is calculated as a residual in the budget, and its sign and magnitude are related to the measured concentrations of reactive trace species within the boundary layer. Relationships between concentration ratios of trace species and ozone concentration are determined in order to understand the influence of complex terrain on the processes that produce and destroy ozone.

2. Ligand Binding to the Androgen Receptor Induces Conformational Changes That Regulate Phosphatase Interactions▿

PubMed Central

Yang, Chun-Song; Xin, Hong-Wu; Kelley, Joshua B.; Spencer, Adam; Brautigan, David L.; Paschal, Bryce M.

2007-01-01

We describe a mechanism for protein phosphatase 2A (PP2A) targeting to the androgen receptor (AR) and provide insight into the more general issue of kinase and phosphatase interactions with AR. Simian virus 40 (SV40) small t antigen (ST) binding to N-terminal HEAT repeats in the PP2A A subunit induces structural changes transduced to C-terminal HEAT repeats. This enables the C-terminal HEAT repeats in the PP2A A subunit, including HEAT repeat 13, to discriminate between androgen- and androgen antagonist-induced AR conformations. The PP2A-AR interaction was used to show that an AR mutant in prostate cancer cells (T877A) is activated by multiple ligands without acquiring the same conformation as that induced by androgen. The correlation between androgen binding to AR and increased phosphorylation of the activation function 1 (AF-1) region implies that changes in AR conformation or chaperone composition are causal to kinase access to phosphorylation sites. However, AF-1 phosphorylation sites are kinase accessible prior to androgen binding. This suggests that androgens can enhance the phosphorylation state of AR either by negatively regulating the ability of the ligand-binding domain to bind phosphatases or by inducing an AR conformation that is resistant to phosphatase action. SV40 ST subverts this mechanism by promoting the direct transfer of PP2A onto androgen-bound AR, resulting in multisite dephosphorylation. PMID:17325038

3. Short peptides from leucyl-tRNA synthetase rescue disease-causing mitochondrial tRNA point mutations

PubMed Central

Perli, Elena; Fiorillo, Annarita; Giordano, Carla; Pisano, Annalinda; Montanari, Arianna; Grazioli, Paola; Campese, Antonio F.; Di Micco, Patrizio; Tuppen, Helen A.; Genovese, Ilaria; Poser, Elena; Preziuso, Carmela; Taylor, Robert W.; Morea, Veronica; Colotti, Gianni; d'Amati, Giulia

2016-01-01

Mutations in mitochondrial (mt) genes coding for mt-tRNAs are responsible for a range of syndromes, for which no effective treatment is available. We recently showed that the carboxy-terminal domain (Cterm) of human mt-leucyl tRNA synthetase rescues the pathologic phenotype associated either with the m.3243A>G mutation in mt-tRNALeu(UUR) or with mutations in the mt-tRNAIle, both of which are aminoacylated by Class I mt-aminoacyl-tRNA synthetases (mt-aaRSs). Here we show, by using the human transmitochondrial cybrid model, that the Cterm is also able to improve the phenotype caused by the m.8344A>G mutation in mt-tRNALys, aminoacylated by a Class II aaRS. Importantly, we demonstrate that the same rescuing ability is retained by two Cterm-derived short peptides, β30_31 and β32_33, which are effective towards both the m.8344A>G and the m.3243A>G mutations. Furthermore, we provide in vitro evidence that these peptides bind with high affinity wild-type and mutant human mt-tRNALeu(UUR) and mt-tRNALys, and stabilize mutant mt-tRNALeu(UUR). In conclusion, we demonstrate that small Cterm-derived peptides can be effective tools to rescue cellular defects caused by mutations in a wide range of mt-tRNAs. PMID:26721932

4. A Characterization for the Hot Flow Behaviors of As-extruded 7050 Aluminum Alloy

NASA Astrophysics Data System (ADS)

Quan, Guo-zheng; Liu, Jin; Mao, An; Liu, Bo; Zhang, Jin-sheng

2015-11-01

The deep understanding of flow behaviors of as-extruded 7050 aluminum alloy significantly contributes to the accuracy simulation for its various plastic forming processes. In order to obtain the improved Arrhenius-type equation with variable parameters for this alloy, a series of compression tests were performed at temperatures of 573 K, 623 K, 673 K, 723 K and strain rates of 0.01 s-1, 0.1 s-1, 1 s-1, 10 s-1 with a height reduction of 60% on Gleeble-1500 thermo-mechanical simulator. It is obvious that strain rate, strain and temperature all have a significant effect on the hot flow behaviors, and the true stress-true strain curves indicate three types after the peak value: decreasing gradually to a steady state with sustaining DRX softening till a balance with work hardening, decreasing continuously with sustaining increasing DRX softening beyond work hardening and maintaining higher stress level after the peak value with a balance between work hardening and DRV softening. Based on the experimental data, the improved Arrhenius-type constitutive model was established to predict the high temperature flow stress of as-extruded 7050 aluminum alloy. The accuracy and reliability of the improved Arrhenius-type model were further evaluated in terms of the correlation coefficient (R), here 0.98428, the average absolute relative error (AARE), here 3.5%. The results indicate that the improved Arrhenius-type constitutive model presents a good predictable ability.

5. Characterization factors for thermal pollution in freshwater aquatic environments.

PubMed

Verones, Francesca; Hanafiah, Marlia Mohd; Pfister, Stephan; Huijbregts, Mark A J; Pelletier, Gregory J; Koehler, Annette

2010-12-15

To date the impact of thermal emissions has not been addressed in life cycle assessment despite the narrow thermal tolerance of most aquatic species. A method to derive characterization factors for the impact of cooling water discharges on aquatic ecosystems was developed which uses space and time explicit integration of fate and effects of water temperature changes. The fate factor is calculated with a 1-dimensional steady-state model and reflects the residence time of heat emissions in the river. The effect factor specifies the loss of species diversity per unit of temperature increase and is based on a species sensitivity distribution of temperature tolerance intervals for various aquatic species. As an example, time explicit characterization factors were calculated for the cooling water discharge of a nuclear power plant in Switzerland, quantifying the impact on aquatic ecosystems of the rivers Aare and Rhine. The relative importance of the impact of these cooling water discharges was compared with other impacts in life cycle assessment. We found that thermal emissions are relevant for aquatic ecosystems compared to other stressors, such as chemicals and nutrients. For the case of nuclear electricity investigated, thermal emissions contribute between 3% and over 90% to Ecosystem Quality damage.

6. Geomorphology and dynamics of supraglacial debris covers in the Western Alps

NASA Astrophysics Data System (ADS)

Deline, P.; Gardent, M.; Kirkbride, M. P.; Le Roy, M.; Martin, B.

2012-04-01

In the alpine regions of France and NW Italy, many glaciers of a variety of sizes are at least partly debris-covered, but these have received less scientific research than clean glaciers. During the present period of glacier shrinkage - the area of glacier cover in France has reduced by 26% over the last 40 years -, growing debris cover needs to be understood as an influence on continuing retreat, with consequences for natural hazards, water resources and tourism. We present the results of a combined ongoing study of an inventory of debris-covered glaciers in France with site-specific studies of c. 12 glaciers of contrasting types, in order to understand spatial and temporal changes in supraglacial debris cover. Our specific aims are: 1. To understand the geomorphology of debris-covers and their formation, investigating the types of debris cover in relation to formative processes including extraglacial supply and development during transport. 2. To document the changing extents of supraglacial debris covers, using historical documents and aerial photographs. 3. To interpret areal changes in terms of glaciological and topographical controls on different glacier and debris cover types (catchment morphology, glacier structure, mass balance history, and rock wall collapse magnitude and frequency). 4. To understand the effect of debris cover on glacier dynamics and geomorphological evolution, related to insulation-related modifications to AAR, long profiles, and length changes on both short and long timescales. This includes investigation of the characteristics of debris-covered glacier depositional systems resulting from their modified dynamics.

7. Spectromicroscopy Mapping of Colloidal/Particulate Organic Matter in Lake Brienz, Switzerland

SciTech Connect

Schäfer,T.; Chanudet, V.; Claret, F.; Filella, M.

2007-01-01

Transmission electron microscopy (TEM), soft X-ray scanning transmission X-ray microscopy (STXM), and {mu}-FTIR spectromicroscopy were used to map colloidal/particulate material in an ultra-oligotrophic lake, Lake Brienz, Switzerland, with a special focus on organic functionality. Within the statistical margin of error and the uncertainties arising from the representativeness of the results, the research reveals that organic material was associated with potassium-rich inorganic colloids present in surface and deep water (depths of 1 and 100 m, respectively), which indicates a vertical transfer of aggregates by sedimentation. Pure organic colloids could only be detected in surface waters. In addition, correlation map analysis of synchrotron-based {mu}-FTIR and carbon K-edge STXM spectromicroscopic data using spectra from the Luetschine and Aare Rivers as target spectra revealed spectral similarities with organic components from both tributary rivers in deeper regions (100 m) of the lake. The results prove that STXM and {mu}-FTIR can characterize colloidal and particulate organic material in low organic carbon systems.

8. Investigation of source location determination from Magsat magnetic anomalies: The Euler method approach

NASA Technical Reports Server (NTRS)

Ravat, Dhananjay

1996-01-01

The applicability of the Euler method of source location determination was investigated on several model situations pertinent to satellite-data scale situations as well as Magsat data of Europe. Our investigations enabled us to understand the end-member cases for which the Euler method will work with the present satellite magnetic data and also the cases for which the assumptions implicit in the Euler method will not be met by the present satellite magnetic data. These results have been presented in one invited lecture at the Indo-US workshop on Geomagnetism in Studies of the Earth's Interior in August 1994 in Pune, India, and at one presentation at the 21st General Assembly of the IUGG in July 1995 in Boulder, CO. A new method, called Anomaly Attenuation Rate (AAR) Method (based on the Euler method), was developed during this study. This method is scale-independent and is appropriate to locate centroids of semi-compact three dimensional sources of gravity and magnetic anomalies. The method was presented during 1996 Spring AGU meeting and a manuscript describing this method is being prepared for its submission to a high-ranking journal. The grant has resulted in 3 papers and presentations at national and international meetings and one manuscript of a paper (to be submitted shortly to a reputable journal).

9. β3 Receptors: Role in Cardiometabolic Disorders

PubMed Central

Bhadada, Shraddha V.; Patel, Bhoomika M.; Mehta, Anita A.; Goyal, Ramesh K.

2011-01-01

Pharmacological and molecular approaches have shown that an atypical β-adrenoceptor (AR), called β3-AR, that is distinct from β1-ARs and β2-ARs, exists in some tissues in heterogeneous populations such as β3a-ARs and β3b-ARs. β3-ARs belong to a superfamily of receptors linked to guanine nucleotide binding proteins (G proteins). The β3-AR gene contains two introns whereas the β1-AR and β2-AR genes are intronless, leading to splice variants. β3-ARs can couple to Gi and Gs and they are reported to be present in brown adipose tissue, vasculature, the heart, among other tissues. β3-ARs cause vasodilation of microvessels in the islets of Langerhans and may participate in the pathogenesis of cardiac failure, during which modification of β1-AR and β2-AR expression occurs. The development of β3-AR agonists has led to the elaboration of promising new drugs, including antiobesity and antidiabetic drugs. This article reviews the various pharmacological actions of β3-ARs and their clinical implications for diabetes and cardiovascular diseases. PMID:23148172

10. Effect of axle misalignments on rolling resistance and wheel wear

SciTech Connect

Leary, J.F.; Wilson, N.G.

1985-01-01

High energy costs impacting the railroad industry and the use of rail lubrication to lower energy consumption have led to investigation of axle misalignment as a cause of train resistance and wear. This paper brings together the results of field and laboratory misalignment tests designed to measure the effects of axle misalignment on roller resistance and wheel wear of standard trucks run on curved and tangent track. These tests employed the Transportation Test Center's Roll Dynamics Unit for the lab tests, an instrumented coupler for field testing, and a modified version of the AAR Curving Model to validate the RDU results and correlate them to field data. All testing was conducted at the Transportation Test Center near Pueblo, Colorado, under the sponsorship of the Association of American Railroads (RDU Test) and the Federal Railroad Administration (Track Test). During testing, deliberate misalignments were introduced in test wheelsets, and measurements were taken in field and laboratory settings. The train resistance and wheel wear data correlated well with the curving model, showing that reasonably accurate results are achievable by modeling within a common range of known conditions. The undesirable effects of axle misalignment on train resistance and wear were confirmed.

11. Autonomous Aerial Refueling Ground Test Demonstration--A Sensor-in-the-Loop, Non-Tracking Method.

PubMed

Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

2015-01-01

An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously. PMID:25970254

12. Alpha1-adrenoreceptor in human hippocampus: binding and receptor subtype mRNA expression.

PubMed

Szot, Patricia; White, Sylvia S; Greenup, J Lynne; Leverenz, James B; Peskind, Elaine R; Raskind, Murray A

2005-10-01

Alpha1-adrenoreceptors (AR), of which three subtypes exist (alpha1A-, alpha1B- and alpha1D-AR) are G-protein-coupled receptors that mediate the actions of norepinephrine and epinephrine both peripherally and centrally. In the CNS, alpha1-ARs are found in the hippocampus where animal studies have shown the ability of alpha1-AR agents to modulate long-term potentiation and memory; however, the precise distribution of alpha1-AR expression and its subtypes in the human brain is unknown making functional comparisons difficult. In the human hippocampus, 3H-prazosin (alpha1-AR antagonist) labels only the dentate gyrus (molecular, granule and polymorphic layers) and the stratum lucidum of the CA3 homogeneously. Human alpha1A-AR mRNA in the hippocampus is observed only in the dentate gyrus granule cell layer, while alpha1D-AR mRNA expression is observed only in the pyramidal cell layers of CA1, CA2 and CA3, regions where 3H-prazosin did not bind. alpha1B-AR mRNA is not expressed at detectable levels in the human hippocampus. These results confirm a difference in hippocampal alpha1-AR localization between rat and humans and further describe a difference in the localization of the alpha1A- and alpha1D-AR mRNA subtype between rats and humans. PMID:16039007

13. Optical Remote Sensing of Glacier Characteristics: A Review with Focus on the Himalaya

PubMed Central

Racoviteanu, Adina E.; Williams, Mark W.; Barry, Roger G.

2008-01-01

The increased availability of remote sensing platforms with appropriate spatial and temporal resolution, global coverage and low financial costs allows for fast, semi-automated, and cost-effective estimates of changes in glacier parameters over large areas. Remote sensing approaches allow for regular monitoring of the properties of alpine glaciers such as ice extent, terminus position, volume and surface elevation, from which glacier mass balance can be inferred. Such methods are particularly useful in remote areas with limited field-based glaciological measurements. This paper reviews advances in the use of visible and infrared remote sensing combined with field methods for estimating glacier parameters, with emphasis on volume/area changes and glacier mass balance. The focus is on the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor and its applicability for monitoring Himalayan glaciers. The methods reviewed are: volumetric changes inferred from digital elevation models (DEMs), glacier delineation algorithms from multi-spectral analysis, changes in glacier area at decadal time scales, and AAR/ELA methods used to calculate yearly mass balances. The current limitations and on-going challenges in using remote sensing for mapping characteristics of mountain glaciers also discussed, specifically in the context of the Himalaya.

14. Evaluating flow laws for dynamically recrystallized quartz based on field data

NASA Astrophysics Data System (ADS)

Peters, Max; Herwegh, Marco

2013-04-01

The extrapolation of experimentally controlled deformation conditions, and the resulting relations between physical parameters acting during ductile deformation, to nature is considered controversial (see Herwegh et al., 2005 and references therein). Whereas the relationship between flow stress and recrystallized grain size can be empirically derived from lab experiments using paleopiezometers (e.g. Stipp & Tullis, 2003), the relation between recrystallized grain size, strain rate, differential stress, temperature and activation energy for dislocation creep requires further constraints. For these relations, various power law flow laws for dynamically recrystallized quartz were proposed over the past years (Paterson & Luan, 1990; Luan & Paterson, 1992; Gleason & Tullis, 1995; Hirth et al., 2001, Rutter & Brodie, 2004). The variations in the flow laws are mainly characterized by different starting materials, experimental conditions, the activation energy for dislocation creep and the stress exponent n. In this study we compare and evaluate experimentally derived flow laws regarding their reliability for the prediction of rheology of background deformation of naturally deformed crystalline samples from mylonites of the Aar massif (Swiss Central Alps). The majority of samples comprises highly deformed rocks (e.g. Central Aare granite), which exhibit severe grain size reduction. This reduction dominantly occurred by subgrain rotation (SGR), in the case of low temperature overprint by bulging recrystallization (BLG). Towards elevated temperatures, grain boundary migration (GBM) and SGR recrystallization were active. Along the metamorphic gradient (300 - 475°C) quartz microstructures and associated recrystallized grain size distributions indicate steady state mean grain sizes. The quantification of the metamorphic gradient (temperature, pressure, water fugacity) over the sampling area allowed the application of flow laws, yielding variations of 6 orders of magnitude in

15. Morphology, sedimentology and stratigraphic implication of debris-covered glacier deposits from the LGM and Lateglacial (Eastern Alps, Austria)

NASA Astrophysics Data System (ADS)

Reitner, Jürgen M.; Seidl, Sabrina; Wagreich, Michael

2013-04-01

Understanding the genesis of Quaternary sediments is crucial for establishing a climato-stratigraphy and, further on, to infer paleoclimatic conditions, if possible. Especially diamictons in the high-mountain environment may be formed by variety of processes, i.e. glacial, periglacial and gravitational. On the other hand, the interpretation of morphological features might be ambiguous as for example ridges may document latero-frontal dump moraines, flow of a rock avalanche event or constituents of a rock-glacier. In addition, equilibrium line altitudes (ELAs) of paleo-glaciers are mostly based on calculations using the reconstructed glacier size and applying a more or less fixed accumulation area ration (e.g. AAR - method). However, such ELAs are of no use for stratigraphic correlations and climatic considerations, if the former glacial system was strongly influenced by supraglacial debris deriving from steep back walls of cirques. We present two examples of reconstructed debris-covered or more specifically debris-mantled paleo-glaciers, their geological and morphological setting as well as their documented sedimentology and morphology. The first example is from the easternmost part of the European Alps (Northern Calcareous Alps / Schneeberg mountains / Puchberg) where an up to 60 m high moraine systems of LGM age shows some striking morphological similarities with relict rock glacier. However, based especially on lithofacies analyses as well as on the lithology of the matrix a glacial genesis could be proven. Lateglacial glacier deposits from the interior of the Alps (Lienz Dolomites / area of Karlsbader Hütte) display a quite similar glacial system. The geometry of the deposits in relation to proglacial sturzstrom sediments, showing typical indications of dynamic fragmentation, and the amount of angular, passively transported clasts in the till point to a rock avalanche event which had hit the glacier surface during a glacier advance. As the glacial system shows

16. An anisotropy- based inclination shallowing correction of the Shepody Fm. of New Brunswick and Nova Scotia and the Deer Lake Group of Newfoundland, Canada.

NASA Astrophysics Data System (ADS)

Bilardello, D.; Kodama, K. P.

2006-12-01

The North American apparent polar wander path (APWP) for the upper Paleozoic is dominated by red beds, which have been reported to suffer from deposition-/ compaction- induced magnetic inclination shallowing. To apply a correction for inclination shallowing, experiments to measure the magnetic fabric of hematite have been designed and performed together with paleo-magnetic investigations on Lower Carboniferous red beds from the Shepody Fm of New Brunswick and Nova Scotia and from the Deer Lake Group of Newfoundland. The corrected poles have been plotted on the existing APWPs for comparison. In a previous anisotropy of magnetic susceptibility (AMS)-based, inclination correction of the Shepody Fm, IRM acquisition, Lowrie and fold tests revealed secondary maghemite, goethite and primary hematite as magnetic carriers, thus indicating that AMS would measure a composite fabric rather than that of hematite only. These results were confirmed by further anisotropy measurements. Anisotropy of Anhysteretic Remanence (AAR) measurements revealed an absence of fabric for maghemite, while high field (5 T) isothermal remanent magnetization (hf-IRM) anisotropy, cleaned of the low coercivity components, revealed a very distinct depositional fabric for primary hematite. An inclination correction performed using the hf-IRM anisotropy gave a similar result to the AMS-based correction (mean corrected inclinations: 29.1° for AMS and 28.8° for hf-IRM indicating respectively 11.1° and 8° of inclination shallowing). These values are consistent with results obtained from three other hematite and magnetite- bearing Lower Carboniferous rocks from North America: the A95 for the four North American paleopoles decreases from an uncorrected value of 12° to a corrected value of 4.6°. These corrections imply a ~ 6° increase in co-latitude for the average Lower Carboniferous paleopole. To determine the corrected inclinations, individual magnetic particle anisotropy of hematite must be measured

17. Irrigation channels of the Upper Rhone valley (Switzerland). Geomorphological analysis of a cultural heritage

NASA Astrophysics Data System (ADS)

Reynard, Emmanuel

2016-04-01

The Upper Rhone valley (Canton of Valais, Switzerland) is characterised by dry climatic conditions that explain the presence of an important network (about 800 km) of irrigation channels - called Bisses in the French-speaking part of the canton or Suonen in the German-speaking area - dating back to the Middle Ages. This network constitutes a cultural heritage and during the last 30 years these agricultural infrastructures have sparked a renewed interest for tourist and cultural reasons. Indeed, the paths along the channels are used as tourist trails and several abandoned channels have been renovated for tourist use. Based on an inventory of the Bisses/Suonen of Valais, the proposed communication has three aims: (1) to analyse the geomorphological context (morphometric analysis, structural geomorphology, main processes) of various types of channels and to show the impact of the geomorphological context on the building techniques; (2) to identify particularly active processes along the channels; (3) to classify the Bisses/Suonen according to their geomorphological value and to their geomorphological sensitivity, and to propose managing measures. Structural and climatic conditions influence the geomorphological context of the channels. In a structural point of view, irrigation channels are developed in three main contexts: (1) in the Aar Massif crystalline basement; (2) in the limestone and marl cover nappes of the Helvetic Alps; (3) in the metamorphic cover nappes of the Penninic domain. The Rhone River valley is boarded by two high mountain ranges: the Penninic Alps in the South and the Bernese Alps in the North. Because of rain shadow effects, the climate is relatively dry and, between Brig and Martigny, annual rainfall is not more than 600 mm at 500 m ASL and 800 mm at 1600 m ASL. Nevertheless, due to important vertical precipitation gradients annual rainfall totals are high at high altitudes. On the southern facing tributary valleys, the dry climatic conditions

18. Response of paleofloods to climate variability in alpine catchments of different size reconstructed from floodplain sediments. Similarities or differences?

NASA Astrophysics Data System (ADS)

Schulte, Lothar; Carvalho, Filipe; Llorca, Jaime; Monterrubio, Glòria; Peña, Juan Carlos; Cabrera-Medina, Paula; Gómez-Bolea, Antonio; Sánchez-García, Carlos

2016-04-01

Continuous palaeohydrological time series are generally attributed to lake sediments rather than to those of fluvial sediments. However, most of the alpine lakes analysed are fed by small catchments (few km2). Recent studies show the high potential of flood reconstruction form sedimentary floodplain proxies of mid-size catchments (hundreds of km2) when calibrated by historical sources or other markers. Despite of different catchment sizes, flood pulses achieved from lake and flood plain sediments coincides in some cases. Nevertheless, these correlations must not be taken for granted, because catchment response can be strongly influenced by local physiographic and climatic parameters such as the unequal spatial distribution of precipitation caused by summer thunderstorms and advective rainfall events. To contribute to this discussion, our study investigate new proxy data of three cores retrieved from a small basin in the Bernese Alps, fed by the alluvial fans of Eistlenbach (4 km2) and Farnigraben (2 km2) which were compared with the floodplain records from the nearby Aare (596 km2) and Lütschine (379 km2) catchments. Following the same methodology developed previously in the other alpine basins, a 3200-yr long flood series were reconstructed from sedimentary and geochemical data applying XRF-core scan techniques, conventional XRF, LOI and grain size analysis. Flood pulses were identified by 30 flood layers, and a higher number of Zr/Ti, Sr/Ti, Ca/Ti peaks and Factor 1 scores. Modern flood signals were calibrated by historical sources, maps, aerial photographs and instrumental data. Not all events were recorded by coarse-grained beds because of the spatial variations of alluvial fan channels and their connectivity to the small distal basin. Recurrence intervals of the tipping points of the fan channel oscillation are traced by key changes of sedimentation rates and facies. However, geochemical proxies correlate not only very close with the historical local data

19. The Alfvén Mission: A possible ESA M4 Mission Candidate

NASA Astrophysics Data System (ADS)

Fazakerley, Andrew; Berthomier, Matthieu; Pottelette, Raymond; Forsyth, Colin

2014-05-01

The Alfvén mission was proposed to the ESA M3 call for missions in 2010. Its scientific objective was to study the Auroral Acceleration Region (AAR), the most accessible laboratory for investigating plasmas at an interface where ideal magneto-hydrodynamics does not apply. Alfvén was designed to teach us where and how the particles that create the aurorae are accelerated, how and why they emit auroral kilometric radiation, what creates and maintains large scale electric fields aligned with the magnetic field, and to elucidate the ion outflow processes which are slowly removing the Earth's atmosphere. The auroral regions are the interface connecting the solar wind-driven collisionless magnetosphere to the collisional ionosphere at the top of Earth's atmosphere. Solar wind energy, transmitted via the magnetosphere, is dissipated in this interface, often explosively during magnetic substorms. The plasma organizes itself on a hierarchy of spatial and temporal scales, manifesting as auroral structures ranging from huge long-lived arcs to tiny flickering filaments. The only way to make substantial further progress in auroral plasma science and to elucidate the fundamental physics of the acceleration processes at the heart of magnetosphere-ionosphere coupling is to combine the advantages of high-time resolution in situ measurements (as pioneered by the FAST mission), with the advantages of multi-point measurements (as pioneered by Cluster) in one mission. The mission concept also envisages continuous auroral imaging from the spacecraft, guaranteeing an understanding of the context (auroral morphology and motion) within which the in situ plasma measurements are made, and strong coordination with the existing dense network of ground based observatories, for more detailed ionospheric and auroral information when Alfvén overflights occur. We will review the ESA M3 Alfvén concept, consider recent scientific progress in this area, and discuss possible developments of the

20. The resurgence of A2B adenosine receptor signaling

PubMed Central

Aherne, Carol M.; Kewley, Emily M.; Eltzschig, Holger K.

2010-01-01

Since its discovery as a low-affinity adenosine receptor (AR), the A2B receptor (A2BAR), has proven enigmatic in its function. The previous discovery of the A2AAR, which shares many similarities with the A2BAR but demonstrates significantly greater affinity for its endogenous ligand, led to the original perception that the A2BAR was not of substantial physiologic relevance. In addition, lack of specific pharmacological agents targeting the A2BAR made its initial characterization challenging. However, the importance of this receptor was reconsidered when it was observed that the A2BAR is highly transcriptionally regulated by factors implicated in inflammatory hypoxia. Moreover, the notion that during ischemia or inflammation extracellular adenosine is dramatically elevated to levels sufficient for A2BAR activation, indicated that A2BAR signaling may be important to dampen inflammation particularly during tissue hypoxia. In addition, the recent advent of techniques for murine genetic manipulation along with development of pharmacological agents with enhanced A2BAR specificity has provided invaluable tools for focused studies on the explicit role of A2BAR signaling in different disease models. Currently, studies performed with combined genetic and pharmacological approaches have demonstrated that A2BAR signaling plays a tissue protective role in many models of acute diseases e.g. myocardial ischemia, or acute lung injury. These studies indicate that the A2BAR is expressed on a wide variety of cell types and exerts tissue/cell specific effects. This is an important consideration for future studies where tissue or cell type specific targeting of the A2BAR may be used as therapeutic approach. PMID:20546702

1. Evaluation of continuous low dose rate versus acute single high dose rate radiation combined with oncolytic viral therapy for prostate cancer

PubMed Central

LIU, CHUNYAN; ZHANG, YONGGANG; LIU, MINZHI MAGGIE; ZHOU, HAOMING; CHOWDHURY, WASIM H.; LUPOLD, SHAWN E.; DEWEESE, TED L.; RODRIGUEZ, RONALD

2011-01-01

Purpose Conditionally Replicative Adenovirus (CRAd) has been previously demonstrated to augment the activity of radiation, resulting in synergy of cell kill. However, previous models combining radiation with CRAd have not focused on the methods of radiation delivery. Materials and methods We model the combination of a novel prostate-specific CRAd, Ad5 PSE/PBN E1A-AR (Ad5: adenovirus 5; PSE: prostate-specific enhancer; PBN: rat probasin promoter; E1A: early region 1A; AR: androgen receptor), with radiation delivered both acutely and continuously, in an effort to better mimic the potential clinical modes of prostate cancer radiotherapy. Results We demonstrate that pre-treatment of cells with acute single high dose rate (HDR) radiation 24 hours prior to viral infection results in significantly enhanced viral replication and virus-mediated cell death. In addition, this combination causes increased level of γ-H2AX (Phosphorylated histone protein H2AX on serine 139), a marker of double-stranded DNA damage and an indirect measure of nuclear fragmentation. In contrast, continuous low dose rate (LDR) radiation immediately following infection of the same CRAd results in no enhancement of viral replication, and only additive effects in virus-mediated cell death. Conclusions These data provide the first direct assessment of the real-time impact of radiation on viral replication and the first comparison of the effect of radiation delivery on the efficacy of CRAd virotherapy. Our data demonstrate substantial differences in CRAd efficacy based on the mode of radiation delivery. PMID:20201650

2. Identification of long chain specific aldehyde reductase and its use in enhanced fatty alcohol production in E. coli.

PubMed

Fatma, Zia; Jawed, Kamran; Mattam, Anu Jose; Yazdani, Syed Shams

2016-09-01

Long chain fatty alcohols have wide application in chemical industries and transportation sector. There is no direct natural reservoir for long chain fatty alcohol production, thus many groups explored metabolic engineering approaches for its microbial production. Escherichia coli has been the major microbial platform for this effort, however, terminal endogenous enzyme responsible for converting fatty aldehydes of chain length C14-C18 to corresponding fatty alcohols is still been elusive. Through our in silico analysis we selected 35 endogenous enzymes of E. coli having potential of converting long chain fatty aldehydes to fatty alcohols and studied their role under in vivo condition. We found that deletion of ybbO gene, which encodes NADP(+) dependent aldehyde reductase, led to >90% reduction in long chain fatty alcohol production. This feature was found to be strain transcending and reinstalling ybbO gene via plasmid retained the ability of mutant to produce long chain fatty alcohols. Enzyme kinetic study revealed that YbbO has wide substrate specificity ranging from C6 to C18 aldehyde, with maximum affinity and efficiency for C18 and C16 chain length aldehyde, respectively. Along with endogenous production of fatty aldehyde via optimized heterologous expression of cyanobaterial acyl-ACP reductase (AAR), YbbO overexpression resulted in 169mg/L of long chain fatty alcohols. Further engineering involving modulation of fatty acid as well as of phospholipid biosynthesis pathway improved fatty alcohol production by 60%. Finally, the engineered strain produced 1989mg/L of long chain fatty alcohol in bioreactor under fed-batch cultivation condition. Our study shows for the first time a predominant role of a single enzyme in production of long chain fatty alcohols from fatty aldehydes as well as of modulation of phospholipid pathway in increasing the fatty alcohol production.

3. The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis.

PubMed

Caetano-Anollés, Gustavo; Kim, Kyung Mo; Caetano-Anollés, Derek

2012-02-01

The complexity of modern biochemistry developed gradually on early Earth as new molecules and structures populated the emerging cellular systems. Here, we generate a historical account of the gradual discovery of primordial proteins, cofactors, and molecular functions using phylogenomic information in the sequence of 420 genomes. We focus on structural and functional annotations of the 54 most ancient protein domains. We show how primordial functions are linked to folded structures and how their interaction with cofactors expanded the functional repertoire. We also reveal protocell membranes played a crucial role in early protein evolution and show translation started with RNA and thioester cofactor-mediated aminoacylation. Our findings allow elaboration of an evolutionary model of early biochemistry that is firmly grounded in phylogenomic information and biochemical, biophysical, and structural knowledge. The model describes how primordial α-helical bundles stabilized membranes, how these were decorated by layered arrangements of β-sheets and α-helices, and how these arrangements became globular. Ancient forms of aminoacyl-tRNA synthetase (aaRS) catalytic domains and ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein synthesis and the ability to generate a code for specificity in their active sites. These structures diversified producing cofactor-binding molecular switches and barrel structures. Accretion of domains and molecules gave rise to modern aaRSs, NRPS, and ribosomal ensembles, first organized around novel emerging cofactors (tRNA and carrier proteins) and then more complex cofactor structures (rRNA). The model explains how the generation of protein structures acted as scaffold for nucleic acids and resulted in crystallization of modern translation.

4. On noise in time-delay integration CMOS image sensors

NASA Astrophysics Data System (ADS)

Levski, Deyan; Choubey, Bhaskar

2016-05-01

Time delay integration sensors are of increasing interest in CMOS processes owing to their low cost, power and ability to integrate with other circuit readout blocks. This paper presents an analysis of the noise contributors in current day CMOS Time-Delay-Integration image sensors with various readout architectures. An analysis of charge versus voltage domain readout modes is presented, followed by a noise classification of the existing Analog Accumulator Readout (AAR) and Digital Accumulator Readout (DAR) schemes for TDI imaging. The analysis and classification of existing readout schemes include, pipelined charge transfer, buffered direct injection, voltage as well as current-mode analog accumulators and all-digital accumulator techniques. Time-Delay-Integration imaging modes in CMOS processes typically use an N-number of readout steps, equivalent to the number of TDI pixel stages. In CMOS TDI sensors, where voltage domain readout is used, the requirements over speed and noise of the ADC readout chain are increased due to accumulation of the dominant voltage readout and ADC noise with every stage N. Until this day, the latter is the primary reason for a leap-back of CMOS TDI sensors as compared to their CCD counterparts. Moreover, most commercial CMOS TDI implementations are still based on a charge-domain readout, mimicking a CCD-like operation mode. Thus, having a good understanding of each noise contributor in the signal chain, as well as its magnitude in different readout architectures, is vital for the design of future generation low-noise CMOS TDI image sensors based on a voltage domain readout. This paper gives a quantitative classification of all major noise sources for all popular implementations in the literature.

5. An asymmetric underlying rule in the assignment of codons: Possible clue to a quick early evolution of the genetic code via successive binary choices

PubMed Central

Delarue, Marc

2007-01-01

Aminoacyl-tRNA synthetases (aaRSs) are responsible for creating the pool of correctly charged aminoacyl-tRNAs that are necessary for the translation of genetic information (mRNA) by the ribosome. Each aaRS belongs to either one of only two classes with two different mechanisms of aminoacylation, making use of either the 2′OH (Class I) or the 3′OH (Class II) of the terminal A76 of the tRNA and approaching the tRNA either from the minor groove (2′OH) or the major groove (3′OH). Here, an asymmetric pattern typical of differentiation is uncovered in the partition of the codon repertoire, as defined by the mechanism of aminoacylation of each corresponding tRNA. This pattern can be reproduced in a unique cascade of successive binary decisions that progressively reduces codon ambiguity. The deduced order of differentiation is manifestly driven by the reduction of translation errors. A simple rule can be defined, decoding each codon sequence in its binary class, thereby providing both the code and the key to decode it. Assuming that the partition into two mechanisms of tRNA aminoacylation is a relic that dates back to the invention of the genetic code in the RNA World, a model for the assignment of amino acids in the codon table can be derived. The model implies that the stop codon was always there, as the codon whose tRNA cannot be charged with any amino acid, and makes the prediction of an ultimate differentiation step, which is found to correspond to the codon assignment of the 22nd amino acid pyrrolysine in archaebacteria. PMID:17164478

6. Communication over the Network of Binary Switches Regulates the Activation of A2A Adenosine Receptor

PubMed Central

Lee, Yoonji; Choi, Sun; Hyeon, Changbong

2015-01-01

Dynamics and functions of G-protein coupled receptors (GPCRs) are accurately regulated by the type of ligands that bind to the orthosteric or allosteric binding sites. To glean the structural and dynamical origin of ligand-dependent modulation of GPCR activity, we performed total ~ 5 μsec molecular dynamics simulations of A2A adenosine receptor (A2AAR) in its apo, antagonist-bound, and agonist-bound forms in an explicit water and membrane environment, and examined the corresponding dynamics and correlation between the 10 key structural motifs that serve as the allosteric hotspots in intramolecular signaling network. We dubbed these 10 structural motifs “binary switches” as they display molecular interactions that switch between two distinct states. By projecting the receptor dynamics on these binary switches that yield 210 microstates, we show that (i) the receptors in apo, antagonist-bound, and agonist-bound states explore vastly different conformational space; (ii) among the three receptor states the apo state explores the broadest range of microstates; (iii) in the presence of the agonist, the active conformation is maintained through coherent couplings among the binary switches; and (iv) to be most specific, our analysis shows that W246, located deep inside the binding cleft, can serve as both an agonist sensor and actuator of ensuing intramolecular signaling for the receptor activation. Finally, our analysis of multiple trajectories generated by inserting an agonist to the apo state underscores that the transition of the receptor from inactive to active form requires the disruption of ionic-lock in the DRY motif. PMID:25664580

7. Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

PubMed Central

Delvaux, Nathália; da Costa, Vanessa Duarte; da Costa, Maristella Matos; Villar, Livia Melo; Coelho, Henrique Sérgio Moraes; Esberard, Eliane Bordalo Cathalá; Flores, Priscila Pollo; Brandão-Mello, Carlos Eduardo; Villela-Nogueira, Cristiane Alves; de Almeida, Adilson José; Lampe, Elisabeth

2015-01-01

Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women. PMID:26154744

8. Comparison of Engine Cycle Codes for Rocket-Based Combined Cycle Engines

NASA Technical Reports Server (NTRS)

Waltrup, Paul J.; Auslender, Aaron H.; Bradford, John E.; Carreiro, Louis R.; Gettinger, Christopher; Komar, D. R.; McDonald, J.; Snyder, Christopher A.

2002-01-01

This paper summarizes the results from a one day workshop on Rocket-Based Combined Cycle (RBCC) Engine Cycle Codes held in Monterey CA in November of 2000 at the 2000 JANNAF JPM with the authors as primary participants. The objectives of the workshop were to discuss and compare the merits of existing Rocket-Based Combined Cycle (RBCC) engine cycle codes being used by government and industry to predict RBCC engine performance and interpret experimental results. These merits included physical and chemical modeling, accuracy and user friendliness. The ultimate purpose of the workshop was to identify the best codes for analyzing RBCC engines and to document any potential shortcomings, not to demonstrate the merits or deficiencies of any particular engine design. Five cases representative of the operating regimes of typical RBCC engines were used as the basis of these comparisons. These included Mach 0 sea level static and Mach 1.0 and Mach 2.5 Air-Augmented-Rocket (AAR), Mach 4 subsonic combustion ramjet or dual-mode scramjet, and Mach 8 scramjet operating modes. Specification of a generic RBCC engine geometry and concomitant component operating efficiencies, bypass ratios, fuel/oxidizer/air equivalence ratios and flight dynamic pressures were provided. The engine included an air inlet, isolator duct, axial rocket motor/injector, axial wall fuel injectors, diverging combustor, and exit nozzle. Gaseous hydrogen was used as the fuel with the rocket portion of the system using a gaseous H2/O2 propellant system to avoid cryogenic issues. The results of the workshop, even after post-workshop adjudication of differences, were surprising. They showed that the codes predicted essentially the same performance at the Mach 0 and I conditions, but progressively diverged from a common value (for example, for fuel specific impulse, Isp) as the flight Mach number increased, with the largest differences at Mach 8. The example cases and results are compared and discussed in this paper.

9. Reconstitution of Protein Translation of Mycobacterium Reveals Functional Conservation and Divergence with the Gram-Negative Bacterium Escherichia coli.

PubMed

Srivastava, Aashish; Asahara, Haruichi; Zhang, Meng; Zhang, Weijia; Liu, Haiying; Cui, Sheng; Jin, Qi; Chong, Shaorong

2016-01-01

Protein translation is essential for all bacteria pathogens. It has also been a major focus of structural and functional studies and an important target of antibiotics. Here we report our attempts to biochemically reconstitute mycobacterial protein translation in vitro from purified components. This mycobacterial translation system consists of individually purified recombinant translation factors from Mycobacterium tuberculosis (M. tuberculosis), purified tRNAs and ribosomes from Mycobacterium smegmatis (M. smegmatis), and an aminoacyl-tRNA synthetase (AARS) mixture from the cell-extract of M. smegmatis. We demonstrate that such mycobacterial translation system was efficient in in vitro protein synthesis, and enabled functional comparisons of translational components between the gram-positive Mycobacterium and the gram-negative E. coli. Although mycobacterial translation factors and ribosomes were highly compatible with their E. coli counterparts, M. smegmatis tRNAs were not properly charged by the E. coli AARSs to allow efficient translation of a reporter. In contrast, both E. coli and M. smegmatis tRNAs exhibited similar activity with the semi-purified M. smegmatis AARSs mixture for in vitro translation. We further demonstrated the use of both mycobacterial and E. coli translation systems as comparative in vitro assays for small-molecule antibiotics that target protein translation. While mycobacterial and E. coli translation were both inhibited at the same IC50 by the antibiotic spectinomycin, mycobacterial translation was preferentially inhibited by the antibiotic tetracycline, suggesting that there may be structural differences at the antibiotic binding sites between the ribosomes of Mycobacterium and E. coli. Our results illustrate an alternative approach for antibiotic discovery and functional studies of protein translation in mycobacteria and possibly other bacterial pathogens. PMID:27564552

10. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

PubMed Central

Liu, Yo-Tsen; Hersheson, Joshua; Plagnol, Vincent; Fawcett, Katherine; Duberley, Kate E C; Preza, Elisavet; Hargreaves, Iain P; Chalasani, Annapurna; Laurá, Matilde; Wood, Nick W; Reilly, Mary M; Houlden, Henry

2014-01-01

Background The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC). Methods We report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient. Results A novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment. Conclusion This study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism. PMID:24218524

11. Spatiotemporal features of the auroral acceleration region as observed by Cluster

NASA Astrophysics Data System (ADS)

Sadeghi, Soheil; Marklund, Göran T.; Karlsson, Tomas; Lindqvist, Per-Arne; Nilsson, Hans; Marghitu, Octav; Fazakerley, Andrew; Lucek, Elisabeth A.

2011-12-01

A pair of negative electric potential structures associated with inverted-V aurora is investigated using electric and magnetic field, ion and electron data from the Cluster spacecraft, crossing the auroral acceleration region (AAR) at different altitudes above the Northern hemisphere midnight auroral oval. The spatial and temporal development of the acceleration structures is studied, given the magnetic conjunction opportunity and the one minute difference between the Cluster spacecraft crossings. The configuration allowed for estimation of characteristic times of development for the two structures and of the parallel electric field and potential drop for the more stable one. The first potential structure had a width of ˜80 km (projected to the ionosphere) and was relatively short-lived, developing in less than 40 s and decaying in one minute. The parallel potential drop increased between altitudes of 1.13 RE and 1.3 RE, whereas the acceleration potential above 1.3 RE remained almost unchanged during that time. This intensification occurred mainly after the time when the associated upward current had reached its maximum value. The second structure had a width of ˜50 km and was subject to an increase by a factor of 3 of the parallel potential drop below 1.3 RE, during about 40 s, after which it remained rather stable for one minute or more. Similarly here, the acceleration potential above 1.3 RE remained roughly unchanged. For the more stable second structure, an average parallel electric field between 1.13 and 1.3 RE could be estimated (˜0.56 mV/m). The conductance along the flux tube was also stable for one minute or more.

12. Cova del Rinoceront (Castelldefels, Barcelona): a terrestrial record for the Last Interglacial period (MIS 5) in the Mediterranean coast of the Iberian Peninsula

NASA Astrophysics Data System (ADS)

Daura, J.; Sanz, M.; Julià, R.; García-Fernández, D.; Fornós, J. J.; Vaquero, M.; Allué, E.; López-García, J. M.; Blain, H. A.; Ortiz, J. E.; Torres, T.; Albert, R. M.; Rodríguez-Cintas, À.; Sánchez-Marco, A.; Cerdeño, E.; Skinner, A. R.; Asmeron, Y.; Polyak, V. J.; Garcés, M.; Arnold, L. J.; Demuro, M.; Pike, A. W. G.; Euba, I.; Rodríguez, R. F.; Yagüe, A. S.; Villaescusa, L.; Gómez, S.; Rubio, A.; Pedro, M.; Fullola, J. M.; Zilhão, J.

2015-04-01

The Cova del Rinoceront, a site in NE Iberia, contains a thick sedimentary fill preserving a faunal archive from the penultimate glacial and the the last interglacial periods. Layers I to III have been dated to between 74 and 147 ka, coinciding with MIS 5a to 5e, a period poorly represented in the Mediterranean terrestrial record. The results from Cova del Rinoceront are of broader interest for the reconstruction of ecological dynamics during warm stages and the understanding of the evolution and geographical variation of several taxa. The palaeoecological evidence suggests a landscape dominated by mixed wooded vegetation with mild climatic conditions, slightly more humid than today. Several vertebrate taxa, including Haploidoceros mediterraneus, Stephanorhinus hundsheimensis and Glis glis, are documented for the first time in the early Upper Pleistocene of Europe, showing that these species persisted across the region for longer than previously thought. In addition, the recovery of a small lithic assemblage indicates human presence in the surroundings of the site. The 11 m-thick stratigraphic section also provides an ideal setting in which to compare several geochronological methods. U-Th dating of the flowstones that cap the deposit, of speleothems formed along the cave walls, and of speleothems buried by the deposit at different elevations provides minimum and maximum ages of 74 and 175 ka, respectively, for the accumulation. The ages obtained by luminescence, electron spin resonance (ESR), amino acid racemisation (AAR), palaeomagnetism and U-series dating of bone are in good agreement with each other and are stratigraphically consistent. This well-dated faunal succession presents a unique opportunity to assess changes in the Pleistocene fauna of the Mediterranean coast over an interval of more than 100 ka.

13. CEH-GEAR: 1 km resolution daily and monthly areal rainfall estimates for the UK for hydrological and other applications

NASA Astrophysics Data System (ADS)

Keller, V. D. J.; Tanguy, M.; Prosdocimi, I.; Terry, J. A.; Hitt, O.; Cole, S. J.; Fry, M.; Morris, D. G.; Dixon, H.

2015-06-01

The Centre for Ecology & Hydrology - Gridded Estimates of Areal Rainfall (CEH-GEAR) data set was developed to provide reliable 1 km gridded estimates of daily and monthly rainfall for Great Britain (GB) and Northern Ireland (NI) (together with approximately 3500 km2 of catchment in the Republic of Ireland) from 1890 onwards. The data set was primarily required to support hydrological modelling. The rainfall estimates are derived from the Met Office collated historical weather observations for the UK which include a national database of rain gauge observations. The natural neighbour interpolation methodology, including a normalisation step based on average annual rainfall (AAR), was used to generate the daily and monthly rainfall grids. To derive the monthly estimates, rainfall totals from monthly and daily (when complete month available) rain gauges were used in order to obtain maximum information from the rain gauge network. The daily grids were adjusted so that the monthly grids are fully consistent with the daily grids. The CEH-GEAR data set was developed according to the guidance provided by the British Standards Institution. The CEH-GEAR data set contains 1 km grids of daily and monthly rainfall estimates for GB and NI for the period 1890-2012. For each day and month, CEH-GEAR includes a secondary grid of distance to the nearest operational rain gauge. This may be used as an indicator of the quality of the estimates. When this distance is greater than 100 km, the estimates are not calculated due to high uncertainty. CEH-GEAR is available from doi:10.5285/5dc179dc-f692-49ba-9326-a6893a503f6e and is free of charge for commercial and non-commercial use subject to licensing terms and conditions.

14. The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis.

PubMed

Caetano-Anollés, Gustavo; Kim, Kyung Mo; Caetano-Anollés, Derek

2012-02-01

The complexity of modern biochemistry developed gradually on early Earth as new molecules and structures populated the emerging cellular systems. Here, we generate a historical account of the gradual discovery of primordial proteins, cofactors, and molecular functions using phylogenomic information in the sequence of 420 genomes. We focus on structural and functional annotations of the 54 most ancient protein domains. We show how primordial functions are linked to folded structures and how their interaction with cofactors expanded the functional repertoire. We also reveal protocell membranes played a crucial role in early protein evolution and show translation started with RNA and thioester cofactor-mediated aminoacylation. Our findings allow elaboration of an evolutionary model of early biochemistry that is firmly grounded in phylogenomic information and biochemical, biophysical, and structural knowledge. The model describes how primordial α-helical bundles stabilized membranes, how these were decorated by layered arrangements of β-sheets and α-helices, and how these arrangements became globular. Ancient forms of aminoacyl-tRNA synthetase (aaRS) catalytic domains and ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein synthesis and the ability to generate a code for specificity in their active sites. These structures diversified producing cofactor-binding molecular switches and barrel structures. Accretion of domains and molecules gave rise to modern aaRSs, NRPS, and ribosomal ensembles, first organized around novel emerging cofactors (tRNA and carrier proteins) and then more complex cofactor structures (rRNA). The model explains how the generation of protein structures acted as scaffold for nucleic acids and resulted in crystallization of modern translation. PMID:22210458

15. Reconstitution of Protein Translation of Mycobacterium Reveals Functional Conservation and Divergence with the Gram-Negative Bacterium Escherichia coli

PubMed Central

Srivastava, Aashish; Asahara, Haruichi; Zhang, Meng; Zhang, Weijia; Liu, Haiying; Cui, Sheng; Jin, Qi; Chong, Shaorong

2016-01-01

Protein translation is essential for all bacteria pathogens. It has also been a major focus of structural and functional studies and an important target of antibiotics. Here we report our attempts to biochemically reconstitute mycobacterial protein translation in vitro from purified components. This mycobacterial translati
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