Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Activating mutations of PIK3CA, the gene encoding the p110α subunit of PI3K, are frequent in breast cancer and selective inhibitors of this enzyme have shown promising clinical activity in breast tumors harboring these mutations. We studied the case of a patient with metastatic breast cancer harboring a PIK3CA mutation that was treated in a clinical trial with BYL719, a highly selective PI3Kα inhibitor. The treatment resulted in a robust partial response that lasted 7 months followed by rapid progression and death. A rapid autopsy was performed with collection of tissue samples from 16 different metastatic sites. We compared by whole genome and exome sequencing the original primary tumor, a rapidly progressing lung metastasis and a periaortic lesion that was still responding to BYL719 at time of death. Besides several common alterations, PTEN loss and a missense mutation were detected only in the lung metastasis. Using targeted exome sequencing we analyzed all the other available samples. Strikingly, we observed a consistent loss in PTEN (via different mechanisms such as deletion, splice site mutation and frameshift mutations) in all the lesions refractory to BYL719 but not in the responding ones. In every case, the loss of PTEN was also documented by lack of protein expression by immunohistochemistry (IHC). Finally, we were able to build a dendrogram showing the phylogenetic evolution of the lesions and the evolutionary convergence of the PTEN alterations.

To validate PTEN loss as a possible mechanism of acquired resistance to selective PI3Kα inhibition, we generated doxycycline-inducible PTEN shRNA stable clones starting from three different BYL719-sensitive cell lines. In all the studied models, induction of PTEN shRNA resulted in resistance to BYL719.

Since PTEN deficient genetic models have been shown to rely on the β subunit of the PI3K holoenzyme, we tested whether the concomitant inhibition of both p110α and p110β was sufficient to revert the resistant phenotype. BKM120 (a pan-PI3K inhibitor) or the addition of AZD6482 (p110β inhibitor) to BYL719 re-sensitized the cells to BYL719.

To expand our findings in vivo, we generated a patient-derived xenograft (PDX) model from a PTEN-null non-responding lesion (lung). Consistently, this PDX model was refractory to the antitumor activity of BYL719 but conserved sensitivity to BKM120 or the combination of AZD6482 and BYL719. In both cases, IHC analysis revealed a decrease in PI3K/AKT downstream effectors pPRAS40 (246) and pS6 (240/4) staining with BKM120 or AZD6482+BYL719, but not with BYL719 alone.

Preliminary analyses of other samples collected from patients treated with BYL719 suggest that PTEN loss is a relatively frequent event upon therapy progression.

Taken together, the different mechanisms that inactivate PTEN in the tumor treated with BYL719 can be explained by convergent phenotypic evolution in a heterogeneous tumor and highlight the importance of PTEN and PI3Kβ in acquired resistance to PI3Kα inhibitors.

Citation Format: Pau Castel, Dejan Juric, Helen Won, Benjamin Ainscough, Haley Ellis, Saya Ebbesen, Malachi Griffith, Obi Griffith, Iyer Gopakumar, Dennis Sgroi, Steven Isakoff, Elaine Mardis, David Solit, Scott Lowe, Cornelia Quadt, Malte Peters, Michael Berger, Maurizio Scaltriti, Jose Baselga. Loss of PTEN leads to clinical resistance to the PI3Kα inhibitor BYL719 and provides evidence of convergent evolution under selective therapeutic pressure. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-327. doi:10.1158/1538-7445.AM2014-LB-327


Abstract. Multi-millennial environmental and climatic changes in central Chilean Patagonia (44–49° S) during the Last Glacial–Interglacial cycle have been of particular interest as changes in the position and strength of the southern westerlies are the major forcing factor conditioning the environmental dynamics. Recent attempts to reconstruct regional environmental and climatic signals from central Chilean Patagonia reveal some discrepancies and unclear issues among the records. This paper presents the 13 ka pollen and charcoal records from Mallin El Embudo (44° 40' S, 71° 42' W) located in the deciduous Nothofagus forest in the middle Rio Cisnes valley. The paper aims to (1) establish the timing and magnitude of local vegetation changes and fire activity since the Late Glacial and (2) integrate these results at the regional scale in order to discuss the discrepancies and depict the environmental and climatic dynamics in central Chilean Patagonia since the Late Glacial. Open landscapes dominated by grasses associated with scattered Nothofagus forest patches dominated the middle Rio Cisnes valley between 13 and 11.2 ka suggesting low effective moisture but also indicating that landscape configuration after glacial retreat was still ongoing. At 11.2 ka, the sudden development of an open and quite dynamic Nothofagus forest probably associated with the synchronous high fire activity occurred, suggesting a rise in effective moisture associated with dry summers. Since 9.5 ka, the record reflects the presence of a closed Nothofagus forest related to higher effective moisture conditions than before combined with moderate dry summers that may have triggered a high frequency of low-magnitude crown fires that did not severely affect the forest. The forest experienced a slight canopy opening after 5.7 ka, probably due to slightly drier conditions than before followed by a sudden change to open forest conditions around 4.2 ka associated with fire and volcanic disturbances. Around 2 ka, the recovery of a closed Nothofagus forest related to slightly wetter conditions (similar to present) occurred and persisted under highly variable climatic conditions up to 0.1 ka when massive forest burning and logging due to European settlements occurred. Central Chilean Patagonian climatic and environmental changes at millennial–centennial timescales since the Late Glacial were driven by changes in the southern westerlies latitudinal position and/or intensity, but during the late Holocene fire, volcanism and humans arose as forces contributing to environmental dynamics.


Method configuration is a specific type of Method Engineering (ME) that takes an existing organization-wide Information Systems Development Method (ISDM) as its point of departure. Existing assembly-based ME approaches are not well suited to this task. As an alternative, this article suggests a metamethod approach to tailoring organization-wide ISDMs. We refer to this approach as the Method for Method Configuration (MMC). MMC takes into account the need to combine structure, which is one reason for choosing an organization-wide ISDM in the first place, with flexibility, which is essential for making the chosen ISDM fit actual projects. The metamethod is built using a three-layered reuse model comprising method components, configuration packages, and configuration templates. These concepts are combined efficiently to produce a situational method and thereby to facilitate the work of method engineers.


The European League Against Rheumatism (EULAR) recently updated the recommendations for cardiovascular disease (CVD) risk management in patients with rheumatoid arthritis (RA).1 In contrast to the 2009 recommendations which advised to multiply by 1.5 the global CVD risk in the presence of certain RA-specific criteria,2 the 2015/2016 update recommends to multiply by 1.5 the global CVD risk for all patients with RA. It also considers the use of carotid ultrasound to screen asymptomatic atherosclerotic plaques. Indeed, the majority of the CVD events occur in the 'low' and 'intermediate' risk groups and carotid plaque detection to classify patients improves cardiovascular risk prediction.3 The European Society of Cardiology guidelines classify patients with carotid plaque at very high CVD risk.4 Immediate statin use is indicated in those patients if low-density lipoprotein cholesterol is ≥0.7 g/L.4 In a post hoc analysis, we evaluated the impact of the updated 2015/2016 EULAR CVD recommendations …


Grafting has proven to mitigate some soil-borne diseases and abiotic stresses as well as improve plant growth, yield and fruit quality. However, in Tanzania the effect of grafting on plant growth, yield and fruit quality of hybrid tomato cultivars is not yet fully explored. Therefore, the objective of this study was to evaluate the effect of grafting eggplant rootstocks on plant growth, yield and fruit quality of hybrid tomato cultivars grown in Tanzania. The study was conducted at Sokoine University of Agriculture in Morogoro, Tanzania, and the experiment was laid out in a Randomized Complete Block Design with eight treatments each replicated three times. Hybrid tomato cv. Assila and Monica were each cleft-grafted onto eggplant EG190, EG195 and EG203 rootstocks and transplanted in the open field. Ungrafted plants of the same tomato cultivars were used as controls. Data were subjected to Analysis of Variance using GenStat v.14 statistical package (VSN International, UK) and treatment means were separated based on Tukey's Test at P≤0.05. Results reveal that grafting eggplant EG190, EG195 and EG203 rootstocks significantly reduced total fruit yield (p = 0.001) and marketable yield (p = 0.001) for all tomato cultivars but significantly (p = 0.001) increased total soluble solids contents for all tomato cultivars, and titratable acidity for Monica in comparison to ungrafted controls. Further studies are required to determine rootstocks that are vigorous enough to carry scions of these hybrid tomato cultivars for yield improvement. Keywords: Marketable yield, Diameter, Firmness, Assila, Monica, Total soluble solids, Titratable acidity


This article explores a possible methodological framework for investigating verbal theatre language. Using an interdisciplinary approach, combining theatre studies with sociolinguistics, it is possible to increase knowledge about conventions and changes in Norwegian theatre language in the 20th century. I will demonstrate how sociolinguistics can provide a broader understanding of the development in Norwegian theatre, through investigating socially meaningful variation in theatre language.


Women run screaming from their village at night, leaving all their clothes behind-possessed by spirits of the wilderness, they climb up a barana tree. It is but one of the fascinating rituals of the Toraja people described in this study. The Toraja people live in the mountainous region of South Sulawesi, Indonesia. Their religion is an ancient one predating the Hindu and Buddhist religions that arrived in Indonesia some 1,500 years ago. It is marked by a dualism in male and female elements, a characteristic of rituals the older people in the western Toraja region, Mamasa, still remember. Three rituals, the headhunting, fertility, and tree-climbing rites, are dealt with in detail, while in the marriage, childbirth, and mortuary rituals point to a shift in Toraja beliefs. Where once both earth and celestial deities were expected to bless ritual participants, the Toraja, influenced by developments in their physical environment, now devote their attention to the deities of the heavens, while those of the earth are disappearing.


In this study, efficiency of AMMI method and pattern analysis were investigated. Seventeen sugar beet varieties were studied in thirteen locations over three cropping seasons and root yield and sugar content were measured. On the basis of combined analysis of variance, effect of variety and variety ×environment interactions for both traits were significant. The yield stabitity estimated-using Eberhart and Russell, Wricke's Ecovalance, Shukla's stabilty variance, AMMI and pattern analysis methods. In all stability methods used, varieties PP8, BR1(developed is Ardabil) and IC1 were the most stable genotypes. Efficiency of Eberhart and Russell's method for estimating of G × E interaction for both traits was lower than IPC1 in AMMI method. The efficiency of IPC1 was greater, by five to six times, than that of Eberhart and Russell's method for root yield and sugar content, respectively. SIPC3 in AMMI method were accounted about 50 % of G × E interaction sum of squars. Biplot of IPC1 and the mean of traits for varieties and locations or environments had good efficiency for detecting of G × E interaction patterns. Ranked correlation coefficients showed that AMMI method often generated more information than the other methods. Furthermore, this method generates new information which cannot be estimated by the other methods. It seems that AMMI and pattern analysis have higher efficiency for stability studies. However, results showed that using only one component of AMMI method is insufficient, and at two components (e.g. IPC1 and SIPCf) should be considered.


With infrared and terahertz ellipsometry we investigated the anisotropy of the infrared active phonon modes in SrTiO3 (110) single crystals in the tetragonal state below the so-called antiferrodistortive transition at T* = 105 K. In particular, we show that the anisotropy of the oscillator strength of the so-called R-mode, which becomes weakly infrared active below T*, is a valuable indicator for the orientation of the structural domains. Our results reveal that a mono-domain state with the tetragonal axis (c-axis) parallel to the [001] direction can be created by applying a moderate uniaxial stress of about 2.3 MPa along the [1-10] direction (with a mechanical clamp). The resulting, intrinsic splitting of the infrared-active phonon modes is reported.


Dehydration is widely involved in tobacco processing such as tobacco leaf curing, tobacco trip redrying and cut tobacco drying, which plays a key role due to its effect on the physical and chemical quality of tobacco. The current drying methods in tobacco processing mainly use heat conduction, heat convection or their combination to dehydrate tobacco materials. However, radiation heat transfer as one of basic heat transferways has not been investigated in the tobacco drying. In the present work, infrared radiation dryer was designed to explore the tobacco infrared radiation drying characteristics. The effect of radiation heat transfer conditions and vacuum on the drying kinetics and temperature of tobacco leaves was investigated. Diffusion coefficient of middle tobacco leaves C2F is between 0.848×10-10 ~ 1.597×10-10 m2/s. At the same time, the pore structure andpetroleum ether tobacco extracts in dried tobacco were also analyzed in order to explore the different effects of infrared radiation drying and traditional drying technology on tobacco quality.   Keywords: Flue-cured tobacco; Infrared radiation; Vacuum; Dryingkinetics; Tobacco quality


Diarrhoea in ulcerative colitis (UC) mainly reflects impaired colonic Na+ and water absorption. Colonocyte membrane potential, an important determinant of electrogenic Na+ absorption, is reduced in UC. Colonocyte potential is principally determined by basolateral IK (KCa3.1) channel activity. To determine whether reduced Na+ absorption in UC might be associated with decreased IK channel expression and activity, we used molecular and patch clamp recording techniques to evaluate IK channels in colon from control patients and patients with active UC. In control patients, immunolabelling revealed basolateral IK channels distributed uniformly along the surface‐crypt axis, with substantially decreased immunolabelling in patients with active UC, although IK mRNA levels measured by quantitative PCR were similar in both groups. Patch clamp analysis indicated that cell conductance was dominated by basolateral IK channels in control patients, but channel abundance and overall activity were reduced by 53% (p = 0.03) and 61% (p = 0.04), respectively, in patients with active UC. These changes resulted in a 75% (p = 0.003) decrease in the estimated basolateral membrane K+ conductance in UC patients compared with controls. Levels of IK channel immunolabelling and activity in UC patients in clinical remission were similar to those in control patients. We conclude that a substantial decrease in basolateral IK channel expression and activity in active UC most likely explains the epithelial cell depolarization observed in this disease, and decreases the electrical driving force for electrogenic Na+ transport, thereby impairing Na+ absorption (and as a consequence, Cl− and water absorption) across the inflamed mucosa. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Interactive, co-creative relation of consumers, users and producers is quickly developing recently. Living Labs (LL) have a bridging role between market pull and technology push. They realise concurrent innovation. LLs are approaches to realise an interactive search for new products/services in real life milieus together with users/consumers, without mediation of marketing experts. Our presentation highlights LLs first as providers of a collaborative working environment for users. It emphasises that LLs have a strong methodology and describes and assesses the "LL Harmonization cubes". It outlines then what LLs can bring advantages for SMEs. Main added value of LLs for SMEs is that they provide for innovation services by integrating SMEs in a collaborative working environment that would otherwise not available for them.


This paper presents a methodology for rapidly analyzing the effect of blending damaged compressor blades on structural integrity. Heavy duty gas turbine compressor blades are subjected to damage from numerous sources. Compressor blades are blended in the field to allow continued operation with minimal risk of failure. By constructing analysis models parametrically, blend limits may be rapidly and reliably established for an entire compressor.Erosion from washing or fogging, foreign object impacts, icing, tip rubs, and clash can damage both stator vanes and blades. Replacement of blades and stator vanes is very costly. The blades on some engines cannot be removed without de-stacking the rotor. The high cost of replacement provides an incentive to determine blend limits that do not compromise mechanical integrity. Field service support of compressor hardware includes the evaluation of compressor damage and the determination of whether such damage can be blended out in situ. Compressors on F-class engines have more than 15 stages, so at least 30 different airfoils must be analyzed when stator vanes are included. One must consider damage in the tips as well as leading and trailing edges at numerous radii. The variation in sizes, locations, and combinations of blends coupled with the number of airfoils results in a intense analytical task. Field service must also support multiple design configurations that include original engine manufacturer (OEM) blades as well as more robust aftermarket designs.By setting up parametric analysis models of each blade, PSM has been able to provide its field service support group with accurate blend limits and has created a tool with which nonstandard blends may be evaluated in nearly real-time. This paper presents a methodology which has been applied to an entire compressor. A pre-stressed large-displacement modal analysis was performed which includes contact effects and considers a wide range of operating speeds using the linear perturbation technique. Combinations of parametrically defined blends are analyzed automatically. The effects of the blends on the modal frequencies were evaluated against in-house criterion. Plots of vibratory stress capability were produced to highlight which airfoils and which portions of airfoils are vulnerable in case of damage. The parametric nature of the analysis allows the user to easily change the position size and shape of the blends. With this methodology PSM is able to rapidly evaluate blends of stator vanes and blades for whole compressors and provide reliable and timely guidance to our field service representatives.© 2012 ASME


The authors review 36 cases of intramedullary spinal tumours, 17 ependymomas, 12 astrocytomas, 6 hemangioblastomas and 1 metastasis of leiomyosarcoma. The tumours were localized in the cervical region in 19 patients, in the thoracic region in 10 in the lumbar region in 4, and in the conus medullaris in 3. All patients presented a clinical picture of myelopathy. No differences were observed between the different hystological types. In 5 patients the tumour was associated with syringomyelia and one of these patients also presented a type I Chiari malformation. All patients were submitted to surgery (using microsurgical techniques in the last seven years). Radiation therapy was also given in 16 cases. Our results demonstrate that microsurgical resection is the only treatment that significantly improves the prognosis of these patients, from both the standpoint of the functional status and survival.


In the past years, the non-conventional treatment of pesticides in wastewater like photocatalytic degradation has been the focus of the attention of researchers to mitigate its impact on both humans and the environment. In this study, synthesized graphitic carbon nitride (g-C3N4) from urea is used in the photocatalytic degradation of diazinon as a photocatalyst with the addition of ferric nitrate (Fe3(NO3)3) and potassium persulfate (K2S2O8) to enhanced degradation. Graphitic carbon nitride was produced using direct calcination of urea at 550°C for 2 h. The physicochemical properties of the synthesized g-C3N4 were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), and X-ray Diffractometer (XRD). The photocatalytic degradation of diazinon was conducted under a g-C3N4/Fe(III)/persulfate system using different parameters such as catalyst loading (75, 100, and 125 mg), Fe3(NO3)3 (325, 350, and 375 mg L–1), and K2S2O8 (275, 300, and 325 mg L–1) resulting to an improved photocatalytic degradation efficiency. The physicochemical results showed a synthesized g-C3N4 that exhibits properties that are following the international standards. The results of photocatalytic degradation showed the highest degradation of g-C3N4 at 37.3%, under the parametric conditions of 125 mg g-C3N4, 325 mg L–1 of Fe3(NO3)3, and 300 mg L–1 of K2S2O8. The degradation efficiency was observed to increase as the catalyst load increases, while an increase in degradation efficiency can only be observed up to a certain value using ferric nitrate and persulfate. Overall, this study provided insight on the possible use of urea, as a source of g-C3N4 and the use of g-C3N4 as a photocatalyst using visible light as a more economic approach and cost-efficient way of handling wastewater.


As state and local budgets tighten, municipalities have turned to civil fines and penalties to fill empty coffers. These fines and fees, often termed legal financial obligations or economic sanctions, arose as a way to shift the costs of criminal adjudication to those charged with criminal activity. But many jurisdictions are now using jail time to coerce poor, mostly minority violators of minor infractions, such as truancy fees, driving offenses, littering, and jaywalking, into paying fees they cannot afford. These fines are only the beginning, as municipalities tack on court fees, payment plan charges, other costs, and interest. Small debts spiral into enormous ones, and nonpayment can result in incarceration. Collection of these debts is often outsourced to private debt collectors, who use aggressive tactics and charge collection fees, creating a never-ending cycle of debt and incarceration. This cycle is not only devastating to the poor and poor communities, but it makes no sense, because people wind up jailed at costs far exceeding their original fines. The result is that the rich may walk away, while the poor must pay or stay.This Note explores the origins of and shift to this system of municipal fines; how the current scheme operates outside the bounds of the Constitution; its disastrous effects on poor communities, particularly communities of color; and several alternatives and avenues for legal reform.


The molten salt heat receiver performance of a solar power tower plant is analyzed in this paper. The numerical model of the heterogeneous heat flux boundary of which a half of the single heat receiver is heating and the other half of that is adiabatic heating, and of the heat convection and heat transfer in the molten salt heat receiver on condition of the convective heat loss and the radiation loss boundary conditions is established. In the numerical model, the wall heat conduction and variable property of the molten salt are considered as well as the roughness of the wall. The flow velocity, the temperature distribution and the heat transfer characteristics of the molten salt heat receiver under the conditions of high temperature and high heat flux are presented as important basis for the design and the operation control of the molten salt heat receiver.


The Burkholderia genus offers a promising potential in medicine because of the diversity of biologically active natural products encoded in its genome. Some pathogenic Burkholderia spp. biosynthesize a specific class of antimicrobial 2-alkyl-4(1H)-quinolones, i.e., 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and their N-oxide derivatives (HMAQNOs). Herein, we report the synthesis of a series of six HMAQs and HMAQNOs featuring a trans-Δ2 double bond at the C2-alkyl chain. The quinolone scaffold was obtained via the Conrad-Limpach approach, while the (E)-2-alkenyl chain was inserted through Suzuki-Miyaura cross-coupling under microwave radiation without noticeable isomerization according to the optimized conditions. Subsequent oxidation of enolate-protected HMAQs cleanly led to the formation of HMAQNOs following cleavage of the ethyl carbonate group. Synthetic HMAQs and HMAQNOs were evaluated in vitro for their antimicrobial activity against different Gram-negative and Gram-positive bacteria as well as against molds and yeasts. The biological results support and extend the potential of HMAQs and HMAQNOs as antimicrobials, especially against Gram-positive bacteria. We also confirm the involvement of HMAQs in the autoregulation of the Hmq system in Burkholderia ambifaria.


Three photothermal initiators (2959-HDHP, 184-HDHP and 1173-HDHP) were designed and synthesized from three commercial photoinitiators (Darocur 2959, Irgacure 184 and Darocur 1173) and characterized by FTIR and 1H NMR. Their absorption spectra and photocleavage processes were investigated using a UV-vis spectrometer. They showed almost the same maximum absorption peaks and much lower photocleavage rates compared with the unmodified photoinitiators respectively. The synthesized photothermal initiators exhibited good deep initiation ability, but due to the photooxidation process of Darocur 2959 which decreased its photoinitiation efficiency, 2959-HDHP showed a relatively worse performance than 184-HDHP and 1173-HDHP. The photothermal initiator 1173-HDHP realized much deeper photoinduced polymerization than the mixture of the corresponding photo- and thermal initiators. This is because for the photothermal initiator, the heat transfer from photopolymerization to the thermal initiator occurs in situ, which has a much higher efficiency than the mixed initiator system that takes place at a longer distance during thermal diffusion.


: As greater numbers of workers come under industrial hearing conservation programs, the problem of nonorganic hearing loss is become critical. The potential malingerer can be identified by behavioral observations both before and during the testing of hearing and by an analysis of test results. Manual, self-recording, and microprocessor audiometry all incorporate validity and reliability checks which assist in detecting the malingerer. Methods of documenting inaccurate hearing tests are detailed, along with ways of obtaining accurate follow-up tests. The key to alleviating the problem of malingering is early detection and immediate resolution of the problem.


Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome characterized by thepresence of a medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. MEN2A arises dueto germline missense mutations of the RET proto-oncogene. Specific RET mutations correlate with the onset of age and the aggressiveness of a medullary thyroid carcinoma. However, the clinical presentation varies even within families, where patients carry the same mutation. Recently, it has been reported that polymorphisms of RET may have a modifier effect on the presentation. We experienced a case of 42-year-old man, whose bilateral pheochromocytoma and medullary thyroid carcinoma were incidentally found. Genetic testing detected a mutation in codon 634 (C634R) and a polymorphism in codon 691 (G691S) of the RET proto-oncogene. His mother, younger brother and his only son had the same mutation and polymorphism. We report this case with a review of the literature about RET gene polymorphisms.


Report of a case of a male child, with hypotonia since birth, along with severe feeding dificulties due to lack of swallowing, that resulted in a permanent gastrostomy. Despite the delayed motor development, he had a normal intelligence. An electromyography was suggestive of primary muscle involvement. A fresh-frozen muscle biopsy stained by the modified Gomori trichrome and processed by histochemistry and electron microscopy presented the typical nemaline rods and deficiency of type II muscle fibers. It is made a brief revision about the clinical symptoms, origin and pathogenesis of nemaline bodies. The case reported probably represents a nemaline myopathy, of the congenital type.


Conventionally, toxicogenic strains of C. diphtheria, C. tetani and B. pertussis are grown on a media of animal origin for production of DTP group of vaccines. This media poses various risks such as Bovine Spongiform Encephalopathy (BSE), microbial contamination and allergic reactions. To avoid such risks, media containing nutrients of vegetative origin are substituted. The present study involves the toxicity, biochemical and sterility testing of DTP group of vaccines produced on such vegetative media to determine their quality and safety. Toxicity tests are based on the observation that there are body weight changes characteristic to each vaccine and such standardized changes can be used as references for evaluating test vaccines. Sterility test was performed on the final bulk and lot to confirm that the product is free of bacterial and mycotic contamination. Biochemical tests were also carried out to determine the content of aluminium, thiomersal and formalin. The results confirmed that the DTP vaccine samples met the criteria set by I.P., 2007 for toxicity, sterility and safety.


The invention relates to a disposable injector with a housing (10) in which are arranged at least one mechanical spring energy store (50), at least one cylinder-piston unit that can be filled at least temporarily with an active substance, at least one piston actuation plunger (60) and at least one triggering unit (80). The spring energy store comprises at least one pre-loaded spring element. The spring-loaded piston actuation plunger has at least one traction rod (61) which can be moved transversely, at least in certain regions, and by means of a supporting portion supports the tensioned spring energy store on at least one resting surface (37) of the housing. An actuatable triggering slide device (82) unlocks the disposable injector and releases the supporting portion to allow it to move away from the resting surface.


Cynanchum wilfordii and Phlomis umbrosa Turcz. are known to contain isoflavone, a representative phytoestrogen. This study was performed to determine whether the extract mixture of C. wilfordii and P. umbrosa Turcz. would induce an estrogenic effect in ovariectomized rats. The extracts were administered to the ovariectomized rats at 30, 60, 120 mg/kg per day for 4 weeks, respectively. They showed no estrogenic effect, which was indicated by the decrease in uterus wall thickness as well as the increase in body weight and the level of cholesterol and triglyceride. The extracts also had no effect on the concentrations of estrogen and growth hormone in the serum. However, the increase in alkaline phosphatase activity, which leads to protection against the bone loss caused by ovariectomy, was noted on administration of the extract. Therefore, it seemed that the extracts of C. wilfordii and P. umbrosa Turcz. had no estrogenic effect in rats.


The spleen of 73 white mice was studied (15 mice were studied by electron microscopy) from 24 to 120 hours after intraperitoneal infection. The successive stages of interaction of parasites with cells of mononuclear phagocytes system were observed. At the early stages of the infection the activation of these cells takes place. During the dissemination of endozoites over the host organism they penetrate the activated mononuclear phagocytes. Activation, however, is not effective enough since in these cells the parasites preserve the ability to hinder the fusion of lysosomes with phagosomes containing endozoites and at later stages of the infection of lyse the membrane of parasitophore vacuole. The ability to reproduce in activated mononuclear phagocytes and to lyse the membrane of parasitophore vacuole is regarded as a factor of the virulence of endozoites of RH strain toxoplasms.


This paper presents a hybrid model that calculates the heads, the discharges in pipes, the head losses in pipes (caused by discharges and valves) and the booster heads in hydraulic networks. The steady state is calculated considering the hydraulic network without valves and boosters. The extended period simulation is calculated considering the presence of valves and/or boosters to solve over pressure and/or under pressure problems respectively. The hybrid model uses a genetic algorithm to minimize the dissipated hydraulic power sum in the whole hydraulic network for all calculation time steps of the extended period simulation (objective function) by setting optimal valve openings. It was studied how it affects the behavior of a hydraulic network. A real hydraulic network that had over pressure and under pressure problems was analyzed. It was necessary to install boosters and valves to solve the pressure problems. The results show that when valves were installed without planning its openings, the total head losses increased from 5.9% to 13.6%, while the total head losses in the same hydraulic network increased 2.7% when planning the installed valves openings. It's concluded that the dissipated power minimization was an effective way to optimize the studied hydraulic network operations by minimizing the head losses increases caused by the installed valves.


Introduction Reports of false-negative quantitative reverse transcription PCR (RT-qPCR) results from patients with high clinical suspension for coronavirus disease 2019 (COVID-19), suggested that a negative result produced by a nucleic acid amplification assays (NAAs) did not always exclude the possibility of COVID-19 infection. Repeat testing has been used by clinicians as a strategy in an to attempt to improve laboratory diagnosis of COVID-19 and overcome false-negative results in particular. Aim To investigate whether repeat testing is helpful for overcoming false-negative results. Methods We retrospectively reviewed our experience with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, focusing on the yield of repeat patient testing for improving SARS-CoV-2 detection by NAA. Results We found that the yield from using repeat testing to identify false-negative patients was low. When the first test produced a negative result, only 6 % of patients tested positive by the second test. The yield decreased to 1.7 and then 0 % after the third and fourth tests, respectively. When comparing the results produced by three assays, the Centers for Disease Control and Prevention (CDC) SARS CoV-2 RT-qPCR panel, Xpert Xpress CoV-2 and ID NOW COVID-19, the ID NOW assay was associated with the highest number of patients who tested negative initially but positive on repeat testing. The CDC SARS CoV-2 RT-qPCR panel produced the highest number of indeterminate results. Repeat testing resolved more than 90 % of indeterminate/invalid results. Conclusions The yield from using repeat testing to identify false-negative patients was low. Repeat testing was best used for resolving indeterminate/invalid results.


Traffic accident data for the Zagreb area for the 1981-1982 period were analyzed to investigate possible relationships between the daily number of accidents and the weather conditions that occurred for the 5 consecutive days, starting two days before the particular day. In the statistical analysis of low accident days weather type classification developed by Poje was used. For the high accident days a detailed analyses of surface and radiosonde data were performed in order to identify possible front passages. A test for independence by contingency table confirmed that conditional probability of the day with small number of accidents is the highest, provided that one day after it "N" or "NW" weather types occur, while it is the smallest for "N1" and "Bc" types. For the remaining 4 days of the examined periods dependence was not statistically confirmed. However, northern ("N", "NE" and "NW") and anticyclonic ("Vc", "V4", "V3", "V2" and "mv") weather types predominated during 5-days intervals related to the days with small number of accidents. On the contrary, the weather types with cyclonic characteristics ("N1", "N2", "N3", "Bc", "Dol1" and "Dol"), that are generally accompanied by fronts, were the rarest. For 85% days with large number of accidents, which had not been caused by objective circumstances (such as poor visibility, damaged or slippery road etc.), at least one front passage was recorded during the 3-days period, starting one day before the day with large number of accidents.


The milk sector has received much attention in Europe due to the abolishment of milk quotas in 2015 and its potential effect on the geographical distribution of milk production across countries. As a way of assessing the competitive advantage of Nordic EU countries, we investigated the productivity level and productivity growth of milk farms across eight countries of the Baltic Sea region from 1995 to 2010. We found considerable discrepancy in productivity performance across countries. TFP growth rates indicate that the competitive positions of the "old" EU members are stable, and that there is no catching up from the newer EU entrants. We offer explanations for this evolution based on the different patterns of structural change followed by the studied countries.


Concrete recycling consists of crushing the concrete provided by demolishing the old constructions, and of using the resulted small pieces as aggregates in the new concrete compositions. The resulted aggregates are called recycled aggregates and the new mix of concrete containing a percentage of recycled aggregates is called recycled concrete. Our previous researches have indicated the optimal percentages of recycled aggregates to be used for different cases of recycled concrete related to the original aggregates nature. All results have shown that the concrete compressive strength is significantly reduced when using recycled aggregates. In order to obtain realistic values of compressive strength, some tests have been carried out by adding water-reducer plasticizer and a specified additional quantity of cement. The results have shown that for a limited range of plasticizer percentage, and a fixed value of additional cement, the compressive strength has reached reasonable value. This paper treats of the effect of using recycled aggregates on the tensile strength of concrete, where concrete results from the special composition defined by our previous work. The aim is to determine the relationship between the compressive and tensile strength of recycled concrete.


Lactic acid bacteria have been reported to be useful as a healt adjunct and are commonly added to food as delivery mechanism. As a probiotic, lactic acid bacteria should have the ability to survive in the digestion process such as resistance towards acidic pH, varieties of bile salt concentrations and enteric pathogan. In this study, lactic acid bacteria were isolated from various sources. Twenty isolated of lactic acid bacteria selected for their resistancy toeards acidic pH (pH 2.5), 0.3% bile salt and their antagonistic activity against enteric pathogan (Esherichia coli, Staphylococcus aureus and Bacillus cereus). The result showed that most of all strauns had good resistance to acidic pH and there were no significant difference among theme (p>0.05). More over, all strains showed tolerance to 0,3% bile salt concentration (varietis among isolates were significant p>0.05). All strains showed inhibition activity against enteric pathogan bacteria, this was estimated from the size of the diameter of the inhibition zones. (The inhibition were significantly different among them (p>0,05)). The best five stains that fulfilled these properties L casei FNCC262, L. acidophilus FNCC116, KL-3 isolate, Da-1 isolate, and Db-2 isolate. These strains could be used as probiotics in further and applications. Key words : acid-tolerant, bile tolerant, antagonistic activity, lactic acid bacteria


Annual and within-season crop type monitoring and mapping is an important ongoing consideration for governments, global agricultural monitoring organizations and private interests worldwide. Successful country-wide operational remote sensing-based inventories are well-established utilizing optical-only and optical/single frequency Synthetic Aperture Radar (SAR) combinations of data. However, the drawbacks of these data combinations are the requirement of multiple sources of imagery throughout the entire growing season, which impedes within-season analysis, and cloud cover effects on the optical data. Currently, C-band SAR data are available with continuous global coverage from Sentinel-1A & B, RADARSAT-2 and from the expected launch of the RADARSAT Constellation Mission (RCM). With current and expected launches of several other frequency (L-, P-, etc.) SAR missions over the next few years (SAOCOM, NISAR, etc.) the opportunity for continuous, multi-frequency SAR coverage edges toward reality. The JECAM SAR Inter-Comparison Experiment is a multi-year, multi-partner project that aims to compare global methods for SAR-based crop monitoring and inventory. The third component of this experiment is the assessment of multi-frequency SAR data for crop classification and mapping. Earth observation (EO) data acquisitions of Sentinel-1A & B, RADARSAT-2/RCM, ALOS-2, SAOCOM1 and TerraSAR-X/TanDEM-X have been planned and requested for the 2019 growing season to complement within field surveys being conducted across the globe. In preparation for these data, this research analyzed ALOS-2, TerraSAR-X and RADARSAT-2 data for crop mapping at the JECAM Canada-Carman site using two dates of multi-frequency SAR data, in comparison to a traditional full season optical/SAR dataset. The multi-frequency data had similar overall accuracies as the optical/SAR dataset, and improved on several individual agricultural class accuracies.


We present two-dimensional hydrodynamic simulations of both jet- and wind-driven models for protostellar outflows in order to make detailed comparisons to the kinematics of observed molecular outflows. The simulations are performed with the ZEUS-2D hydrodynamic code using a simplified equation of state, simplified cooling and no external heating, and no self-gravity. In simulations of steady jets, swept-up ambient gas forms a thin shell that can be identified as a molecular outflow. We find a simple ballistic bow shock model is able to reproduce the structure and transverse velocity of the shell. Position-velocity (PV) diagrams for the shell cut along the outflow axis show a convex spur structure with the highest velocity at the bow tip and low-velocity red and blue components at any viewing angle. The power-law index of the mass-velocity (MV) relationship ranges from 1.5 to 3.5, depending strongly on the inclination. If the jet is time-variable, the PV diagrams show multiple convex spur structures, and the power-law index becomes smaller than the steady jet simulation. In simulations of isothermal steady wide-angle winds, swept-up ambient gas forms a thin shell that at early stages has a similar shape to the shell in the jet-driven model; it becomes broader at later times. We find the structure and kinematics of the shell is well described by a momentum-conserving model similar to that of Shu et al. (1991). In contrast to the results from jet simulations, the PV diagrams for the shell cut along the outflow axis show a lobe structure tilted with source inclination, with components that are primarily either red or blue unless the inclination is nearly in the plane of sky. The power-law index of the MV relationship ranges from 1.3 to 1.8. If the wind is time-variable, the PV diagrams also show multiple structures, and the power-law index becomes smaller than the steady wind simulation. Comparing the different simulations with observations, we find that some outflows, e.g., HH 212, show features consistent with the jet-driven model, while others, e.g., VLA 0548, are consistent with the wind-driven model.


BACKGROUND Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. OBJECTIVE To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. METHODS Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. FINDINGS Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. CONCLUSIONS The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.


The syntheses of new C2Symmetric N,N'-((2R,3R)-2,3-dihydroxybutane-1,4-diyl)bis(N-(2-chloro-3-(trifluoromethyl) benzyl) benzenesulfonamide) from N,N'-((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)bis(N-(2- chloro-3 (trifluorom ethyl )benz yl)benzenesulfonamide)derivatives aredescribedC2 Symmetric N,N'-((4R,5R)-2,2- dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)bis(N-(2-chloro-3 (trifluo romethyl)benzyl)benzene sulfonamide) derivatives fromN,N'-((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl) bis (meth ylene)bis(benzenesulfonamide) derivatives are described. C2-symmetrical diamines were prepared via direct ((4R,5R)-2,2-dimethyl-1,3-dioxolane- 4,5-diyl)dimethanamine sinthesized by using(4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxamide this is followed from the (4S,5S)-dimethyl 2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate molecule. For C2-symmetrical compounds, for the above targeted molecule reaction used to form the key intermediate, is a corboxamide from corboxilate. Some of the new chiral compounds, produced in good to high yields, potentially useful as asymmetric sterio chemical chemotherapeutic HIV agents. Thus, a bisulphonamido diamino 1, 3- dioxolane derivatives, used in substoichiometric amounts, was found to their broad spectrum of antibacterial activity. A series of novel sulfonamide derivatives were screened in hydrogen bond interactions with hydrolase. The results showed that the derivatives exhibited moderate hydrogen bond interactions against human hydrolase activity. The structure— activity relationships were also briefly discussed.


This is a valuable book of readings which draws on knowledge developed by many disciplines. Its unique contribution lies in the view of the family presented by the editor, the essential quality of which is contained in the title. Handel views the family as a viable psychosocial system. As a system the whole is characterized by functions experienced as processes that are not simply the sum of their parts but serve purposes of the system as a whole. The readings are coherently organized in seven sections, each offering a central theme. Part I presents a framework for observing families as wholes. Part VII analyzes and evaluates where the study of families as wholes stands at the present time as well as suggesting some future directions. The papers in the intervening sections consist of a number of previously unpublished as well as previously published works. As usual in an


We analyze local indeterminacy and sunspot-driven fluctuations in the standard two-sector model with additively separable preferences. We provide a detailed theoretical analysis enabling us to derive relevant bifurcation loci and to characterize the steady-state local stability properties as a function of various structural parameters influencing the degree of increasing returns to scale, the amount of intertemporal substitution in consumption, and the elasticity of the aggregate labor supply curve. On the theoretical side, we prove the existence of both a flip and a Hopf bifurcation locus in the corresponding parameter space. We also show that local indeterminacy can be obtained under any labor supply elasticity or under an arbitrarily low elasticity of intertemporal substitution in consumption. On the empirical side, we find that indeterminacy and sunspot fluctuations are robust features of two-sector models, prevailing for most empirically plausible calibrations for these parameters.


While most security projects have focused on fending off attacks coming from outside the organizational boundaries, a real threat has arisen from the people who are inside those perimeter protections. Insider threats have shown their power by hugely affecting national security, financial stability, and the privacy of many thousands of people. What is in the news
is the tip of the iceberg, with much more going on under the radar, and some threats never being detected. We propose a hybrid framework based on graphical analysis and anomaly detection approaches, to combat this severe cyber security threat. Our framework analyzes heterogeneous data in isolating possible malicious users hiding behind others. Empirical results reveal this framework to be effective in distinguishing the majority of users who demonstrate typical behavior
from the minority of users who show suspicious behavior.


Organ donation is a health issue which involves a process of an individual freely giving consent to donate organs or tissue for very ill or dying recipients. In Malaysia, the notion of organ donation has been facilitated by many government authorities since 1970s. However, recent statistics show that the number of patients requiring donated organs far outnumbers the donors. The unwillingness to donate is commonly associated with spiritual beliefs, myths, misunderstanding, lack of knowledge and lack of trust. Most of the studies conducted in Malaysia highlighted the reasons impeding Malaysians to become donors rather than looking at the aspect of communication that influences the attitude of the potential organ donor. Thus, this study is designed to focus on the values and norms which are commonly transmitted by the socialization agents that consist of parents, peers, educational institution, traditional mass media and new media, which are presumed to have significant effects on behaviour development of the potential donor towards organ donation. Particularly, this research attempted to examine the influence of these socialization agents on Generation Y's attitude formation towards organ donation. Generation Y was selected based on the conclusion made by previous scholars that this group of individuals is at the stage of discovering themselves on how to fit into society and the social world, where they mostly consume ideas from their socialization agents to achieve their life goals. The study employed quantitative method using survey questionnaire. Individuals were chosen based on non-probability sampling and the age range was between 18-24 years old. The socialization agents were measured in terms of informational and supportive influence. The findings of this study indicated that the supportive influence from all the agents of socialization affected the attitude of Generation Y and parents appeared as the most influential agent. However, their attitude was negatively correlated with the intention to sign up as an organ donor. The implications for social marketers were also discussed.


Phase-pure K0.5Na0.5NbO3 (KNN) fine powders were synthesized via a solid-state route from a homogeneous solid mixture. A colloidal dispersion comprising a mixed ethanol solution of potassium and sodium acetates and Nb2O5 fine particles was attrition milled and dried carefully to avoid water absorption. Two-step calcination in air at 450°C and 625°C, each for 3 h, resulted in the phase-pure KNN powders. The volume-based median diameter of the final product was ca. 0.8 μm. Starting from the same precursors without dissolving the acetates, the phase-pure KNN was never achieved even when the two calcination temperatures were increased to 550°C and 700°C, in spite of the same milling conditions. Key issues of eliminating second phases were (i) starting from a wet-milled mixture with a single solution containing both of the A-site species, and (ii) repeated wet milling of the reaction mixture to disintegrate reaction-induced agglomerates. These enabled rapid nuclei growth from chemically interacted precursor prior to calcination, and short diffusion path due to repeated deagglomeration, excluding formation of off-stoichiometric second phases. All these items were confirmed by different analytical tools, among others, thermo-gravimetry and differential thermal analysis (TG-DTA), particle size analyses, and XPS at various reaction stages. On the heating stage microscope, a shrinkage onset was observed at 850°C, that is, 150 K lower than that of conventionally prepared KNN, that is, via a solid-state synthesis from carbonates by a two-step calcination at 800°C and 750°C, for 4 h each. No second phase was observed after sintering up to 1100°C.


PURPOSE
Measuring the growth of young children's vocabulary is important for researchers seeking to understand language learning as well as for clinicians aiming to identify early deficits. The MacArthur-Bates Communicative Development Inventories (CDIs) are parent report instruments that offer a reliable and valid method for measuring early productive and receptive vocabulary across a number of languages. CDI forms typically include hundreds of words, however, and so the burden of completion is significant. We address this limitation by building on previous work using item response theory (IRT) models to create computer adaptive test (CAT) versions of the CDIs. We created CDI-CATs for both comprehension and production vocabulary, for both American English and Mexican Spanish.

METHOD
Using a data set of 7,633 English-speaking children ages 12-36 months and 1,692 Spanish-speaking children ages 12-30 months, across three CDI forms (Words & Gestures, Words & Sentences, and CDI-III), we found that a 2-parameter logistic IRT model fits well for a majority of the 680 pooled vocabulary items. We conducted CAT simulations on this data set, assessing simulated tests of varying length (25-400 items).

RESULTS
Even very short CATs recovered participant abilities very well with little bias across ages. An empirical validation study with N = 204 children ages 15-36 months showed a correlation of r = .92 between language ability estimated from full CDI versus CDI-CAT forms.

CONCLUSION
We provide our item bank along with fitted parameters and other details, offer recommendations for how to construct CDI-CATs in new languages, and suggest when this type of assessment may or may not be appropriate.


Abstract:A long and rich history recognizes the important role empathy plays in both group and individual therapy. The discovery of mirror neurons and related systems in the human brain has initiated renewed interest in the subject. This article deconstructs empathy in an effort to provide a deeper understanding of its developmental value as the highest form of emotional intelligence and thus provide a rationale for greater emphasis on education and training for psychotherapists.


Coastal hazards emerge from the combined effect of wave conditions and sea level anomalies associated with storms or low‐frequency atmosphere‐ocean oscillations. Rigorous characterization of wave climate is limited by the availability of spectral wave observations, the computational cost of dynamical simulations, and the ability to link wave‐generating atmospheric patterns with coastal conditions. We present a hybrid statistical‐dynamical approach to simulating nearshore wave climate in complex coastal settings, demonstrated in the Southern California Bight, where waves arriving from distant, disparate locations are refracted over complex bathymetry and shadowed by offshore islands. Contributions of wave families and large‐scale atmospheric drivers to nearshore wave energy flux are analyzed. Results highlight the variability of influences controlling wave conditions along neighboring coastlines. The universal method demonstrated here can be applied to complex coastal settings worldwide, facilitating analysis of the effects of climate change on nearshore wave climate.


Lung function is a strong predictor of mortality. While inflammatory markers have been associated with lung function decrease, pathways are still poorly understood and epigenetic changes may participate in lung function decline mechanisms. We studied the cross-sectional association between DNA methylation in nine inflammatory genes and lung function in a cohort of 756 elderly men living in the metropolitan area of Boston. Participants donated a blood sample for DNA methylation analysis and underwent spirometry at each visit every 3 to 5 y from 1999–2006. We used separate multivariate mixed effects regression models to study the association between each lung function measurement and DNA methylation within each gene. Decreased CRAT, F3 and TLR2 methylation was significantly associated with lower lung function. One interquartile range (IQR) decrease in DNA methylation was associated with lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), respectively by 2.94% (p < 10−4) and 2.47% (p < 10−3) for F3, and by 2.10% (p < 10−2) and 2.42% (p < 10−3) for TLR2. Decreased IFNγ and IL6 methylation was significantly associated with better lung function. One IQR decrease in DNA methylation was associated with higher FEV1 by 1.75% (p = 0.02) and 1.67% (p = 0.05) for IFNγ and IL6, respectively. These data demonstrate that DNA methylation may be part of the biological processes underlying the lung function decline and that IFNγ and IL6 may have ambivalent roles through activation of negative feedback.


The genomic data that can be collected from a single DNA molecule by the best chemical and optical methods (e.g., using technologies from OpGen, BioNanoGenomics, NABSys, PacBio, etc.) are badly corrupted by many poorly understood noise processes. Thus, single molecule technology derives its utility through powerful probabilistic modeling, which can provide precise lower and upper bounds on various experimental parameters to create the correct map or validate sequence assembly. As an example, this analysis shows how as the number of "imaged" single molecules (i.e., coverage) is increased in the optical mapping data, the probability of successful computation of the map jumps from 0 to 1 for fairly small number of molecules.


Fitri DS, Pangastuti A, Susilowati A, Sutarno. 2017. Endophytic bacteria producing antibacterial against methicillin-resistant Staphylococcus aureus (MRSA) in seagrass from Rote Ndao, East Nusa Tenggara, Indonesia. Biodiversitas 18: 733-740. Methicillinresistant Staphylococcus aureus (MRSA) are bacteria that resistant to the various type of antibiotics and yet cannot be handled comprehensively. The discovery of new antibiotic from endophytic bacteria in seagrass of Rote Island is an option to overcome the resistance. The aims of this research were to screen endophytic bacteria inhibit MRSA from seagrass, to determine the species of the endophytic bacteria and the genetic relationship. Isolation of endophytic bacteria has carried out by inoculating surface sterilization seagrass leaves on Marine Agar (MA) medium. Selection of potential endophytic bacteria-producing anti-MRSA has done using overlay method against MRSA, gram-positive Bacillus subtilis, and gram-negative Escherichia coli. Identification of the endophytic bacteria based on the sequence of 16S rRNA encoding gene. The results showed that there were eight isolates of endophytic bacteria which have antibacterial activity against MRSA of seagrass Enhalus acoroides, Thalassia hemprichii, and Cymodocea rotundata in the Litianak and Oeseli Beaches, Rote Ndao. The diameter of inhibition zone was between 0.65-18.27 mm with narrow spectrum with broad spectrum antibacterial activity. The eight potential endophytic bacteria identity were Bacillaceae E2M1, Bacillaceae E2M3, Bacillus E2M4, Bacillus E2M7, Bacillaceae E2M8, Pseudomonadaceae C1M7, Shewanellaceae C2M3, and Rhodobacteraceae T1M3. Most of the isolates can be said to be a new species as the percent similarity of 16S rRNA gene sequence was less than 95% and promising to produce new antibacterial compounds. Phylogenetic relationship showed some isolates clustering in different groups that present the diverse groups of endophytic bacteria were found.


Introduction Pharmacologic dilation of the pupil results in twice the sensitivity of detection of diabetic retinopathy compared with undilated retinal examination. The potential risk of acute angle-closure glaucoma after pupil dilation has been hypothesized to be higher in Asian patients with diabetes mellitus. Clinical case A 61-year-old man with diabetes mellitus and hypertension was incidentally found to have elevated intraocular pressure (IOP) before routine retinal photography. He was asymptomatic and the visual acuity was 0.67 for both eyes. An ophthalmologist later found he had anatomical narrow-angle borderline glaucoma. Topical administration of pilocarpine and oral administration of acetazolamide were initiated, and laser iridotomy was later performed. IOP screening Among 1736 diabetic and/or hypertensive patients who underwent IOP screening, 31 patients (1.8%) had IOP of any eye persistently higher than 21 mm Hg on at least two occasions. The mean (standard deviation) IOP of the right eye was 24.1 (2.1) mm Hg, while that of the left eye was 24.6 (2.5) mm Hg. Four patients (12.9%) were found to have glaucoma, and treatment was initiated by an ophthalmologist. Therefore further study should be conducted to evaluate the cost-effectiveness of IOP screening among this group of patients.


Aneurysms of the superficial temporal artery (STA) are a rare and potentially critical cause of facial masses. Usually, these aneurysms are Pseudoaneurysm and occur following blunt or penetrating trauma to the head or following surgery in the temporal region. Most cases (about 75%) are the result of blunt head injury. Only 11 cases of spontaneous aneurysms were reported. These aneurysms are assumed to have been congenital or arteriosclerotic. Pseudoaneurysm has occurred mainly in the anterior branch of the STA. The first case of a STA Pseudoaneurysm was described by Thomas Bertholin in 1740 and since then about 400 cases have been published in the literatures. I present two cases of traumatic pseudoaneurysm of the STA and I discuss pertinent diagnosis and treatment options, as well as provide a brief review of the anatomy and histopathology of pseudoaneurysms.


This paper proposes a peer-to-peer video streaming delivery system within the framework of Next Generation Networks using Application Level Multicast. Increased efficiency and reliability is achieved in two ways. First, the system uses path diversity by splitting the video traffic in several stripes and distributing each stripe via different multicast trees. Second, the proposed architecture lies within a Next Generation Network framework that enables network resource reservations with different classes of service. Therefore, the video stripes can receive different priorities making possible the usage of Layered Coding techniques such as Multi-Description Coding and Scalable Video Coding. The peer-to-peer protocol takes advantage of the multipath delivery and resources reservation by optimising the searches for a parent in the multicast tree, thus minimising the service access time and service interruptions. These ideas can be improved using always-on central devices like Residential Gateways as peer nodes.


The effectiveness of external consulting for road construction companies is considered. It was found out that the companies-clients of consulting, as a party of consulting interaction, need practical convenient tools for evaluating the effectiveness of the ordered consulting services. It is determined that the effectiveness of consulting should not be assessed by two indicators of the ratio of results to goals — efficiency and results to costs — efficiency. The third equally important indicator for assessing effectiveness is the indicator of expediency as the ratio of the established purpose of consulting to the problems of the enterprise, which company-client identifies and plans to solve with the help of consulting. Thus, the first step in consulting interaction for the customer is to diagnose his problems by interviewing staff at all levels. This parameter determines the features of the industry in which the company operates, because the problems of each industry, their structure are specific. The goal is calculated by an integrated indicator based on the desired growth rates of the main performance indicators for the customer. The ratio of the set goal to the problems of the enterprise determines the feasibility. Two other parameters that allow in addition to the feasibility of calculating efficiency and effectiveness are cost and result. The latter is also an integral parameter based on the growth rate of the actual performance of the enterprise after the implementation of consulting services. Thus, the performance indicator as a ratio of results to goals allows you to determine how effective external consulting is precisely on the basis of achieving the set goals. The cost-effectiveness indicator is traditional and is defined as the ratio of the result to the cost of consulting. The cost parameter is proposed to be determined taking into account not only the payment of the consultant for the work performed, but also the exposure — the level of interaction between the customer and the consultant, and the probability that the consultant's recommendations will be implemented by the customer. The level of consulting efficiency is determined by the above three indicators as critical, sufficient or high. Interpretation of the three-component model for evaluating the effectiveness of consulting services is based on the criteria and qualitative characteristics of these indicators.


In 2002, a census of Mute Swans Cygnus olor was carried out in Great Britain and the Isle of Man, to determine the size of the Mute Swan population during the breeding season and to distinguish between the numbers of breeding and non-breeding birds. Coverage of the whole country had been attempted previously, in 1955/56, 1978, 1983 and 1990, but was deemed impractical for this census. Instead, coverage of randomly selected 10-km squares was undertaken, which reduced the amount of fieldwork required and made it possible to calculate confidence intervals for the estimated population size. The population size was estimated at 31,700 birds, with 95% confidence levels of 28,600–35,200 birds. Separate estimates were made of the breeding or territorial component (6,150 pairs, with 95% confidence levels of 5,550–6,740 pairs) and non-breeding component (19,400 unpaired non-breeding individuals, 95% confidence levels of 16,700–22,200 birds). The Mute Swan population in Britain and the Isle of Man has thus increased by 23% over the period 1990–2002, a slower rate than during the 1980s. Coverage was achieved for all but 96 (92%) of the 1,100 10-km squares originally selected for surveying, a major improvement on previous censuses. This high level of coverage contributed to the accuracy of the population size estimate in 2002.


BACKGROUND Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. AIMS To determine trends in management and prognosis of rectal cancer in two French regions. SUBJECTS 1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. METHODS Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. RESULTS Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17.7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978–1981 period to 57.0% for the 1985–1989 period). CONCLUSIONS Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival.


Economic inequalities referring to specific regions are crucial in deepening spatial heterogeneity. Income surveys are generally planned to produce reliable estimates at countries or macroregion levels, thus we implement a small area model for a set of inequality measures (Gini, Relative Theil and Atkinson indexes) to obtain microregion estimates. Considering that inequality estimators are unit-interval defined with skewed and heavy-tailed distributions, we propose a Bayesian hierarchical model at area level involving a Beta mixture. An application on EU-SILC data is carried out and a design-based simulation is performed. Our model outperforms in terms of bias, coverage and error the standard Beta regression model. Moreover, we extend the analysis of inequality estimators by deriving their approximate variance functions.


The fate of NO(x) (=NO + NO(2)) is important to understand because NO(x) is a significant player in air quality determination through its role in O(3) formation. Here we show that renoxification of the urban atmosphere may occur through the photolysis of HNO(3) deposited onto urban grime. The photolysis occurs 4 orders of magnitude faster than in water with J values at noon on July 1 in Toronto of 1.2 × 10(-3) s(-1) for nitrate on urban grime and 1.0 × 10(-7) s(-1) for aqueous nitrate. Photolysis of nitrate present on urban grime probably follows the same mechanism as aqueous nitrate photolysis, involving the formation of NO(2), OH, and possibly HONO. Thus NO(x) may be rapidly returned to the atmosphere rather than being ultimately removed from the atmosphere through film wash off.


Two new triptycene-based polyimides, 6FDA-1,4-trip_ortho and 6FDA-2,6-trip_para, were synthesized to investigate the effect of varying polymer backbone geometry on chain packing and gas transport properties. Changing the imide linkage geometry from para to ortho reduced gas permeabilities by ∼48% due to more efficient chain packing of the asymmetric ortho structure, which is demonstrated by decreased d-spacing and fractional free volume. Varying the triptycene orientation from the 1,4- to 2,6-connection also caused a decrease in permeability (e.g., 29% decrease for PCO2). This is likely the result of reduced chain mobility, as evidenced by increased Tg, and a shift in free volume distribution toward smaller cavities, as supported by smaller d-spacing. Physical aging studies show that the equilibrium specific volume of these isomeric polymers is similar, as evidenced by nearly identical gas transport properties exhibited by all aged samples.


If we want to replace the use of fossil fuels with sustainable energy, we have to continue to
meet the energy demands of the consumers. One way of doing this is to optimize and
control the energy consumption in each household, so that the total consumption is as
even as possible during the whole day. The question is, whether it is probable that an
average household will be able to redistribute their energy consumption enough for it to
have a notable effect on the total energy consumption.
SmartGrid is the energy companies' solution to power shortage. It's an easy way for the
supplier to control the energy consumption for a private household. It enables the
companies to raise the price of energy when the demand is great and lower the prices
during the night when the total consumption is less. Because the consumption is much
greater during the morning and evening, it forces the suppliers to make sure there's no
energy shortage by increasing the amount of energy made from fossil fuels.
Our project focuses on the advantages of SmartGrid for a normal household with a heat
pump. Using MatLab we will model the heat flow in an average house equipped with a heat
pump. We will look at the water flow in connection to underfloor heating and strive to
control the heat pump, so that it will take advantage of the low energy prices during the
night. Our goal is to be able to control the heat pump in a way that allows the household to
maintain a comfortable room temperature.
We are hoping to lower the consumption peaks by shutting of the heat pump during these
periods of time. This will smooth the peaks out and thereby decrease the total energy
demand during these hours. Hopefully this will allow the energy companies to produce less
energy from coal power plants and thereby reduce the amount of energy from fossil fuels.


The use of mass spectrometry to study of proteins and their non-covalent complexes has grown during the last few decades thanks to the introduction of soft ionisation techniques capable of preserving the weak molecular bonds present in higher order protein structure. The integration of the shape selective technique ion mobility with mass spectrometry has allowed the study of conformation and dynamics of native proteins. The work presented in this thesis focuses on the use of ion mobility mass spectrometry to investigate both protein conformation, and conformational differences induced by mutation.

Prolyl oligopeptidase family enzymes are proteases characterised by their unique function; these enzymes are only capable of digesting short amino acid sections of no more than thirty amino acids. These proteins have been implicated in a number of neurological disorders and have been targeted as potential drug candidates. PREP is an 80.7 kDa monomeric protein that has been targeted as a potential drug candidate. PREP has been crystallised in two distinct conformations, open and closed, and it has been suggested that the protein exists in equilibrium between the two states in solution, with only the open conformation allowing substrate entry via a domain separation mechanism. Ion mobility mass spectrometry has been used to confirm the presence of both conformations, and to investigate the effect of ligand binding on conformation. It was found that, at lower energy states, PREP was only capable of adopting a single conformation, and that more extended conformations were only present following activation of the protein. Binding of ligand appeared to increase the relative stability of the protein. DPP IV, is a larger, dimeric, protein from the same family. Unlike PREP, DPP IV has only been crystallised in a single conformation and it was proposed that small loop movements, rather than domain separation, allowed substrate entry. Ion mobility measurements show only a single conformation of DPP IV, consistent with no large conformational changes, supporting this hypothesis.

Haemoglobin is the main protein involved in gas transport in mammalian systems, taking oxygen from the lungs to the tissues of the body. Disorders of haemoglobin represent the most common of all inherited disorders, with an estimated 7% of the global population being carriers for a haemoglobin disorder. A previous study by Scarff et al used ion mobility mass spectrometry to identify conformational differences between normal HbA and HbS, the haemoglobin mutant responsible for sickle cell disease. Recent experimental improvements in sample preparation, data collection and data processing have been used in this research to provide improved experimental information. HbA, HbS and HbC, a third haemoglobin variant known to form crystals within erythrocytes, were investigated using ion mobility mass spectrometry. Calibration of ion mobility data using native protein standards indicated that the structural differences between HbA and HbS were smaller than previously reported, and that the CCS measurements of the two proteins were similar for the native charge states. The HbC molecule does however adopt a smaller conformation. All three proteins unfold as a factor of increased protonation, with HbS and HbC showing evidence of adopting a more extended conformation at lower charge states when compared to HbA, suggesting possible differences in protein stability. These stability differences were investigated using collision-induced activation of the protein, the results suggesting that HbA is more resistant to unfolding that either HbS or HbC.

Monoclonal antibodies represent a new generation of biotherapeutic capable of high specificity and selectivity, with diminished risk of inducing a host immune response. Antibodies therapeutics have an added benefit of interacting with host cellular systems, promoting host immune response. Engineering of antibodies has become well established to improve or diminish antibody-receptor binding in order to increase or abolish this interaction. Four antibody Fc variants have been studied using a combination of ion mobility mass spectrometry and hydrogen deuterium exchange mass spectrometry; a wild type, a TM mutant, a YTE mutant and a TMYTE double mutant. Previous studies have shown that the introduction of both TM and YTE mutations leads to a decrease in the thermal stability of the protein, and it was an aim of the study to provide structural information to explain this thermal destabilisation. Ion mobility mass spectrometry measurements suggest that there is little change in global conformation between the four variants. HDX results show that mutation introduces changes in local conformation across the protein, with increases in deuterium uptake observed at sites distant to the mutation sites. One region, located between the TM and YTE mutation sites, showed a greater than additive increase in deuterium uptake in TMYTE mutant compared with either TM or YTE mutants, indicating a region that hade become destabilised in the double mutant. These changes could be responsible for the observed loss of thermal stability.


Gun violence and mass shootings are talked about a lot in today's media. Guns are also used frequently in many films. America has an undeniable problem with the frequency of mass shootings, and gun control has been at the forefront to try and solve this problem. However, this thesis examines how masculinity plays a role in these shootings and gun violence in general. This study aims to look at how guns are represented in film and media and how this is tied to masculinity, specifically by closely analyzing three films: The Man Who Shot Liberty Valance (John Ford, 1962), Elephant (Gus Van Sant, 2003), and Loves Her Gun (Geoff Marslett, 2013). Guns play a central role in the classic western, The Man Who Shot Liberty Valance, and masculinity is put into question and regained by the use of the gun. One of the most infamous mass shootings in American history is recreated and explored in Elephant, which also has masculine implications. Loves Her Gun looks at how masculine power is attained by a woman who has been attacked on the streets of New York. This thesis aims to explore and argue that America's gun violence problem has more to do with masculinity, but first-and-foremost needs to be looked at in a different light and discussed more thoroughly.


This article discusses consumer activism not as an ethical, but as a political phenomenon. A political concept of consumer activism implies, first, that consumers sometimes express support or opposition to products and services or consumer and business practices at least partly in order to advance nonmarket agendas, and, second, that consumer activism in the economic sphere occasionally has palpable impact on the organization of social life. Early contributors to the debate were optimistic that political consumer activism might be able to extend democracy into the economic sphere. In recent years, however, scholars have increasingly voiced misgivings about this, arguing that political consumer activism may suffer from a democratic deficit: it may amount to an impermissible form of vigilantism or facilitate the illegitimate conversion of market power into political power. This article systematizes and reassesses these concerns, focusing in particular on arguments that dispute the compatibility of political consumer activism with liberal democracy as a procedural ideal. I conclude that political consumer activism does not face problems to do with legitimacy in this regard, most importantly because money does not play a more important role in market-based politics than in official democratic processes. Political consumer activism takes many forms, yet it is hardly ever about voting with the pocketbook.


Hunchback is a bifunctional transcription factor that can activate and repress gene expression in Drosophila development. We investigated the regulatory DNA sequence features that control Hunchback function by perturbing enhancers for one of its target genes, even-skipped. While Hunchback directly represses the eve stripe 3+7 enhancer, we found that in the eve stripe 2+7 enhancer, Hunchback repression is prevented by Caudal binding—this relationship is called counter-repression. We found evidence that this relationship is conserved by comparing predicted binding sites for Hunchback and Caudal across orthologous eve stripe 2 enhancers. These results alter the textbook view of eve stripe 2 regulation wherein Hb is depicted as a direct activator. Instead, to generate stripe 2, Hunchback repression must be counteracted by Caudal binding. We discuss the implications of this interaction for eve stripe 2 regulation and evolution.


Biosorption of cadmium and chromium (III) ions by means of selected yeast species has been estimated. Kinetics and equilibrium measurements have shown the reliable efficiency of both metals removal for Candida tropicalis. The influence of pH and ionic strength on biosorption process has been examined as well. For both metals the adsorption isotherms have been presented. The equilibrium of chromium (III) sorption has appeared compatible to Langmiur model and the maximum sorption capacity has been determined.


and localise to atherosclerotic plaques in experimental atherosclerosis. These targeted NPs have the potential to amplify fluorescent signal for imaging and carry a therapeutic cargo for targeted drug delivery to atherosclerotic plaques


Background: The present study aimed at comparing psychological problems between smoker and non-smoker students and also males and females. Materials and Methods: A total of 22 faculty members of public and private universities in Tehran were selected through random sampling and 913 students from the same universities were selected through convenient sampling and enrolled in this study with a 2-step sampling method. Hopkins symptom checklist was used for data collection. Result: significant differences were detected between smoker and non-smoker students in Hopkins score, anxiety and somatization. In addition, smoker women gained higher Hopkins score, somatization, anxiety and interpersonal sensitivity scores compared to smoker males. Conclusion: Incidence of signs and symptoms of depression, anxiety and other psychological disorders was higher among smoker individuals. Therefore, smoking control strategies should further focus on this subject.


Much has been recently written about the Multilateral Agreement on Investment (MAI) that has been negotiated by OECD countries. Perhaps even more has been said by the critics of those who would like to see an agreement of this kind extended among other countries. There has indeed been a great deal of toing and froing about the desirability of MAI and even misunderstandings about its merits. The principal question of this paper is whether there is any need for MAI. There are arguments in favour and against and this paper provides a short review. On balance, the positive aspects of a multilateral agreement should outweigh the negative ones. The novelty of the paper is the attempt to address the critical voices. Given the lukewarm reaction in some countries, it would seem sensible to pay more attention to these arguments - a feature that may only now become something of pressing need in the light of the difficulties encountered in the OECD negotiations.


The issue of suicide among Asian Americans has been understudied to date, largely because suicide rates for Asian Americans in the United States have been historically lower than Caucasians. The current special issue gathers studies that represent progress in the state of science, both advancing the current state of knowledge about suicide in Asian American communities and highlighting innovative approaches to suicide prevention and management. We discuss how the articles in the special issue address the nature and salience of suicide among Asian Americans, risk factors, culturally based expression of suicidal ideation and behaviors, and recommendations for suicide prevention and interventions. We conclude by noting directions for future research.


Smartphones have become a commodity item. In combination with their seemingly infinite extensions through mobile applications, they hold great economic potential for businesses. Location Based Services (LBS) take advantage of their portability by providing relevant information to the user regarding their location. Utilizing the user's position to create personalized location-specific marketing messages enables businesses to yield value for their customers. The main objective of this paper is to identify factors, which influence the acceptance of LBS apps in the context of retail since there is a lack of research in this field. A qualitative research approach was chosen to investigate the relevant variables. Based on the conducted interviews, theories were derived and verified against further data retrievals. Similar to findings of previous research the factors ease of use (usability) and usefulness were confirmed as being crucial in forming consumers' attitudes.


Abstract. Launched in October 2017, the TROPOspheric Monitoring Instrument (TROPOMI) aboard Sentinel-5 Precursor provides the potential to monitor air quality over point sources across the globe with a spatial resolution as high as 5.5 km × 3.5 km (7 km × 3.5 km before 6 August 2019). The DLR nitrogen dioxide (NO2) retrieval algorithm for the TROPOMI instrument consists of three steps: the spectral fitting of the slant column, the separation of stratospheric and tropospheric contributions, and the conversion of the slant column to a vertical column using an air mass factor (AMF) calculation. In this work, an improved DLR tropospheric NO2 retrieval algorithm from TROPOMI measurements over Europe is presented. The stratospheric estimation is implemented using the STRatospheric Estimation Algorithm from Mainz (STREAM), which was developed as a verification algorithm for TROPOMI and does not require chemistry transport model data as input. A directionally dependent STREAM (DSTREAM) is developed to correct for the dependency of the stratospheric NO2 on the viewing geometry by up to 2×1014 molec./cm2. Applied to synthetic TROPOMI data, the uncertainty in the stratospheric column is 3.5×1014 molec./cm2 in the case of significant tropospheric sources. Applied to actual measurements, the smooth variation of stratospheric NO2 at low latitudes is conserved, and stronger stratospheric variation at higher latitudes is captured. For AMF calculation, the climatological surface albedo data are replaced by geometry-dependent effective Lambertian equivalent reflectivity (GE_LER) obtained directly from TROPOMI measurements with a high spatial resolution. Mesoscale-resolution a priori NO2 profiles are obtained from the regional POLYPHEMUS/DLR chemistry transport model with the TNO-MACC emission inventory. Based on the latest TROPOMI operational cloud parameters, a more realistic cloud treatment is provided by a Clouds-As-Layers (CAL) model, which treats the clouds as uniform layers of water droplets, instead of the Clouds-As-Reflecting-Boundaries (CRB) model, in which clouds are simplified as Lambertian reflectors. For the error analysis, the tropospheric AMF uncertainty, which is the largest source of NO2 uncertainty for polluted scenarios, ranges between 20 % and 50 %, leading to a total uncertainty in the tropospheric NO2 column in the 30 %–60 % range. From a validation performed with ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements, the new DLR tropospheric NO2 data show good correlations for nine European urban/suburban stations, with an average correlation coefficient of 0.78. The implementation of the algorithm improvements leads to a decrease of the relative difference from −55.3 % to −34.7 % on average in comparison with the DLR reference retrieval. When the satellite averaging kernels are used to remove the contribution of a priori profile shape, the relative difference decreases further to ∼ −20 %.


With the emergence of photonics, new technologies and fast computed methods, optical imaging becomes a promising tool for medical applications. We focus here our interest on prostate cancer which is the most common one in the male population and which suffers from a lack of clinical imaging techniques. Hence, the current approach to localize tumors inside the organ relies on an excessive use of biopsies to sample the prostate until reaching the suspicious region. This process is obviously invasive for the patients and requires often to be repeated. Some methods based on diffuse optics tomography give encouraging results [1] but still require an acquisition duration not compatible with a clinical intervention. For faster localization of the tumor, we propose to use time resolved fluorescent tomography preceded by an injection of a fluorescent marker to the patient. The goal of our approach is to perform a single biopsy, by guiding it towards the identified fluorescent region. The detection is coupled with ultrasound imaging which is a current and convenient technique in interventional radiology.


We present an approach to solid-state electronic-structure calculations based on the finite-element method. In this method, the basis functions are strictly local, piecewise polynomials. Because the basis is composed of polynomials, the method is completely general and its convergence can be controlled systematically. Because the basis functions are strictly local in real space, the method allows for variable resolution in real space; produces sparse, struc-tured matrices, enabling the effective use of iterative solution methods; and is well suited to parallel implementation. The method thus combines the significant advantages of both real-space-grid and basis-oriented approaches and so promises to be particularly well suited for large, accurate ab initio calculations. We develop the theory of our approach in detail, discuss advantages and disadvantages, and report initial results, including the first fully three-dimensional electronic band structures calculated by the method.


Abstract. A new long-term data record of Fram Strait sea ice area export from 1935 to 2014 is developed using a combination of satellite radar images and station observations of surface pressure across Fram Strait. This data record shows that the long-term annual mean export is about 880 000 km2, representing 10 % of the sea-ice-covered area inside the basin. The time series has large interannual and multi-decadal variability but no long-term trend. However, during the last decades, the amount of ice exported has increased, with several years having annual ice exports that exceeded 1 million km2. This increase is a result of faster southward ice drift speeds due to stronger southward geostrophic winds, largely explained by increasing surface pressure over Greenland. Evaluating the trend onwards from 1979 reveals an increase in annual ice export of about +6 % per decade, with spring and summer showing larger changes in ice export (+11 % per decade) compared to autumn and winter (+2.6 % per decade). Increased ice export during winter will generally result in new ice growth and contributes to thinning inside the Arctic Basin. Increased ice export during summer or spring will, in contrast, contribute directly to open water further north and a reduced summer sea ice extent through the ice–albedo feedback. Relatively low spring and summer export from 1950 to 1970 is thus consistent with a higher mid-September sea ice extent for these years. Our results are not sensitive to long-term change in Fram Strait sea ice concentration. We find a general moderate influence between export anomalies and the following September sea ice extent, explaining 18 % of the variance between 1935 and 2014, but with higher values since 2004.


A  kind  of  novel  2‐DOF  micromanipulator  is designed  and  analysed based on  the  two  scales of  level amplifier  principle,  which  adopts  the  flexure  hinge  to replace  the  traditional  hinge. The  kinematics,  static  and dynamic  modelling  are  established,  and  the  input stiffness  and  actual  amplification  ratios  are  calculated. Meanwhile, the finite element analysis (FEA) is applied in order  to  validate  the  calculation  by  using  ANSYS software. Then,  the  theoretical, calculated and simulated values diagrams are compared. Thereafter, the stress and the  natural  frequency  of  the  stage  are  also  analysed  to optimize  the  platform  dimensions.  Parasitic  motion values are calculated and analysed, and  their values are compared in a diagram. The Particle Swarm Optimization (POS)  is  applied  to  design  and  optimize  the  structure parameters, and  finally  the optimal structure parameters are obtained and the values of parameters are used by the finite  element  model  (FEM).  In  addition,  a  dynamic equation  and  a  suitable  control  flow  chart  are designed for  the mechanism, and  the control strategy  is proposed accordingly. Finally,  the  simulation analysis of  the  stage control adopting the MATLAB software is performed.


This thesis argues that Gilles Deleuze, as philosopher, reader, and critic, recognised the
central importance of a defined authorial subjectivity, closely associated with a
philosophical or intellectual project, and that his analyses of philosophy, literature, visual art
and cinema were shaped and determined by his recognition of that authority. In this
respect, my reading challenges those critics who find in the work of Deleuze an assault on
'author-centric' interpretations of texts, and more generally on the concept of a unified self,
and which uphold experimentation on the part of the reader or critic rather than
interpretation. I argue that Deleuze has a coherent and meaningful conception of an author
as a consciousness which persists through time, learns, plans and makes projects,
differentiates itself from the work of other authors, is inspired and creative, takes positions
in relation to the inheritance of artistic and philosophical traditions, and which is capable of
entering into collaboration with others.
Through close reading of Deleuze's texts, I demonstrate that he consistently relies on the
authorial function to impose unity and coherence on the distinctive - and often remarkable
- body of work of an individual theorist or practitioner. I argue that the historical, political
and social situation of an author is of great importance to the analysis of a text. Finally,
unlike Roland Barthes or other critics invested in the 'death' or displacement of the author, I
argue that Deleuze considers the competing interpretations of a text advanced by the
reader or spectator to be of little or no importance.