Formulation of improved basis sets for the study of polymer dynamics through diffusion theory methods.
In this work a new method is proposed for the choice of basis functions in diffusion theory (DT) calculations. This method, named hybrid basis approach (HBA), combines the two previously adopted long time sorting procedure (LTSP) and maximum correlation approximation (MCA) techniques; the first emphasizing contributions from the long time dynamics, the latter being based on the local correlations along the chain. In order to fulfill this task, the HBA procedure employs a first order basis set corresponding to a high order MCA one and generates upper order approximations according to LTSP. A test of the method is made first on a melt of cis-1,4-polyisoprene decamers where HBA and LTSP are compared in terms of efficiency. Both convergence properties and numerical stability are improved by the use of the HBA basis set whose performance is evaluated on local dynamics, by computing the correlation times of selected bond vectors along the chain, and on global ones, through the eigenvalues of the diffusion operator L. Further use of the DT with a HBA basis set has been made on a 71-mer of syndiotactic trans-1,2-polypentadiene in toluene solution, whose dynamical properties have been computed with a high order calculation and compared to the "numerical experiment" provided by the molecular dynamics (MD) simulation in explicit solvent. The necessary equilibrium averages have been obtained by a vacuum trajectory of the chain where solvent effects on conformational properties have been reproduced with a proper screening of the nonbonded interactions, corresponding to a definite value of the mean radius of gyration of the polymer in vacuum. Results show a very good agreement between DT calculations and the MD numerical experiment. This suggests a further use of DT methods with the necessary input quantities obtained by the only knowledge of some experimental values, i.e., the mean radius of gyration of the chain and the viscosity of the solution, and by a suitable vacuum trajectory, with great savings in computational time required. This offers a theoretical bridge between the experimental static and dynamical properties of polymers.


The level of diagnostic assessment in severe asthma: A nationwide real-life study.
Systematic assessment of patients with severe asthma is pivotal to decide which patients are eligible to new biological therapies. However, the level of diagnostic work-up in patients with severe asthma is only poorly investigated. To describe the diagnostic work-up in a complete population of patients with severe asthma including: objective confirmation of the asthma diagnosis, and identification of potential treatment barriers, such as poor adherence and poor inhaler technique. A retrospective cross-sectional multicenter study was performed in 2013. We evaluated patient record forms of all patients (aged 18-65 years) consecutively referred with asthma to one of five respiratory outpatient clinics over two years. Patients were included in the study, if they fulfilled ERS/ATS guidelines for having severe asthma. Among 1563 patients with asthma, 98 (6.3%) patients fulfilled the criteria for having severe asthma. The diagnosis of asthma was confirmed objectively in 53/98 patients (54.1%). In total, 83.7% underwent at least one diagnostic test for asthma: reversibility test: 63.3%, PEF: 52% and bronchial challenge test: 21.4%. Among patients eligible for a bronchial challenge test (FEV1 ≥ 70%; negative PEF measurement/reversibility test), only 23.1% had such a test performed. Inhalation technique and adherence were assessed in 19.4 and 30.6% of patients, respectively. Among patients managed for severe asthma in a specialist setting, only half had the asthma diagnosis confirmed objectively, and adherence and inhaler technique were infrequently assessed.


The dose-area product, a new parameter for the dosimetry of narrow photon beams.
In the dosimetry of narrow photon fields with side lengths of the order of 1 cm, the traditional parametrisation via the absolute dose on the beam axis and the relative lateral dose distribution has to deal with the difficulty to find sufficiently small detectors and to adjust them accurately on the narrow-beam axis. This can be avoided by reconsidering the parametrisation, using as normalization factor the surface integral of the dose in the plane perpendicular to the beam axis, abbreviated as the "dose-area product" (DAP). We investigated and confirmed the ability of a large-area parallel-plate ionisation chamber, with a sensitive volume shaped as a flat cylinder of 81.6 mm diameter and 2 mm thickness, to perform the integration over the full lateral dose profile of narrow photon beams with side lengths up to 5 cm. The lateral adjustment of this large-area detector relative to a narrow photon beam is not critical. The large-area ionisation chamber was calibrated in terms of the DAP by reference to a 0.3 cm3 ionisation chamber. A field-size dependent "modified output factor" was defined as the ratio of the DAP measured at 5 cm phantom depth for 100 cm SSD, and the monitor reading. A prominent phenomenon of narrow photon fields is the field-size and source-distance independence of the relative axial profile of the DAP as function of the thickness of a pre-absorber or of the depth in a phantom. For narrow-beam treatment planning in IMRT, the DAP is combined with the energy- and field size-dependent relative lateral dose distribution which is represented, for example, by a Gaussian convolution kernel. Another useful feature of the DAP is the possibility of its direct control during patient irradiation by means of an on-line monitor with spatial resolution, arranged in the accessory holder.


Capsulate bacteria and the lung.
Capsulate bacteria cause the majority of community-acquired pneumonia presenting to hospital world-wide, at all ages. They are united by the virulence factor of their differing capsular polysaccharides, enabling them to evade phagocytosis. All cause invasive disease beyond the respiratory tract, including septicaemia and central nervous system infection. Recent advances in vaccine development have made the capsular polysaccharide an achievable target for vaccine strategies across all ages, with impacts already seen upon Streptococcus pneumoniae and Haemophilus influenzae type b pneumonia in countries able to afford these new vaccines.


Outcome With the Repositionable and Retrievable Boston Scientific Lotus Valve Compared With the Balloon-Expandable Edwards Sapien 3 Valve in Patients Undergoing Transfemoral Aortic Valve Replacement.
New generation devices for transfemoral aortic valve replacement were optimized on valve positioning and reduction of residual aortic regurgitation. We compared 30-day, 12-month, and 24-month outcomes of the Boston Scientific Lotus valve (Lotus) and the balloon-expandable Edwards Sapien 3 (ES3) valve. Primary end point was all-cause mortality or disabling stroke within 12 months. Between 2014 and 2016, 537 patients were enrolled at our center, and 202 patients received Lotus and 335 ES3. There was no residual moderate or severe aortic regurgitation. Rate of mild aortic regurgitation was lower with the repositionable and retrievable Lotus valve compared with the ES3. Rate of pacemaker implantation was significantly higher with the Lotus valve compared with the ES3 valve (36.1% versus 14.9%, P<0.01). Valve Academic Research Consortium-2 early safety end point at 30 days was 7.4% with both devices with no difference in all-cause mortality (Lotus, 1.9%; ES3, 1.8%; P=0.87), rate of disabling stroke (Lotus, 1.5%; ES3, 2.1%; P=0.62), or major vascular complications (Lotus, 2.9%; ES3, 2.4%; P=0.69). The primary end point at 12 months was similar between groups. In a propensity score-matched comparison, there was no difference in the primary end point within 12 months (Lotus, 15.5%; ES3, 18.6%; P=0.69) and 24 months (Lotus, 21.9%; ES3, 26.4%; P=0.49). Transfemoral aortic valve replacement with the ES3 and the Lotus were associated with similar 30-day, 12-month, and 24-month clinical outcomes. Need for permanent pacemaker implantation was significantly higher with the repositionable Lotus device. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02162069.


Cognitive analysis of multiple personality disorder.
Multiple personality disorder is not rare, and it can be treated using the principles of cognitive therapy. Noncognitive techniques are also required. The purpose of this paper is to define the basic cognitive map of multiple personality disorder, one which recurs in the majority of cases. Multiple personality patients commonly make the classical cognitive errors such as selective abstraction and dichotomization, but they also have a set of schemata and cognitions derived from their abusive childhoods that are specific for the disorder.


Plant-mediated interactions between whiteflies, herbivores, and natural enemies.
Whiteflies (Homoptera: Aleyrodidae) comprise tiny phloem-sucking insects. The sessile development of their immatures and their phloem-feeding habits (with minimal physical plant damage) often lead to plant-mediated interactions with other organisms. The main data come from the polyphagous pest species Bemisia tabaci (Gennadius) and Trialeurodes vaporariorum (Westwood), which are intricately associated with their host plants. Although these associations might not represent aleyrodids in general, we rely on them to highlight the fundamental role of host plants in numerous ecological interactions between whiteflies, other herbivores, and their natural enemies. Plant traits often affect the activity, preference, and performance of the whiteflies, as well as their entomopathogens, predators, and parasitoids. Leaf structure (primarily pubescence) and constitutive and induced chemical profiles (defensive and nutritional elements) are critically important determinants of whitefly fitness. Pest management-related and evolutionary biology studies could benefit from future research that will consider whiteflies in a multitrophic-level framework.


ERBBs in the gastrointestinal tract: recent progress and new perspectives.
The gastrointestinal epithelium does much more than provide a physical barrier between the intestinal lumen and our internal milieu. It is actively engaged in absorption and secretion of salt and water via ion transporters, exchangers and selective ion channels. It is also a continuously self-renewing epithelium that undergoes ordered growth and differentiation along its vertical axis. From this dual perspective, we will consider the actions of the ERBB family of ligands and receptors in the maintenance of gastrointestinal homeostasis and discuss instances when the actions of this family go awry such as in cancer and Ménétrier's disease.


Liquid chromatography-mass spectrometry and related techniques for purity assessment in early drug discovery.
The combination of HPLC and MS has become the most valuable analytical tool to determine the identity and purity of a drug substance in the drug discovery arena over the past decade. This article describes different LC/MS configurations and their broad applicability to meet the fundamental analytical requirements involved in discovering new drugs. In addition, the value of chemiluminescence nitrogen detection for absolute purity determination and the convenience of CE as an orthogonal separation technique to HPLC are also discussed. In summary, LC/MS-based methodologies that implicate automation, various levels of throughput and open access systems have proved to be an integral part of the drug discovery process. As a result, the paradigm of high-quality/-quantity information is fulfilled in a timely fashion.


Transcriptional changes following restoration of SERCA2a levels in failing rat hearts.
Heart failure is characterized at the cellular level by impaired contractility and abnormal Ca2+ homeostasis. We have previously shown that restoration of a key enzyme that controls intracellular Ca(2+) handling, the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), induces functional improvement in heart failure. We used high-density oligonucleotide arrays to explore the effects of gene transfer of SERCA2a on genetic reprogramming in a model of heart failure. A total of 1,300 transcripts were identified to be unmodified by the effect of virus alone. Of those, 251 transcripts were found to be up- or down-regulated upon failure. A total of 51 transcripts which were either up--(27) or down--(24) regulated in heart failure were normalized to the nonfailing levels by the restoration of SERCA2a by gene transfer. The microarray analysis identified new genes following SERCA2a restoration in heart failure, which will give us insights into their role in the normalization of multiple pathways within the failing cell.


Magnetron sputtered zinc oxide nanorods as thickness-insensitive cathode interlayer for perovskite planar-heterojunction solar cells.
Suitable electrode interfacial layers are essential to the high performance of perovskite planar heterojunction solar cells. In this letter, we report magnetron sputtered zinc oxide (ZnO) film as the cathode interlayer for methylammonium lead iodide (CH3NH3PbI3) perovskite solar cell. Scanning electron microscopy and X-ray diffraction analysis demonstrate that the sputtered ZnO films consist of c-axis aligned nanorods. The solar cells based on this ZnO cathode interlayer showed high short circuit current and power conversion efficiency. Besides, the performance of the device is insensitive to the thickness of ZnO cathode interlayer. Considering the high reliability and maturity of sputtering technique both in lab and industry, we believe that the sputtered ZnO films are promising cathode interlayers for perovskite solar cells, especially in large-scale production.


Randomized pilot study comparing oral ibuprofen with intravenous ibuprofen in very low birth weight infants with patent ductus arteriosus.
We conducted a prospective, randomized, single-masked pilot study with the principal aim of comparing efficacy and tolerance between oral and intravenous ibuprofen in early closure of patent ductus arteriosus in very low birth weight infants. The possibility of ductal closure with only 1 or 2 doses of treatment was a secondary objective. Sixty-four very low birth weight patients with echocardiographically confirmed patent ductus arteriosus and respiratory distress were studied. The patients were randomly assigned to receive either oral (group O, n=32) or intravenous (group I, n=32) ibuprofen starting on the third day of life. After the first dose of treatment in both groups, echocardiographic evaluation was performed to determine the need for a second or third dose. The rate of ductal closure, adverse effects, complications, and the patient's clinical course were recorded. In each group, 24 (75%) patients were born after 28 weeks' gestation. The rate of ductal closure tended to increase in group O (84.3% vs 62.5%). Closure of the ductus was obtained after 1 or 2 doses of treatment in 19 (70.3%) of 27 patients in group O and 14 (70%) of 20 patients in group I. The adverse effects were increased in group I (31.2% vs 9.3%). There were no significant differences with respect to complications during the stay. Adverse effects were significantly fewer when closure was achieved after an incomplete course of treatment (23.1% vs 76.9%). In very low birth weight infants, the rate of early ductal closure with oral ibuprofen is at least as good as with the intravenous route. Ductal closure may be obtained with an incomplete course of ibuprofen. Oral ibuprofen is associated with fewer adverse effects. However, a larger sample is needed for more definitive conclusions.


Psychotherapy and temporal lobe epilepsy.
This paper describes psychotherapy of a thirty-year-old man with documented temporal lobe epilepsy. After describing the commonly associated neuropsychiatric symptoms and personality syndrome, a case history and summary of treatment are presented. Changes in frequency, duration, and severity of seizures are discussed in relation to psychotherapy.


Selective development of one cone photoreceptor type in retinal organ culture.
The authors have established an organ culture method in which the the postnatal development and the structural integrity of the mouse retina can be maintained for at least 6 weeks. Additionally, they have examined the emergence and in vitro morphogenesis of the photoreceptors and the development of insoluble components of the interphotoreceptor matrix. Neural retinas and retinal pigment epithelia from 48-hour-old C3H ++/++ mice were cultured. At various ages, the tissues were fixed and cryosectioned or wholemounted. Photoreceptor development was studied by immunocytochemistry with visual pigment antibodies and by lectin cytochemistry. The ultrastructure of the photoreceptors was studied by electron microscopy. Immunopositive rods and short-wave sensitive cones were detectable as early as 3 days after explantation. From this time on, matrix domains around cones were also identifiable and labelled with peanut agglutinin lectin. However, the antibody specific to the middle-wave sensitive cone pigment failed to recognize any cones throughout the 6-week culture period. Both basic photoreceptor types appeared and developed in this organ culture system according to a timetable comparable to normal in vivo development. Surprisingly, under these circumstances, one of the two cone pigments was not expressed by any photoreceptors.


Center of Pressure Behavior in Response to Unexpected Base of Support Shifting: A New Objective Tool for Dynamic Balance Assessment.
The translation of the base of support represents a promising approach for the objective assessment of dynamic balance control. Therefore, this study aimed to present a servo-controlled, electrically driven movable plate and a new set of parameters based on the center-of-pressure (CoP) trajectory. Twenty subjects were assessed on a force platform screwed over a movable plate that could combine the following settings: direction (forward (FW) and backward (BW)), displacement (25 mm, 50 mm, and 100 mm), and ramp rate (100 mm/s and 200 mm/s). The subjects underwent two sets of 12 trials randomly combining the plate settings. From the CoP trajectory of the 2.5 s time window after the perturbation, the 95% confidence-interval ellipse (Area95) and the CoP mean velocity (Unit Path) were calculated. Within the same time window, the first peak (FP), the maximal oscillations (ΔCoPMax), and the standard deviation (PPV) of the CoP anterior-posterior trajectory were calculated. The plate direction (p < 0.01), ramp rate (p < 0.001), and displacement (p < 0.01) affected the Area95, FP, and ΔCoPMax, while the Unit Path and PPV were influenced only by the ramp rate (p < 0.001) and displacement (p < 0.001). The servo-controlled, electrically driven movable plate and the CoP-related parameters presented in this study represent a new promising objective tool for dynamic balance assessment.


Reconstitution of Semliki forest virus membrane.
The spike glycoproteins of the Semliki forest virus membrane have been incorporated into vesicular phospholipid bilayers by a detergent-dialysis method. The detergent used was beta-D-octylglucoside which is nonionic and has an exceptionally high critical micellar concentration which facilitates rapid removal by dialysis. The vesicles obtained were of varying sizes and had spikes on their surface. Two classes of vesicles were preferentially formed, small protein-rich and large lipid-rich (average lipid to protein weight ratios, 0.22 and 3.5, respectively). Both classes of vesicles retained the hemagglutinating activity of the virus. The proteins were attached to the lipid bilayer by hydrophobic peptide segments, as in the viral membrane. Most of the proteins were accessible to proteolytic digestion from the outside, suggesting an asymmetric orientation.


Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes.
The dominant feature in neurodegenerative diseases is protein aggregations that lead to neuronal loss. Immunotherapies using antibodies or antibody fragments to target the aggregations are a highly perused approach. The molecular mechanisms underlying the amyloid-based immunotherapy are complex. Deciphering the properties of amyloidogenic proteins responsible for these diseases is essential to obtain insights into antibody recognition of the amyloid antigens. We systematically explore all available crystal structures of antibody-amyloid complexes related to neurodegenerative diseases, including antibodies that recognize the Aβ peptide, tau protein, prion protein, alpha-synuclein, huntingtin protein (mHTT), and polyglutamine. We found that antibodies mostly use the conformational selection mechanism to recognize the highly flexible amyloid antigens. In particular, solanezumab bound to Aβ12-28 tripeptide motif conformation (F19F20A21), which is shared with the Aβ42 fibril. This motif, which is trapped by the antibody, may provide the missing link in amyloid formation. Water molecules often bridge between the antibody and amyloid, contributing to the recognition. This paper provides the structural basis for antibody recognition of amyloidogenic proteins. The analysis and discussion of known structures are expected to help in the design and optimization of antibodies in neurodegenerative diseases. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.


Local field effect on charge-capture/emission dynamics.
Charge-capture/emission is ubiquitous in electron devices. Its dynamics often play critical roles in device operation and reliability. Treatment of this basic process is found in many text books and is considered well understood. As in many electron device models, the individuality of immobile charge is commonly replaced with the average quantity of charge density. This has worked remarkably well when large numbers of individual charges (ensemble) are involved. As device geometries become very small, the ensemble "averaging" becomes far less accurate. In this work, the charge-capture/emission dynamic of Metal-Oxide-Semiconductor-Field-Effect-Transistor (MOSFET) is re-examined with full consideration of individual charges and the local field in their immediate vicinity. A dramatic modification of the local band diagram resulted, forcing a drastic change in emission mechanism. The implication is that many well-understood phenomena involving charge capture/emission will need to be reconsidered. As an example, this new picture is applied to the random telegraph noise (RTN) phenomenon. When the screening of a trapped charge by a polar medium such as SiO2 is quantitatively accounted for in this local field picture, a new physically sound RTN emission mechanism emerges. Similarly, the dynamics of post-stress recovery of Negative-Bias-Instability of p-channel MOSFET can be more rationally explained.


Preliminary pioneer 10 encounter results from the ames research center plasma analyzer experiment.
Preliminary results from the Ames Research Center plasma analyzer experiment for the Pioneer 10 Jupiter encounter indicate that Jupiter has a detached bow shock and magnetopause similar to the case at Earth but much larger in spatial extent. In contrast to Earth, Jupiter's outer magnetosphere appears to be highly inflated by thermal plasma and therefore highly responsive in size to changes in solar wind dynamic pressure.


Insulin-receptor kinase activity of adipose tissue from morbidly obese humans with and without NIDDM.
We have determined glucose transport, insulin binding, and insulin-receptor kinase activity in adipose tissue from morbidly obese patients with and without non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity and responsiveness of glucose transport in freshly isolated adipocytes were significantly reduced in NIDDM subjects compared with nondiabetics. This was due in part to decreased insulin binding in adipocytes. Reduced specific 125I-labeled insulin binding was also observed in crude detergent extracts and partially purified insulin receptors from adipose tissue. In addition, the basal and insulin-stimulated tyrosine-specific protein kinase activity per milligram of protein was significantly decreased in NIDDM patients compared with nondiabetics. The differences between maximally insulin-stimulated and basal kinase activities expressed by insulin-binding activity were also significantly reduced in NIDDM subjects. We conclude that insulin resistance in morbidly obese patients with NIDDM is due to both insulin-binding and postbinding defects. One of the postbinding defects in NIDDM appears to be impaired insulin-receptor kinase activity of fat tissue.


Hyperacute rejection of skin allografts in the mouse. Sensitivity of ingrowing skin grafts to the action of alloantibody and rabbit complement.
The destructive action of alloantiserum and exogenous complement on ingrowing skin allografts was studied. B6AF1 recipients of a B10.D2 skin graft received a single intravenous injection of B6AF1 anti-B10.D2 serum (antiserum to H-2K.31) together with rabbit complement (RC) within the first 10 days after transplantation. Different models were used: recipients without immunosuppression, recipients treated with antilymphocyte serum, x-irradiation, or enhancing antibody. If the injection was given between day 5 and 10 after grafting, hyperacute rejection occurred in all cases. The rejection seemed to be most violent when the injection was given on days 7 or 8. Injections given on days 1, 2 or 3 after grafting could not induce hyperacute-rejection, but resulted, on the contrary, in a prolongation of graft survival, probably due to immunological enhancement. Injections on day 4 produced patchy necrosis, but the grafts recovered and the residual tissue showed a prolonged survival. The results suggest that the presence of a functioning vascular network is a prerequisite for the occurrence of hyperacute rejection of skin allografts in the mouse.


Lymphocytic cholecystitis/cholangitis.
To describe four cases of an uncommon type of acalculous cholecystitis/cholangitis characterized by increased intraepithelial lymphocytes within the biliary epithelium. Cases were prospectively compiled during regular surgical pathology sign-out. Clinical information was obtained from the electronic medical record and the gross appearance from the surgical pathology reports. Microscopic examination was performed with emphasis on the type, location, and distribution of the inflammatory pattern; presence of intraepithelial lymphocytes (>30 per 100 biliary cells); and presence of metaplasia and epithelial hyperplasia. Immunohistochemical stains for CD3, CD8, and IgG4 were performed in some cases. All patients were adults who had either biliary pain or obstructive symptoms. All gallbladders had a relatively normal gross appearance and did not contain gallstones or biliary sludge. Microscopic examination showed numerous intraepithelial lymphocytes in the biliary epithelium. The mucosa was frequently expanded by dense inflammatory cell infiltrates. The inflammatory process was more severe in the infundibulum and bile ducts than in the body of the gallbladder. The intraepithelial lymphocytes were CD3+, CD8+. IgG4+ plasma cells were absent. The term lymphocytic cholecystitis/cholangitis is proposed. The potential clinical implications and pathogenesis of this inflammatory pattern and the differential diagnosis with other forms of acalculous cholecystitis are discussed.


The mitochondrial protein frataxin is essential for heme biosynthesis in plants.
Frataxin, a conserved mitochondrial protein implicated in cellular iron homeostasis, has been involved as the iron chaperone that delivers iron for the Fe-S cluster and heme biosynthesis. However, its role in iron metabolism remains unclear, especially in photosynthetic organisms. In previous work, we found that frataxin deficiency in Arabidopsis results in decreased activity of the mitochondrial Fe-S proteins aconitase and succinate dehydrogenase, despite the increased expression of the respective genes, indicating an important role for Arabidopsis thaliana frataxin homolog (AtFH). In this work, we explore the hypothesis that AtFH can participate in heme formation in plants. For this purpose, we used two Arabidopsis lines, atfh-1 and as-AtFH, with deficiency in the expression of AtFH. Both lines present alteration in several transcripts from the heme biosynthetic route with a decrease in total heme content and a deficiency in catalase activity that was rescued with the addition of exogenous hemin. Our data substantiate the hypothesis that AtFH, apart from its role in protecting bioavailable iron within mitochondria and the biogenesis of Fe-S groups, also plays a role in the biosynthesis of heme groups in plants.


Delayed correction of anorectal incontinence due to anal sphincteral injury.
True anorectal incontinence, often the result of obstetrical or surgical injury to the anal sphincteral muscles, can be identified precisely. Although a variety of surgical procedures are available for correction of this defect, this report describes the repair method of overlapping the severed ends of the anal sphincteral muscles. Five patients had injuries associated with the birth of children; one patient had had a previous surgical injury; and one patient had anal tuberculosis. Only the last patient did not have an excellent result, and he experienced considerable improvement.


Neurosciences, empathy, and healthy interpersonal relationships: recent findings and implications for counseling psychology.
In this article, we define the construct of empathy and its relevance for counseling psychology. The importance of deficits in empathic processes for most of the psychological disorders is presented within the context of the social brain hypothesis (Frith, 2007). We provide a review of empirical research about the neural correlates of empathy in terms of both the central and peripheral nervous system. We present recent evidence on the cortical and subcortical regions involved in different dimensions of empathy-emotional contagion, cognitive and emotional empathy, and self-regulation. Regarding the autonomic correlates of empathy, we present evidence about the correlates of sympathetic arousal associated with empathic processes and review data supporting the idea of the physiological linkage or synchrony as indicator of empathy in interpersonal relationships. The implications of these findings for counseling psychology, particularly for the psychotherapist-client relationship and for context of intimate relationships or couples therapy, are discussed.


Long-term a posteriori dietary patterns and risk of hip fractures in a cohort of women.
Dietary pattern analysis is a useful tool to study the importance of food components in the context of a diet and how they relate to health and disease. The association between dietary patterns and fractures is at present uncertain. We aimed to study associations between dietary patterns and risk of hip fracture in the Swedish Mammography Cohort, including 56,736 women (median baseline age 52 years). Diet data was collected in food frequency questionnaires at two investigations and dietary patterns were defined by principal component analysis using 31 food groups. Information on hip fractures was collected from the Swedish National Patient Register. Multivariable adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated in Cox proportional hazards regression analysis. The two patterns identified-the healthy and Western/convenience dietary patterns-were time-updated and analysed. During a median follow-up time of 25.5 years, 4997 women experienced a hip fracture. Hip fracture rate was 31% lower in the highest compared to the lowest quartile of the healthy dietary pattern [HR (95% CI) 0.69 (0.64; 0.75)]. In contrast, women in the highest compared to the lowest quartile of the Western/convenience dietary pattern had a 50% higher [HR (95% CI) 1.50 (1.38; 1.62)] hip fracture rate. Further, in each stratum of a Western/convenience dietary pattern a higher adherence to a healthy dietary pattern was associated with less hip fractures. The present results suggest that a varied healthy diet may be beneficial for the prevention of fragility fractures in women.


A new species of myxozoa in the skeletal striated musculature of Rhamdia quelen (Quoy Gaimard) (Siluriforme: Pimelodidae) Amazonian fish, Marajó island, Brazil.
A new myxozoan was found parasitizing the freshwater catfish, Rhamdia quelen (Quoy Gaimard), in the Marajó island, Amazon region, Brazil. The new species is described based on the results of morphological and molecular analyses. The parasite is approximately 1.5 mm in diameter and develops in the musculature of the host in the form of spherical, whitish cysts, which are visible macroscopically between the epaxial and hypaxial layers. When ruptured, these cysts produced ellipsoidal spores with a mean length of 11.4 μm (10.7-12.6) and width of 7.2 μm (6.4-7.9). Anomalous spores with a caudal elongation, vesicles in the peripheral portion of the spore and ornamentation of the valves were also observed. The results of the phylogenetic analysis of sequences of the 18S rDNA gene using Bayesian Inference indicated clear differences among the Myxobolus species that reinforced the taxonomic position of the parasite, confirming its status as a new species, denominated Myxobolus arariensis n. sp.


miR‑21 promotes α‑SMA and collagen I expression in hepatic stellate cells via the Smad7 signaling pathway.
The aim of the present study was to investigate the role of microRNA (miR)‑21 in regulating collagen I and Smad7 expression in activated rat hepatic stellate cells (HSCs). Rat HSCs were isolated by single‑step density gradient centrifugation with Nycodenz. Cellular content of miR‑21, SMAD7, α‑smooth muscle actin (α‑SMA), collagen type I alpha 1 (COLLA1) and COLL alpha 2 (A2) mRNA was examined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and cellular content of Smad7 and α‑SMA protein was detected by western blotting. Binding of miR‑21 to the 3'‑untranslated region (UTR) of Smad7 was verified by dual‑luciferase assay. The authors observed that, in activated HSCs, expression of miR‑21 was significantly increased in a time‑dependent manner, while expression of Smad7 mRNA and protein was significantly reduced. In addition, miR‑21 mimics significantly enhanced cellular α‑SMA mRNA and protein content, while miR‑21 inhibitor significantly reduced α‑SMA mRNA and protein levels. Similarly, cellular content of COLLA1 and COLLA2 mRNA was significantly elevated by miR‑21 mimics, but reduced by miR‑21 inhibitor, in activated HSCs. Moreover, cellular content of Smad7 mRNA and protein was significantly reduced by miR‑21 mimics, but significantly increased by miR‑21 inhibitor. Furthermore, miR‑21 mimics activated firefly luciferase in HEK293 cells transfected with the wild type 3'‑UTR of Smad7. miR‑21 regulates expression of α‑SMA and collagen I in activated rat HSCs by directly targeting Smad7.


Sexual and reproductive health challenges facing minority ethnic girls in Vietnam: a photovoice study.
This paper describes a study that examined the challenges faced by Vietnamese ethnic minority girls regarding their sexual and reproductive health. The study employed photovoice, a research method which treats photographs and the accompanying stories provided by participants as qualitative data. Twenty-six (26) minority ethnic girls took photographs of aspects of their lives as a way of documenting the challenges, difficulties and barriers that they faced in looking after their sexual and reproductive health. Findings indicated limited access to sexual health knowledge, the exclusion of young people from mainly adult-focused sexual and reproductive health services in minority ethnic communities and the prevalence of cultural beliefs and practices that negatively affected young people's sexual and reproductive health. The intersection of ethnicity, age and gender places Vietnamese ethnic minority girls at risk, as everyday practices informed by culture and tradition curtail their access to the limited sexual and reproductive health information and services available in their communities. Understanding these challenges is needed in developing appropriate policies, programmes and services aimed at enhancing the sexual and reproductive health of this segment of the population.


Lipophilicity of oils and fats estimated by TLC.
A representative series of natural toxins belonging to alkaloids and mycotoxins classes was investigated by TLC on classical chemically bonded plates and also on oils- and fats-impregnated plates. Their lipophilicity indices are employed in the characterization and comparison of oils and fats. The retention results allowed an accurate indirect estimation of oils and fats lipophilicity. The investigated fats and oils near classical chemically bonded phases are classified and compared by means of multivariate exploratory techniques, such as cluster analysis, principal component analysis, or fuzzy-principal component analysis. Additionally, a concrete hierarchy of oils and fats derived from the observed lipophilic character is suggested. Human fat seems to be very similar to animal fats, but also possess RP-18, RP-18W, and RP-8.


Functional characterization of the low-molecular-mass phosphotyrosine-protein phosphatase of Acinetobacter johnsonii.
The ptp gene of Acinetobacter johnsonii was previously reported to encode a low-molecular-mass protein, Ptp, whose amino acid sequence, predicted from the theoretical analysis of the nucleotide sequence of the gene, exhibits a high degree of similarity with those of different eukaryotic and prokaryotic phosphotyrosine-protein phophatases. We have now overexpressed the ptp gene in Escherichia coli cells, purified the Ptp protein to homogeneity by a single-step chromatographic procedure, and analysed its functional properties. We have shown that Ptp can catalyse the dephosphorylation of p-nitrophenyl phosphate and phosphotyrosine, but has no effect on phosphoserine or phosphothreonine. Its activity is blocked by ammonium molybdate and sodium orthovanadate, which are strong inhibitors of phosphotyrosine-protein phosphatases, as well as by N-ethylmaleimide and iodoacetic acid. Such specificity of Ptp for phosphotyrosine has been confirmed by the observation that it can dephosphorylate endogenous proteins phosphorylated on tyrosine, but not proteins modified on either serine or threonine. In addition, Ptp has been shown to quantitatively dephosphorylate two exogenous peptides, derived respectively from leech hirudin and human gastrin, previously phosphorylated on tyrosine. Moreover, site-directed mutagenesis experiments performed on Cys11 and Arg16, which are both present in the sequence motif (H/V)C(X5)R(S/T) typical of eukaryotic phosphotyrosine-protein phosphatases, have demonstrated that each amino acid residue is essential for the catalytic activity of Ptp. Taken together, these data provide evidence that Ptp is a member of the phosphotyrosine-protein phosphatase family. Furthermore, in search for the biological function of Ptp, we have found that it can specifically dephosphorylate an endogenous protein kinase, termed Ptk, which is known to autophosphorylate at multiple tyrosine residues in the inner membrane of Acinetobacter johnsonii cells. This represents the first identification of a protein substrate for a bacterial phosphotyrosine-protein phosphatase, and therefore constitutes a possible model for analysing the role of reversible phosphorylation on tyrosine in the regulation of microbial physiology.


Effects of cerebroventricular administration of ouabain on renal hemodynamics in anesthetized dogs: evidence for the participation of renal dopaminergic vasodilator fibers.
Cerebroventricular infusion of ouabain (10(-6) M) in cerebrospinal fluid produced significant increases in renal blood flow and reductions in renal vascular resistance in chloralose anesthetized, vagotomized dogs; these renal effects were not accompanied by any changes in arterial blood pressure and heart rate. Infusion of a higher concentration of ouabain (10(-5) M) enhanced significantly blood pressure, heart rate, renal vascular resistance and reduced renal blood flow. The renal vasodilator effects precipitated by lower concentration of ouabain have not been documented before and the mechanisms involved in these observations were investigated in the present study. Pretreatment of the dogs with indomethacin did not prevent renal vasodilator effects of ouabain, indicating that prostaglandins were not involved. Acute renal denervation abolished these actions suggesting that these renal vascular effects were mediated neurogenically. In the dogs, pretreated with i.v. sulpiride, a dopamine receptor antagonist, central infusions of ouabain (10(-6) M) produced significant increases in blood pressure, renal vascular resistance and reduced renal blood flow. These effects were opposite to those noted in control animals. These data suggested that vasodilatation induced by central ouabain was mediated via activation of renal dopaminergic fibers. Prior intraventricular infusion of small doses of sulpiride that antagonized central dopamine receptors, without affecting peripheral sites, also prevented but did not reverse the renal effects of ouabain. Selective blockade of central alpha receptors with phentolamine also abolished ouabain-induced renal vasodilatation. In addition, after central alpha receptor blockade ouabain increased arterial blood pressure. In the dogs pretreated with i.v. phentolamine, cerebroventricular ouabain did not produce any changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)


Pregnancy Increases Ca2+ Sparks/Spontaneous Transient Outward Currents and Reduces Uterine Arterial Myogenic Tone.
Spontaneous transient outward currents (STOCs) at physiological membrane potentials of vascular smooth muscle cells fundamentally regulate vascular myogenic tone and blood flow in an organ. We hypothesize that heightened STOCs play a key role in uterine vascular adaptation to pregnancy. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Ca2+ sparks were measured by confocal microscopy, and STOCs were determined by electrophysiological recording in smooth muscle cells. Percentage of Ca2+ spark firing myocytes increased dramatically at the resting condition in uterine arterial smooth muscle of pregnant animals, as compared with nonpregnant animals. Pregnancy upregulated the expression of RyRs (ryanodine receptors) and significantly boosted Ca2+ spark frequency. Ex vivo treatment of uterine arteries of nonpregnant sheep with estrogen and progesterone imitated pregnancy-induced RyR upregulation. STOCs occurred at much more negative membrane potentials in uterine arterial myocytes of pregnant animals. STOCs in uterine arterial myocytes were diminished by inhibiting large-conductance Ca2+-activated K+ (BKCa) channels and RyRs, thus functionally linking Ca2+ sparks and BKCa channel activity to STOCs. Pregnancy and steroid hormone treatment significantly increased STOCs frequency and amplitude in uterine arteries. Of importance, inhibition of STOCs with RyR inhibitor ryanodine eliminated pregnancy- and steroid hormone-induced attenuation of uterine arterial myogenic tone. Thus, the present study demonstrates a novel role of Ca2+ sparks and STOCs in the regulation of uterine vascular tone and provides new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.


Pain complaints in adolescent patients with affective disorders versus adolescent psychiatric controls.
To ascertain the frequencies of 4 prospectively determined pain complaints among adolescents meeting the criteria for major depressive episode (MDE) relative to non-affectively ill controls. In a community mental health clinic for the indigent situated on the border of the United States and Mexico (Rio Grande City, Tex.), adolescents (age range, 12-17 years) who consecutively presented to the clinic from August 2001 to November 2003 received structured psychiatric diagnostic screens for depression and mania using the modules from the DSM-IV. Subsequently, all subjects were asked whether they had had significant (distressing or bothersome) backache, abdominal pain, headaches, or myalgia in the last 7 days. We compared patients meeting the criteria for MDE with individuals without affective symptomatology. Significance of the differences between groups was assessed using the Fisher exact test and multivariate logistic regression analysis. The odds ratios were adjusted for age and sex. One hundred thirty-two subjects met the criteria for MDE. Forty-eight had non-affective disorders. Seventy-six percent of the subjects meeting the criteria for MDE had at least 1 pain complaint compared to 33% of the control subjects (p < .0001). Fifty percent of the subjects in the midst of a MDE had at least 2 pain complaints compared to 6% of the control subjects (p < .0001). Twenty-nine percent of the subjects in the midst of a MDE had at least 3 pain complaints compared to 2% of the control subjects (p < .0001). Fourteen percent of the subjects in the midst of a MDE had all 4 pain complaints compared to none of the control subjects (p = .002). The odds ratio of subjects with a MDE having a pain complaint relative to control subjects was 5.8 (p < .0001). That in excess of three fourths of clinically depressed adolescents had 1 or more pain complaints has important implications for adolescent psychiatry and primary care, as well as somatic medicine.


Tight Embrace in a Molecular Knot with Eight Crossings.
When it takes eight to tango: Since the synthesis of the simplest of all knots, the trefoil knot, in 1989, the formation of more complex knots has remained extremely challenging. The synthesis of the most complex molecular knot made to date, the 819 , by Leigh and co-workers thus represents a major step towards building topologically complex architectures.


Comparison of clinical outcomes in all-arthroscopic versus mini-open repair of rotator cuff tears: A randomized clinical trial.
The aim of the study was to compare the clinical outcomes of patients undergoing all-arthroscopic (AA) or mini-open (MO) rotator cuff repair. The present study evaluated 50 patients who had undergone AA repair and 50 patients who had undergone MO repair with a minimum 1-year follow-up. Every patient was asked to complete the Disabilities of the Arm, Shoulder and Hand (DASH) and visual analog scale (VAS) questionnaires. Constant-Murley score (CMS) and active ranges, forward flexion and external rotation, were also evaluated and documented. One year after surgery, ultrasound evaluation was done to determine the integrity of the rotator cuff for each patient. The average age of enrolled patients at the time of surgery was 53.0 years (range, 40-59 years), and average follow-up was 16.6 months (range, 12-24 months). At 2 weeks, the range of forward flexion in the AA group was larger than that in the MO group (136.5 ± 10.2 vs 132.5 ± 7.7, P = 0.03). On postoperative day 1, the VAS in the MO group was significantly higher than that in the AA group (6.5 ± 0.6 vs 6.1 ± 0.6, P < 0.01). At 1 month, the difference in VAS between both groups reappeared (2.9 ± 0.6 vs 2.6 ± 0.6, P = 0.03). At 1 month, the CMS score of patients in the AA group was higher than that in the MO group (52.8 ± 3.6 vs 50.9 ± 5.0, P = 0.03). At 3 and 6 months, the DASH score of patients in the AA group was lower than that in the MO group (43.8 ± 8.2 vs 47.8 ± 4.4, P < 0.01 and 38.6 ± 4.3 vs 42.7 ± 9.9, P < 0.01, respectively). Mean operative time was longer in the AA group compared with that in the MO group (71.9 ± 17.6 vs 64.7 ± 12.7 minutes, P < 0.01). Five patients (10.0%) in the AA group and 4 patients (8.2%) in the MO group had rotator cuff retear, and 6 patients (12.0%) in the AA group and 8 patients (16.3%) in the MO group had adhesive capsulitis by the end of follow-up. There is no significant difference between the 2 groups in the incidence of complications. We also found that joint exercising at least 3 times per week was associated with better short- and long-term joint function recovery. The AA approach was associated with less pain and lower DASH score as well as higher CMS score in the early recovery period. No difference was found between the 2 groups in primary and secondary outcomes in the long term, or incidence of complications such as adhesive capsulitis and rotator cuff retear. In conclusion, we consider that the AA procedure has better recovery at short-term follow-ups, while both techniques are equivalent regarding long-term outcomes.


Prevalence of refractive error and other eye diseases in schoolchildren in the Greater Accra region of Ghana.
To determine the prevalence of refractive error and other eye diseases in schoolchildren in the Greater Accra region of Ghana. Research assistants tested visual acuity (VA) using a Snellen chart in students randomly selected from 24 schools (i.e., 8 metropolitan, 8 urban, and 8 rural). An ophthalmologist examined students with VA of 6/12 or worse in either eye and students with other eye problems. Nine hundred fifty-seven students aged 6 to 22 years were screened: 67 had myopia with VA of 6/12 or worse in the better eye, 3 were unilaterally blind (2 from squint or amblyopia, 1 from a hypoplastic disk), and 4 had unilateral low vision from macular scars. Other eye diseases observed were congenital glaucoma (1), vernal conjunctivitis (2), and infective conjunctivitis (6). The prevalence of refractive error reducing vision to at least 6/12 was 7.0%. The prevalence of squint and amblyopia was 0.2%. The most common eye defect in the students was refractive error. Squint and amblyopia were rare.


Remote detection NMR imaging of gas phase hydrogenation in microfluidic chips.
The heterogeneous hydrogenation reaction of propene into propane in microreactors is studied by remote detection (RD) nuclear magnetic resonance (NMR). The reactors consist of 36 parallel microchannels (50 × 50 μm(2) cross sections) coated with a platinum catalyst. We show that RD NMR is capable of monitoring reactions with sub-millimeter spatial resolution over a field-of-view of 30 × 8 mm(2) with a steady-state time-of-flight time resolution in the tens of milliseconds range. The method enables the visualization of active zones in the reactors, and time-of-flight is used to image the flow velocity variations inside the reactor. The overall reaction yields determined by NMR varied from 10% to 50%, depending on the flow rate, temperature and length of the reaction channels. The reaction yield was highest for the channels with the lowest flow velocity. Propane T1 relaxation time in the channels, estimated by means of RD NMR images, was 270 ± 18 ms. No parahydrogen-induced polarization (PHIP) was observed in experiments carried out using parahydrogen-enriched H2, indicating fast spreading of the hydrogen atoms on the sputtered Pt surface. In spite of the low concentration of gases, RD NMR made imaging of gas phase hydrogenation of propene in microreactors feasible, and it is a highly versatile method for characterizing on-chip chemical reactions.


Comparison of different methods of assessing in vitro resistance of Mycobacterium tuberculosis to rifampicin.
Definitions of in vitro resistance to rifampicin in strains of Mycobacterium tuberculosis by different methods have not been consistent, leading to variations in the interpretation and validity of results. This study compared three methods of defining in vitro resistance to rifampicin. (i) A total of 598 clinical isolates of M. tuberculosis were concurrently compared by the minimal inhibitory concentration (MIC) and the proportion method on Lowenstein-Jensen medium; (ii) 54 strains tested by the MIC method were retested by the proportion method and the BACTEC radiometric method; and (iii) 72 strains which yielded an MIC of 64 mg/l by the MIC method were retested by the same method. Out of 598 cultures tested by the MIC and the proportion methods, identical classification as susceptible or resistant was observed in 99.7 per cent. A 100 per cent agreement was observed when 54 strains were tested by the MIC, proportion and BACTEC radiometric methods. When 72 strains with an MIC of 64 mg/l were retested by the same method, 61 (85%) yielded a lower MIC, 9 (12%) gave the same MIC while 2 (3%) yielded a higher MIC of 128 mg/l, reflecting perhaps the inherent limitations of the variations in the inoculum size. All 3 definitions of resistance, viz., an MIC of 128 mg/l, a proportion of 1 per cent or more on 40 mg/l by the proportion method, both on L-J medium and a growth of 1 per cent or more on 2 mg/l by the radiometric method were found to be equally satisfactory.


[Epidemiological study of hepatitis B and C in 34,336 patients operated at Hiroshima Prefectural Hospital during the period from 1993 to 2000].
We have many chances to deal with blood transfusion in the operation room, and it is important for us to pay more attention to prevent hospital infection. We surveyed epidemiologically the prevalence of hepatitis B virus surface antigen (HBV) and hepatitis C virus antibody (HCV) in 34,336 patients operated at Hiroshima Prefectural Hospital from April 1993 through March 2001. The prevalence of HBV seropositivity was 1.8% in total, 1.6% in scheduled, and 2.5% in emergent cases. The prevalence of HCV seropositivity was 7.1% in total, 6.8% in scheduled, and 8.0% in emergent cases. Prevalences of both of them in emergent cases were higher than scheduled. The prevalence of HBV was highest (3.4%) in patients with age of 40's, and the prevalence of HCV increased with age. The prevalences of HBV and HCV were highest (4.5% and 19.0%) in the division of surgery and dialysis-kidney disease center. It is important to carry out standard precautions for all patients to prevent hospital infection. Furthermore, we should pay attention to emergent operative cases and operative cases in dialyzed patients.


The Effects of an Online Mind-Body Training Program on Stress, Coping Strategies, Emotional Intelligence, Resilience and Psychological State.
The goal of this study was to evaluate the effects of an online mind-body training (MBT) program on participants' stress, anger, coping strategies, emotional intelligence, resilience, and positive and negative affect. Forty-two healthy women participated in an online MBT program for approximately 8-10 minutes a day for 8 weeks; a control group of 45 healthy women did not participate in the program. Self-report psychological questionnaires were administered before the beginning of the program and at 4 and 8 weeks following its onset. Data from the MBT group and the control group were compared using repeated measures ANOVA and Student's t-tests. Significant time x group interaction effects were found with respect to stress, coping strategies, anger, emotional intelligence, negative affect and resilience. These results demonstrate beneficial effects of the online MBT program and significant improvements in the psychological capabilities of participants compared with the control group. The effects of online MBT program were similar with those of the previous offline MBT in psychological aspects, suggesting further studies for neuroscientific evidence related stress and emotion of online MBT effects.


Design and analysis of a displacement amplifier with high load capacity by combining bridge-type and Scott-Russell mechanisms.
To improve the load capacity of flexure-based amplification mechanisms, a flexure-based displacement amplification mechanism is developed in this study by combining the bridge-type and the Scott-Russell mechanisms. The four arms of the traditional bridge mechanism are replaced by four Scott-Russell mechanisms that provide the advantages of good symmetry, compact structure, and higher load capacity. An analytical model is formulated using a stiffness matrix to analyze the natural frequency, input and output stiffnesses, displacement amplification ratio, and load capacity of the proposed mechanism. The design model was subjected to both experimental methods and finite element analysis for verification, and the two sets of results were in good agreement. This proves the effectiveness and applicability of the analytical model and the proposed amplification mechanism. The output stiffnesses of the modified bridge-type amplifier and the traditional bridge-type amplifier are 0.158 N/μm and 0.041 N/μm, respectively, indicating excellent load performance of the modified bridge-type amplifier.


The production of alpha-amylase in batch and chemostat culture by Bacillus stearothermophilus.
The production of alpha-amylase (alpha-1,4-glucan 4-glucanohydrolase; EC 126.96.36.199) by a strain of Bacillus stearothermophilus isolated from leaf litter was investigated in a tryptone-maltose medium at 55 degrees C in batch and chemostat culture. Amylase production was growth-limited and restricted to the exponential phase in batch culture. The enzyme yield was reduced by 40% when the culture pH was maintained at pH 7.2. Amylase production in chemostat culture was influenced by the growth rate throughout the dilution rate range used.


Tumor immunology of experimental osteosarcoma.
A spontaneous AP positive C3H murine OS was used to determine the effects of various treatment modalities. AP served as a useful circulating biomarker of the in vivo tumor growth. In animals whose tumor was amputated, the elevation of the marker indicated the presence of pulmonary metastases. It was used to establish the time of recurrence after a partially effective chemotherapy or combination modality. In this model, when the neoplasm was surgically excised at 10 days posttransplantation, 70--80% of the mice showed presence of lung metastases. Specific immunotherapy with irradiated tumor cells did not alter the course of the disease. Passively transferred immune allogeneic cells to tumor bearing mice at an effector to target cell ratio of 1:1 in vivo were ineffective. The murine OS model is extremely useful to plan and institute different combinations of treatment modalities and optimize the conditions for an effective treatment in a relatively short time.


Nanoscale light-matter interactions in atomic cladding waveguides.
Alkali vapours, such as rubidium, are being used extensively in several important fields of research such as slow and stored light nonlinear optics quantum computation, atomic clocks and magnetometers. Recently, there is a growing effort towards miniaturizing traditional centimetre-size vapour cells. Owing to the significant reduction in device dimensions, light-matter interactions are greatly enhanced, enabling new functionalities due to the low power threshold needed for nonlinear interactions. Here, taking advantage of the mature platform of silicon photonics, we construct an efficient and flexible platform for tailored light-vapour interactions on a chip. Specifically, we demonstrate light-matter interactions in an atomic cladding waveguide, consisting of a silicon nitride nano-waveguide core with a rubidium vapour cladding. We observe the efficient interaction of the electromagnetic guided mode with the rubidium cladding and show that due to the high confinement of the optical mode, the rubidium absorption saturates at powers in the nanowatt regime.


Comparative evaluation of mitral valve repair and replacement with Starr, Björk, and porcine valve prostheses.
Four hundred consecutive patients with isolated mitral valve disease who were operated on between 1974 and 1977 underwent long-term evaluation. In this group there were 100 valve repairs, 100 porcine valves, 100 Starr valves, and 100 Björk valves. There were no significant differences in the preoperative clinical conditions of the patients in the four groups. Cumulative follow-up was 2058 patient-years. We concluded from the data that mitral valve repair was associated with fewer valve-related complications than valve replacement. Thromboembolism was the most significant parameter with respect to determining long-term results of the use of the porcine, Starr, and Björk valve prostheses.


Autoimmune processes resulting from perturbations of self-nonself recognition.
The cellular events involved in the induction, maintenance and termination of experimentally induced immunologic tolerance have been used to better define the cellular and subcellular mechanisms of autoimmunity. Based on these cellular events a model of self-nonself discrimination is presented which assumes that 1) the degree of tolerance to self constituents is determined by the concentration of self antigens in the microenvironment of potential self reactive cells; 2) the induction and maintenance of tolerance to self in B cells require much higher concentrations of self antigens in this microenvironment than in T cells; and 3) self tolerance is a central unresponsive state resulting from clonal deletion. Using these basic assumptions, polyclonal activation of competent B cells, bypassing the requirement for direct activation of specific T cells was discussed as a possible mechanism for the circumvention of self tolerance. Several models of experimental autoimmunity were presented to support these putative mechanisms, and the possible role of regulatory cells in the initiation and progression of autoimmunity was discussed.


Engineered Exosome-Mediated Near-Infrared-II Region V2C Quantum Dot Delivery for Nucleus-Target Low-Temperature Photothermal Therapy.
The limited penetration depth of photothermal agents (PTAs) active in the NIR-I biowindow and the thermoresistance caused by heat shock protein (HSP) significantly limit the therapeutic efficiency of photothermal therapy (PTT). To address the problem, we introduce a strategy of low-temperature nucleus-targeted PTT in the NIR-II region achieving effective tumor killing by combining the vanadium carbide quantum dots (V2C QDs) PTA and an engineered exosomes (Ex) vector. The small fluorescent V2C QDs with good photothermal effect in the NIR-II region were modified with TAT peptides and packaged into Ex with RGD modification (V2C-TAT@Ex-RGD). The resulting nanoparticles (NPs) exhibited good biocompatibility, long circulation time, and endosomal escape ability, and they could target the cell and enter into the nucleus to realize low-temperature PTT with advanced tumor destruction efficiency. The fluorescent imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capability of the NPs were also revealed. The low-temperature nucleus-targeted PTT in the NIR-II region provides more possibilities toward successful clinical application of PTT.


Integrin-like proteins are localized to plasma membrane fractions, not plastids, in Arabidopsis.
Integrins are a large family of integral membrane proteins that function in signal transduction in animal systems. These proteins are conserved in vertebrates, invertebrates, and fungi. Evidence from previous research suggests that integrin-like proteins may be present in plants as well, and that these proteins may function in signal transduction during gravitropism. In past studies, researchers have used monoclonal and polyclonal antibodies to localize beta 1 integrin-like proteins in plants. However, there is a disparity between data collected from these studies, especially since molecular weights obtained from these investigations range from 55-120 kDa for integrin-like proteins. To date, a complete investigation which employs all three basic immunolabeling procedures, immunoblotting, immunofluorescence microscopy, and immunogold labeling, in addition to extensive fractionation and exhaustive controls, has been lacking. In this paper, we demonstrate that use of a polyclonal antibody against the cytoplasmic domain of avian beta 1-integrin can produce potential artifacts in immunolocalization studies. However, these problems can be eliminated through use of starchless mutants or proper specimen preparation prior to electrophoresis. We also show that this antibody, when applied within the described parameters and with careful controls, identifies a large (100 kDa) integrin-like protein that is localized to plasma membrane fractions in Arabidopsis.


Adapting Nielsen's Design Heuristics to Dual Processing for Clinical Decision Support.
The study objective was to improve the applicability of Nielson's standard design heuristics for evaluating electronic health record (EHR) alerts and linked ordering support by integrating them with Dual Process theory. Through initial heuristic evaluation and a user study of 7 physicians, usability problems were identified. Through independent mapping of specific usability criteria to support for each of the Dual Cognitive processes (S1 and S2) and deliberation, agreement was reached on mapping criteria. Finally, usability errors from the heuristic and user study were mapped to S1 and S2. Adding a dual process perspective to specific heuristic analysis increases the applicability and relevance of computerized health information design evaluations. This mapping enables designers to measure that their systems are tailored to support attention allocation. System 1 will be supported by improving pattern recognition and saliency, and system 2 through efficiency and control of information access.


Bioprospecting in potato fields in the Central Andean Highlands: screening of rhizobacteria for plant growth-promoting properties.
The Central Andean Highlands are the center of origin of the potato plant (Solanum tuberosum). Ages of mutualism between potato plants and soil bacteria in this region support the hypothesis that Andean soils harbor interesting plant growth-promoting (PGP) bacteria. Therefore, the aim of this study was to isolate rhizobacteria from Andean ecosystems, and to identify those with PGP properties. A total of 585 bacterial isolates were obtained from eight potato fields in the Andes and they were screened for suppression of Phytophthora infestans and Rhizoctonia solani. Antagonistic mechanisms were determined and antagonistic isolates were further tested for phosphate solubilization, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, and production of NH3- and indole-3-acetic acid (IAA). PGP was studied in healthy and R. solani diseased plantlets under growth room conditions. Performance was compared to the commercial strain B. subtilis FZB24(®) WG. Isolates were dereplicated with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), and identified with 16S rRNA gene sequencing and multi locus sequence analysis (MLSA). A total of 10% of the isolates were effective antagonists, of which many were able to solubilize phosphate, and produce IAA, ACC deaminase, NH3 and hydrogen cyanide (HCN). During growth room experiments, 23 antagonistic isolates were associated with plant growth-promotion and/or disease suppression. Ten isolates had a statistically significant impact on test parameters compared to the uninoculated control. Three isolates significantly promoted plant growth in healthy plantlets compared to the commercial strain, and seven isolates outperformed the commercial strain in in vitro R. solani diseased plantlets.


[Intraoperative three-dimensional imaging with an isocentric mobile C-arm at the wrist].
In addition to conventional radiological C-arm image amplifiers used for intraoperative imaging, now a new mobile C-arm image amplifier with an option for three dimensional imaging (Iso-C 3D) is available to visualize reduction of fractures and position of implants. In a wrist-model three titanium pins were placed and three holes of different length were drilled. Distances between the pins and the depths of the drilled holes were calculated in conventional computer tomographic scans and Iso-C 3D scans in perpendicular, 30 degree and 90 degree position of the gantry and compared to actual distances and depths. There were no significant differences between the actual measured distances and those measured by CT scans and Iso-C 3D scans. Furthermore, gantry position had no significant effect upon the results. Iso-C 3D scans are as reliable as conventional CT scans for intraoperative controlling of implant positioning.


Lower bound for entropy production rate in stochastic systems far from equilibrium.
We show that the Schnakenberg's entropy production rate in a master equation is lower bounded by a function of the weight of the Markov graph, here defined as the sum of the absolute values of probability currents over the edges. The result is valid for time-dependent nonequilibrium entropy production rates. Moreover, in a general framework, we prove a theorem showing that the Kullback-Leibler divergence between distributions P(s) and P^{'}(s):=P(m(s)), where m is an involution, m(m(s))=s, is lower bounded by a function of the total variation of P and P^{'}, for any m. The bound is tight and it improves on Pinsker's inequality for this setup. This result illustrates a connection between nonequilibrium thermodynamics and graph theory with interesting applications.


CHOROIDAL VASCULARITY INDEX QUANTIFICATION IN GEOGRAPHIC ATROPHY USING BINARIZATION OF ENHANCED-DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHIC SCANS.
To evaluate choroidal structural changes occurring over time in geographic atrophy (GA) secondary to age-related macular degeneration using choroidal vascularity index (CVI). Enhanced-depth imaging optical coherence tomography scans of 34 patients with GA and 32 control subjects were retrospectively analyzed. Data were collected at baseline and after a mean follow-up of 18.3 ± 8.3 months. Choroidal images were binarized using the ImageJ software, and the luminal area and stromal area were segmented. Choroidal vascularity index was defined as the ratio of luminal area to total choroid area. Patients with GA showed significantly lower values of CVI, total choroid area, luminal area, and subfoveal choroidal thickness compared to control subjects (65.83 ± 3.95 vs. 69.33 ± 3.11, P < 0.001; 0.400 ± 0.239 mm vs. 0.491 ± 0.132, P = 0.006; 0.263 ± 0.152 mm vs. 0.340 ± 0.094, P = 0.002; 185.2 ± 79.8 µm vs. 216.8 ± 58.8 µm, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = -0.509; P = 0.002). During the follow-up period in patients with GA, subfoveal choroidal thickness decreased from 185.2 ± 79.8 to 152.2 ± 73.1 (P = 0.001), stromal area increased from 0.138 ± 0.090 mm to 0.156 ± 0.068 (P = 0.028), and CVI decreased from 65.83 ± 3.95 to 62.24 ± 3.63 (P < 0.001). This study showed for the first time that CVI is reduced in patients with GA, and that this metric further worsened during the follow-up period.


A pilot trial of telephone-based collaborative care management for PTSD among Iraq/Afghanistan war veterans.
Collaborative care and care management are cornerstones of Primary Care-Mental Health Integration (PC-MHI) and have been shown to reduce depressive symptoms. Historically, the standard of Veterans Affairs (VA) collaborative care was referring patients with posttraumatic stress disorder (PTSD) to specialty care. Although referral to evidence-based specialty care is ideal, many veterans with PTSD do not receive such care. To address this issue and reduce barriers to care, VA currently recommends veterans with PTSD be offered treatment within PC-MHI as an alternative. The current project outlines a pilot implementation of an established telephone-based collaborative care model-Translating Initiatives for Depression into Effective Solutions (TIDES)-adapted for Iraq/Afghanistan War veterans with PTSD symptoms (TIDES/PTSD) seen in a postdeployment primary care clinic. Structured medical record extraction and qualitative data collection procedures were used to evaluate acceptability, feasibility, and outcomes. Most participants (n=17) were male (94.1%) and white (70.6%). Average age was 31.2 (standard deviation=6.4) years. TIDES/PTSD was successfully implemented within PC-MHI and was acceptable to patients and staff. Additionally, the total number of care manager calls was positively correlated with number of psychiatry visits (r=0.63, p<0.05) and amount of reduction in PTSD symptoms (r=0.66, p<0.05). Overall, participants in the pilot reported a significant reduction in PTSD symptoms over the course of the treatment (t=2.87, p=0.01). TIDES can be successfully adapted and implemented for use among Iraq/Afghanistan veterans with PTSD. Further work is needed to test the effectiveness and implementation of this model in other sites and among veterans of other eras.


Risk factors for gun-related behaviors among urban out-of-treatment substance using women.
We examine the prevalence and factors associated with lifetime gun-carrying among 858 urban out-of-treatment substance using women using data collected between 2000 and 2004 in a large Midwestern city. Instruments assessed gun ownership, carrying and access, psychopathology and personal lifestyle risk factors. Analyses were conducted using logistic regression. Illegal activities for income and lifetime violent victimization were the most significant predictors of gun carrying. The implications for practice and future research are discussed along with the study's limitations. The work was supported by grants from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism.


The core competencies and MFT education: practical aspects of transitioning to a learning-centered, outcome-based pedagogy.
The MFT core competencies and latest COAMFTE accreditation standards usher in a new paradigm for MFT education. This transition necessitates not only measuring student mastery of competencies but also, more importantly, adopting a contemporary pedagogical model. This article provides an overview of the changes, a review of parallel trends in other health professions, definitions of learning-centered and outcome-based pedagogy, and a detailed description of a systematic approach for developing a competency-based curriculum, including a list of educator competencies necessary for successful implementation.


Dielectric behavior of DNA solution at radio and microwave frequencies (at 20 degrees C).
The dielectric constant and conductivity of calf thymus DNA were investigated at frequencies between 0.1 MHz and 70 GHz. This work is to investigate the dielectric properties of DNA in low gigahertz region and also to study whether the dielectric behavior of the water is affected by the presence of highly charged DNA. The results of these measurements indicate the presence of two anomalous dispersions, the one between 1 MHz and 1 GHz and the second one above 1 GHZ. The dispersion at low frequencies is likely to arise from polar groups in the DNA molecule. The relaxation behavior of unbound water in DNA solution is only slightly affected by the presence of DNA at concentrations below 1%.


Chelating agents in combination with rosmarinic acid for boar sperm freeze-drying.
The presence of DNA protective agents in the medium is necessary to maintain sperm functionality after freeze-drying procedure. The objective of this study was to investigate the effect of chelating agents, ethylene diaminetetraacetic acid (EDTA) and ethylene glycoltetraacetic acid (EGTA), in combination with rosmarinic acid (RA) on DNA integrity of freeze-dried boar sperm. We also examined the effect of these agents on the in vitro developmental ability of porcine oocytes following sperm injection (ICSI). Heterospermic mix, obtained from ejaculated sperm of three boars, was freeze-dried in two different chelating agents' media: 50mM EDTA or 50mM EGTA, and in these media supplemented with 105μM of rosmarinic acid. Frozen-thawed sperm was used as control. After rehydration, samples were subjected to DNA damage detection using Sperm Chromatin Dispersion test. ICSI was performed to verify the ability of freeze-dried sperm to participate in embryonic development. Five replicated trials were carried out for each group. In the presence of rosmarinic acid, the percentage of spermatozoa with DNA damage decreased significantly (p=0.010), without differences between the two chelating agents combination. EDTA solution preserves more efficiently DNA integrity of boar sperm than EGTA solution (p=0.002). There were no significant differences among the studied groups related to the blastocyst formation rate. Results suggested that the addition of rosmarinic acid to the medium improves sperm DNA integrity after freeze-drying, but does not promote fertilization and blastocyst development. We also observed a similar percentage of embryos production with freeze-dried and with frozen-thawed sperm.


Empirical Antibiotic Therapy in Diabetic Foot Ulcer Infection Increases Hospitalization.
We evaluated the outcomes associated with initial antibiotic management strategies for infected diabetic foot ulcers (DFUs) diagnosed in an outpatient multidisciplinary center. Consecutive outpatient individuals with infected DFUs, stratified according to Infectious Diseases Society of America infection severity, were followed for 1 year from the initial antibiotic administration to treat acute infection. The main outcomes were hospitalization rates for a diabetes-related foot complication within 30 days of diagnosis and requiring an amputation or death during follow-up. Outcomes were analyzed by regression analysis, accounting for demographics, clinical characteristics, and antibiotic therapy. Among 147 outpatients with infected DFUs, 116 were included. Infections were categorized as mild (68%), moderate (26%), and severe (6%). Empirical antibiotics (not culture-guided) were prescribed as initial treatment in 39 individuals, while 77 received culture-based antibiotics. There were no differences in demographic or clinical characteristics between the antibiotic administration groups, except for a higher body mass index and prevalence of chronic kidney disease in the empirical cohort. Forty-two infected DFU patients required hospitalization within 30 days of diagnosis for the same reason. The relative risk for hospitalizations was 1.87 greater in those with mild infections when treated with empirical antibiotics compared with culture-directed antibiotics. There were no differences in amputations and/or death at 1 year follow-up. These data support obtaining tissue culture to guide antibiotic therapy, regardless of DFU infection severity, to decrease hospitalizations.


Resonance in the kidney system of rats.
The pressure wave of the abdominal aorta and the flow wave of the renal artery were recorded simultaneously from a rat. The impedance of a kidney system that is derived by dividing the pressure of the corresponding frequency by that of the flow was studied in six rats. The data show that the system has two resonant frequencies, at the second and third harmonics. At the second harmonic, the pressure wave and fluid flow in a round trip through the branch of the kidney. Whereas it is difficult for the third harmonic flow to enter the kidney, it flows directly through the aorta. To obtain further proof, we compared the frequency components of the two flows measured simultaneously on the abdominal aorta and the renal artery and found the same result. The kidney, renal artery, and aorta combined show a coupled oscillation that is analogous to that of resonance circuits. The kidney vascular system exhibits a resonant frequency at the second harmonic of the heartbeat.


Aging is protective against pressure overload cardiomyopathy via adaptive extracellular matrix remodeling.
When challenged by hemodynamic stress, aging hearts respond differently to young hearts. Preclinical models of heart disease should take into account the effects of age. However, in the transverse aortic constriction (TAC) model of pressure-overload cardiomyopathy, the larger aorta of aging mice has not previously been taken into account. First, we studied the aortic size in mice, and found that the aortic cross-sectional area (CSA) is 28% larger in aging mice than in young adult mice (P=0.001). We then performed TAC to make the same proportional reduction in CSA in young and aging mice. This produced the same pressure gradient across the constriction and the same rise in B-type natriuretic peptide expression. Young mice showed acute deterioration in systolic function assessed by pressure-volume loops, progressive LV remodeling on echocardiography, and a 50% mortality at 12 weeks post-TAC. In contrast, aging mice showed no acute deterioration in systolic function, much less ventricular remodeling and were protected from death. Aging mice also showed significantly increased levels of matrix metalloproteinase-3 (MMP-3; 3.2 fold increase, P<0.001) and MMP-12 (1.5-fold increase, P<0.001), which were not seen in young mice. Expression of tissue inhibitor of MMP-1 (TIMP-1) increased 8.6-fold in aging hearts vs 4.3-fold in young hearts (P<0.01). In conclusion, following size-appropriate TAC, aging mice exhibit less LV remodeling and lower mortality than young adult mice. This is associated with induction of protective ECM changes.


Lattice gas dynamics: application to driven vortices in two dimensional superconductors.
A continuous time Monte Carlo lattice gas dynamics is developed to model driven steady states of vortices in two dimensional superconducting networks. Dramatic differences are found when compared to a simpler Metropolis dynamics. Subtle finite size effects are found at low temperature, with a moving smectic that becomes unstable to an anisotropic liquid on sufficiently large length scales.


Studies toward the biological efficacy of (99m)Tc-labeled dextran-cysteine-mannose ([(99m)Tc(CO)(3)]DCM20) for sentinel lymph node detection.
Abstract The aim of this work was to determine the potential of (99m)Tc carbonyl-labeled dextran-cysteine-mannose (DCM20) as a mannose receptor targeting agent for sentinel lymph node (SLN) detection using biological in vitro and in vivo assays. (99m)Tc labeling of the previously reported DCM20 ligand was carried out via the [(99m)Tc(H(2)O)(3)(CO)(3)](+) synthon. High-performance liquid chromatography (HPLC) showed >99% radiolabeling yield using 50 μg of the ligand. In vitro cell uptake studies performed in RAW 264.7 mouse macrophage precursor cells showed a specific uptake of the preparation. In vivo distribution and scintigraphic imaging were studied in the Wistar rat model. Appreciable uptake and retention of the radiolabeled conjugate was observed in the SLN (4.53%±0.29% at 15 minutes and 3.35%±0.72% at 180 minutes postinjection [p.i.] for 2.5 μg/animal) with a high percentage of popliteal extraction (≥98% at all time points studied), and negligible activity in other nodes as well as blood and nontarget organs. The radiolabeled conjugate also exhibited rapid clearance from the injection site (from ~39.1% clearance at 15 minutes to ~56.5% clearance at 180 minutes p.i.), comparable to current clinically employed agents for SLN detection. These results suggest that [(99m)Tc(CO)(3)]DCM20 could be a potentially useful receptor-based SLN detection agent.


Poor prognosis for thin ulcerated melanomas and implications for a more aggressive approach to treatment.
Clinical guidelines for the treatment of melanoma are based largely on the behavior of thicker tumors. As a result, little is known about survival differences among patients with thinner tumors. To investigate the variability in survival for American Joint Committee on Cancer stage T1 thin melanoma tumors, defined as tumors less than 1 mm thick at diagnosis. This population-based series included 43,008 non-Hispanic whites in whom cutaneous melanoma was diagnosed between 2004 and 2013 from the California Cancer Registry. Survival outcomes were estimated using the Kaplan-Meier method. Cox proportional hazard models were used to estimate risk of death. Survival for patients with thin ulcerated tumors was comparable to that for patients with stage II tumors, who are currently treated more aggressively. At 12 months, patients with thin ulcerated tumors had approximately 6% lower survival (92.5% [95% confidence interval (CI), 90.6%-93.9%]) compared with patients with thin nonulcerated tumors (98.2% [95% CI, 98.0%-98.3%]). At 24 months, this survival difference increased (85.2% [95% CI, 82.8%-87.4%] vs 96.1% [95% CI, 95.8-96.3%] for those with thin ulcerated and thin nonulcerated tumors, respectively) and a greater than 15% survival difference was seen at 60 months. Previous reports of cancer registry data have noted some evidence of miscoding of thin tumors. The poorer survival in patients with ulcerated tumors less than 1 mm thick implies the need for additional studies to determine potential benefits of more aggressive treatment.


Instituting a research ethic: chilling and cautionary tales.
The ethical review of research on human beings, and indeed the ethical review of broader ranges of human activity, is a growth industry. I want to look here at the ethical review of research on humans and raise some questions about the direction it is taking. I am pessimistic about where the institutions that we have set up are leading us and I want to sound a warning note and suggest some changes that are needed in the practice of ethical review.


MOXIBUSTION HAS A POSITIVE EFFECT ON PULMONARY FIBROSIS: AN ALTERNATIVE APPROACH.
An increasing number of people suffered idiopathic fibrosis (IPF) and the current treatment was far from clinical satisfaction. Moxibustion, another effective and safe unconventional therapy, had been introduced to treat this refractory disease. The study aimed to investigate the effect of moxibustion on a bleomycin A5-induced pulmonary fibrosis model. Sprague-dawley (SD) rats were randomly allocated to the blank group, model group, moxibustion group, and prednisone group, for which they received no treatment, modeling, moxibustion treatment and prednisone treatment. After four-week treatment, the rats were euthanized for Hematoxylin and Eosin (H.E.) staining, and TGF-β1 and IFN-γ protein and mRNA detection in lungs. In the model group, TGF-β1 was significantly increased and IFN-γ was significantly decreased at both protein and mRNA levels in comparison to the blank group. In the moxibustion and prednisone group, however, TGF-β1 was decreased and IFN-γ was increased at both protein and mRNA levels in comparison to the model groups. Compared with prednisone, moxibustion showed comparable effect in lowing TGF-β1 (P>0.05) and better effect in up-regulating IFN-γ (P>0.05). The study concludes moxibustion protected pulmonary fibrosis by downregulating TGF-β1 and upregulating IFN-γ cytokines at both mRNA and protein levels, and the effect was comparable to prednisone. Moxibustion could be used as a therapeutic alternative treatment for pulmonary fibrosis.


The Fas system confers protection against alveolar disruption in hyperoxia-exposed newborn mice.
The functional significance of the Fas/Fas-ligand (FasL) system in hyperoxia-induced lung injury and alveolar disruption in newborn lungs in vivo remains undetermined. To assess the role of the Fas/FasL system, we compared the effects of hyperoxia (95% O2 from birth to Postnatal Day [P]7) in Fas-deficient lpr mice and wild-type mice. Alveolar disruption was more severe in hyperoxic lpr mice than in wild-type mice. In addition, a transient alveolarization defect was noted in normoxic lpr mice. Hyperoxia induced marked up-regulation of pulmonary Fas expression in wild-type mice, as well as elevated mRNA levels of pro-apoptotic Bax, Bad, and Bak. Pulmonary apoptotic activity was similar in hyperoxic wild-type and lpr mice. In contrast, lung growth and proliferation, assessed by stereologic volumetry and Ki67 proliferation studies, were significantly higher in hyperoxic wild-type mice compared with lpr mice, suggesting the Fas/FasL system has a pro-proliferative role in hyperoxic conditions. Levels of the prosurvival MAPkinase, pERK1/2, were significantly higher in hyperoxic wild-type mice compared with lpr mice, while pAkt levels were similar. These data suggest that the primary role of the Fas/FasL system in hyperoxic newborn lungs is pro-proliferative, rather than pro-apoptotic, and likely mediated through a Fas-ERK1/2 pathway. Fas-induced proliferation and lung growth in hyperoxic newborn lungs may counteract, in part, the detrimental effects of apoptosis mediated by non-Fas pathways, such as pro-apoptotic Bax/Bcl-2 family members. The capacity of the Fas/FasL signaling pathway to mediate protective rather than destructive functions in hyperoxic newborn lungs highlights the versatility of this complex pathway.


Modular Integration of Upconverting Nanocrystal-Dendrimer Composites for Folate Receptor-Specific NIR Imaging and Light-Triggered Drug Release.
Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.


Hydration structures of bromides on cationic micelles.
The peripheral structures of bromides on dodecyltrimethylammonium bromide (DTAB) and hexadecyltrimethylammonium bromide (HTAB) micelles have been studied by X-ray absorption fine structure (XAFS) at the Br-K edge. The XAFS spectra indicate that water is a dominant scattering group for Br- even in these micellar solutions. However, the oscillation intensity decreases with increasing micellar concentration, suggesting that the bromides are dehydrated to some extent when they are bound to the micelles. A XAFS analysis routine gives unusually short Br-O (water) distances and is inapplicable to the present systems. This comes from the structure of the first coordination shell, in which two or more scattering paths are involved. The second scattering group is obviously the head group of the surfactants forming the micelles. The detailed analysis has allowed us to estimate the hydration number of the bromides bound on the DTAB and HTAB micelles (N = ca. 4.2). The assumption that all of the bromides form direct ion-associates with the head groups causes the contradiction to the results of the XAFS analyses. This strongly implies that some of the bromides partitioned into the micelle are completely hydrated as far as their first coordination shell is concerned. Assuming that the maximum hydration number of the bromides bound to the head groups of the micelle is three, 40% of the bromides partitioned into the micelle are completely hydrated.


Ring chromosomes in parosteal osteosarcoma contain sequences from 12q13-15: a combined cytogenetic and comparative genomic hybridization study.
Seven parosteal osteosarcoma (POS) samples, six of which were cytogenetically characterized, were studied by using comparative genomic hybridization (CGH). All samples showed DNA sequence copy number changes (mean, six aberrations/tumor; range, 1-13); gains were more frequent than losses. Gain of 12q13-15 sequences was found in every tumor and correlated with the presence of ring chromosomes. High-level amplification, which was detected in four tumors, was seen only in chromosome 12, with 12q13-14 as the minimal common region. By using chromosome painting, one of the rings of one case was shown to be composed entirely of chromosome 12 material. Together with previous data, our findings show that gain of 12q13-15 sequences is a characteristic feature of POS and that these sequences are contained within the ring chromosomes.


The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation.
Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whether eGIPR can be blocked using a GIP antagonist not tested previously in horses, and to establish whether there is any association between GIP concentrations and body mass in this species. Archived tissues from healthy horses were used to establish that eGIPR gene expression was strong in pancreas, heart, liver, kidney, and duodenum and absent in gluteal muscle. Pancreatic islets were isolated from fresh horse pancreas using collagenase digestion and layering through a density gradient. Islet viability was confirmed microscopically and by demonstrating that insulin production was stimulated by glucose in a concentration-dependent manner. Insulin release was also shown to be concentration-dependent with GIP up to 0.1µM, and the response to GIP was decreased ( = 0.037) by the antagonist (Pro3)GIP. As for the relationship between body mass and GIP in vivo postprandial GIP concentrations in archived plasma samples were positively correlated with body condition and cresty neck scores ( < 0.05). Thus, the eGIPR is a potential therapeutic target for insulin dysregulation and obesity in horses.


Portable sample processing for molecular assays: application to Zika virus diagnostics.
This paper introduces a digital microfluidic (DMF) platform for portable, automated, and integrated Zika viral RNA extraction and amplification. The platform features reconfigurable DMF cartridges offering a closed, humidified environment for sample processing at elevated temperatures, as well as programmable control instrumentation with a novel thermal cycling unit regulated using a proportional integral derivative (PID) feedback loop. The system operates on 12 V DC power, which can be supplied by rechargeable battery packs for remote testing. The DMF system was optimized for an RNA processing pipeline consisting of the following steps: 1) magnetic-bead based RNA extraction from lysed plasma samples, 2) RNA clean-up, and 3) integrated, isothermal amplification of Zika RNA. The DMF pipeline was coupled to a paper-based, colorimetric cell-free protein expression assay for amplified Zika RNA mediated by toehold switch-based sensors. Blinded laboratory evaluation of Zika RNA spiked in human plasma yielded a sensitivity and specificity of 100% and 75% respectively. The platform was then transported to Recife, Brazil for evaluation with infectious Zika viruses, which were detected at the 100 PFU mL-1 level from a 5 μL sample (equivalent to an RT-qPCR cycle threshold value of 32.0), demonstrating its potential as a sample processing platform for miniaturized diagnostic testing.


Correction: Enantioselective copper catalysed intramolecular C-H insertion reactions of α-diazo-β-keto sulfones, α-diazo-β-keto phosphine oxides and 2-diazo-1,3-diketones; the influence of the carbene substituent.
Correction for 'Enantioselective copper catalysed intramolecular C-H insertion reactions of α-diazo-β-keto sulfones, α-diazo-β-keto phosphine oxides and 2-diazo-1,3-diketones; the influence of the carbene substituent' by Amy E. Shiely et al., Org. Biomol. Chem., 2017, 15, 2609-2628.


Prevalence of Maternal Cytomegalovirus Antibodies and Neonatal Congenital Cytomegalovirus at Less than 34 Weeks of Gestation: A Prospective Study.
Congenital cytomegalovirus (cCMV) acquired postnatally can lead to hearing loss and adverse central nervous system (CNS) function, especially in the preterm neonate. We prospectively determined the prevalence of maternal serum CMV-immunoglobulin (IgG) and the incidence of cCMV at <34 weeks of gestation. Study was conducted in the United States and India. Maternal blood was collected within 5 days after delivery. CMV-IgG antibodies were quantitated by an immunoassay. Baby's urine at birth was tested for CMV-DNA by the polymerase chain reaction. In total, 65 women and 74 neonates were studied. In the United States, 6 out of 21 (76%), while in India, 42 out of 44 (96%) mothers were seropositive (combined 89%). In the United States, none of the neonates had CMV in the urine, while in India 4 out of 52 (7.7%) were positive (combined 5.4%) CONCLUSION: Mother's blood and baby's urine should be tested for serum CMV-IgG antibodies and CMV-DNA at delivery at <34-weeks of gestational age. Targeted screening will help in making an early diagnosis of cCMV, initiate therapy, and detect and treat early CNS problems including hearing loss. · Maternal serum CMV screening after premature delivery at less than 34 weeks of gestation.. · Neonatal urine CMV screening at less than 34 weeks of gestation.. · Prematurity: importance of CMV during premature labor and delivery at less than 34 weeks..


Synthesis and antidepressant properties of novel 2-substituted 4,5-dihydro-1H-imidazole derivatives.
A unique combination of alpha 2-adrenoreceptor antagonist and serotonin-selective reuptake inhibitory activities has been identified in a series of 2-substituted 4,5-dihydro-1H-imidazole derivatives. This combination of blocking activities has provided one of these derivatives, napamezole hydrochloride (2), with potential as an antidepressant. A discussion of the syntheses of these compounds includes a convenient method for the conversion of nitriles to imidazolines with ethylenediamine and trimethylaluminum.