Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Endothelium: Target for Aldosterone

Abstract—Aldosterone has long been known to control water and electrolyte balance by acting on mineralocorticoid receptors in kidney. However, recent studies demonstrated the presence of these receptors in nonclassical locations, including the cardiovascular system. We tested the hypothesis whether endothelial cells respond to aldosterone with changes in cell volume, a measure for ion-mediated water movement across the cell membrane. By means of atomic force microscopy in fluid, we measured volume of adherent human umbilical venous endothelial cells exposed for 72 hours to 10 nmol/L aldosterone. Over this period of time, cells swell by ≈ 18%. Aldosterone-induced swelling is prevented by 100 nmol/L of the mineralocorticoid receptor antagonist spironolactone, added to the primary endothelial cell culture. Aldosterone-treated cells dramatically shrink when 1 μmol/L of the diuretic amiloride is applied. Cells deprived of aldosterone do not respond to amiloride. Our conclusions are: (1) aldosterone leads to sustained cell swelling inhibited by administration of spironolactone or the sodium channel blocker amiloride; (2) cells respond to amiloride after aldosterone exposure; (3) renal diuretics act on endothelial cells; and (4) both amiloride and spironolactone could be useful for medical applications to prevent aldosterone-mediated endothelial dysfunction.
Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A

ABSTRACT Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic alphacoronavirus. In the United States, highly virulent PEDV strains cause between 80 and 100% mortality in suckling piglets and are rapidly transmitted between animals and farms. To study the genetic factors that regulate pathogenesis and transmission, we developed a molecular clone of PEDV strain PC22A. The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. Using reverse genetics, we removed open reading frame 3 (ORF3) and replaced this region with a red fluorescent protein (RFP) gene to generate icPEDV-ΔORF3-RFP. icPEDV-ΔORF3-RFP replicated efficiently in vitro and in vivo, was efficiently transmitted among pigs, and produced lethal disease outcomes. However, the diarrheic scores in icPEDV-ΔORF3-RFP-infected pigs were lower than those in wild-type-virus- or icPEDV-infected pigs, and the virus formed smaller plaques than those of PC22A. Together, these data describe the development of a robust reverse-genetics platform for identifying genetic factors that regulate pathogenic outcomes and transmission efficiency in vivo, providing key infrastructural developments for developing and evaluating the efficacy of live attenuated vaccines and therapeutics in a clinical setting. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) emerged in the United States in 2013 and has since killed 10% of U.S. farm pigs. Though the disease has been circulating internationally for decades, the lack of a rapid reverse-genetics platform for manipulating PEDV and identifying genetic factors that impact transmission and virulence has hindered the study of this important agricultural disease. Here, we present a DNA-based infectious-clone system that replicates the pathogenesis of circulating U.S. strain PC22A both in vitro and in piglets. This infectious clone can be used both to study the genetics, virulence, and transmission of PEDV coronavirus and to inform the creation of a live attenuated PEDV vaccine. Porcine epidemic diarrhea virus (PEDV) emerged in the United States in 2013 and has since killed 10% of U.S. farm pigs. Though the disease has been circulating internationally for decades, the lack of a rapid reverse-genetics platform for manipulating PEDV and identifying genetic factors that impact transmission and virulence has hindered the study of this important agricultural disease. Here, we present a DNA-based infectious-clone system that replicates the pathogenesis of circulating U.S. strain PC22A both in vitro and in piglets. This infectious clone can be used both to study the genetics, virulence, and transmission of PEDV coronavirus and to inform the creation of a live attenuated PEDV vaccine.
Antiretroviral Therapy and Viral Suppression Among Foreign-Born HIV-Infected Persons Receiving Medical Care in the United States

AbstractImmigrants to the United States are more likely to be diagnosed with human immunodeficiency virus (HIV) infection compared with native-born persons. Navigating access to healthcare in the United States can be challenging for foreign-born persons, and HIV treatment outcomes may be suboptimal for these persons. We compared characteristics of and assessed disparities in clinical outcomes of foreign-born persons in care for HIV in the United States.The Medical Monitoring Project is a complex sample, cross-sectional survey designed to be nationally representative of HIV-infected adults receiving medical care in the United States.Using data from 2009, 2010, and 2011, we conducted descriptive analyses and multivariable logistic regression to assess associations between foreign-born status and antiretroviral therapy (ART) prescription, and between foreign-born status and viral suppression.In all, 13.4% of HIV-infected persons were self-identified as foreign-born; the most common regions of birth were Central America and Mexico (45.4%) and the Caribbean (16.0%). Nearly 90% of foreign-born persons were diagnosed with HIV after entry into the United States. Compared with US-born persons, foreign-born persons were more likely to be younger, Hispanic, less educated, and uninsured. The prevalence of ART prescription (prevalence ratio 1.00; 95% confidence interval 0.98–1.02) was not significantly different between foreign-born and US-born persons. A higher percentage of foreign-born persons achieved viral suppression compared with US-born persons (prevalence ratio 1.05; 95% confidence interval 1.00–1.09). No major disparities in ART prescription and viral suppression were found between foreign-born and US-born HIV-infected persons receiving medical care, despite higher percentages being uninsured.
Absence of mutations in the growth hormone (GH)‐releasing hormone receptor gene in GH‐secreting pituitary adenomas

GH‐releasing hormone (GHRH) is a potent stimulator of somatotroph cell proliferation and GH secretion. GHRH acts via binding to a G‐protein coupled receptor (GPCR) (GHRH‐R), that activates adenylyl cyclase (AC) and increases growth and function of somatotroph cells. Indeed, a subset (30–40%) of somatotrophic adenomas contain somatic mutations of the GNAS1 gene that encodes the alpha subunit of the G‐protein (Gsα) that stimulates AC. As activating mutations of other GPCRs cause development of endocrine tumours, we hypothesized that somatic activating mutations of the GHRH‐R might provide the molecular basis for somatotroph cell proliferation in a subset of human GH‐secreting pituitary adenomas.
In Situ Synthesis of TiB2-TiC0.8-40vol%SiC by Hot Pressing

TiB2-TiC0.8-40vol%SiC multiphase ceramics were prepared by in-situ hotpressing sintering. The phase composition and microstructures of the materials were characterized by optical mic- oscope, X-ray diffraction and scanning electron microscopy. The effects of sintering temperature on the phases, microstructures and mechanical properties of the ceramics were investigated. The results show that density, bending strength and fracture toughness of the ceramics are increased with the elevation of sintering temperature (1800-1950°C). High densified TiB2-TiC0.8-40vol%SiC multipha- se ceramics and optimized microstructure is obtained by sintering at 1900°C, in which the uniform distribution of lath-shape TiB2 and bulk TiC0.8 grains can be observed obviously. Nano-SiC particles distributed dispersively in the TiB2 and TiC0.8 grains and at boundaries. The Vickers hardness, fract- ure toughness, flexural strength and electrical conductivity of the TiB2-TiC0.8-40vol%SiC multipha- se ceramics sintered at 1900°C are 24.055GPa, 8.27±1.0MPa∙m1/2, 516.69MPa and 2.2×106S∙m-1, respectively. However, up to 1950°C, TiB2 and TiC0.8 grains gradually grew up, the bending stren- gth of multiphase ceramics was decreased greatly. In addition, TiB2, TiC0.8 and SiC particles were incorporated together to improve the particulate strength and toughness of composite material by the synergistic mechanism effects among the crystal phases in the multiphase ceramics, such as crack deflection, grain’s pull-out and fine-grain toughening.
The effect of temperature on linear dimensional stability of elastomers

Objectives: The objective of this study was to investigate the effect of temperature on dimensional stability of elastomeric impression materials. Materials and Methods: Polyether and polyvinyl siloxane impressions of an International Organization for Standardization-specified test-block were photographed at two temperatures and 3 time intervals. This resulted in 12 groups (n = 10). Images were digitally calibrated and measured. Mean percentage dimensional change (%DC) was analyzed using the Variance Estimation and Precision module of Statistica 10 (Statsoft®, Southern Africa) (95% confidence), with Fisher least significant difference correction for multiple pairwise comparisons. Results: For silicone, dimensional accuracy was highest when stored at 21°C for 14 days (%DC = 0.006). This was significantly better than all other silicone groups (P < 0.05). Dimensional accuracy was worst when stored at 21°C for 8 h (%DC = 0.237) and after cooling-off from 66°C (%DC = 0.300), with no difference between latter groups (P = 0.187). For polyether, dimensional accuracy was highest when stored at 21°C for 14 days (%DC = −0.272). This was significantly better than all other polyether groups (P < 0.05). Dimensional accuracy was worst when stored at 21°C for 8 h (%DC = 0.364) and after cooling-off from 66°C (%DC = 0.306), with no difference between latter groups (P = 0.199). Comparing polyether with silicone, %DC did not differ between the two materials when kept at 21°C for 14 days and when cooled-off after heat exposure for 8 h. At all other instances, the %DC between the two materials differed, with silicone always closest to zero %DC. Conclusions: Exposing silicone and polyether to high temperature doesn′t lead to higher dimensional inaccuracy on the short-term compared to keeping them at 21°C. However, heat has an effect on shelf-life (14 days) of impressions, decreasing accuracy. This effect is worse for polyether.
Stochastic modelling of reaction–diffusion processes: algorithms for bimolecular reactions

Several stochastic simulation algorithms (SSAs) have recently been proposed for modelling reaction–diffusion processes in cellular and molecular biology. In this paper, two commonly used SSAs are studied. The first SSA is an on-lattice model described by the reaction–diffusion master equation. The second SSA is an off-lattice model based on the simulation of Brownian motion of individual molecules and their reactive collisions. In both cases, it is shown that the commonly used implementation of bimolecular reactions (i.e. the reactions of the form A + B → C or A + A → C) might lead to incorrect results. Improvements of both SSAs are suggested which overcome the difficulties highlighted. In particular, a formula is presented for the smallest possible compartment size (lattice spacing) which can be correctly implemented in the first model. This implementation uses a new formula for the rate of bimolecular reactions per compartment (lattice site).
Entropy and Free Energy of a Mobile Loop Based on the Crystal Structures of the Free and Bound Proteins

A mobile loop changes its conformation from "open" (free enzyme) to "closed" upon ligand binding. The difference in the Helmholtz free energy, ΔF(loop) between these states sheds light on the mechanism of binding. With our "hypothetical scanning molecular dynamics" (HSMD-TI) method ΔF(loop) = F(free) - F(bound) where F(free) and F(bound) are calculated from two MD samples of the free and bound loop states; the contribution of water is obtained by a thermodynamic integration (TI) procedure. In previous work the free and bound loop structures were both attached to the same "template" which was "cut" from the crystal structure of the free protein. Our results for loop 287-290 of AcetylCholineEsterase agree with the experiment, ΔF(loop)~ -4 kcal/mol if the density of the TIP3P water molecules capping the loop is close to that of bulk water, i.e., N(water) = 140 - 180 waters in a sphere of a 18 Å radius. Here we calculate ΔF(loop) for the more realistic case, where two templates are "cut" from the crystal structures, 2dfp.pdb (bound) and 2ace.pdb (free), where N(water) = 40 - 160; this requires adding a computationally more demanding (second) TI procedure. While the results for N(water) ≤ 140 are computationally sound, ΔF(loop) is always positive (18 ± 2 kcal/mol for N(water) = 140). These (disagreeing) results are attributed to the large average B-factor, 41.6 of 2dfp (23.4 Å(2) for 2ace). While this conformational uncertainty is an inherent difficulty, the (unstable) results for N(water) = 160 suggest that it might be alleviated by applying different (initial) structural optimizations to each template.
What do Danish children eat, and does the diet meet the recommendations? Baseline data from the OPUS School Meal Study

Abstract A child's diet is an important determinant for later health, growth and development. In Denmark, most children in primary school bring their own packed lunch from home and attend an after-school care institution. The aim of the present study was to evaluate the food, energy and nutrient intake of Danish school children in relation to dietary guidelines and nutrient recommendations, and to assess the food intake during and outside school hours. In total, 834 children from nine public schools located in the eastern part of Denmark were included in this cross-sectional study and 798 children (95·7 %) completed the dietary assessment sufficiently (August–November 2011). The whole diet was recorded during seven consecutive days using the Web-based Dietary Assessment Software for Children (WebDASC). Compared with the food-based dietary guidelines and nutrient recommendations, 85 % of the children consumed excess amounts of red meat, 89 % consumed too much saturated fat, and 56 % consumed too much added sugar. Additionally 35 or 91 % of the children (depending on age group) consumed insufficient amounts of fruits and vegetables, 85 % consumed insufficient amounts of fish, 86 % consumed insufficient amounts of dietary fibre, 60 or 84 % had an insufficient Fe intake (depending on age group), and 96 % had an insufficient vitamin D intake. The study also showed that there is a higher intake of fruits and bread during school hours than outside school hours; this is not the case with, for example, fish and vegetables, and future studies should investigate strategies to increase fish and vegetable intake during school hours.
Data-Driven Control for Relative Degree Systems via Iterative Learning

Iterative learning control (ILC) is a kind of effective data-driven method that is developed based on online and/or offline input/output data. The main purpose of this paper is to supply a unified 2-D analysis approach for both continuous-time and discrete-time ILC systems with relative degree. It is shown that the 2-D Roesser system framework can be established for general ILC systems regardless of relative degree, under which convergence conditions can be provided to guarantee both asymptotic stability and monotonic convergence of the ILC processes. In particular, conditions for the monotonic convergence of ILC can be given in terms of linear matrix inequalities, and formulas for the updating law can be derived simultaneously. Simulation results are presented to illustrate the effectiveness of ILC determined through the 2-D design approach in dealing with the higher order relative degree problem of ILC systems, as well as the robustness of such ILC against uncertainties.
Cytotoxic CD8+ T Cell–Neuron Interactions: Perforin-Dependent Electrical Silencing Precedes But Is Not Causally Linked to Neuronal Cell Death

Cytotoxic CD8+ T cells are considered important effector cells contributing to neuronal damage in inflammatory and degenerative CNS disorders. Using time-lapse video microscopy and two-photon imaging in combination with whole-cell patch-clamp recordings, we here show that major histocompatibility class I (MHC I)-restricted neuronal antigen presentation and T cell receptor specificity determine CD8+ T-cell locomotion and neuronal damage in culture and hippocampal brain slices. Two separate functional consequences result from a direct cell–cell contact between antigen-presenting neurons and antigen-specific CD8+ T cells. (1) An immediate impairment of electrical signaling in single neurons and neuronal networks occurs as a result of massive shunting of the membrane capacitance after insertion of channel-forming perforin (and probably activation of other transmembrane conductances), which is paralleled by an increase of intracellular Ca2+ levels (within <10 min). (2) Antigen-dependent neuronal apoptosis may occur independently of perforin and members of the granzyme B cluster (within ∼1 h), suggesting that extracellular effects can substitute for intracellular delivery of granzymes by perforin. Thus, electrical silencing is an immediate consequence of MHC I-restricted interaction of CD8+ T cells with neurons. This mechanism is clearly perforin-dependent and precedes, but is not causally linked, to neuronal cell death.
Evaluating robust features on deep neural networks for speech recognition in noisy and channel mismatched conditions

Deep Neural Network (DNN) based acoustic models have shown significant improvement over their Gaussian Mixture Model (GMM) counterparts in the last few years. While several studies exist that evaluate the performance of GMM systems under noisy and channel degraded conditions, noise robustness studies on DNN systems have been far fewer. In this work we present a study exploring both conventional DNNs and deep Convolutional Neural Networks (CNN) for noiseand channel-degraded speech recognition tasks using the Aurora4 dataset. We compare the baseline mel-filterbank energies with noise-robust features that we have proposed earlier and show that the use of robust features helps to improve the performance of DNNs or CNNs compared to melfilterbank energies. We also show that vocal tract length normalization has a positive role in improving the performance of the robust acoustic features. Finally, we show that by combining multiple systems together we can achieve even further improvement in recognition accuracy.
Layout and process improvements to double-sided silicon 3D detectors fabricated at FBK

In the past few years, very important progress has been made in the development of silicon 3D detectors, passing from the R&D phase with performance demonstration of a few prototypes to an industrialization phase, which led to the first production of 3D sensors to cover 25% of the ATLAS Insertable B-Layer (IBL) staves. Double-side 3D sensor technology developed at FBK (Trento, Italy) in collaboration with INFN proved successful to yield good quality detectors for the IBL. In spite of the good performance of the IBL sensors, it is possible to further improve the electrical characteristics of these devices while reducing the fabrication complexity and therefore the time required for a medium volume production. To this purpose, with the aid of TCAD simulations, we have investigated some modifications at both the layout and fabrication level aimed at improving the sensor breakdown voltage, both before and after irradiation, while reducing the number of lithographic steps required during fabrication. This paper reports on simulation results and preliminary experimental results from a new batch of 3D sensors implementing the proposed improvements.
EVIDENCE BASED CHILD HEALTH 1 Principles of evidence based medicine

These include: References http://adc.bmjjournals. com/cgi/content/full/90/8/845#BIBL This article cites 11 articles, 10 of which can be accessed free at: Rapid responses http://adc.bmjjournals. com/cgi/eletter-submit/90/8/845 You can respond to this article at: service Email alerting top right corner of the article Receive free email alerts when new articles cite this article sign up in the box at the
The Influence of Unimanual Response on Pseudoneglect Magnitude

Various factors influence the degree of leftward error (pseudoneglect) (Bowers & Heilman, 1980) that typifies the performance of normal subjects in line bisection tasks (Jewell & McCourt, 2000). The results of this experiment show that unimanual responding also exerts a subtle but significant modulating influence on spatial attention, as indexed by the differential magnitude of pseudoneglect. Using a forced-choice tachistoscopic line bisection protocol, 184 subjects (92 male and 92 female) bisected horizontally oriented lines (22.3 degrees wide x 0.39 degrees height) presented to central vision in two conditions, in which bisection responses were executed via button presses using the first two fingers of either the left (LH) or right (RH) hand. Perceived line midpoint deviated significantly leftward of veridical (p <.05) in both conditions. There was no significant influence of subject sex (p >.05). A significant influence of unimanual response was revealed (p <.05) where pseudoneglect magnitude was greater in the LH than the RH condition. The results are interpreted within the framework of the activation-orientation theory of attentional asymmetry.
Noninvasive Coronary Angiography by 320-Row Computed Tomography With Lower Radiation Exposure and Maintained Diagnostic Accuracy: Comparison of Results With Cardiac Catheterization in a Head-to-Head Pilot Investigation

Background— Noninvasive coronary angiography with the use of multislice computed tomography (CT) scanners is feasible with high sensitivity and negative predictive value; however, the radiation exposure associated with this technique is rather high. We evaluated coronary angiography using whole-heart 320-row CT, which avoids exposure-intensive overscanning and overranging. Methods and Results— A total of 30 consecutive patients with suspected coronary artery disease referred for clinically indicated conventional coronary angiography (CCA) were included in this prospective intention-to-diagnose study. CT was performed with the use of up to 320 simultaneous detector rows before same-day CCA, which, together with quantitative analysis, served as the reference standard. The per-patient sensitivity and specificity for CT compared with CCA were 100% (95% confidence interval [CI], 72 to 100) and 94% (95% CI, 73 to 100), respectively. Per-vessel versus per-segment sensitivity and specificity were 89% (95% CI, 62 to 98) and 96% (95% CI, 90 to 99) versus 78% (95% CI, 56 to 91) and 98% (95% CI, 96 to 99), respectively. Interobserver agreement between the 2 readers was significantly better for CCA (97% of 121 coronary arteries) than for CT (90%; P=0.04). Percent diameter stenosis determined with the use of CT showed good correlation with CCA (P<0.001, R=0.81) without significant underestimation or overestimation (−3.1±24.4%; P=0.08). Intraindividual comparison of CT with CCA revealed a significantly smaller effective radiation dose (median, 4.2 versus 8.5 mSv; P<0.05) and amount of contrast agent required (median, 80 versus 111 mL; P<0.001) for 320-row CT. The majority of patients (87%) indicated that they would prefer CT over CCA for future diagnostic imaging (P<0.001). Conclusions— CT with the use of emerging technology has the potential to significantly reduce the radiation dose and amount of contrast agent required compared with CCA while maintaining high diagnostic accuracy.