Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Mammalian Retromer Component, Vps26B

The mammalian retromer protein complex, which consists of three proteins – Vps26, Vps29, and Vps35 – in association with members of the sorting nexin family of proteins, has been implicated in the trafficking of receptors and their ligands within the endosomal/lysosomal system of mammalian cells. A bioinformatic analysis of the mouse genome identified an additional transcribed paralog of the Vps26 retromer protein, which we termed Vps26B. No paralogs were identified for Vps29 and Vps35. Phylogenetic studies indicate that the two paralogs of Vps26 become evident after the evolution of the chordates. We propose that the chordate Vps26‐like gene published previously be renamed Vps26A to differentiate it from Vps26B. As for Vps26A, biochemical characterization of Vps26B established that this novel 336 amino acid residue protein is a peripheral membrane protein. Vps26B co‐precipitated with Vps35 from transfected cells and the direct interaction between these two proteins was confirmed by yeast 2‐hybrid analysis, thereby establishing Vps26B as a subunit of the retromer complex. Within HeLa cells, Vps26B was found in the cytoplasm with low levels at the plasma membrane, while Vps26A was predominantly associated with endosomal membranes. Within A549 cells, both Vps26A and Vps26B co‐localized with actin‐rich lamellipodia at the cell surface. These structures also co‐localized with Vps35. Total internal reflection fluorescence microscopy confirmed the association of Vps26B with the plasma membrane in a stable HEK293 cell line expressing cyan fluorescent protein (CFP)‐Vps26B. Based on these observations, we propose that the mammalian retromer complex is located at both endosomes and the plasma membrane in some cell types.
Hypersensitivity pneumonitis in children

Hypersensitivity pneumonitis in children is an underrecognized form of immune-mediated interstitial lung disease that results from repeated exposure to the inhalation of organic antigens. Because overt disease develops in only a small percentage of exposed individuals, complex interactions between the nature of the antigen, the intensity and duration of the exposure, and the host response in susceptible individuals are most likely involved. In most reported pediatric cases, hypersensitivity pneumonitis results from exposure to avian antigens, but it has also been seen with exposure to molds and methotrexate. The diagnosis is established by documented exposure, compatible clinical presentation, and consistent radiologic features; it is supported by positive precipitating antibodies, lymphocytosis in bronchoalveolar lavage fluid, and characteristic histologic changes on lung biopsy. Treatment consists of antigen avoidance in all cases, and corticosteroids in severe cases. The prognosis is excellent when prompt recognition and treatment are initiated.
Development of the arterial chemoreflex and turnover of carotid body catecholamines in the newborn rat.

1. The peripheral, arterial chemoreceptors in the carotid body are active and responsive in the fetus. At birth, when oxygenation increases, the chemoreceptors are silenced. Over the next few days the sensitivity is reset toward the adult level and the chemoreceptors influence breathing during normal conditions. In order to investigate the underlying mechanisms of this resetting we examined the strength of the chemoreflex in newborn rats and correlated this to the contents of dopamine and noradrenaline in the carotid bodies of the newborn pups and near‐term fetuses. Furthermore, turnover rates of dopamine and noradrenaline were determined in newborn rats up to 1 week of age by analysis of catecholamine decreases after inhibition of synthesis with alpha‐methyl‐p‐tyrosine. 2. Chemoreceptor influence was assessed by the method of ‘physiological chemodenervation’ with hyperoxia of 15‐20 s duration in unanaesthetized rat pups. Relative changes in ventilation elicited by hyperoxia were determined by body plethysmography. We found no change in ventilation on the day of birth either in vaginally born rats or in near‐term pups delivered by Caesarean section. After 1 day there was a significant decrease in ventilation of ‐19.4 +/‐ 2.3% (mean +/‐ S.E.M.) and at 7 days of age the decrease was ‐28.8 +/‐ 2.2%, suggesting an increasing influence from the peripheral chemoreceptors. 3. The contents of dopamine and noradrenaline were measured by high‐performance liquid chromatography. Dopamine increased from 3.7 +/‐ 0.4 pmol (pair of carotid bodies)‐1 in the fetus to a peak of 15.9 +/‐ 2.6, 6‐12 h after birth followed by a decline to 7.1 +/‐ 0.7 at 7 days of age. Noradrenaline levels increased from 1.3 +/‐ 0.3 in the fetus to 9.6 +/‐ 1.1 pmol (pair of carotid bodies)‐1 after 4 days. The turnover rate of dopamine decreased from 4.4 pmol (pair of carotid bodies)‐1 h‐1 0‐6 h after birth to 1.0 at 6‐12 h of age. The turnover rate of noradrenaline also decreased over the first hours following delivery. 4. Since dopamine is an inhibitory neuromodulator in this system, we suggest that the increase in sensitivity seen after the first day of life is, at least in part, due to a decrease in the release of dopamine and thus a removal of an inhibitory mechanism.
Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation

Peroxidized lipid metabolites trigger calcium influx through the channel TRPA1 to dilate cerebral arteries. Blood Vessel Dilation with Peroxidized Lipids Cerebral arteries must maintain constant blood flow to the brain even though blood pressure fluctuates constantly. Sullivan et al. characterized a signaling pathway that is specific to the endothelial cells that line cerebral arteries. Reactive oxygen species (ROS) cause lipid peroxidation. In endothelial cells in cerebral arteries, locally produced ROS oxidized lipids, which triggered calcium influx through the ion channel TRPA1. In turn, this calcium influx activated a potassium-permeable channel, resulting in dilation of cerebral arteries. Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of cerebral arteries but not in other vascular beds. We recorded and characterized ROS-triggered Ca2+ signals representing Ca2+ influx through single TRPA1 channels, which we called “TRPA1 sparklets. ” TRPA1 sparklet activity was low under basal conditions but was stimulated by NOX-generated ROS. Ca2+ entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca2+ channel sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1 channels were more common in endothelial cells than in human embryonic kidney (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated intermediate-conductance, Ca2+-sensitive K+ channels, resulting in smooth muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries. These data suggest that in the cerebral circulation, lipid peroxidation metabolites generated by ROS activate Ca2+ influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation.
Effects of porosity on the fatigue performance of polymethyl methacrylate bone cement: An analytical investigation

Abstract Porosity has been shown to affect the fatigue life of bone cements, but, although vacuum mixing is widely used to reduce porosity in the clinical setting, results have been mixed and the effects of porosity are not well understood. The aim of this study was to investigate the effects of porosity using stress analysis and fracture mechanics techniques. The stress concentrations arising at voids in test specimens were found using analytical solutions and boundary element methods. The fatigue life of specimens containing voids of various sizes was predicted using fracture mechanics techniques. For spherical voids that do not occupy a significant proportion of the cross-section, the resulting stress concentration is independent of void size and too small to account for the observed crack initiation. Cracks must therefore initiate at additional stress raisers such as radiopacifier particles or additional voids. For large voids, the stress increases as the remaining cross-section of the specimen decreases, and this may account for much of the observed reduction in fatigue strength in hand-mixed cement. Although crack initiation may be largely independent of void size, there is an effect on crack growth rate. Cracks are predicted to grow faster around larger voids, since they remain in the stress concentration around the void for longer. This effect may account for the relationship between porosity and fatigue life that has been observed in samples without large voids. Since porosity appears to affect crack growth more than initiation, it may be less damaging in high-cycle clinical fatigue, which may be predominantly initiation controlled, than in short laboratory tests.
Kernel based support vector machine for the early detection of syncope during head-up tilt test

This study aims to analyze the autonomic nervous system response during head-up tilt test (HUTT), by exploring the changes in dynamic properties of heart rate variability in subjects with and without syncopes, to predict the outcome of HUTT. Baroreflex response, as well as linear and non-linear parameters of RR-interval time series, have been extracted from the ECG of 66 subjects: 35 with and 31 without syncope during HUTT. The results show that, when considering the first 15 min of tilting position, the total power spectrum, the standard deviation, the long-term fractal scale of RR-interval and ΔRR-interval of time series increase, while the sample entropy decreases in the positive group compared to the negative one. These indices may be good predictors of positive response in patients with reflex syncope. Additionally, an analysis of the first 15 min of tilting position using kernel support vector machines leads to a correct classification of 85% of patients, within negative and positive response groups (specificity = 80.6% and sensitivity = 88.5%). In medical applications, it is important to avoid false negative diagnosis of syncopes during HUTT. Taking this into account, an overall accuracy of 72.1% can be obtained in the same window allowing the reduction of the examination time in the clinical domain.
Revealing the Drug‐Resistant Mechanism for Diarylpyrimidine Analogue Inhibitors of HIV‐1 Reverse Transcriptase

Diaryltriazine (DATA) and diarylpyrimidine (DAPY) were two category inhibitors with highly potent activity for wild type (wt) and four principal mutant types (L100I, K103N, Y181C and Y188L) of HIV‐1 reverse transcriptase (RT). We had revealed the drug‐resistant mechanism of DATA analogue inhibitors with molecular dynamics simulation and three‐dimensional quantitative structure–activity relationship (3D‐QSAR) methods. In this work, we investigated the drug‐resistant mechanism of DAPY analogue inhibitors. It was found that DAPY analogue inhibitors form more hydrogen bonds and hydrophobic contacts with wild type and mutants of HIV‐1 RT than DATA inhibitors. This could explain that DAPY analogue inhibitors are more potent than DATA for the wild type and mutants of HIV‐1 RT. Then, 3D‐QSAR models were constructed for these inhibitors of wild type and four principal mutant types HIV‐1 RT and evaluated by test set compounds. These combined models can be used to design new chemical entities and make quantitative prediction of the bioactivities for HIV‐1 RT inhibitors before resorting to in vitro and in vivo experiment.
Analysis of Ceiling Effects Occurring with Speech Recognition Tests in Adult Cochlear-Implanted Patients

This article presents a simple method of analysing speech test scores which are biased through ceiling effects. Eighty postlingually deafened adults implanted with a MED-EL COMBI 40/40+ cochlear implant (CI) were administered a numbers test and a sentence test at initial device activation and at 1, 3, 6, 12 and 24 months thereafter. As a measure for speech recognition performance, the number of patients who scored at the ‘ceiling level’ (i.e. at least 95% correct answers) was counted at each test interval. Results showed a quick increase in this number soon after device activation as well as a continuous improvement over time (numbers test: 1 month: 51%; 6 months: 73%; 24 months: 88%; sentence test: 1 month: 33%; 6 months: 49%; 24 months: 64%). The new method allows for the detection of speech recognition progress in CI patient samples even at late test intervals, where improvement curves based on averaged scores are usually assuming a flat shape.
Determinants of HIV Drug Resistance and Public Health Implications in Low- and Middle-Income Countries

Global scale-up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is an unprecedented public health achievement. With planned efforts of expanded ART access including earlier treatment initiation and the use of antiretroviral (ARV) drugs for prophylaxis, increasing levels of HIV drug resistance (HIVDR) are expected. Several factors may lead to selection and transmission of significant HIVDR in LMICs, which will lead to decreased population-level efficacy of standard first- and second-line ART regimens. These factors include low genetic barrier of some ARVs to resistance development, drug–drug interactions, inappropriate prescribing practices, interruption of drug supply, poor retention in care and lack of routine viral load monitoring. To maximize long-term effectiveness of available ARVs, policy makers and programme managers in LMICs should routinely monitor programme factors associated with emergence and transmission of HIVDR and implement routine HIVDR surveillance following standardized methods. When surveillance results suggest the need for action, specific public health interventions must be taken to adjust ART programme functioning to minimize further emergence and transmission of HIVDR. In this paper, we review ARV drug, HIV, patient and programme-related determinants of HIVDR. Additionally, we summarize the World Health Orgnization's global HIVDR surveillance and prevention strategy and describe resulting public health and policy implications.
Guidelines for maternal codeine use during breastfeeding.

QUESTION In light of the recent evidence of adverse events in infants whose mothers use codeine medication, we have been struggling with the issue of how to manage codeine analgesia in our postpartum patients. What are some guidelines for the safe use of codeine during breastfeeding? ANSWER Motherisk has summarized recent scientific evidence into suggested guidelines for the safe use of codeine during breastfeeding.
The biochemistry of white and brown adipocytes analysed from a selection of proteins.

Adipocytes are generally considered cells solely or mainly involved in storage of triacylglycerols. These cells have been studied by biochemists and endocrinologists with the aim of understanding, on the one hand, the mechanisms of fatty acid uptake, synthesis and esterification, and, on the other hand, the mechanisms of lipolysis. Most enzymes and components involved in these two sorts of mechanisms have been characterized, purified or cloned. Recent research on adipocytes has highlighted several findings. Analysis of adipocyte differentiation has led to the discovery and cloning of several proteins which have been extensively studied both at the protein and gene level. In other respects, it is now well established that besides energy-storing white adipocytes, mammals possess energy-dissipating brown adipocytes. The relative importance of these two sorts of cells varies widely depending on species, age, environmental conditions, pathological situations. The intriguing thermogenic function of the brown adipose tissue of hibernators, newborns and cold-adapted mammals has stimulated research on the adipocytes forming this organ. Research on brown adipocytes has led to identification of proteins predominantly expressed in these cells or unique to these cells.
Decentralized estimation over noisy channels in cluster‐based wireless sensor networks

In this paper, the problem of decentralized parameter estimation over noisy channels in a cluster‐based sensor network is studied. Each cluster head generates a local estimate by adopting a sample mean estimator. The local estimates from all cluster heads are compressed by using a one‐bit quantizer and then the bits are transmitted to a fusion center over independent binary symmetric channels. Two maximum likelihood estimators are proposed for estimating the parameter based on the received bits in two different scenarios: (i) all clusters have the same number of cluster members and (ii) the number of cluster members in the clusters are different. The Cramér–Rao lower bounds for the proposed estimators in both scenarios are derived. Simulation results show that the estimation performance for clustering with the same number of cluster members can be comparable to that for cluster‐free sensor networks. However, the estimation performance for clustering with a different number of cluster members is not as good as that for cluster‐free sensor networks. The trade off between estimation performance and energy consumption exists in both scenarios. The energy consumed for executing the estimation task in cluster‐based sensor networks is less than that in cluster‐free sensor networks. Copyright © 2011 John Wiley & Sons, Ltd.
Single Giant Unilamellar Vesicle Method Reveals Effect of Antimicrobial Peptide, Magainin 2, and Antibacterial Substance, Tea Catechin, on Membrane Permeability and Membrane Structure

Almost all studies of biomembrane function have previously been carried out on suspensions of many small-size vesicles such as large unilamellar vesicles (LUVs). In these studies, the average values of the physical parameters of vesicles have been obtained from large numbers of vesicles, and thereby a lot of information has been lost. Recently we have proposed a novel method, the single GUV method. In this method we observe and measure physical properties of single giant unilamellar vesicles (GUVs) with diameters ges 10 mum, and analyze these results over many GUVs statistically, which provide a lot of novel information that cannot be obtained by the studies of suspensions of small-size vesicles. In this report, we investigated effect of antimicrobial peptide, magainin 2, and antibacterial substance, tea catechin, on structure and physical property of lipid membranes using the single GUV method, and succeeded in obtaining detailed information of their effects on lipid membranes
Learning to learn by gradient descent by reinforcement learning

Learning rate is a free parameter in many optimization algorithms including Stochastic Gradient Descent (SGD). Choosing a good value of learning rate is non-trivial for important non-convex problems such as training of Deep Neural Networks. In this work, we formulate the optimization process as a Partially Observable Markov Decision Process and pose the the choice of learning rate per time step as a reinforcement learning problem. On a simple quadratic function family, our agents using Deep Q Networks are able to outperform two simple baselines. We also implement a strong baseline given by ‘Graduate Student Descent’ and show that DQN agents approach its performance. Finally, we present several visualizations that may be helpful to understand the DQN training process.
Mechano‐sensitive regulation of gene expression during the embryonic development

Cell movements during embryogenesis produce mechanical tensions that shape the embryo and can also regulate gene expression, thereby affecting cell differentiation. Increasing evidence indicates that mechanosensitive regulation of gene expression plays important roles during embryogenesis by coupling the processes of morphogenesis and differentiation. However, the molecular mechanisms of this phenomenon remain poorly understood. This review focuses on the molecular mechanisms that “translate” mechanical stimuli into gene expression.
Characterization of Scale‐Dependent Dispersivity in Fractured Formations Through a Divergent Flow Tracer Test

Scale‐dependency of dispersivity has been reported from field tracer tests. We present a simple methodology for characterization of dispersivity as a linear function of scale around an injection well using divergent flow tracer test data conducted in fractured formations. Results show that the slope of this linear dispersivity function can be estimated using tracer concentration measurements in a monitoring well. The characterized dispersivity function has applications in modeling of field‐scale transport processes in fractured formations.
Organization of the chick blastoderm edge.

A band of cells forming the edge of the chick blastoderm, and attached to the vitelline membrane, causes the expansion of the blastoderm in the first few days of incubation by active migration across the vitelline membrane. The structure and organization of these cells was examined by light microscopy (both on whole mounts and sections) and transmission electron microscopy. The account presented differs markedly from previous descriptions of these cells. The band of cells at the blastoderm edge is an association, between 90 and 130 µm wide, of flattened, non-dividing cells forming a multilayer; some of these cells, and no other cells of the blastoderm, are attached to the vitelline membrane. Each attached cell has a thin flattened lamella, centrifugally oriented and underlapping the next cell distally, except (1) the most distal cell, whose lamella is thick and long, though tapering, and is not overlain by other cells; and (2) the most proximal attached cell which has a short centripetally oriented lamella, as well as a centrifugal underlapping one. The cells of the edge band not attached to the vitelline membrane also have flattened lamellae attached to the cells below; these lamellae are, however, unoriented. The cells of the edge band all have plentiful cortical filaments and cytoplasmic microtubules. Specialized plaques are involved in the attachment of edge band cells to the vitelline membrane. The form of this edge structure is compared with the outgrowth edge of a chick yolk sac epiblast explant cultured on vitelline membrane. It seems likely that the way the blastoderm edge cells are organized may explain their prodigious migratory activity.