Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of Chronic Antidepressant Treatments in a New Model of Extreme Anxiety in Rats

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders.
Toolbox for Non-Intrusive Structural and Functional Analysis of Recombinant VLP Based Vaccines: A Case Study with Hepatitis B Vaccine

Background Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP) approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg) VLP-based vaccine. Methodology The epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR) and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA). The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM) and in-solution atomic force microscopy (AFM). Principal Findings SPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turn-around, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images – confirming the previously proposed octahedral structure and the established lipid-to-protein ratio of HBsAg particles. Results from these non-intrusive biophysical and immunochemical analyses coalesced into a comprehensive understanding of rHBsAg vaccine epitope structure and function that was important for assuring the desired epitope formation, determinants for vaccine potency, and particle stability during vaccine design, development, and manufacturing. Significance Together, the methods presented here comprise a novel suite of non-intrusive VLP structural and functional characterization tools for recombinant vaccines. Key VLP structural features were defined and epitope-specific antigenicity was quantified while preserving epitope integrity and particle morphology. These tools should facilitate the development of other VLP-based vaccines.
Proposal of Autonomous Flight Wireless Nodes with Delay Tolerant Networks for Disaster Use

Many cities or towns are located in mountain and sea areas, and these areas would be isolated from others because of the disconnection of networks or transportation if a large scale disaster should happen. In this paper, Delay Tolerant Networking (DTN) based on the Data Triage Method with the user policies and the Autonomous Flight Wireless Nodes (AFW) based on autonomous flights and data deliveries are introduced. In the proposed system, the drone with wireless interfaces is applied, and it actively supports the proposed DTN routings for the Disaster Information System (DIS). That is, the AFW automatically flies for seeking possible wireless nodes, send and receive disaster information by the proposed DTN routings, and return to the possible stations that wireless charge units are equipped when the battery needs to charge. Then, the implementations and the field experiments are discussed for the effectiveness of the proposed methods.
Is culture associated with patient safety in the emergency department? A study of staff perspectives.

OBJECTIVE To describe the patient safety culture of Dutch emergency departments (EDs), to examine associations between safety culture dimensions and patient safety grades as reported by ED staff and to compare these associations between nurses and physicians. DESIGN Cross-sectional survey conducted in 2007. SETTING Thirty-three non-academic EDs in the Netherlands. PARTICIPANTS Four hundred and eighty nurses, 159 physicians and 91 other professionals. MAIN OUTCOME MEASURE Self-reported level of patient safety. RESULTS In unadjusted analyses, all dimensions of safety culture were positively associated with the reported level of patient safety and six of these associations with patient safety were statistically significant after adjustment ('teamwork across units', 'frequency of event reporting', communication openness', 'feedback about and learning from errors', 'hospital management support for patient safety'). Differences between nurses and physicians were found on two dimensions ('frequency of event reporting' and ' hospital management support for patient safety'). Physicians tended to grade patient safety higher than nurses whilst having equal judgements on these two dimensions. CONCLUSIONS Staff identified several dimensions of safety culture that are associated with staff-reported safety in the ED. Physicians and nurses identified distinct dimensions of safety culture as associated with reported level of patient safety.
The Psychometric Assessment of Internalized Stigma Instruments: A Systematic Review

Objective: To rate the psychometric properties of instruments to measure internalized (or self-) stigma in health conditions where stigma plays a major role. Method: We conducted a systematic literature review by searching relevant databases and by reviewing the bibliographies of relevant papers. Quantitative studies were included if the items used, or a sample of the instrument, was included in the paper and if the studies focussed on the initial development or validation of the instrument. Health conditions included were HIV/AIDS, mental health, leprosy, asthma, epilepsy, cancer, obesity, and tuberculosis. Psychometric properties of the included studies were assessed using the quality criteria proposed by Terwee et al. and the COSMIN consortium: content validity, internal consistency, construct validity, criterion validity, reproducibility, responsiveness, floor and ceiling effects, and interpretability. Results: Thirty-three papers were included of which 21 were identified as actual instrument development studies. Only two instruments received three positive quality ratings, 12 received at least three indeterminate ratings, especially for the internal consistency and construct validity. At least one negative rating was given to five instruments. Content and construct validity as well as internal consistency were most often assessed, whereas agreement and responsiveness received least attention. Conclusions: We rated the psychometric properties of available instruments to measure internalized stigma using standard quality criteria. Only the Child Attitude Towards Illness Scale and the Internalized Stigma of Mental Illness received three positive ratings indicating that the majority of the instruments need further testing. Implications: The need was identified for a simplified testing protocol to design an instrument development study, to assess certain psychometric properties, and to specify the preferred statistical methods for testing these. In addition, researchers should be aware that re-validation of instruments is necessary before they are used in cultures and study populations other than those for which they were developed.
A Biomechanical Study of Three Wiring Techniques for Cerclage‐Plating

Summary: Transverse fractures at the distal tip of a well-fixed femoral prosthesis are difficult to stabilize using plates and screws due to the presence of the underlying intramedullary stem. The attachment of plates using cerclage wires obviates the need for screws, but the stability provided by cerclage plating is a clinical concern. In this study we compared the mechanical performance of three wire-cerclage plating techniques: (a) simple cerclage (each wire wrapped around the bone and plate once); (b) double cerclage (each wire wrapped around the bone and plate twice); and (c) a new method that used small stainless steel inserts that fit into the plate holes and permit the direct coupling of the cercelage wires to the plate. To compare the performance of the three fixation constructs, synthetic femora were osteotomized, stabilized with a wire cerclage plating technique, and subjected to monotonic and cyclic loading using a Materials Testing System (Minneapolis, MN) servo-hydraulic testing system. The performance of each construct was evaluated using seven different mechanical parameters (four monotonic, three cyclic). Double cerclage performed significantly better than did simple cerclage for three of the seven mechanical parameters. The insert technique performed significantly better than did the sample and double cerclage techniques for all seven of the measured mechanical parameters. For both monotonic and cyclic loading, the use of inserts resulted in an improvement in fixation strength and stability in comparison with conventional simple and double cerclage plating techniques. The insert technique shows promise in the treatment of this difficult type of fracture at the distal tip of a well-fixed femoral prosthesis.
Cerebellar-Motor Dysfunction in Schizophrenia and Psychosis-Risk: The Importance of Regional Cerebellar Analysis Approaches

Motor abnormalities in individuals with schizophrenia and those at-risk for psychosis are well documented. An accumulating body of work has also highlighted motor abnormalities related to cerebellar dysfunction in schizophrenia including eye-blink conditioning, timing, postural control, and motor learning. We have also recently found evidence for motor dysfunction in individuals at ultra high-risk for psychosis (1–3). This is particularly relevant as the cerebellum is thought to be central to the cognitive dysmetria model of schizophrenia, and these overt motor signs may point to more general cerebellar dysfunction in the etiology of psychotic disorders. While studies have provided evidence indicative of motor cerebellar dysfunction in at-risk populations and in schizophrenia, findings with respect to the cerebellum have been mixed. One factor potentially contributing to these mixed results is the whole-structure approach taken when investigating the cerebellum. In non-human primates, there are distinct closed-loop circuits between the cerebellum, thalamus, and brain with motor and non-motor cortical regions. Recent human neuroimaging has supported this finding and indicates that there is a cerebellar functional topography (4), and this information is being missed with whole-structure approaches. Here, we review cerebellar-motor dysfunction in individuals with schizophrenia and those at-risk for psychosis. We also discuss cerebellar abnormalities in psychosis, and the cerebellar functional topography. Because of the segregated functional regions of the cerebellum, we propose that it is important to look at the structure regionally in order to better understand its role in motor dysfunction in these populations. This is analogous to approaches taken with the basal ganglia, where each region is considered separately. Such an approach is necessary to better understand cerebellar pathophysiology on a macro-structural level with respect to the pathogenesis of psychosis.
Assessment of executive functions in obese individuals with binge eating disorder.

OBJECTIVE The aim of this study was to assess executive functions of obese individuals with binge eating disorder. METHOD Thirty-eight obese individuals with binge eating disorder were compared to thirty-eight obese controls without binge eating disorder in terms of their executive functions. All individuals were assessed using the following instruments: Digit Span, Trail Making Tests A and B, Stroop Test and the Wisconsin Card Sorting Test. In addition, four subtests from the Behavioral Assessment of the Dysexecutive Syndrome Battery were also used, namely the Zoo Map Test, the Modified Six Elements Test, the Action Program Test and the Rule Shift Cards Test. RESULTS When compared to obese controls, obese individuals with binge eating disorder presented significant impairment in the following tests: Digit Span backward, Zoo Map Test, Modified Six Elements Test, and Action Program Test. Subjects with binge eating disorder also showed significant more set shifting and perseverative errors in the Wisconsin Card Sorting Test. In other measures such as the Digit Span Forward, the Trail Making Test, the Stroop Test and the Rule Shift Cards Test, obese subjects with binge eating disorder did not differ significantly from obese subjects without binge eating disorder. CONCLUSION These results suggest that, in the present sample, obese individuals with binge eating disorder presented executive deficits, especially impairments relating to problem-solving, cognitive flexibility and working memory.
Cytoplasmic ATP Inhibition of CLC-1 Is Enhanced by Low pH

The CLC-1 Cl− channel is abundantly expressed on the plasma membrane of muscle cells, and the membrane potential of muscle cells is largely controlled by the activity of this Cl− channel. Previous studies showed that low intracellular pH increases the overall open probability of recombinant CLC-1 channels in various expression systems. Low intracellular pH, however, is known to inhibit the Cl− conductance on the native muscle membrane, contradicting the findings from the recombinant CLC-1 channels in expressed systems. Here we show that in the presence of physiological concentrations of ATP, reduction of the intracellular pH indeed inhibits the expressed CLC-1, mostly by decreasing the open probability of the common gate of the channel.
Highly Precise Measurement of HIV DNA by Droplet Digital PCR

Deoxyribonucleic acid (DNA) of the human immunodeficiency virus (HIV) provides the most sensitive measurement of residual infection in patients on effective combination antiretroviral therapy (cART). Droplet digital PCR (ddPCR) has recently been shown to provide highly accurate quantification of DNA copy number, but its application to quantification of HIV DNA, or other equally rare targets, has not been reported. This paper demonstrates and analyzes the application of ddPCR to measure the frequency of total HIV DNA (pol copies per million cells), and episomal 2-LTR (long terminal repeat) circles in cells isolated from infected patients. Analysis of over 300 clinical samples, including over 150 clinical samples assayed in triplicate by ddPCR and by real-time PCR (qPCR), demonstrates a significant increase in precision, with an average 5-fold decrease in the coefficient of variation of pol copy numbers and a >20-fold accuracy improvement for 2-LTR circles. Additional benefits of the ddPCR assay over qPCR include absolute quantification without reliance on an external standard and relative insensitivity to mismatches in primer and probe sequences. These features make digital PCR an attractive alternative for measurement of HIV DNA in clinical specimens. The improved sensitivity and precision of measurement of these rare events should facilitate measurements to characterize the latent HIV reservoir and interventions to eradicate it.
Topographic Relationship between the Supratrochlear Nerve and Corrugator Supercilii Muscle—Can This Anatomical Knowledge Improve the Response to Botulinum Toxin Injections in Chronic Migraine?

Chronic migraine has been related to the entrapment of the supratrochlear nerve within the corrugator supercilii muscle. Recently, research has shown that people who have undergone botulinum neurotoxin A injection in frontal regions reported disappearance or alleviation of their migraines. There have been numerous anatomical studies conducted on Caucasians revealing possible anatomical problems leading to migraine; on the other hand, relatively few anatomical studies have been conducted on Asians. Thus, the aim of the present study was to determine the topographic relationship between the supratrochlear nerve and corrugator supercilii muscle in the forehead that may be the cause of migraine. Fifty-eight hemifaces from Korean and Thai cadavers were used for this study. The supratrochlear nerve entered the corrugator supercilii muscle in every case. Type I, in which the supratrochlear nerve emerged separately from the supraorbital nerve at the medial one-third portion of the orbit, was observed in 69% (40/58) of cases. Type II, in which the supratrochlear nerve emerged from the orbit at the same location as the supraorbital nerve, was observed in 31% (18/58) of cases.
Isolation, cell culture, and characterization of oviduct epithelial cells of the cow

This report describes an easy method of isolation and cell culture of the epithelial cells of cow oviduct. Incubation of cow oviduct with 0.1 mg/ml collagenase in the lumen for 90 minutes helped to dislodge large numbers of ciliated and secretory epithelial cells. The isolated cells, when seeded on plastic, proliferated very quickly and became confluent in 8–10 days in 35 mm Petri dishes. The isolated ciliated cells which attached to the plastic dish lost their cilia after 4–5 days in culture. The cultured epithelial cells were keretin positive. The isolated bovine oviduct epithelial cells, when cultured on plastic precoated with 10 mg/ml matrigel, organized themselves into hollow tubes or spheres with microvilli directed towards the lumen. The epithelial cells seeded on 2 mg/ml matrigel became subconfluent in 15–20 days after seeding. The histoarchitecture of the secretory cells growing in vitro on matrigel resembled that of intact oviduct secretory epithelial cells. Occasional ciliated cells containing large number of mitochondria were observed in the monolayer cultured on 2 mg/ml matrigel substratum but possessed few cilia. The oviduct epithelial cells cultured on 2 mg/ml matrigel incorporated 35S‐methionine linearily into protein up to 8 hours in the presence of estradiol or progesterone. The fluorograph of the newly synthesized proteins indicated the presence of an additional 60 kd protein in the cell extract of epithelial cells incubated with estradiol. © 1995 Wiley‐Liss, Inc.
Characterisation of Weibel–Palade body fusion by amperometry in endothelial cells reveals fusion pore dynamics and the effect of cholesterol on exocytosis

Summary Regulated secretion from endothelial cells is mediated by Weibel–Palade body (WPB) exocytosis. Plasma membrane cholesterol is implicated in regulating secretory granule exocytosis and fusion pore dynamics; however, its role in modulating WPB exocytosis is not clear. To address this we combined high-resolution electrochemical analysis of WPB fusion pore dynamics, by amperometry, with high-speed optical imaging of WPB exocytosis following cholesterol depletion or supplementation in human umbilical vein endothelial cells. We identified serotonin (5-HT) immunoreactivity in WPBs, and VMAT1 expression allowing detection of secreted 5-HT as discrete current spikes during exocytosis. A high proportion of spikes (∼75%) had pre-spike foot signals, indicating that WPB fusion proceeds via an initial narrow pore. Cholesterol depletion significantly reduced pre-spike foot signal duration and increased the rate of fusion pore expansion, whereas cholesterol supplementation had broadly the reverse effect. Cholesterol depletion slowed the onset of hormone-evoked WPB exocytosis, whereas its supplementation increased the rate of WPB exocytosis and hormone-evoked proregion secretion. Our results provide the first analysis of WPB fusion pore dynamics and highlight an important role for cholesterol in the regulation of WPB exocytosis.
Glutamine Metabolism Is Essential for Human Cytomegalovirus Infection

ABSTRACT Human fibroblasts infected with human cytomegalovirus (HCMV) were more viable than uninfected cells during glucose starvation, suggesting that an alternate carbon source was used. We have determined that infected cells require glutamine for ATP production, whereas uninfected cells do not. This suggested that during infection, glutamine is used to fill the tricarboxylic acid (TCA) cycle (anaplerosis). In agreement with this, levels of glutamine uptake and ammonia production increased in infected cells, as did the activities of glutaminase and glutamate dehydrogenase, the enzymes needed to convert glutamine to α-ketoglutarate to enter the TCA cycle. Infected cells starved for glutamine beginning 24 h postinfection failed to produce infectious virions. Both ATP and viral production could be rescued in glutamine-starved cells by the TCA intermediates α-ketoglutarate, oxaloacetate, and pyruvate, confirming that in infected cells, a program allowing glutamine to be used anaplerotically is induced. Thus, HCMV infection activates the mechanisms needed to switch the anaplerotic substrate from glucose to glutamine to accommodate the biosynthetic and energetic needs of the viral infection and to allow glucose to be used biosynthetically.
Improving preemptive prioritization via statistical characterization of OLTP locking

OLTP and transactional workloads are increasingly common in computer systems, ranging from e-commerce to warehousing to inventory management. It is valuable to provide priority scheduling in these systems, to reduce the response time for the most important clients, e.g. the "big spenders". Two-phase locking, commonly used in DBMS, makes prioritization difficult, as transactions wait for locks held by others regardless of priority. Common lock scheduling solutions, including non-preemptive priority inheritance and preemptive abort, have performance drawbacks for TPC-C type workloads. The contributions of this paper are two-fold: (i) We provide a detailed statistical analysis of locking in TPC-C workloads with priorities under several common preemptive and non-preemptive lock prioritization policies. We determine why non-preemptive policies fail to sufficiently help high-priority transactions, and why preemptive policies excessively hurt low-priority transactions, (ii) We propose and implement a policy, POW, that provides all the benefits of preemptive prioritization without its penalties.