Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing Glutamate Transport: Mechanism of Action of Parawixin1, a Neuroprotective Compound from Parawixia bistriata Spider Venom

Previous studies have shown that a compound purified from the spider Parawixia bistriata venom stimulates the activity of glial glutamate transporters and can protect retinal tissue from ischemic damage. To understand the mechanism by which this compound enhances transport, we examined its effects on the functional properties of glutamate transporters after solubilization and reconstitution in liposomes and in transfected COS-7 cells. Here, we demonstrate in both systems that Parawixin1 promotes a direct and selective enhancement of glutamate influx by the EAAT2 transporter subtype through a mechanism that does not alter the apparent affinities for the cosubstrates glutamate or sodium. In liposomes, we observed maximal enhancement by Parawixin1 when extracellular sodium and intracellular potassium concentrations are within physiological ranges. Moreover, the compound does not enhance the reverse transport of glutamate under ionic conditions that favor efflux, when extracellular potassium is elevated and the sodium gradient is reduced, nor does it alter the exchange of glutamate in the absence of internal potassium. These observations suggest that Parawixin1 facilitates the reorientation of the potassium-bound transporter, the rate-limiting step in the transport cycle, a conclusion further supported by experiments showing that Parawixin1 does not stimulate uptake by an EAAT2 transport mutant (E405D) defective in the potassium-dependent reorientation step. Thus, Parawixin1 enhances transport through a novel mechanism targeting a step in the transport cycle distinct from substrate influx or efflux and provides a basis for the design of new drugs that act allosterically on transporters to increase glutamate clearance.
The Specificity of Trimming of MHC Class I-Presented Peptides in the Endoplasmic Reticulum1

Aminopeptidases in the endoplasmic reticulum (ER) can cleave antigenic peptides and in so doing either create or destroy MHC class I-presented epitopes. However, the specificity of this trimming process overall and of the major ER aminopeptidase ERAP1 in particular is not well understood. This issue is important because peptide trimming influences the magnitude and specificity of CD8 T cell responses. By systematically varying the N-terminal flanking sequences of peptides in a cell-free biochemical system and in intact cells, we elucidated the specificity of ERAP1 and of ER trimming overall. ERAP1 can cleave after many amino acids on the N terminus of epitope precursors but does so at markedly different rates. The specificity seen with purified ERAP1 is similar to that observed for trimming and presentation of epitopes in the ER of intact cells. We define N-terminal sequences that are favorable or unfavorable for Ag presentation in ways that are independent from the epitopes core sequence. When databases of known presented peptides were analyzed, the residues that were preferred for the trimming of model peptide precursors were found to be overrepresented in N-terminal flanking sequences of epitopes generally. These data define key determinants in the specificity of Ag processing.
Usability and presence evaluation of a 3D virtual world learning environment simulating information security threats

The use of 3-D immersive Virtual World Learning Environments (VWLE) for educational purposes has been rapidly increased in the last few decades. Recent studies focusing on the evaluation of such environments have shown the great potential of virtual worlds in e-learning, providing improvement in factors such as satisfaction, enjoyment, concentration and presence compared to traditional educational practices. In this paper we present the 3D VWLE that has been developed at the framework of the V-ALERT project; the system's main goal is to contribute to the improvement of Information Security(IS) issues awareness. In particular, we present the methodology followed to evaluate critical aspects of the implemented platform, such as usability, presence and educational value. The data analysis has shown that the implemented system is usable, offered to the users high presence perception and increased their knowledge regarding IS. In addition, the evaluation results have shown that interface improvements should be considered and the training session should be enhanced in order to strengthen the system's functionality and educational scope.
Shippers-Providers Perception of Third-Party Logistics Services – An Importance-Performance Matrix Analysis

Using a sample of companies drawn from Logistics Association Australia’s current membership list, this study assessed the relative importance assigned by shippers and logistics service providers (LSP) to various elements of third party logistics services. The importance-performance matrix (IPM) analysis was conducted to assess the gap between what is required by the shippers and what is provided by the LSPs, and categorised the logistics service elements into four categories such as ‘low priority’, ‘possible overkill’, ‘concentrate here’, and ‘keep up the good work’. The results indicate that the LSPs must improve image in terms of their capability to provide service and at a necessary quality level. They must be able to shorten delivery time, reduce product/service cost and be flexible while providing services. It is critical that they use EDI and stand-alone IT platform to integrate with the shippers.
No strings attached: the ESCRT machinery in viral budding and cytokinesis

Since the initial discovery of the endosomal sorting complex required for transport (ESCRT) pathway, research in this field has exploded. ESCRT proteins are part of the endosomal trafficking system and play a crucial role in the biogenesis of multivesicular bodies by functioning in the formation of vesicles that bud away from the cytoplasm. Subsequently, a surprising role for ESCRT proteins was defined in the budding step of some enveloped retroviruses, including HIV-1. ESCRT proteins are also employed in this outward budding process, which results in the resolution of a membranous tether between the host cell and the budding virus particle. Remarkably, it has recently been described that ESCRT proteins also have a role in the topologically equivalent process of cell division. In the same way that viral particles recruit the ESCRT proteins to the site of viral budding, ESCRT proteins are also recruited to the midbody – the site of release of daughter cell from mother cell during cytokinesis. In this Commentary, we describe recent advances in the understanding of ESCRT proteins and how they act to mediate these diverse processes.
Affective Computing and Applications of Image Emotion Perceptions

Images can convey rich semantics and evoke strong emotions in viewers. The research of my PhD thesis focuses on image emotion computing (IEC), which aims to predict the emotion perceptions of given images. The development of IEC is greatly constrained by two main challenges: affective gap and subjective evaluation. Previous works mainly focused on finding features that can express emotions better to bridge the affective gap, such as elements-of-art based features and shape features. According to the emotion representation models, including categorical emotion states (CES) and dimensional emotion space (DES), three different tasks are traditionally performed on IEC: affective image classification, regression and retrieval. The state-of-the-art methods on the three above tasks are image-centric, focusing on the dominant emotions for the majority of viewers. For my PhD thesis, I plan to answer the following questions: (1) Compared to the low-level elements-of-art based features, can we find some higher level features that are more interpretable and have stronger link to emotions? (2) Are the emotions that are evoked in viewers by an image subjective and different? If they are, how can we tackle the user-centric emotion prediction? (3) For image-centric emotion computing, can we predict the emotion distribution instead of the dominant emotion category?
Pharmacotherapy in the treatment of patients with borderline personality disorder: results of a survey among psychiatrists in private practices

Pharmacotherapy still seems to play a major role in the treatment of patients suffering from borderline personality disorder (BPD). However, little is known about psychiatrists’ detailed perspective on indication and significance of medication. A total of 233 psychiatrists in the city of Munich and in Upper Bavaria were asked by questionnaire about their treatment habits in the medical treatment of patients with BPD. One hundred and forty-one psychiatrists answered the questionnaire (60.5%). In total, 94% of BPD patients were treated with psychotropic medication. Psychiatrists predominantly saw an indication to prescribe antidepressants (98%), followed by antipsychotics, mood stabilizers, and benzodiazepines. Citalopram/escitalopram and quetiapine were mentioned most frequently. The results are discussed in conjunction with the international guidelines for the treatment of BPD.
Primary Care Physicians' Discussion of Emotional Distress and Patient Satisfaction

Objectives: To assess: a) the prevalence and determinants of self-reported emotional distress in the Israeli population; b) the rate of self-reported discussion of emotional distress with family physicians; and c) the association between such discussions and patient satisfaction with care. Method: Design: Retrospective, cross-sectional survey that was conducted through structured telephone interviews in Hebrew, Arabic, and Russian. This study was part of a larger study assessing patients' perceptions of the quality of health services. Participants: A representative sample of 1,849 Israeli citizens aged 22 to 93 (response rate: 84%). Independent variables: Gender, age, ethnicity (spoken language), education, income, self-reported chronic disease, self-reported episode(s) of emotional distress during the last year, and having discussed emotional distress with the family physician. Outcome measure: satisfaction with care. Results: 28.4% reported emotional distress and 12.5% reported discussion of emotional distress with a primary care physician in the past year. Logistic regression identified female gender, Arab ethnicity, low income, and chronic illness as independent correlates of emotional distress. These as well as Russian speakers and having experienced emotional distress during the past year were identified as independent correlates of discussion of emotional distress with the family physician. Patients who reported discussion of emotional distress with their family physician were significantly more satisfied with care. Conclusions: Encouraging physicians to detect and discuss emotional distress with their patients may increase patient satisfaction with care, and possibly also improve patients' well-being and reduce health care costs.
Difficulties with telephone‐based surveys on alcohol consumption in high‐income countries: the Canadian example

Accurate information concerning alcohol consumption level and patterns is vital to formulating public health policy. The objective of this paper is to critically assess the extent to which survey design, response rate and alcohol consumption coverage obtained in random digit dialling, telephone‐based surveys impact on conclusions about alcohol consumption and its patterns in the general population. Our analysis will be based on the Canadian Alcohol and Drug Use Monitoring Survey (CADUMS) 2008, a national survey intended to be representative of the general population. The conclusions of this paper are as follows: (1) ignoring people who are homeless, institutionalized and/or do not have a home phone may lead to an underestimation of the prevalence of alcohol consumption and related problems; (2) weighting of observations to population demographics may lead to a increase in the design effect, does not necessarily address the underlying selection bias, and may lead to overly influential observations; and (3) the accurate characterization of alcohol consumption patterns obtained by triangulating the data with the adult per capita consumption estimate is essential for comparative analyses and intervention planning especially when the alcohol coverage rate is low like in the CADUMS with 34%. Copyright © 2012 John Wiley & Sons, Ltd.
Origin and Diversification Dynamics of Self-Incompatibility Haplotypes

Self-incompatibility (SI) is a genetic system found in some hermaphrodite plants. Recognition of pollen by pistils expressing cognate specificities at two linked genes leads to rejection of self pollen and pollen from close relatives, i.e., to avoidance of self-fertilization and inbred matings, and thus increased outcrossing. These genes generally have many alleles, yet the conditions allowing the evolution of new alleles remain mysterious. Evolutionary changes are clearly necessary in both genes, since any mutation affecting only one of them would result in a nonfunctional self-compatible haplotype. Here, we study diversification at the S-locus (i.e., a stable increase in the total number of SI haplotypes in the population, through the incorporation of new SI haplotypes), both deterministically (by investigating analytically the fate of mutations in an infinite population) and by simulations of finite populations. We show that the conditions allowing diversification are far less stringent in finite populations with recurrent mutations of the pollen and pistil genes, suggesting that diversification is possible in a panmictic population. We find that new SI haplotypes emerge fastest in populations with few SI haplotypes, and we discuss some implications for empirical data on S-alleles. However, allele numbers in our simulations never reach values as high as observed in plants whose SI systems have been studied, and we suggest extensions of our models that may reconcile the theory and data.
Evaluation Of Atrial Fibrillation Burden Before Catheter Ablation Predicts Outcome After Pulmonary Vein Isolation

Background Paroxysmal atrial fibrillation (PAF) is defined as recurrent AF terminating spontaneously within 7 days. This definition allows the consideration of any AF occurrence lasting < 7 days as paroxysmal, irrespective of the frequency and duration of episodes. The aim of this study was to investigate symptomatic AF burden (AFB) defined as total duration of symptomatic AF episodes within 3 months prior to abalation, for prediction of outcome after pulmonary vein isolation (PVI). Methods A total of 320 consecutive patients with symptomatic AF (PAF=244, men=214, age=58 y) were enrolled. AFB in patients with PAF was defined as time spent in AF within 3 months prior to PVI. After the AFB cut-off point was optimized at 500 h, patients with PAF were categorized into 2 groups: Group 1 - patients with AFB< 500 h (n=192), Group 2 - patients with AFB≥ 500 h (n=52). Patients with persistent AF (PersAF, n = 76) comprised control group (Group 3). PVI was performed either with irrigated tip catheter (n=215) or using cryoballoon (n=105). The endpoint of study was first documented recurrence of AF >30 sec. Results Symptomatic AFB was found to be appropriate for prediction of outcome after PVI. The freedom from AF within 2 years was observed in 69%, 31%, and 43% patients in Group 1, 2 and 3, respectively (Group 1 vs. Group 2, p < .001; Group 1 vs. Group 3, p< .001; Group 2 vs. Group 3, p = 0.46). Conclusions Low AFB < 500 h /3 months was associated with better outcome after PVI. Patients with PAF and high AFB should be treated as patients with PersAF.
Using the Alfa-1 simulated processor for educational purposes

Alfa-1 is a simulated computer designed for computer organizationcourses. Alfa-1 and its accompanying toolkit allow students toacquire practical insights into developing hardware by extendingexisting components. The DEVS formalism is used to model individualcomponents and to integrate them into a hierarchy that describesthe detailed behavior of different levels of a computer'sarchitecture. We introduce Alfa-1 and the toolkit, show how toextend existing components, and describe how to use Alfa-1 foreducational purposes. We also explain how to assemble, link, andexecute applications and how to test new extensions usingthetesting tools.
Clusterlike Headache in a Patient With a Pituitary Adenoma. With a Review of Literature

A man had left‐sided atypical clusterlike headache for II years before he developed symptoms and signs consistent with acromegaly. Preoperative evaluation revealed raised levels of somatomedin C and growth hormone. An MR indicated a left‐sided intrasellar mass measuring 8 x 7.5 x 10 mm. He underwent surgery and microscopy confirmed the diagnosis of a benign hypophyseal adenoma. Postoperatively, the acromegalic features regressed, and for the last 4 years the patient has been completely free from headache attacks. On pharmacological testing of the pupillary response to 19 and 5% phenylephrine and 2% tyramine solutions, there was no convincing evidence of persistent sympathetic dysfunction on the earlier symptomatic side.
Malignant lesions in the ventral prostate of alloxan‐induced diabetic rats

The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra‐epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl‐2‐positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.
Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial

Background The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study (‘CLEOPATRA’ study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i. d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. Methods and results A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i. d. was well tolerated, and the overall safety profile was comparable with placebo. Conclusion Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity.
The Inclusion of Arbitrary Load Histories in the Strength Decay Model for Stress Rupture

Stress rupture is a failure mechanism where failures can occur after a period of time, even though the material has seen no increase in load. Carbon/epoxy composite materials have demonstrated the stress rupture failure mechanism. In a previous work, a model was proposed for stress rupture of composite overwrap pressure vessels (COPVs) and similar composite structures based on strength degradation. However, the original model was limited to constant load periods (holds) at constant load. The model was expanded in this paper to address arbitrary loading histories and specifically the inclusions of ramp loadings up to holds and back down. The broadening of the model allows for failures on loading to be treated as any other failure that may occur during testing instead of having to be treated as a special case. The inclusion of ramps can also influence the length of the "safe period" following proof loading that was previously predicted by the model. No stress rupture failures are predicted in a safe period because time is required for strength to decay from above the proof level to the lower level of loading. Although the model can predict failures during the ramp periods, no closed-form solution for the failure times could be derived. Therefore, two suggested solution techniques were proposed. Finally, the model was used to design an experiment that could detect the difference between the strength decay model and a commonly used model for stress rupture. Although these types of models are necessary to help guide experiments for stress rupture, only experimental evidence will determine how well the model may predict actual material response. If the model can be shown to be accurate, current proof loading requirements may result in predicted safe periods as long as 10(13) years. COPVs design requirements for stress rupture may then be relaxed, allowing more efficient designs, while still maintaining an acceptable level of safety.