Miracle-dz/UniFAR-FTUs huggingface dataset:
The Isomerase Active Site of Cyclophilin A Is Critical for Hepatitis C Virus Replication*

Cyclosporine A and nonimmunosuppressive cyclophilin (Cyp) inhibitors such as Debio 025, NIM811, and SCY-635 block hepatitis C virus (HCV) replication in vitro. This effect was recently confirmed in HCV-infected patients where Debio 025 treatment dramatically decreased HCV viral load, suggesting that Cyps inhibitors represent a novel class of anti-HCV agents. However, it remains unclear how these compounds control HCV replication. Recent studies suggest that Cyps are important for HCV replication. However, a profound disagreement currently exists as to the respective roles of Cyp members in HCV replication. In this study, we analyzed the respective contribution of Cyp members to HCV replication by specifically knocking down their expression by both transient and stable small RNA interference. Only the CypA knockdown drastically decreased HCV replication. The re-expression of an exogenous CypA escape protein, which contains escape mutations at the small RNA interference recognition site, restored HCV replication, demonstrating the specificity for the CypA requirement. We then mutated residues that reside in the hydrophobic pocket of CypA where proline-containing peptide substrates and cyclosporine A bind and that are vital for the enzymatic or the hydrophobic pocket binding activity of CypA. Remarkably, these CypA mutants fail to restore HCV replication, suggesting for the first time that HCV exploits either the isomerase or the chaperone activity of CypA to replicate in hepatocytes and that CypA is the principal mediator of the Cyp inhibitor anti-HCV activity. Moreover, we demonstrated that the HCV NS5B polymerase associates with CypA via its enzymatic pocket. The study of the roles of Cyps in HCV replication should lead to the identification of new targets for the development of alternate anti-HCV therapies.
Ego Ergo Sum

Abstract Modern sleep and dream science not only fails to support the central tenets of Freudian dream theory but raises serious questions about other strongly held psychodynamic assumptions including the nature of the unconscious mind, infantile sexuality, the tripartite model of the mind, the concept of ego defense, free association and the analysis of the transference as a way of effecting adaptive change. This article summarizes a radical revision of psychodynamic theory in terms of the neurobiological findings of the last half century and proposes an alternative theoretical model which posits a virtual reality generator for the brain that arises late in evolution and early in the development of thermoregulating animals. The author's training and clinical experience are used to highlight these theoretical considerations and inform a forthcoming treatment-oriented book in progress entitled EGO DAMAGE AND REPAIR.
Moving beyond access: towards a quality-orientated substance abuse treatment system in South Africa.

There is growing concern about the increased demand for and limited access to substance abuse treatment in South Africa. The government has responded by allocating more money to the delivery of substance abuse treatment, expanding the number of state-funded treatment slots, and training additional health and social workers to deliver these services, particularly in provinces where the prevalence of substance-related problems is high, such as the Western Cape. While these efforts should be commended and continued, steps to improve service availability have occurred without adequate consideration of the quality of services provided. This is not surprising, as there is little or no routine monitoring and evaluation of substance abuse services in the country. It is also disquieting, as access to treatment is necessary but not sufficient for positive treatment outcomes.
On the safety assessment of human exposure in the proximity of cellular communications base-station antennas at 900, 1800 and 2170 MHz

In this work, the procedures for safety assessment in the close proximity of cellular communications base-station antennas at three different frequencies (900, 1800 and 2170 MHz) are analysed. For each operating frequency, we have obtained and compared the distances to the antenna from the exposure places where electromagnetic fields are below reference levels and the distances where the specific absorption rate (SAR) values in an exposed person are below the basic restrictions, according to the European safety guidelines. A high-resolution human body model has been located, in front of each base-station antenna as a worst case, at different distances, to compute whole body averaged SAR and maximum 10 g averaged SAR inside the exposed body. The finite-difference time-domain method has been used for both electromagnetic fields and SAR calculations. This paper shows that, for antenna–body distances in the near zone of the antenna, the fact that averaged field values be below the reference levels could, at certain frequencies, not guarantee guidelines compliance based on basic restrictions.
How personality and moral identity relate to individuals' ethical ideology

Two studies tested the relationship between three facets of personalityâ€”conscientiousness, agreeableness, and openness to experienceâ€”as well as moral identity, on individualsâ€™ ethical ideology. Study 1 showed that moral personality and the centrality of moral identity to the self were associated with a more principled (versus expedient) ethical ideology in a sample of female speech therapists. Study 2 replicated these findings in a sample of male and female college students, and showed that ideology mediated the relationship between personality, moral identity, and two organizationally relevant outcomes: organizational citizenship behavior and the propensity to morally disengage. Implications for business ethics are discussed.
Modeling the Growth/No-Growth Boundaries of Postprocessing Listeria monocytogenes Contamination on Frankfurters and Bologna Treated with Lactic Acid

ABSTRACT This study developed models to predict lactic acid concentration, dipping time, and storage temperature combinations determining growth/no-growth interfaces of Listeria monocytogenes at desired probabilities on bologna and frankfurters. L. monocytogenes was inoculated on bologna and frankfurters, and 75 combinations of lactic acid concentrations, dipping times, and storage temperatures were tested. Samples were stored in vacuum packages for up to 60 days, and bacterial populations were enumerated on tryptic soy agar plus 0.6% yeast extract and Palcam agar on day zero and at the end point of storage. The combinations that allowed L. monocytogenes increases of ≥1 log CFU/cm2 were assigned the value of 1 (growth), and the combinations that had increases of <l log CFU/cm2 were given the value of 0 (no growth). These binary growth response data were fitted to logistic regression to develop a model predicting probabilities of growth. Validation with existing data and various indices showed acceptable model performance. Thus, the models developed in this study may be useful in determining probabilities of growth and in selecting lactic acid concentrations and dipping times to control L. monocytogenes growth on bologna and frankfurters, while the procedures followed may also be used to develop models for other products, conditions, or pathogens.
Assessing the raters agreement in the diagnostic catheter tube connector production process using novel fuzzy similarity coefficient

The aim of the paper is to present the authors' novel approach to methodology for assessing the level of raters agreement (process operators, quality controllers and/or experts) and its interpretation, that is the methodology for study of reliability for qualitative characteristics. Both mathematical tools and study organizational guidelines are discussed. The method is based on the novel fuzzy similarity coefficient SC. The proposed methodology was used in a measurement system study for attributes of a tube connector of Swan-Ganz catheter production process.
Integrated radio frequency synthetizers for wireless applications

This thesis consists of six publications and an overview of the research topic, which is also a summary of the work. The research described in this thesis concentrates on the design of phase-locked loop radio frequency synthesizers for wireless applications. In particular, the focus is on the implementation of the prescaler, the phase detector, and the chargepump. This work reviews the requirements set for the frequency synthesizer by the wireless standards, and how these requirements are derived from the system specifications. These requirements apply to both integer-N and fractional-N synthesizers. The work also introduces the special considerations related to the design of fractional-N phase-locked loops. Finally, implementation alternatives for the different building blocks of the synthesizer are reviewed. The presented work introduces new topologies for the phase detector and the chargepump, and improved topologies for high speed CMOS prescalers. The experimental results show that the presented topologies can be successfully used in both integer-N and fractional-N synthesizers with state-of-the-art performance. The last part of this work discusses the additional considerations that surface when the synthesizer is integrated into a larger system chip. It is shown experimentally that the synthesizer can be successfully integrated into a complex transceiver IC without sacrificing the performance of the synthesizer or the transceiver.
BuzzSaw at SemEval-2017 Task 7: Global vs. Local Context for Interpreting and Locating Homographic English Puns with Sense Embeddings

This paper describes our system participating in the SemEval-2017 Task 7, for the subtasks of homographic pun location and homographic pun interpretation. For pun interpretation, we use a knowledge-based Word Sense Disambiguation (WSD) method based on sense embeddings. Pun-based jokes can be divided into two parts, each containing information about the two distinct senses of the pun. To exploit this structure we split the context that is input to the WSD system into two local contexts and find the best sense for each of them. We use the output of pun interpretation for pun location. As we expect the two meanings of a pun to be very dissimilar, we compute sense embedding cosine distances for each sense-pair and select the word that has the highest distance. We describe experiments on different methods of splitting the context and compare our method to several baselines. We find evidence supporting our hypotheses and obtain competitive results for pun interpretation.
From Farms to Markets: Gram-Negative Bacteria Resistant to Third-Generation Cephalosporins in Fruits and Vegetables in a Region of North Africa

The role of food in human exposure to antimicrobial-resistant bacteria is a growing food safety issue. The contribution of fruits and vegetables eaten raw to this exposure is still unclear. The evaluation of contamination levels of fruits, vegetables and the agricultural environment by third-generation cephalosporin (3GC)-resistant Gram-negative bacteria was performed by analyzing 491 samples of fruits and vegetables collected from 5 markets and 7 farms in Bejaia area, north-eastern Mediterranean coast of Algeria. Ninety soil samples and 45 irrigation water samples were also sampled in farms in order to assess them as potential inoculum sources. All samples were investigated at the same time on ceftazidime-containing selective media for 3GC-resistant Gram-negative bacteria detection and on Hektoen media, for Salmonella spp. presence. The bacteria isolated (n = 30) from fruits and vegetables, soil and irrigation water collected in the farms were almost all non-fermenting bacterial species (Stenotrophomonas, Acinetobacter, Pseudomonas, Ochrobactrum) except one strain of Enterobacter cloacae and two strains of Citrobacter murliniae, isolated on one cucumber and two tomato samples in the same farm. Greater diversity in bacterial species and antimicrobial resistance profiles was observed at markets: Enterobacteriaceae (n = 41) were as strongly represented as non-fermenting bacteria (n = 37). Among Enterobacteriaceae, E. cloacae (n = 21), and Klebsiella pneumoniae (n = 13) were the most common isolates. Most of the K. pneumoniae isolates were extended-spectrum beta-lactamase (ESBL) producers (n = 11). No Salmonella spp. was recovered in any sample. This study showed that fruits and vegetables including those which may be eaten up raw constitute a reservoir of 3GC-resistant Gram-negative bacteria and multi-drug resistant-bacteria in general that can be transferred to humans through food. The general public should be informed of this hazard for health in order to encourage good domestic hygiene practices. In addition, further investigation is needed throughout the production chain to enrol professionals in actions to reduce this contamination.
Designing ADC by means of soft computing

In this paper, the designing of ADC is studied by means of son computing. It is shown when fuzzy system has single input it can be multiplied in the premise rules by introducing proper fuzzy words and linguistic operator for amplifying knowledge base. Instinctive and learning behaviors, knowledge base and topology of circuit are found using fuzzy voronoi diagram in a POE model based program. This converter implements a set of processes during the analog to digital converting. It can be a fast ADC with more proper structure for hybrid neural network because its parameters are applied in training algorithms.
Chronically ill mothers experiencing pain: relational coping strategies used while parenting young children

Objective: There has been little research on women who are parenting while they experience pain and none of this research has focused on mothers with young children. The purpose of this study was to consider relational coping strategies generated by mothers that they used when parenting young children and experiencing pain. Methods: Two-hundred sixty-two mothers participated in this survey research; 171 who have either multiple sclerosis (MS) or rheumatoid arthritis (RA), and a comparison group of 91well mothers. Mothers completed questionnaires inquiring about (a) their coping strategies, (b) levels of pain, fatigue and physical functioning, and (c) if they were currently experiencing an exacerbation of their chronic illness. Results: Well mothers reported using more self-care when parenting while experiencing pain. Mothers with RA were more likely to set boundaries around their behaviour. Women with MS who were experiencing an exacerbation changed their coping strategies to include more child activities and encourage more mature child behaviour when compared to women with RA who were experiencing an exacerbation. Discussion: From the perspective of relational coping theory, mothers consider their own pain while simultaneously attending to their responsibilities as a parent. Previous research has suggested that women may withdraw or reduce their parenting activities when they are in pain and this study supported the previous research, especially for women with RA.
Emotional and behavioural difficulties in young children with and without developmental delay: a bi-national perspective.

BACKGROUND Relatively high rates of emotional and behavioural difficulties have been reported among children with intellectual or developmental disabilities. Little is known about nature of the relationship between cognitive development and psychopathology in very young children. METHODS Secondary analysis of data from the first two waves of the UK's Millennium Cohort Study (n = 11,389) and the first two waves of the Longitudinal Study of Australian Children (n = 4,606). RESULTS Two- to three-year- old children with developmental delay show significantly higher rates of emotional and behavioural difficulties than their peers. These differences appear to reflect a general association between cognitive performance and emotional/behavioural difficulties in the bottom half of the ability spectrum and threshold-based discontinuities within the bottom 3% of the distribution. In the UK, but to a much lesser extent in Australia, higher rates of emotional and behavioural difficulties among children with developmental delay may be partially attributed to greater risk of exposure to adverse socio-economic circumstances. CONCLUSIONS The results highlight the potential value of targeted preventative interventions for young children with developmental delay.
Optimal Selling Rules in a Regime-Switching Exponential Gaussian Diffusion Model

This paper develops optimal selling rules in asset trading using a regime-switching exponential Gaussian diffusion model. The optimization problem is solved by a combined approach of boundary value problems and probabilistic analysis. A system of linear differential equations with variable coefficients and two-point boundary conditions, satisfied by the objective function of the problem, is derived. The existence and uniqueness of the solution are proved. A closed-form solution in terms of Weber functions is obtained for one-dimensional cases. For m-dimensional cases, a stochastic recursive algorithm for numerically searching the optimal value is developed. Numerical results are reported.
Food Supply and Seawater pCO2 Impact Calcification and Internal Shell Dissolution in the Blue Mussel Mytilus edulis

Progressive ocean acidification due to anthropogenic CO2 emissions will alter marine ecosytem processes. Calcifying organisms might be particularly vulnerable to these alterations in the speciation of the marine carbonate system. While previous research efforts have mainly focused on external dissolution of shells in seawater under saturated with respect to calcium carbonate, the internal shell interface might be more vulnerable to acidification. In the case of the blue mussel Mytilus edulis, high body fluid pCO2 causes low pH and low carbonate concentrations in the extrapallial fluid, which is in direct contact with the inner shell surface. In order to test whether elevated seawater pCO2 impacts calcification and inner shell surface integrity we exposed Baltic M. edulis to four different seawater pCO2 (39, 142, 240, 405 Pa) and two food algae (310–350 cells mL−1 vs. 1600–2000 cells mL−1) concentrations for a period of seven weeks during winter (5°C). We found that low food algae concentrations and high pCO2 values each significantly decreased shell length growth. Internal shell surface corrosion of nacreous ( = aragonite) layers was documented via stereomicroscopy and SEM at the two highest pCO2 treatments in the high food group, while it was found in all treatments in the low food group. Both factors, food and pCO2, significantly influenced the magnitude of inner shell surface dissolution. Our findings illustrate for the first time that integrity of inner shell surfaces is tightly coupled to the animals' energy budget under conditions of CO2 stress. It is likely that under food limited conditions, energy is allocated to more vital processes (e.g. somatic mass maintenance) instead of shell conservation. It is evident from our results that mussels exert significant biological control over the structural integrity of their inner shell surfaces.
Inactivation of a T cell receptor-associated GTP-binding protein by antibody-induced modulation of the T cell receptor/CD3 complex

TCR modulation induced by anti-TCR or anti-CD3 mAbs leads to a transient state of refractoriness of the T cell to all signals given via cell surface structures. To investigate the underlying mechanisms, we have used human CTL permeabilized with the alpha toxin of S. aureus. This method of permeabilization allows manipulation of the interior milieu of the cell, but maintains its functional and structural integrity. Introduction of the G protein activator GTP gamma S into permeabilized CTL leads to triggering of granule exocytosis. The G protein inactivator GDP beta S inhibited exocytosis induced by TCR triggering but not that induced by activation of protein kinase C. This indicates that the G protein that triggers exocytosis is localized after CD3 triggering but before formation of the polyphosphoinositol breakdown product diacylglycerol. In TCR-modulated CTL, GTP gamma S is no longer able to activate exocytosis. Such CTL, however, still respond to PKC activators. This demonstrates that a TCR-associated G protein has been functionally inactivated by TCR modulation.
The effect of construal level on time perceptions, confidence in judgements and future preferences

Purpose – This paper aims to examine how activating an abstract versus concrete construal as a retrieval cue – prior to providing estimates but after exposure to the stimulus – affects retrospective duration estimates of a hedonic experience, the kind of experience one might wish to repeat. Recent research has examined the effect of construal mindsets on prospective time perceptions (Hans and Trope, 2013) as well as the prediction of future durations (Kanten, 2011; Siddiqui et al., 2014). Design/methodology/approach – Two experiments are presented to test four hypotheses. The effect of construal level on time perceptions, confidence in duration judgments and future preferences using two different construal level manipulation techniques and a range of measures for the dependent variables is demonstrated. Findings – This research found that compared to a neutral experience, time perceptions of an enjoyable event are not explained by differences in the level of attention paid to the stimuli; that duration es.
Vascular cell apoptosis in remodeling, restenosis, and plaque rupture.

This Review is part of a thematic series on Apoptosis in the Cardiovascular System , which includes the following articles: Apoptosis and Heart Failure: A Critical Review of the Literature Vascular Cell Apoptosis in Remodeling, Restenosis, and Plaque Rupture Apoptosis During Cardiovascular Development Myocyte Apoptosis in Ischemic Heart Disease Endothelial Cell Apoptosis in Angiogenesis and Vessel Regression Richard Kitsis, Guest Editor Apoptotic death of vascular cells is a prominent feature of blood vessel remodeling that occurs during normal development and fibroproliferative disorders of the vessel wall. This review summarizes a large number of studies that have provided evidence for apoptotic cell death in the vasculature. We also describe reports that shed light on the molecular mechanisms that may control this process. Finally, we highlight the relatively small number of studies that suggest a function for vascular cell apoptosis in controlling the morphology and cellular composition of the blood vessel wall. A number of studies have demonstrated apoptotic death of vascular cells in vessels that remodel postnatally. Regionalized apoptosis has been found in vascular smooth muscle cells (VSMCs) during the regression and closure of the human ductus arteriosus before birth1 and in VSMCs and endothelial cells of the arteries and veins of the umbilical cord, which are subject to dramatic hemodynamic changes at birth.2 Evidence of VSMC apoptosis in the human neonate has also been found at the branch points of the great arteries arising from the aortic arch when they are exposed to a disturbed blood flow, whereas VSMC apoptosis was not observed in the aorta when a normal flow pattern is maintained.2 Finally, VSMC apoptosis has been observed during the remodeling of the abdominal aorta in lambs, resulting from the large decrease in blood flow that occurs after the loss of the placenta at birth.3 …