Miracle-dz/UniFAR-FTUs huggingface dataset:
T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity

T cell self-tolerance is thought to involve peripheral tolerance and negative selection, involving apoptosis of autoreactive thymocytes. However, evidence supporting an essential role for negative selection is limited. Loss of Bim, a Bcl-2 BH3-only protein essential for thymocyte apoptosis, rarely results in autoimmunity on the C57BL/6 background. Mice with T cell-specific over-expression of Bcl-2, that blocks multiple BH3-only proteins, are also largely normal. The nuclear receptor Nur77, also implicated in negative selection, might function redundantly to promote apoptosis by associating with Bcl-2 and exposing its potentially pro-apoptotic BH3 domain. Here, we report that T cell-specific expression of a Bcl2 BH3 mutant transgene results in enhanced rescue of thymocytes from negative selection. Concomitantly, Treg development is increased. However, aged BH3 mutant mice progressively accumulate activated, autoreactive T cells, culminating in development of multi-organ autoimmunity and lethality. These data provide strong evidence that negative selection is crucial for establishing T cell tolerance. DOI: http://dx.doi. org/10.7554/eLife.03468. 001
Impact of Synaptic Neurotransmitter Concentration Time Course on the Kinetics and Pharmacological Modulation of Inhibitory Synaptic Currents

The time course of synaptic currents is a crucial determinant of rapid signaling between neurons. Traditionally, the mechanisms underlying the shape of synaptic signals are classified as pre- and post-synaptic. Over the last two decades, an extensive body of evidence indicated that synaptic signals are critically shaped by the neurotransmitter time course which encompasses several phenomena including pre- and post-synaptic ones. The agonist transient depends on neurotransmitter release mechanisms, diffusion within the synaptic cleft, spill-over to the extra-synaptic space, uptake, and binding to post-synaptic receptors. Most estimates indicate that the neurotransmitter transient is very brief, lasting between one hundred up to several hundreds of microseconds, implying that post-synaptic activation is characterized by a high degree of non-equilibrium. Moreover, pharmacological studies provide evidence that the kinetics of agonist transient plays a crucial role in setting the susceptibility of synaptic currents to modulation by a variety of compounds of physiological or clinical relevance. More recently, the role of the neurotransmitter time course has been emphasized by studies carried out on brain slice models that revealed a striking, cell-dependent variability of synaptic agonist waveforms ranging from rapid pulses to slow volume transmission. In the present paper we review the advances on studies addressing the impact of synaptic neurotransmitter transient on kinetics and pharmacological modulation of synaptic currents at inhibitory synapses.
A rectangular dielectric waveguide technique for determination of permittivity of materials at W-band

The rectangular dielectric waveguide (RDWG) technique has been previously described for the determination of complex permittivity of a wide class of dielectric materials of various thicknesses and cross sections. This paper presents a unified RDWG technique for the determination of the dielectric constant of materials. Some measurement results are reported at W-band frequencies to demonstrate the usefulness of the RDWG technique where other techniques are usually constrained by the sample dimensions.
On Boredom and Social Identity

People who feel bored experience that their current situation is meaningless and are motivated to reestablish a sense of meaningfulness. Building on the literature that conceptualizes social identification as source of meaningfulness, the authors tested the hypothesis that boredom increases the valuation of ingroups and devaluation of outgroups. Indeed, state boredom increased the liking of an ingroup name (Study 1), it increased hypothetical jail sentences given to an outgroup offender (Study 2 and Study 3), especially in comparison to an ingroup offender (Study 3), it increased positive evaluations of participants’ ingroups, especially when ingroups were not the most favored ones to begin with (Study 4), and it increased the appreciation of an ingroup symbol, mediated by people’s need to engage in meaningful behavior (Study 5). Several measures ruled out that these results could be explained by other affective states. These novel findings are discussed with respect to boredom, social identity, and existential psychology research.
In Silico Reconstruction of the Metabolic Pathways of Lactobacillus plantarum: Comparing Predictions of Nutrient Requirements with Those from Growth Experiments

ABSTRACT On the basis of the annotated genome we reconstructed the metabolic pathways of the lactic acid bacterium Lactobacillus plantarum WCFS1. After automatic reconstruction by the Pathologic tool of Pathway Tools (http://bioinformatics.ai.sri.com/ptools/ ), the resulting pathway-genome database, LacplantCyc, was manually curated extensively. The current database contains refinements to existing routes and new gram-positive bacterium-specific reactions that were not present in the MetaCyc database. These reactions include, for example, reactions related to cell wall biosynthesis, molybdopterin biosynthesis, and transport. At present, LacplantCyc includes 129 pathways and 704 predicted reactions involving some 670 chemical species and 710 enzymes. We tested vitamin and amino acid requirements of L. plantarum experimentally and compared the results with the pathways present in LacplantCyc. In the majority of cases (32 of 37 cases) the experimental results agreed with the final reconstruction. LacplantCyc is the most extensively curated pathway-genome database for gram-positive bacteria and is open to the microbiology community via the World Wide Web (www.lacplantcyc.nl ). It can be used as a reference pathway-genome database for gram-positive microbes in general and lactic acid bacteria in particular.
Application of Parametric Models to a Survival Analysis of Hemodialysis Patients

Background Hemodialysis is the most common renal replacement therapy in patients with end stage renal disease (ESRD). Objectives The present study compared the performance of various parametric models in a survival analysis of hemodialysis patients. Methods This study consisted of 270 hemodialysis patients who were referred to Imam Khomeini and Fatima Zahra hospitals between November 2007 and November 2012. The Akaike information criterion (AIC) and residuals review were used to compare the performance of the parametric models. The computations were done using STATA Software, with significance accepted at a level of 0.05. Results The results of a multivariate analysis of the variables in the parametric models showed that the mean serum albumin and the clinic attended were the most important predictors in the survival of the hemodialysis patients (P < 0.05). Among the parametric models tested, the results indicated that the performance of the Weibull model was the highest. Conclusions Parametric models may provide complementary data for clinicians and researchers about how risks vary over time. The Weibull model seemed to show the best fit among the parametric models of the survival of hemodialysis patients.
An Update on Supereulerian Graphs

A graph is supereulerian if it has a spanning Eulerian subgraph. Motivated by the Chinese Postman Problem, Boesch, Suffel, and Tindell ([2]) in 1997 proposed the supereulerian problem, which seeks a characterization of graphs that have spanning Eulerian subgraphs, and they indicated that this problem would be very difficult. Pulleyblank ([71]) later in 1979 proved that determining whether a graph is supereulerian, even within planar graphs, is NP-complete. Since then, there have been lots of researches on this topic. Catlin ([7]) in 1992 presented the first survey on supereulerian graphs. This paper is intended as an update of Catlin’s survey article and will focus on the developments in the study of supereulerian graphs and the related problems over the past 20 years. Key–Words: Eulerian graphs, Supereulerian graphs, Collapsible graphs, Catlin’s reduction method, Line graphs, Claw-free graphs
Piezoresponse Force Microscopy: A Window into Electromechanical Behavior at the Nanoscale

Piezoresponse force microscopy (PFM) is a powerful method widely used for nanoscale studies of the electromechanical coupling effect in various materials systems. Here, we review recent progress in this field that demonstrates great potential of PFM for the investigation of static and dynamic properties of ferroelectric domains, nanofabrication and lithography, local functional control, and structural imaging in a variety of inorganic and organic materials, including piezoelectrics, semiconductors, polymers, biomolecules, and biological systems. Future pathways for PFM application in high-density data storage, nanofabrication, and spectroscopy are discussed.
Experimental study on the effects of fine aggregate on the strength and creep of asphalt sand

The effect of fine aggregates with different gradations, sizes and volume fractions on the compressive strength and creep behavior of asphalt sand was investigated by a systematical experimental study. The fine aggregates were referred to those of sizes smaller than 2.36 mm. 8 types of asphalt sand specimens were designed and used for the uniaxial compression and creep tests conducted at different loading conditions. Obtained experimental results show that the volume fraction was found to have significant effect on the properties of asphalt sand, however, the different size does not result in significant differences in compressive strength and creep behavior of the asphalt sand with 64% volume fraction of fine aggregates.
Reinventing Tradition?

Focusing upon the trajectory of emergence of reassurance policing, this article seeks to interrogate the symbolic and material dimensions of contemporary policing reform programmes. It considers how a need for something labelled ‘Reassurance Policing’ was identified and the various social forces that coalesced to bring it into being. Exploring the contested meanings of reassurance policing, the article details how it has come to be defined as a strategy composed of three constitutive components: high visibility patrols performed by officers who are known to the local public; the targeting of ‘signal crimes’ and ‘signal disorders’; and informal social control performed by communities. The article concludes by postulating what the emergence of the reassurance policing perspective indicates about the future of policing reform.
HYBRID TAG RECOMMENDATION IN COLLABORATIVE TAGGING SYSTEMS

x List of Symbols and Abbreviations Used . xi Chapter
The Role of Cognitive and Emotional Perspective Taking in Economic Decision Making in the Ultimatum Game

We conducted a simple resource allocation game known as the ultimatum game (UG) with preschoolers to examine the role of cognitive and emotional perspective-taking ability on allocation and rejection behavior. A total of 146 preschoolers played the UG and completed a false belief task and an emotional perspective-taking test. Results showed that cognitive perspective taking ability had a significant positive effect on the proposer’s offer and a negative effect on the responder’s rejection behavior, whereas emotional perspective taking ability did not impact either the proposer’s or responder’s behavior. These results imply that the ability to anticipate the responder’s beliefs, but not their emotional state, plays an important role in the proposer’s choice of a fair allocation in an UG, and that children who have not acquired theory of mind still reject unfair offers.
Global Program Optimization: Register Allocation of Static Scalar Objects

Performing certain optimizations on whole programs offers huge potential for code improvement. To exploit this possibility, we implemented a framework that allows sophisticated analysis and transformation of machine code, during or after linkage. This paper presents one of the many applications of our framework: the allocation of global scalar variables into registers. We present the algorithms that select the variables and remove the load and store instructions associated with them. The simulations of the unscheduled code of our benchmarks show that up to 10% of the execution cycles is saved by applying this technique.
CONSTRAINING THE SPIN OF THE BLACK HOLE IN FAIRALL 9 WITH SUZAKU

We report on the results of spectral fits made to data obtained from a 168 ks Suzaku observation of the Seyfert 1 galaxy Fairall 9. The source is clearly detected out to 30 keV. The observed spectrum is fairly simple; it is well described by a power law with soft excess and disk reflection. A broad iron line is detected, and easily separated from distinct narrow components owing to the resolution of the CCDs in the X-ray Imaging Spectrometer (XIS). The broad line is revealed to be asymmetric, consistent with a disk origin. We fit the XIS and Hard X-ray Detector spectra with relativistically blurred disk reflection models. With the assumption that the inner disk extends to the innermost stable circular orbit, the best-fit model implies a black hole spin parameter of a = 0.60 ± 0.07 and excludes extremal values at a high level of confidence. We discuss this result in the context of Seyfert observations and models of the cosmic distribution of black hole spin.
Effectiveness of high interest rate policy on exchange rates: A reexamination of the Asian financial crisis

One of the most controversial issues in the aftermath of the Asian financial crisis has been the appropriate response of monetary policy to a sharp decline in the value of some currencies. In this paper, we empirically examine the effects on Asian exchange rates of sharply higher interest rates during the Asian financial crisis. Taking account of the currency contagion effect, our results indicate that sharply higher interest rates helped to support the exchange rates of South Korea, the Philippines, and Thailand. For Malaysia, no significant causal relation is found from the rate of interest to exchange rates, as the authorities in Malaysia did not actively adopt a high interest rate policy to defend the currency.
Incorporating Alternative Sources of Reinforcement through Online CRA Goal Setting and the Effect on Substance Use in College Students

Emerging adulthood is a transition period where many college students choose to engage in high-risk substance use (e.g., binge drinking). This choice to misuse substances occurs during a developmental period when students are faced with an increased responsibility to structure and manage their time across multiple personal (and potentially competing) goals. The current study approached the problem of college drinking by using two procedures from the Community Reinforcement Approach (CRA). Rating current happiness and coupling it with goal setting was evaluated as a potential means of increasing substance-free reinforcement that could compete with (i.e., reduce) alcohol use. Males and females ages 18-25 years who consumed alcohol in the last 30 days were randomized to either a control condition (n = 89) or a goal-setting condition (n = 79). Both conditions reported their substance use and levels of happiness at
Minorities and Mistrust: The Cushioning Impact of Informal Social contqacts and Political-Institutional Fairness

The great enthusiasm that originally was attached to the concepts of social capital and social trust has recently been defused by the combined problems of ethnic diversity and immigration. The question has been raised if increased community heterogeneity may diminish or even destroy social capital. For example, a recent article concludes that " more extensive diversity in terms of nationalities within the community is significantly and negatively associated with social capital " {Coffé, 2006 #1850, p. 1068}. This causality could occur at both the individual level and the contextual level. At the individual level, members of ethnic minorities have often been exposed to distinct formative experiences. As a population incorporates a greater number of immigrants and ethnic minorities, the level of social trust may go down. Of course, in principle this process could both enhance and erode social capital and trust depending on how trusting immigrants and ethnic natives are respectively. For several reasons, however, the effect is probably negative in most cases as immigrants and refugees arriving in a new country are more likely than the native population to have experienced oppression, discrimination and other types of social hardship that are negatively related to social trust. By the same token, immigrants and ethnic minorities—once settled in a new country—tend to be more socioeconomically vulnerable: they run a higher risk of becoming unemployed, they tend to live in the roughest urban neighbourhoods, etc. In short, they are in many important ways not equal to the majority population and inequality seem to breed distrust (Uslaner 2002). Especially if minority mistrust is passed on to new generations through socialisation mechanisms, a " minority culture of mistrust " may arise. This culture may be extremely hard to eradicate as it is rooted in the almost universally precarious situation and experiences of immigrant minorities. Moving to the contextual level, it has been argued that also ethnic natives and majorities themselves are affected by diversity. Increasing diversity, the argument goes, not only changes the composition of the individuals that make up the population, but also alters the context in which everybody's socio-political attitudes are formed. The arguments here are simple and seemingly compelling. People tend to have most of their social contacts with and thereby develop a propensity to trust people from their own ethnic/religious group (Alesina and La Ferrara 2000). One explanation is that individuals from different ethnic groups may 3 have different norms …
Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice

Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium. This is a review article summarizing its mechanism, effects on bone and its applicability in traumatology clinical practice. In postmenopausal osteoporosis, this drug has been proven to decrease accelerated bone turnover, increase bone mineral density (BMD), and to structurally recover bone, decreasing the risk of vertebral fractures and the risk of non-vertebral fractures in patients with previous, severe vertebral fractures. Moreover, raloxifene appears to lower the risk of invasive breast cancer. Raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis. We can therefore conclude that raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis, while reducing the risk of breast cancer when used at the indicated dose of 60 mg/day and with a low incidence of side effects.
Whose City? Kyiv and its River After Socialism

Abstract This article looks at changing land use along the banks of the Dnipro River (formerly Dnieper River) in Kyiv, Ukraine (formerly Kiev) as an example of rising social inequality since the collapse of Soviet socialism. A working assumption is that tangible symbols of power and privilege such as lavish private housing and land development for profit are more evident in post-socialist society than they were during Communism, and that the amenity-rich river zone in the center of Kyiv is ripe for gentrification of beaches, parks, and high hills with river views. The research is based on detailed field work along the Dnipro and study of maps and air photographs. Our data indicate that prime space along the river is being appropriated by private interests for profit or personal use, often without respect to environmental considerations, treasured historic landscapes, and the rule of land use law. In this way, the historic character of Kyiv is being eroded, and public access to the river and its resources is reduced.
Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis

Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions.
CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48

Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared the formed metabolites to human liver microsomal (HLM) incubations with specific inhibitors against CYP2D6, 2C19, and 3A4, respectively. The data reported here demonstrate CYP3A4 to be the major CYP enzyme responsible for the oxidative metabolism of AKB-48, preferentially performing the oxidation on the adamantyl moiety. Genetic polymorphisms are likely not important with regard to toxicity given the major involvement of CYP3A4. Adverse drug-drug interactions (DDIs) could potentially occur in cases with co-intake of strong CYP3A4 inhibitors, e.g., HIV antivirals and azole antifungal agents.
The Change of Lateral Shift of Center of Pressure according to the Gait Improvement in Post-Stroke Hemiplegic Patients

Objectives: The aim of this study was to analyze the change of lateral shift of Center of Pressure (CoP) according to the gait improvement in post-stroke hemiplegic patients and to investigate relationship between the change of motor grade and lateral shift of CoP. Methods: We measured the lateral shift of CoP and motor grade of eight post-stroke hemiplegic patients at the beginning of dependent gait and independent gait. Results: We found that CoP tended to be shifted to the non-affected side when patients started to walk independently. Furthermore, there was no relationship between the change of motor grade and lateral shift of CoP. Conclusions: This result may suggest it is more important to control the non-affected side than the affected side, at least until the beginning independent gait.