Miracle-dz/UniFAR-FTUs huggingface dataset:
P2X4 receptors in activated C8-B4 cells of cerebellar microglial origin

We investigated the properties and regulation of P2X receptors in immortalized C8-B4 cells of cerebellar microglial origin. Resting C8-B4 cells expressed virtually no functional P2X receptors, but largely increased functional expression of P2X4 receptors within 2–6 h of entering the activated state. Using real-time polymerase chain reaction, we found that P2X4 transcripts were increased during the activated state by 2.4-fold, but this increase was not reflected by a parallel increase in total P2X4 proteins. In resting C8-B4 cells, P2X4 subunits were mainly localized within intracellular compartments, including lysosomes. We found that cell surface P2X4 receptor levels increased by ∼3.5-fold during the activated state. This change was accompanied by a decrease in the lysosomal pool of P2X4 proteins. We next exploited our findings with C8-B4 cells to investigate the mechanism by which antidepressants reduce P2X4 responses. We found little evidence to suggest that several antidepressants were antagonists of P2X4 receptors in C8-B4 cells. However, we found that moderate concentrations of the same antidepressants reduced P2X4 responses in activated microglia by affecting lysosomal function, which indirectly reduced cell surface P2X4 levels. In summary, our data suggest that activated C8-B4 cells express P2X4 receptors when the membrane insertion of these proteins by lysosomal secretion exceeds their removal, and that antidepressants indirectly reduce P2X4 responses by interfering with lysosomal trafficking.
Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine

Background: Tenofovir (TDF) and didanosine (ddI) are both adenosine analogues with convenient posology, strong potency and a relatively high genetic barrier for resistance. The popularity of this combination, however, has been questioned due to concerns about pharmacokinetic interactions and increased risk of pancreatitis and hyperglycemia. Less information is available about other possible side effects. Patients and methods: HIV-infected individuals who initiated a protease inhibitor-sparing regimen between September 2002 and June 2003 at five hospitals, and had at least one subsequent visit within the next 12 months, always with complete virus suppression, were retrospectively assessed. Only drug-naive individuals and patients who simplified a prior successful antiretroviral regimen were analysed. Results: Outcomes were analysed in 570 individuals according to treatment modality (98 drug-naive versus 472 simplified); the nucleoside analogue (NA) backbone (298 with TDF + ddI, 88 with ddI, 44 with TDF, and 140 with neither ddI nor TDF); and the third agent used (378 with non-nucleoside analogues versus 192 with NA). Significant CD4+ T-cell declines were seen in patients taking ddI + TDF with respect to all other NA combinations, including ddI or TDF separately. Patients exposed to high ddI doses or taking a third NA showed more pronounced CD4 declines. Plasma levels of ddI correlated with the extent of CD4+ T-cell loss. Conclusion: Patients receiving ddI + TDF-based combinations show CD4+ T-cell declines despite achieving complete virus suppression. This effect generally progresses with time. An imbalance in adenosine metabolites within CD4+ T lymphocytes may explain this phenomenon, which resembles the genetic purine nucleoside phosphorylase deficiency syndrome.
Exploring the Key Factors of Knowledge Sharing via Employee Weblogs

In this study, two dependent variables of individual's intention and attitude have been defined for knowledge sharing via the employee weblog and independent variables have been determined in 3 groups of social influence factor, technology acceptance factor and social cognitive factor with subset variables including the subjective norm, social identity, group norm (first group), perceived usefulness, perceived ease of use, perceived enjoyment (second group), self-efficacy, personal outcome expectation, altruism and trust (third group). This research reviews the previous studies in the field of knowledge sharing via the employee weblog. The main difference of this research with other studies is to collect and complete a full set of factors affecting the knowledge sharing according to the factors raised in previous studies. Finally the suggestions have been provided for conducting the statistical studies in Iran.
Do medical students watch video clips in eLearning and do these facilitate learning?

Background: There is controversial evidence of the impact of individual learning style on students' performance in computer-aided learning. Aims: We assessed the association between the use of multimedia materials, such as video clips, and collaborative communication tools with learning outcome among medical students. Method: One hundred and twenty-one third-year medical students attended a course in medical informatics (0.7 credits) consisting of lectures, small group sessions and eLearning material. The eLearning material contained six learning modules with integrated video clips and collaborative learning tools in WebCT. Learning outcome was measured with a course exam. Results: Approximately two-thirds of students (68.6%) viewed two or more videos. Female students were significantly more active video-watchers. No significant associations were found between video-watching and self-test scores or the time used in eLearning. Video-watchers were more active in WebCT; they loaded more pages and more actively participated in discussion forums. Video-watching was associated with a better course grade. Conclusions: Students who watched video clips were more active in using collaborative eLearning tools and achieved higher course grades. Practice points Almost 20% of third year medical students neglected video clips as a multimedia learning tool. Female medical students more actively used multimedia content in eLearning. Video-watchers more frequently used the collaborative discussion tools. Students who watched video clips were more active in using collaborative eLearning tools and achieved higher course grades.
Multiple description Delta-Sigma quantization with individual and central receivers

In this work we present a practical scheme for L-channel symmetric Multiple Description coding when one is only interested in receiving either a single description or all L descriptions. This scheme is based on oversampling and dithered Delta-Sigma quantization and is an extension of a scheme previously presented by Østergaard and Zamir. The oversampling process creates L redundant representations of the source, while the delta-sigma quantization with feedback-loop enables trading-off side distortion (receiving one description) for central distortion (receiving all the descriptions). We prove that the proposed scheme is asymptotically optimal (at large lattice quantizer dimension and high noise-shaping filter order) at any resolution for a Gaussian source and MSE fidelity criterion. In order to prove this optimality result we give an explicit expression for the rate-distortion function, which was previously known as a non explicit optimization problem.
Energy-efficient mechanisms for managing thread context in throughput processors

Modern graphics processing units (GPUs) use a large number of hardware threads to hide both function unit and memory access latency. Extreme multithreading requires a complicated thread scheduler as well as a large register file, which is expensive to access both in terms of energy and latency. We present two complementary techniques for reducing energy on massively-threaded processors such as GPUs. First, we examine register file caching to replace accesses to the large main register file with accesses to a smaller structure containing the immediate register working set of active threads. Second, we investigate a two-level thread scheduler that maintains a small set of active threads to hide ALU and local memory access latency and a larger set of pending threads to hide main memory latency. Combined with register file caching, a two-level thread scheduler provides a further reduction in energy by limiting the allocation of temporary register cache resources to only the currently active subset of threads. We show that on average, across a variety of real world graphics and compute workloads, a 6-entry per-thread register file cache reduces the number of reads and writes to the main register file by 50% and 59% respectively. We further show that the active thread count can be reduced by a factor of 4 with minimal impact on performance, resulting in a 36% reduction of register file energy.
Renal Hypoxia Hypoxia as a key player in the AKIto-CKD transition

Tanaka S, Tanaka T, Nangaku M. Hypoxia as a key player in the AKI-to-CKD transition. Am J Physiol Renal Physiol 307: F1187–F1195, 2014. First published October 1, 2014; doi:10.1152/ajprenal.00425. 2014. — Recent clinical and animal studies have shown that acute kidney injury (AKI), even if followed by complete recovery of renal function, can eventually result in chronic kidney disease (CKD). Renal hypoxia is emerging as a key player in the pathophysiology of the AKI-toCKD transition. Capillary rarefaction after AKI episodes induces renal hypoxia, which can in turn profoundly affect tubular epithelial cells, (myo)fibroblasts, and inflammatory cells, culminating in tubulointerstitial fibrosis, i.e., progression to CKD. Damaged tubular epithelial cells that fail to redifferentiate might supply a decreased amount of vascular endothelial growth factor and contribute to capillary rarefaction, thus aggravating hypoxia and forming a vicious cycle. Mounting evidence also shows that epigenetic changes are closely related to renal hypoxia in the pathophysiology of CKD progression. Animal experiments suggest that targeting hypoxia is a promising strategy to block the transition from AKI to CKD. However, the precise mechanisms by which hypoxia induces the AKI-toCKD transition and by which hypoxia-inducible factor activation can exert a protective effect in this context should be clarified in further studies.
Complex tactics in a dynamic large herbivore–carnivore spatiotemporal game

1318 –––––––––––––––––––––––––––––––––––––––– © 2019 The Authors. Oikos published by John Wiley & Sons Ltd on behalf of Nordic Society Oikos This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Subject Editor: Leif Egil Loe Editor-in-Chief: Dries Bonte Accepted 12 April 2019 128: 1318–1328, 2019 doi: 10.1111/oik.06166 doi: 10.1111/oik.06166 128 1318–1328
Cdx mediates neural tube closure through transcriptional regulation of the planar cell polarity gene Ptk7

The vertebrate Cdx genes (Cdx1, Cdx2 and Cdx4) encode homeodomain transcription factors with well-established roles in anteroposterior patterning. To circumvent the peri-implantation lethality inherent to Cdx2 loss of function, we previously used the Cre-loxP system to ablate Cdx2 at post-implantation stages and confirmed a crucial role for Cdx2 function in events related to axial extension. As considerable data suggest that the Cdx family members functionally overlap, we extended this analysis to assess the consequence of concomitant loss of both Cdx1 and Cdx2. Here, we report that Cdx1-Cdx2 double mutants exhibit a severely truncated anteroposterior axis. In addition, these double mutants exhibit fused somites, a widened mediolateral axis and craniorachischisis, a severe form of neural tube defect in which early neurulation fails and the neural tube remains open. These defects are typically associated with deficits in planar cell polarity (PCP) signaling in vertebrates. Consistent with this, we found that expression of Ptk7, which encodes a gene involved in PCP, is markedly reduced in Cdx1-Cdx2 double mutants, and is a candidate Cdx target. Genetic interaction between Cdx mutants and a mutant allele of Scrib, a gene involved in PCP signaling, is suggestive of a role for Cdx signaling in the PCP pathway. These findings illustrate a novel and pivotal role for Cdx function upstream of Ptk7 and neural tube closure in vertebrates.
Malignant paragangliomas associated with mutations in the succinate dehydrogenase D gene.

INTRODUCTION Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene. AIM The aim of the study was to report the different clinical expression patterns of malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution. RESULTS Metastasis and/or local tumor invasion was documented 0 (n=2), 1, 18, and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n=2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone, and locally invasive paraganglioma of the bladder with lymph node metastases. Four of the five patients developed catecholamine excess during follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n=1), extra adrenal paraganglioma (n=2), and presumed subclinical disease (n=1). CONCLUSION SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.
Striking a balance between trust and control in a virtual organization: a content analysis of open source software case studies

Abstract. Many organization theorists have predicted the emergence of the networked or virtual firm as a model for the design of future organizations. Researchers have also emphasized the importance of trust as a necessary condition for ensuring the success of virtual organizations. This paper examines the open source software (OSS) ‘movement’ as an example of a virtual organization and proposes a model that runs contrary to the belief that trust is critical for virtual organizations. Instead, I argue that various control mechanisms can ensure the effective performance of autonomous agents who participate in virtual organizations. Borrowing from the theory of the ‘McDonaldization’ of society, I argue that, given a set of practices to ensure the control, efficiency, predictability and calculability of processes and outcomes in virtual organizations, effective performance may occur in the absence of trust. As support for my argument, I employ content analysis to examine a set of published case studies of OSS projects. My results show that, although that trust is rarely mentioned, ensuring control is an important criterion for effective performance within OSS projects. The case studies feature few references to other dimensions of McDonaldization (efficiency, predictability and calculability), however, and I conclude that the OSS movement relies on many other forms of social control and self‐control, which are often unacknowledged in OSS projects. Through these implicit forms of control, OSS projects are able to secure the cooperation of the autonomous agents that participate in project teams. I conclude by extrapolating from these case studies to other virtual organizations.
A friendly smoothed analysis of the simplex method

Explaining the excellent practical performance of the simplex method for linear programming has been a major topic of research for over 50 years. One of the most successful frameworks for understanding the simplex method was given by Spielman and Teng (JACM ‘04), who the developed the notion of smoothed analysis. Starting from an arbitrary linear program with d variables and n constraints, Spielman and Teng analyzed the expected runtime over random perturbations of the LP (smoothed LP), where variance σ Gaussian noise is added to the LP data. In particular, they gave a two-stage shadow vertex simplex algorithm which uses an expected O(n86 d55 σ−30) number of simplex pivots to solve the smoothed LP. Their analysis and runtime was substantially improved by SpielmanDeshpande (FOCS ‘05) and later Vershynin (SICOMP ‘09). The fastest current algorithm, due to Vershynin, solves the smoothed LP using an expected O(d3 log3 n σ−4 + d9log7 n) number of pivots, improving the dependence on n from polynomial to logarithmic. While the original proof of SpielmanTeng has now been substantially simplified, the resulting analyses are still quite long and complex and the parameter dependencies far from optimal. In this work, we make substantial progress on this front, providing an improved and simpler analysis of shadow simplex methods, where our main algorithm requires an expected O(d2 √logn σ−2 + d5 log3/2 n) number of simplex pivots. We obtain our results via an improved shadow bound, key to earlier analyses as well, combined with algorithmic techniques of Borgwardt (ZOR ‘82) and Vershynin. As an added bonus, our analysis is completely modular, allowing us to obtain non-trivial bounds for perturbations beyond Gaussians, such as Laplace perturbations.
Long-term modifiability of anomalous and delayed rectification in guinea pig inferior olivary neurons

Delayed and anomalous rectification was studied in inferior olivary (I.O.) neurons in guinea pig brain stem slices maintained in vitro. Hyperpolarization of the I.O. cell beyond rest membrane potential was accompanied by anomalous rectification (AR). This consisted of 2 parts: an instantaneous and a time-dependent component. The “instantaneous” component was blocked by bath addition of Ba2+ or Cs+ and demonstrated inactivation following prolonged hyperpolarization. The time-dependent component, referred to as the gK(ol), was blocked by harmaline in concentrations of 0.1 mg/ml or by substitution of Co2+, Cd2+, or Mn2+ for Ca2+ in the bath. The gK(ol) was blocked by extracellular Cs+ but not by Ba2+. Delayed rectification (DR), consisting of 2 distinct components, was observed after membrane depolarization by more than 10 mV with respect to rest (usually at -65 mV). One of the components of the DR was found to be quite similar to the classical gK. It did not demonstrate significant inactivation with membrane potential change and was reduced by Ba2+ or tetraethylammonium (TEA). A second component of the DR demonstrated voltage-dependent inactivation and was thus referred to as gK(inact). This inactivation determined by current-clamp measurements had a sigmoidal time course, with approximately a 1 sec onset latency and a half-time to peak of 7 sec. The inactivation of gK(inact) outlasted current injection for tens of seconds to several minutes, depending on the duration and amplitude of the preceding depolarization. During this period, I.O. neurons could be easily activated and demonstrated full dendritic spikes following current injection or excitatory synaptic input that had previously been subthreshold for spike initiation. The inactivation component of the DR was removed by prolonged membrane hyperpolarization beyond rest. gK(inact) was blocked by 4-aminopyridine (4-AP; 100 microM) but not by Ba2+. This inactivation was dependent on the presence of extracellular Ca2+ or Ba2+. Addition of Co2+ or Cd2+ to the bath did not block gK(inact) but did prevent its inactivation. The modulatory effects of these different membrane conductances on the integrative properties of I.O. neurons are described. The long duration of the inactivation of DR and AR is considered as the basis for a dynamic long-term modulation of the electroresponsive and integrated properties of I.O. neurons.
Clinical and environmental isolates of Burkholderia cepacia exhibit differential cytotoxicity towards macrophages and mast cells

Burkholderia cepacia is an emerging opportunistic pathogen that causes fatal infections in patients suffering from cystic fibrosis (CF) and chronic granulomatous disease. Various environmental isolates of B. cepacia are, however, capable of degrading environmental pollutants, such as trichloroethylene, 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T), etc., and are also highly effective in controlling plant diseases caused by nematodes and fungi. Such strains have therefore been proposed for environmental release to clean up toxic dump sites or as biopesticides. Various efforts to distinguish between clinical and environmental isolates of B. cepacia with regard to their virulence characteristics have produced ambiguous results, suggesting that newer methods are needed to test for the presence or absence of pathogenic potential in B. cepacia strains proposed for environmental release. We now report that several clinical strains of B. cepacia secrete cytotoxic factors that allow macrophage and mast cell death in the presence of external ATP. Several environmental strains had reduced activity in this regard. We also demonstrate that, while all the strains secrete enzymes that have nucleoside diphosphate kinase (Ndk), adenylate kinase (Ak) and 5′‐nucleotidase activity, the level of secretion of the 5′‐nucleotidase (and/or ATPase/phosphatase) appears to be lower in the environmental strains than in the clinical strains. The secretion of these enzymes is specifically activated in the presence of eukaryotic proteins such as α2‐macroglobulin. As macrophage‐ or mast cell surface‐associated P2Z receptors promote their cell death in the presence of mM concentrations of ATP, and as the secreted ATP‐using enzymes generate various phosphorylated or non‐phosphorylated adenine nucleotides that may even be better agonists than ATP in activating the P2Z receptors or may act through the activation of additional purinergic receptors, such enzymes may play an important role in allowing B. cepacia to evade host defence.
A General Verification Result for Stochastic Impulse Control Problems

This paper establishes existence of optimal controls for a general stochastic impulse control problem. For this, the value function is characterized as the pointwise minimum of a set of superharmonic functions, as the unique continuous viscosity solution of the quasi-variational inequalities (QVIs), and as the limit of a sequence of iterated optimal stopping problems. A combination of these characterizations is used to construct optimal controls without relying on any regularity of the value function beyond continuity. Our approach is based on the stochastic Perron method and the assumption that the associated QVIs satisfy a comparison principle.
Optimization of ultrasound-assisted extraction of bioactive compounds from jabuticaba (Myrciaria cauliflora) fruit through a Box-Behnken experimental design

Jabuticaba is a very popular fruit in Brazil being a great source of compounds with considerable biological activities. Novel optimized ultrasound-assisted extraction (UAE) methods have been proposed for anthocyanins and total phenolic compounds from jabuticaba. A Box–Behnken experimental design (BBD) with a response surface methodology (RSM) was used to investigate the effect of six independent variables (solvent composition, solvent-to-sample ratio, ultrasound amplitude and cycle, pH, and temperature) on the UAE. Solvent composition was found to be the most significant variable for the extraction of both anthocyanins (51%) and total phenolic compounds (72%). The other optimum conditions for anthocyanins were as followsI: pH 7.00, 39.8 ºC, 20I:1.5 mLI:g solvent-to-sample ratio, 34% ultrasound amplitude and cycle of 0.47 seconds. The optimum conditions for the extraction of phenolic compounds wereI: pH 7.00, 26.0 ºC, 20I:1.5 (mLI:g) solvent-to-sample ratio, 68.5% ultrasound amplitude and cycle of 0.5 seconds. The extraction kinetic was also evaluated. The developed methods showed a high precision, with coefficients of variation of less than 5% for both repeatability and intermediate precision (within-lab reproducibility). The applicability of the new methods was successfully evaluated on several fruits and jams from jabuticaba.