Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear Localization of the Nipah Virus W Protein Allows for Inhibition of both Virus- and Toll-Like Receptor 3-Triggered Signaling Pathways

ABSTRACT The Nipah virus V and W proteins, which are encoded by the P gene via RNA editing, have a common N-terminal domain but unique C-terminal domains. They localize to the cytoplasm and nucleus, respectively, and have both been shown to function as inhibitors of JAK/STAT signaling. Here we report that V and W proteins also block virus activation of the beta interferon (IFN-β) promoter and the IFN regulatory factor 3 (IRF3)-responsive IFN-stimulated gene 54 promoter. Surprisingly, only W protein shows strong inhibition of promoter activation in response to stimulation of Toll-like receptor 3 (TLR3) by extracellular double-stranded RNA. This activity is dependent on the nuclear localization of W protein. Within the unique C-terminal domain of W protein, we have identified a nuclear localization signal (NLS) that requires basic residues at positions 439, 440, and 442. This NLS is responsible for mediating the preferential interaction of W protein with karyopherin-α 3 and karyopherin-α 4. Nuclear localization of W protein therefore enables it to target both virus and TLR3 pathways, whereas the cytoplasmic V protein is restricted to inhibiting the virus pathway. We propose that this discrepancy is in part due to the V protein being less able to block signaling in response to the kinase, TBK-1, whereas both V and W can prevent promoter activation in response to IKKε. We demonstrate that, when the TLR3 pathway is stimulated, the levels of phosphorylated IRF3 are reduced in the presence of W protein but not V protein, confirming the differential effects of these proteins and illustrating that W protein-mediated inhibition is due to a loss of active IRF3.
Primary pulmonary hypertension in Israel: a national survey.

OBJECTIVES To characterize the incidence of patients with primary pulmonary hypertension (PPH) in Israel and their outcomes. METHODS We have evaluated retrospectively all the patients in Israel in whom PPH was diagnosed between the years 1988 and 1997. We looked at medical history, hemodynamic data, pulmonary function and gas exchange, and demographic variables. Patients were followed up for survival until November 1997. Life table analysis and Kaplan-Meier statistics were used to estimate the overall survival distribution. Regression analysis was used to examine the relations between survival and selected variables. RESULTS Overall, we found 44 patients with PPH. The estimated incidence of PPH in Israel is 1.4 new cases per year per million population. The mean (+/- SD) age at diagnosis was 43 +/- 13 years. In the Jewish population, PPH was more frequent among immigrants from Europe and the United States. The mean interval from the onset of symptoms to diagnosis was 3 years (median, 2 years). The median survival time was 4 years. The 1-year, 3-year, and 5-year survival rates were 82%, 57%, and 43%, respectively. The major variables influencing the survival rate were the following: interval from symptom onset to diagnosis; and hemodynamic measurements (ie, mean pulmonary artery pressure, mean right atrial pressure, and cardiac index). In comparison to rates discerned from the National Institutes of Health registry data, the survival rate in Israel is somewhat better and prognosis is influenced by similar hemodynamic variables. CONCLUSION PPH is a rare and fatal disease in Israel. New therapeutic modalities such as prostacyclin therapy and lung transplantation may improve survival among patients with this malignant disease.
Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults

Objectives: Although age‐related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a 4‐year interval. Experimental design: Forty‐four cognitively healthy middle‐age adults underwent baseline DTI and longitudinal T1‐weighted magnetic resonance imaging. Tensor‐based morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, whereas gray and white matter atrophy rates as indexed by Tensor‐based morphometry were the dependent variables. Principal observations: Over a 4‐year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (P < 0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (P < 0.001, uncorrected for multiple comparisons). Conclusions: Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases. Hum Brain Mapp 35:2044–2054, 2014. © 2013 Wiley Periodicals, Inc.
Molecular Evolution and Structural Features of IRAK Family Members

The interleukin-1 receptor-associated kinase (IRAK) family comprises critical signaling mediators of the TLR/IL-1R signaling pathways. IRAKs are Ser/Thr kinases. There are 4 members in the vertebrate genome (IRAK1, IRAK2, IRAKM, and IRAK4) and an IRAK homolog, Pelle, in insects. IRAK family members are highly conserved in vertebrates, but the evolutionary relationship between IRAKs in vertebrates and insects is not clear. To investigate the evolutionary history and functional divergence of IRAK members, we performed extensive bioinformatics analysis. The phylogenetic relationship between IRAK sequences suggests that gene duplication events occurred in the evolutionary lineage, leading to early vertebrates. A comparative phylogenetic analysis with insect homologs of IRAKs suggests that the Tube protein is a homolog of IRAK4, unlike the anticipated protein, Pelle. Furthermore, the analysis supports that an IRAK4-like kinase is an ancestral protein in the metazoan lineage of the IRAK family. Through functional analysis, several potentially diverged sites were identified in the common death domain and kinase domain. These sites have been constrained during evolution by strong purifying selection, suggesting their functional importance within IRAKs. In summary, our study highlighted the molecular evolution of the IRAK family, predicted the amino acids that contributed to functional divergence, and identified structural variations among the IRAK paralogs that may provide a starting point for further experimental investigations.
Learning Distributed Representations of Data in Community Question Answering for Question Retrieval

We study the problem of question retrieval in community question answering (CQA). The biggest challenge within this task is lexical gaps between questions since similar questions are usually expressed with different but semantically related words. To bridge the gaps, state-of-the-art methods incorporate extra information such as word-to-word translation and categories of questions into the traditional language models. We find that the existing language model based methods can be interpreted using a new framework, that is they represent words and question categories in a vector space and calculate question-question similarities with a linear combination of dot products of the vectors. The problem is that these methods are either heuristic on data representation or difficult to scale up. We propose a principled and efficient approach to learning representations of data in CQA. In our method, we simultaneously learn vectors of words and vectors of question categories by optimizing an objective function naturally derived from the framework. In question retrieval, we incorporate learnt representations into traditional language models in an effective and efficient way. We conduct experiments on large scale data from Yahoo! Answers and Baidu Knows, and compared our method with state-of-the-art methods on two public data sets. Experimental results show that our method can significantly improve on baseline methods for retrieval relevance. On 1 million training data, our method takes less than 50 minutes to learn a model on a single multicore machine, while the translation based language model needs more than 2 days to learn a translation table on the same machine.
The Relationship Between Male Dominance and Militarism : Quantitative Tests of Several Theories i

This paper asserts that an understudied question in war research is the possibility of a relationship between militarism and male dominance. Several hypotheses proposed to explain a possible connection were tested using cross-cultural research methodology and a sample of non-industrialized societies (n=186). The hypothesis that war leads to increased male political participation because of their increased “importance” to a society was only weakly supported, but appeared to have more validity than the notion that male dominance and militarism are related because both flow from a society’s level of authoritarianism. The tests for the hypothesis that male participation in warfare leads to their glorification were shown to produce varying results dependent on the aims of the warfare engaged in. No support was found for the hypothesis that aggression against the “enemy” and women vary inversely according to a Freudian “drive-discharge” model, although some support was found for the hypothesis that male absence due to war can sometimes improve women’s status. Finally two scenarios of male dominated militarist cultures suggested by the results are presented and discussed.
The Provision of Wage Insurance by the Firm: Evidence from a Longitudinal Matched Employer-Employee Dataset

We evaluate the impact of product market uncertainty on workers wages, addressing the questions: To what extent do firms provide insurance to their workforce, insulating their wages from shocks in product markets? How does the amount of insurance provided vary with firm and worker attributes? We use a longitudinal matched employer-employee dataset of remarkable quality. The empirical strategy is based on Guiso et al. (2005). We first estimate dynamic models of sales and wages to retrieve consistent estimates of shocks to firms’ sales and to workers' earnings. We are then able to estimate the sensitivity of wages to permanent and transitory shocks to firm performance. Results point to the rejection of the full insurance hypothesis. Workers' wages respond to permanent shocks to firm performance, whereas they are not sensitive to transitory shocks. Managers are not fully insured against transitory shocks, while they receive the same protection against permanent shocks as workers in other occupations. Firms with higher variability in their sales, and those operating in different industries, offer more insurance against permanent shocks. Comparison with Guiso et al. (2005) indicates that Portuguese firms provide less insurance than Italian firms, corroborating evidence on the high degree of wage flexibility in Portugal.
Distributed Beamforming in Multiuser Multi-Relay Networks with Guaranteed QoS

This paper considers optimal distributed beamforming designs in a multi-relay network with multiple sources and multiple destinations. It is assumed that all source-destination pairs operate in orthogonal channels to avoid inter-user interference at the destinations. The distributed beamforming designs are carried out to minimize the sum relay power with guaranteed quality of service (QoS) in terms of signal-to-noise-ratio (SNR) at the destinations. Considered are optimization problems with and without per-relay power constraints. Although the two optimization problems can be readily transformed into convex second-order conic programs (SOCPs), the paper proposes simple and fast iterative algorithms to efficiently solve them.
Soybeans Grown in the Chernobyl Area Produce Fertile Seeds that Have Increased Heavy Metal Resistance and Modified Carbon Metabolism

Plants grow and reproduce in the radioactive Chernobyl area, however there has been no comprehensive characterization of these activities. Herein we report that life in this radioactive environment has led to alteration of the developing soybean seed proteome in a specific way that resulted in the production of fertile seeds with low levels of oil and β-conglycinin seed storage proteins. Soybean seeds were harvested at four, five, and six weeks after flowering, and at maturity from plants grown in either non-radioactive or radioactive plots in the Chernobyl area. The abundance of 211 proteins was determined. The results confirmed previous data indicating that alterations in the proteome include adaptation to heavy metal stress and mobilization of seed storage proteins. The results also suggest that there have been adjustments to carbon metabolism in the cytoplasm and plastids, increased activity of the tricarboxylic acid cycle, and decreased condensation of malonyl-acyl carrier protein during fatty acid biosynthesis.
Path planning approach for the amplification of electrical energy exchange in multi axis robotic systems

A new path planning approach for energy demand minimization of general multi axis robots by model-based trajectory optimization is presented. In the proposed method, the efficient utilization of recuperated energy is induced by amplification of energy exchange via the internal DC bus. The energy-based system model includes the robot dynamics, mechanical and drive losses, as well as the exchange of electrical energy. The nonlinear optimization problem is solved using global methods, considering kinematic and dynamic limitations. Simulations results are presented that prove the performance of the algorithm and demonstrate the beneficial effect of electrical energy exchange. Minimum time criteria can be retained if required and the approach is applicable to different multi axis manipulator types with no need for additional investment or hardware modification.
Effects of combined inspiratory muscle and cycle ergometer training on exercise performance in patients with COPD.

Cycle ergometer training plays an important role in the rehabilitation of patients with chronic obstructive pulmonary disease (COPD), but the usefulness of specific inspiratory muscle training as part of pulmonary rehabilitation remains uncertain. To determine whether inspiratory muscle training could intensify the known beneficial effects of cycle ergometer training on exercise performance in these patients, we compared the effect of an 8 week inspiratory muscle training combined with cycle ergometer training with that of an 8 week cycle ergometer training alone on inspiratory muscle performance and general exercise capacity. Patients were randomly assigned to the two training groups; 21 patients received additional inspiratory muscle training (Group 1) and 21 did not (Group 2). Maximal sniff assessed oesophageal and transdiaphragmatic pressures served as parameters for global inspiratory muscle strength and diaphragmatic strength, respectively. The duration for which the patient could breathe against a constant inspiratory pressure load was used as an index of inspiratory muscle endurance. Exercise capacity was determined by an incremental symptom-limited cycle ergometer test. After the training period, inspiratory muscle performance improved significantly in the patients with inspiratory muscle training, but not in those without. Both training regimens increased maximal power output and oxygen uptake, but this improvement was significantly greater in the patients with inspiratory muscle training than in those without. (ABSTRACT TRUNCATED AT 250 WORDS)
Sp1 Binding Is Critical for Promoter Assembly and Activation of the MCP-1 Gene by Tumor Necrosis Factor*

The monocyte chemoattractant protein-1 gene (MCP-1) is induced by the inflammatory cytokine tumor necrosis factor through the coordinate assembly of an NF-κB-dependent distal regulatory region and a proximal region that has been suggested to bind Sp1 as well as other factors. To provide a genetic correlation for Sp1 activity in this system, a cell line homozygous for a targeted truncation of the Sp1 gene was derived and examined. We found that the lack of Sp1 binding activity resulted in the inability of both the distal and proximal regions to assemble in vivo even though the binding of NF-κB to distal region DNA was unaffected in vitro. We also found that Sp1 and NF-κB were the minimal mammalian transcription factors required for efficient activity when transfected into Drosophila Schneider cells. Additionally, Sp3 was able to compensate for Sp1 in the Drosophila tissue cell system but not in the Sp1−/− cell line suggesting that Sp1 usage is site-specific and is likely to depend on the context of the binding site. Together, these data provide genetic and biochemical proof for Sp1 in regulating the MCP-1 gene.
Behavioral and Electrophysiological Effects of Cortical Microstimulation Parameters

Electrical microstimulation has been widely used to artificially activate neural circuits on fast time scales. Despite the ubiquity of its use, little is known about precisely how it activates neural pathways. Current is typically delivered to neural tissue in a manner that provides a locally balanced injection of positive and negative charge, resulting in negligible net charge delivery to avoid the neurotoxic effects of charge accumulation. Modeling studies have suggested that the most common approach, using a temporally symmetric current pulse waveform as the base unit of stimulation, results in preferential activation of axons, causing diffuse activation of neurons relative to the stimulation site. Altering waveform shape and using an asymmetric current pulse waveform theoretically reverses this bias and preferentially activates cell bodies, providing increased specificity. In separate studies, measurements of downstream cortical activation from sub-cortical microstimulation are consistent with this hypothesis, as are recent measurements of behavioral detection threshold currents from cortical microstimulation. Here, we compared the behavioral and electrophysiological effects of symmetric vs. asymmetric current waveform shape in cortical microstimulation. Using a go/no-go behavioral task, we found that microstimulation waveform shape significantly shifts psychometric performance, where a larger current pulse was necessary when applying an asymmetric waveform to elicit the same behavioral response, across a large range of behaviorally relevant current amplitudes. Using voltage-sensitive dye imaging of cortex in anesthetized animals with simultaneous cortical microstimulation, we found that altering microstimulation waveform shape shifted the cortical activation in a manner that mirrored the behavioral results. Taken together, these results are consistent with the hypothesis that asymmetric stimulation preferentially activates cell bodies, albeit at a higher threshold, as compared to symmetric stimulation. These findings demonstrate the sensitivity of the pathway to varying electrical stimulation parameters and underscore the importance of designing electrical stimuli for optimal activation of neural circuits.
Financial Development, Financial Fragility, and Growth

This paper studies the apparent contradiction between two strands of the literature on the effects of financial intermediation on economic activity. On the one hand, the empirical growth literature finds a positive effect of financial depth as measured by, for instance, private domestic credit and liquid liabilities (e.g., Levine, Loayza, and Beck 2000). On the other hand, the banking and currency crisis literature finds that monetary aggregates, such as domestic credit, are among the best predictors of crises and their related economic downturns (e.g., Kaminsky and Reinhart 1999). The paper accounts for these contrasting effects based on the distinction between the short- and long-run impacts of financial intermediation. Working with a panel of cross-country and time-series observations, the paper estimates an encompassing model of short- and long-run effects using the Pooled Mean Group estimator developed by Pesaran, Shin, and Smith (1999). The conclusion from this analysis is that a positive long-run relationship between financial intermediation and output growth co-exists with a mostly negative short-run relationship. The paper further develops an explanation for these contrasting effects by relating them to recent theoretical models by linking the estimated short-run effects to measures of financial fragility (namely, banking crises and financial volatility) and by jointly analyzing the effects of financial depth and fragility in classic panel growth regressions.
Cocaine-inducible circuitry reorganization as a basis for addiction-related memory traces

Drug addiction has been conceptualized as an extreme, pathological form of memory. One potential mechanism underlying addiction-related memories is drug-induced plastic changes at glutamatergic synapses within the brain reward pathway. Presumably the changes in glutamatergic projections from the prefrontal cortex (PFC) and amygdala onto GABAergic neurons in the nucleus accumbens (NAc) transmit differential aspects of addiction-associated information. However the synaptic properties of specific glutamatergic afferents and their contribution to cocaine-induced plasticity changes are largely unknown. Using a combination of optogenetic tools to dissect specific afferents and variance-mean analysis to examine synaptic properties, I demonstrate that repeated exposure to cocaine via either i.p. injections or self-administration increased the release probability of medial PFC-to-NAc synapses but not basolateral amygdala–to-NAc synapses. Those presynaptic adaptations were long-lasting and further strengthened specifically in a contingent cocaine procedure. These data identified a presynaptic mechanism in altering the synaptic drive onto NAc medium spiny neurons, which might chronically shift the balance between amygdala and PFC inputs onto MSNs and contribute to the pathology of the addicted state. Exposure to cocaine generates nascent excitatory synaptic connections in the NAc that could be the key substrates for the development of addiction. These nascent synapses critically contributed to the formation and persistence of cocaine-induced memories in a conditioned place preference paradigm. Silent synapses were increased in the NAc of PSD-95 KO and the number was further increased after cocaine procedures. In control animals these silent synapses were presumably incorporated in new neuronal connections during and after the CPP training, demonstrated by the recovery of the reduced AMPAR/NMDAR ratio and the accumulation of CP-AMPARs at 21 days of withdrawal. Although PSD-95 KO animals acquired initially a higher CPP score, the CPP extinguished after 21 days. Furthermore the AMPAR/NMDAR ratio remained low and no CP-AMPARs accumulated in the synapses. These findings are consistent with a role of the cocaine-induced silent synapses as plasticity substrates for new drug-related memories, which require PSD-95 and a mechanism through CP-AMPARs for consolidation. Together with the selective presynaptic enhancement of specific projections to the NAc, these data support the conclusion of drug related shifts in synaptic drive of different NAc projection pathways and drug-related new connections in the mesocorticolimbic pathways.