Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAA Receptors Via PKCδ Activation

Alcohol (ethanol, EtOH) is one of the most widely abused drugs with profound effects on brain function and behavior. GABAA receptors (GABAARs) are one of the major targets for EtOH in the brain. Temporary plastic changes in GABAARs after withdrawal from a single EtOH exposure occur both in vivo and in vitro, which may be the basis for chronic EtOH addiction, tolerance and withdrawal symptoms. Extrasynaptic δ-GABAAR endocytosis is implicated in EtOH-induced GABAAR plasticity, but the mechanisms by which the relative abundance and localization of specific GABAARs are altered by EtOH exposure and withdrawal remain unclear. In this study, we investigated the mechanisms underlying rapid regulation of extrasynaptic δ-GABAAR by a single EtOH withdrawal in cultured rat hippocampal neurons. Thirty-minutes EtOH (60 mM) exposure increased extrasynaptic tonic current (Itonic) amplitude without affecting synaptic GABAAR function in neurons. In contrast, at 30 min after withdrawal, Itonic amplitude and responsiveness to acute EtOH were both reduced. Similar results occurred in neurons with okadaic acid (OA) or phorbol 12,13-dibutyrate (PDBu) exposure. Protein kinase C (PKC) inhibition prevented the reduction of Itonic amplitude and the tolerance to acute EtOH, as well as the reduction of GABAAR-δ subunit abundance induced by a single EtOH withdrawal. Moreover, EtOH withdrawal selectively increased PKCδ level, whereas PKCδ inhibition specifically rescued the EtOH-induced alterations in GABAAR-δ subunit level and δ-GABAAR function. Together, we provided strong evidence for the important roles of PKCδ in the rapid regulation of extrasynaptic δ-GABAAR induced by a single EtOH withdrawal.
Reliability Analysis of Bond Behaviour of CFRP–Concrete Interface under Wet–Dry Cycles

Effective bonding between adherents plays a key role in retrofitting concrete structures in civil engineering using fibre-reinforced polymers (FRPs). To ensure structural safety, it is critical to develop design codes, which account for uncertainties of materials, the environment, and load, to estimate bond behaviour under long-term exposure to harsh environments. Therefore, a reliability analysis was performed to study the bond behaviour of FRP–concrete interface under wet–dry cycles and sustained loading. Thirty double-lap, shear-bonded carbon FRP (CFRP)–concrete composite specimens were tested after wet–dry cycles and sustained loading exposure. The fracture energy Gf of the bond behavior between CFRP and concrete was directly obtained from the measured local bond-slip curves. Five widely used test methods were adopted to verify the possible distribution types of Gf. Based on the best fit distribution of Gf, a reliability index β was then calculated for the specimens. The effects of wet–dry exposure and sustained loading on β were analysed separately. The effects of the mean and standard deviation of the load on β were compared. It was found that the mean had a greater impact on reliability than the standard deviation, but neither changed the regulation of the exponential reduction of β with increasing wet–dry cycle time. Their impact was significant for a small number of wet–dry cycles but insignificant for more than 4000 wet–dry cycles.
AVIAN LIFE HISTORY VARIATION AND CONTRIBUTION OF DEMOGRAPHIC TRAITS TO THE POPULATION GROWTH RATE

A central goal in ecology is to predict population dynamics from demographic information. Based on the asymptotic population growth rate l, calculated from a projection matrix model as a descriptor of the population dynamics, we analyze published data of 49 species of birds to determine how l is influenced by variation in different demographic traits. Across species, the mean elasticity of the adult survival rate was significantly larger than the mean elasticity of the fecundity rate. The contribution of the fecundity rate to the population growth rate increased with increasing clutch size and decreasing adult survival rate, while the greatest contribution of adult survival rate occurred among long-lived species that matured late and laid few eggs. This represents a continuum from ''highly reproductive species'' at one end to ''survivor species'' at the other end. In addition, a high contribution of adult survival rate was found in some relatively long-lived species with early age at maturity (and a large clutch size) which was assumed to represent a bet-hedging strategy, i.e., producing a large number of offspring in some occasional good years. In a retrospective analysis, interspecific differences in the effects of actual temporal variation in adult survival rate and fecundity rate on the variability of l were analyzed. These effects are expected to be large when the variance or the sensitivity of the trait is large. Because there was a negative relationship among species, both for the adult survival rate and the fecundity rate between the variability and the sensitivity of the trait, contribution of a trait to the variance in l decreased with sensitivity. Similarly, within species, less temporal variation was found in traits with high elasticities than in traits with less contribution to l. In some species, covariance among matrix elements also influenced the contribution of a demographic trait to l. Monitoring schemes of bird demography should be designed in such a way that temporal variances and covariances among demographic traits can be estimated. Further- more, it is important in such schemes to include data from a combination of traits that either have large sensitivities or high temporal variation.
MedOBIS: biogeographic information system for the eastern Mediterranean and Black Sea

Recent online initiatives in sharing marine biological data, such as the European Regis- ter of Marine Species (ERMS) and the Ocean Biogeographic Information System (OBIS), identified gaps in data from the eastern Mediterranean and Black Sea. Such data are now being collected, for- matted and disseminated by MedOBIS (the Mediterranean Ocean Biogeographic Information Sys- tem) initiative involving Greece, the Ukraine and Israel (test version available at: www.medobis.org). The aim is to develop a taxon-based biogeography database and online data server with links to sur- vey and satellite environmental data. MedOBIS is currently undergoing 4 stages of development, namely, data assembly, formatting, analysis and dissemination. The primary features of the MedOBIS application are its offline GIS (Geographic Information Systems) data formatting capabilities and its online Java- and JavaScript-enabling data server with taxon-based search, mapping and data down- loading capabilities. It is an independent source of biological and environmental data, as well as an online GIS tool designed to facilitate access to historical and current data by marine researchers. As more data become available and are inserted into the system, MedOBIS will function as the eastern Mediterranean and Black Sea node of EurOBIS (the European node of the international OBIS initia- tive, part of the 'Census of Marine Life').
Complete loss of murine Xin results in a mild cardiac phenotype with altered distribution of intercalated discs.

AIMS Xin is a striated muscle-specific F-actin binding protein that has been implicated in cardiomyopathies. In cardiomyocytes, Xin is localized at intercalated discs (IDs). Mice lacking only two of the three Xin isoforms (XinAB(-/-) mice) develop severe cardiac hypertrophy. To further investigate the function of Xin variants in the mammalian heart, we generated XinABC(-/-) mice deficient in all Xin isoforms. METHODS AND RESULTS XinABC(-/-) mice showed a very mild phenotype: heart weight, heart weight to tibia length ratios, and cardiac dimensions were not altered. Increased perivascular fibrosis was only observed in hearts of young XinABC(-/-) mice. Striking differences were revealed in isolated cardiomyocytes: XinABC(-/-) cells demonstrated a significantly increased number of non-terminally localized ID-like structures. Furthermore, resting sarcomere length was increased, sarcomere shortening, peak shortening at 0.5-1 Hz, and the duration of shortening were decreased, and shortening and relengthening velocities were accelerated at frequencies above 4 Hz in XinABC(-/-) cardiomyocytes. ECG showed a significantly shorter HV interval and a trend towards shorter QRS interval in XinABC(-/-) mice, suggesting a faster conduction velocity of the ventricular-specific conduction system. In human cardiac tissue, expression of XinC protein was detected solely in samples from patients with cardiac hypertrophy. CONCLUSION Total Xin deficiency leads to topographical ID alterations, premature fibrosis and subtle changes in contractile behaviour; this is a milder cardiac phenotype than that observed in XinAB(-/-) mice, which still can express XinC. Together with the finding that XinC is detected solely in cardiomyopathic human tissues, this suggests that its expression is responsible for the stronger dominant phenotype in XinAB(-/-) mice. Furthermore, it indicates that XinC may be involved in the development of human cardiac hypertrophy.
Huntington's disease: Current and future therapeutic prospects

Huntington's disease is a progressive neurodegenerative disorder for which therapies are woefully inadequate and do not prevent inevitable progression. Currently approved therapies are primarily aimed at treating chorea, but do not address the more clinically meaningful motor, behavioral, and cognitive features of the disease. However, there are a number of promising new therapies that are currently being studied in the laboratory, and in the clinic. This article will review the wide variety of therapies currently being tested, the advances in clinical trials and end points, and the many potentially relevant new targets. © 2018 International Parkinson and Movement Disorder Society
Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs

ABSTRACT Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy of new antiviral drugs and vaccines. ALX-0171 is a trivalent Nanobody targeting the hRSV fusion (F) protein and its therapeutic potential was evaluated in newborn lambs infected with a human strain of RSV followed by daily ALX-0171 nebulization for 3 or 5 consecutive days. Colostrum-deprived newborn lambs were infected with hRSV-M37 before being treated by daily nebulization with either ALX-0171 or placebo. Two different treatment regimens were examined: day 1–5 or day 3–5 post-infection. Lambs were monitored daily for general well-being and clinical parameters. Respiratory tissues and bronchoalveolar lavage fluid were collected at day 6 post-inoculation for the quantification of viral lesions, lung viral titers, viral antigen and lung histopathology. Administration by inhalation of ALX-0171 was well-tolerated in these hRSV-infected newborn lambs. Robust antiviral effects and positive effects on hRSV-induced lung lesions and reduction in symptoms of illness were noted. These effects were still apparent when treatment start was delayed and coincided with peak viral loads (day 3 post-infection) and at a time point when signs of RSV disease were apparent. The latter design is expected to have high translational value for planned clinical trials. These results are indicative of the therapeutic potential of ALX-0171 in infants.
Value generalization in human avoidance learning

Generalization during aversive decision-making allows us to avoid a broad range of potential threats following experience with a limited set of exemplars. However, over-generalization, resulting in excessive and inappropriate avoidance, has been implicated in a variety of psychological disorders. Here, we use reinforcement learning modelling to dissect out different contributions to the generalization of instrumental avoidance in two groups of human volunteers (N=26, N=482). We found that generalization of avoidance could be parsed into perceptual and value-based processes, and further, that value-based generalization could be subdivided into that relating to aversive and neutral feedback - with corresponding circuits including primary sensory cortex, anterior insula, and ventromedial prefrontal cortex, respectively. Further, generalization from aversive, but not neutral, feedback was associated with self-reported anxiety and intrusive thoughts. These results reveal a set of distinct mechanisms that mediate generalization in avoidance learning, and show how specific individual differences within them can yield anxiety.
Correlation Analysis between User's Emotional Comments and Popularity Measures

On user generated contents sites, user's comments include the user's impression to the content. The authors believe that user's comments can be used as the data mining resource to evaluate the contents. In this paper, the authors focus on bilibili.tv, a Chinese video sharing site, and analyze user's emotional comments on the site. Toward development of content quality measurement based on emotional comments, they investigate co-relation between emotional comments and popularity measures such as number of replay and bookmark. They pick up the phrase "233", which is a Chinese network jargon which represents lot of laugh, and studied the number of "233" related comments and other popularity measures.
Mesophyll Cells Are the Main Site of Abscisic Acid Biosynthesis in Water-Stressed Leaves1[OPEN]

Analysis of leaves from one angiosperm and four conifers where the mesophyll and vasculature can be mechanically separated revealed that the mesophyll produces substantial amounts of abscisic acid. The hormone abscisic acid (ABA) plays a critical role in enhancing plant survival during water deficit. Recent molecular evidence suggests that ABA is synthesized in the phloem companion cells and guard cells. However, the nature of cell turgor and water status in these two cell types cannot easily account for the rapid, water status-triggered ABA biosynthesis observed in leaves. Here, we utilize the unique foliar anatomies of an angiosperm (Hakea lissosperma) and four conifer species (Saxegothaea conspicua, Podocarpus latifolius, Cephalotaxus harringtonii, and Amentotaxus formosana) in which the mesophyll can be isolated from the vascular tissue to identify the main site of ABA biosynthesis in water-stressed leaves. In all five species tested, considerable ABA biosynthesis occurred in mesophyll tissue that had been separated from vascular tissue. In addition, the removal of the epidermis from the mesophyll in two conifer species had no impact on the observed increase in ABA levels under water deficit. Our results suggest that mesophyll cells are the predominant location of water deficit-triggered ABA biosynthesis in the leaf.
Indoor initial positioning using single clock pseudolite system

Pseudolite system is good alternative for indoor navigation in where GPS signal can not reach. There are two types of pseudolite system. The one is synchronous system and the other is asynchronous system. For the asynchronous system, user requires RF link to be provided augmentation data for timing and reference station for monitoring timing offsets of pseudolites. For the synchronous system, User does not require RF link for augmentation data but it still need reference station for monitoring timing offsets of pseudolites and the reference station need RF link with pseudolites for providing timing offset information for synchronizing slave pseudolites with master pseudolite. A synchronous pseudolite system with single clock which can cut down cost for the pseudolite system is presented in this paper. Also we will present configuration, operation concept, and preliminary simulation result for it.
Pharmaceutical Machine Learning: Virtual High-Throughput Screens Identifying Promising and Economical Small Molecule Inhibitors of Complement Factor C1s

When excessively activated, C1 is insufficiently regulated, which results in tissue damage. Such tissue damage causes the complement system to become further activated to remove the resulting tissue damage, and a vicious cycle of activation/tissue damage occurs. Current Food and Drug Administration approved treatments include supplemental recombinant C1 inhibitor, but these are extremely costly and a more economical solution is desired. In our work, we have utilized an existing data set of 136 compounds that have been previously tested for activity against C1. Using these compounds and the activity data, we have created models using principal component analysis, genetic algorithm, and support vector machine approaches to characterize activity. The models were then utilized to virtually screen the 72 million compound PubChem repository. This first round of virtual high-throughput screening identified many economical and promising inhibitor candidates, a subset of which was tested to validate their biological activity. These results were used to retrain the models and rescreen PubChem in a second round vHTS. Hit rates for the first round vHTS were 57%, while hit rates for the second round vHTS were 50%. Additional structure–property analysis was performed on the active and inactive compounds to identify interesting scaffolds for further investigation.
Driving Maneuvers Prediction Based on Cognition-driven and Data-driven Method

Advanced Driver Assistance Systems (ADAS) improve driving safety significantly. They alert drivers from unsafe traffic conditions when a dangerous maneuver appears. Traditional methods to predict driving maneuvers are mostly based on data-driven models alone. However, existing methods to understand the driver’s intention remain an ongoing challenge due to a lack of intersection of human cognition and data analysis. To overcome this challenge, we propose a novel method that combines both the cognition-driven model and the data-driven model. We introduce a model named Cognitive Fusion-RNN (CF-RNN) which fuses the data inside the vehicle and the data outside the vehicle in a cognitive way. The CF-RNN model consists of two Long Short-Term Memory (LSTM) branches regulated by human reaction time. Experiments on the Brain4Cars benchmark dataset demonstrate that the proposed method outperforms previous methods and achieves state-of-the-art performance.
Exploiting Row-Level Temporal Locality in DRAM to Reduce the Memory Access Latency

This paper summarizes the idea of ChargeCache, which was published in HPCA 2016 [51], and examines the work's significance and future potential. DRAM latency continues to be a critical bottleneck for system performance. In this work, we develop a low-cost mechanism, called ChargeCache, that enables faster access to recently-accessed rows in DRAM, with no modifications to DRAM chips. Our mechanism is based on the key observation that a recently-accessed row has more charge and thus the following access to the same row can be performed faster. To exploit this observation, we propose to track the addresses of recently-accessed rows in a table in the memory controller. If a later DRAM request hits in that table, the memory controller uses lower timing parameters, leading to reduced DRAM latency. Row addresses are removed from the table after a specified duration to ensure rows that have leaked too much charge are not accessed with lower latency. We evaluate ChargeCache on a wide variety of workloads and show that it provides significant performance and energy benefits for both single-core and multi-core systems.
Effects of moderate, voluntary ethanol consumption on the rat and human gut microbiome

Many alcohol‐induced health complications are directly attributable to the toxicity of alcohol or its metabolites, but another potential health impact of alcohol may be on the microbial communities of the human gut. Clear distinctions between healthy and diseased‐state gut microbiota have been observed in subjects with metabolic diseases, and recent studies suggest that chronic alcoholism is linked to gut microbiome dysbiosis. Here, we investigated the effects of moderate levels of alcohol consumption on the gut microbiome in both rats and humans. The gut microbiota of rats voluntarily consuming a 20 percent ethanol solution, on alternate days, were compared with a non‐exposed control group to identify differential taxonomic and functional profiles. Gut microbial diversity profiles were determined using culture‐independent amplification, next‐generation sequencing and bioinformatic analysis of bacterial 16S ribosomal RNA gene sequence libraries. Our results showed that, compared with controls, ethanol‐consuming rats experienced a significant decline in the biodiversity of their gut microbiomes, a state generally associated with dysbiosis. We also observed significant shifts in the overall diversity of the gut microbial communities and a dramatic change in the relative abundance of particular microbes, such as the Lactobacilli. We also compared our results to human fecal microbiome data collected as part of the citizen science American Gut Project. In contrast to the rat data, human drinkers had significantly higher gut microbial biodiversity than non‐drinkers. However, we also observed that microbes that differed among the human subjects displayed similar trends in the rat model, including bacteria implicated in metabolic disease.
The Share Price Neglect: Inverse Exponential Relation between Initial Share Price and Risk Tolerance

In an experiment, we systematically tested the risk tolerance for trading stock shares that vary in the initial price of the shares. Persons inexperienced with the stock market had to set the selling points for 60 stocks in the case of (a) decreasing or (b) rising prices. First, a stronger risk aversion for falling compared to rising prices was obtained. Second, the experiment revealed a dramatic increase in risk tolerance the lower the buying prices of the stocks were; nearly perfectly following a power function (Pearson-R’s>.93). Furthermore, it seemed very difficult for persons to grasp the consequences of share price neglect, namely that the initial share price has a significant impact on the readiness to take higher risks, whether in a positive or negative direction. Therefore, we are also referring to it as a “hidden risk tolerance”. This paper offers insights into irrational decision making in trading stocks. It allows the formation of estimates regarding trading volume and share price potential on the basis of the initial share price. Furthermore, it provides clues for the consequent reduction of risk-seeking behavior.
Experimental Intrastriatal Applications of Botulinum Neurotoxin-A: A Review

Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. Its main pathophysiological characteristic is the loss of dopaminergic neurons in the substantia nigra pars compacta followed by a lack of striatal dopaminergic input and a consequent disinhibition of tonically active cholinergic interneurons. The resulting striatal hypercholinism causes major motor symptoms in PD. Anticholinergic pharmacotherapies have antiparkinsonian effects on motor symptoms, but, due to systemic actions, also numerous severe side effects occur on a regular basis. To circumvent these side effects, a local anticholinergic therapy acting exclusively in the striatum would be reasonable. Botulinum neurotoxin-A (BoNT-A) is synthesized by Clostridium botulinum and blocks the release of acetylcholine from the presynaptic bouton. For several decades, BoNT-A has been used successfully for medical and cosmetic purposes to induce controlled paralyses of single muscles. Our group and others investigated the experimental treatment of striatal hypercholinism by the direct injection of BoNT-A into the striatum of rats and mice as well as of hemiparkinsonian animal models. This review gives an overview of the most important results of the experimental intrastriatal BoNT-A application, with a focus on hemiparkinsonian rats.