Miracle-dz/UniFAR-FTUs huggingface dataset:
Recurrent inhibition in striatum enables transfer of time-flexible skills to basal ganglia

The basal ganglia play a major role in directing learned action sequences such as reaching and pressing, particularly in cases where precise timing plays an important role, as shown in experiments on rodents performing delayed lever press tasks. A comprehensive understanding of the relative roles of cortex and basal ganglia in learning and performing such behaviors, however, is still lacking. Inspired by recent experimental results showing that motor cortex is necessary for learning certain types of motor sequences but not for performing them once learned, we develop a model of the striatum, the major input structure of the basal ganglia, in which recurrently connected inhibitory neurons receive cortical input. An anti-Hebbian plasticity rule at the recurrent synapses in the striatum allows our model to learn a sparse, sequential pattern of neural activity similar to the patterns observed in experimental population recordings. After learning, the network can reproduce the same dynamics autonomously without patterned cortical input, and can further speed up or slow down the activity pattern simply by adjusting the level of tonic external input. The general mechanisms used in this model can also be applied to circuits with both excitatory and inhibitory populations, and hence may underlie sequential neural activity patterns that have been observed throughout other brain areas in addition to basal ganglia.
Treatment of chronic hepatitis B with the combination of pegylated interferon with lamivudine

Several agents are currently approved for the treatment of chronic hepatitis B: interferon alpha (IFN), pegylated interferon‐α (PEG IFN), lamivudine, adefovir, and entecavir. Each agent has inherent limitations. IFN is effective in a minority of patients and has frequent side effects that limit its tolerability. Large randomized controlled trials have demonstrated the efficacy of PEG IFN in the treatment of chronic hepatitis B. The efficacy of lamivudine is limited by the emergence of drug‐resistant hepatitis B virus (HBV) mutants, restricting its utility as a long‐term therapy. Adefovir is well tolerated and is associated with low incidence of resistance, but its antiviral effect is not optimal. Entecavir has a high antiviral effect and is well tolerated. However, its long term efficacy and resistance profile are not yet determined. Lamivudine, adefovir and entecavir have the advantages of oral administration and excellent safety profiles. However, theyinduce a sustained response after withdrawal of therapy in only a minority of patients, and therefore, the treatment needs to be indefinitely administered in most patients. IFNs have two mechanisms of action: (i) direct antiviral effect by inhibiting synthesis of viral DNA and by activating antiviral enzymes; and (ii) exaggeration of the cellular immune response against hepatocytes infected with HBV. PEG IFN, administered for 48 weeks, gives an overall sustained response rate of approximately 30%. Two large randomized controlled trials have conducted to registration of PEG IFN‐α‐2a in the treatment of chronic hepatitis B.
Synthesis of C5-dicarboxylic acids from C2-units involving crotonyl-CoA carboxylase/reductase: The ethylmalonyl-CoA pathway

Fifty years ago, Kornberg and Krebs established the glyoxylate cycle as the pathway for the synthesis of cell constituents from C2-units. However, since then, many bacteria have been described that do not contain isocitrate lyase, the key enzyme of this pathway. Here, a pathway termed the ethylmalonyl-CoA pathway operating in such organisms is described. Isotopically labeled acetate and bicarbonate were transformed to ethylmalonyl-CoA by cell extracts of acetate-grown, isocitrate lyase-negative Rhodobacter sphaeroides as determined by NMR spectroscopy. Crotonyl-CoA carboxylase/reductase, catalyzing crotonyl-CoA + CO2 + NADPH → ethylmalonyl-CoA− + NADP+ was identified as the key enzyme of the ethylmalonyl-CoA pathway. The reductive carboxylation of an enoyl-thioester is a unique biochemical reaction, unprecedented in biology. The enzyme from R. sphaeroides was heterologously produced in Escherichia coli and characterized. Crotonyl-CoA carboxylase/reductase (or its gene) can be used as a marker for the presence of the ethylmalonyl-CoA pathway, which functions not only in acetyl-CoA assimilation. In Streptomyces sp. , it may also supply precursors (ethylmalonyl-CoA) for antibiotic biosynthesis. For methylotrophic bacteria such as Methylobacterium extorquens, extension of the serine cycle with reactions of the ethylmalonyl-CoA pathway leads to a simplified scheme for isocitrate lyase-independent C1 assimilation.
How "good" is bad News? Exploring Sentiments of Corporate Disclosures

To satisfy legal requirements, listed companies are required to continuously publish a wide range of disclosures and reports. Regulatory authorities such as the SEC in the US or the FSA in the UK have developed a complex set of rules and regulations that aim at expanding transparency of capital markets. Therefore, corporations hire professional editorial teams, often being supported by financial service communication consultancies. While the regulatory objective is to increase transparency, the management has an inherent motivation to give the reports a positive spin. We aim to explore this conflict by analyzing the sentiment of corporate disclosures and to compare this tone with the price reactions following the disclosures’ publication. On the basis of an empirical analysis of intraday stock price reactions and word lists which provide means to assess the tone of documents, our results provide evidence that corporates follow a strategy to positively adjust their external reporting.
Identification of income–leisure preferences and evaluation of income tax policy

The merits of alternative income tax policies depend on the population distribution of preferences for income and leisure. Standard theory, which supposes that persons want more income and more leisure, does not predict how they resolve the tension between these desires. Empirical studies of labor supply have imposed strong preference assumptions that lack foundation. This paper examines anew the problem of inference on income–leisure preferences and considers the implications for evaluation of tax policy. I first perform a basic revealedpreference analysis assuming only that persons prefer more income and leisure. This shows that observation of a person’s time allocation under a status quo tax policy may bound his allocation under a proposed policy or may have no implications, depending on the tax schedules and the person’s status quo time allocation. I next explore the identifying power of two classes of assumptions that restrict the distribution of income–leisure preferences. One assumes that groups of persons who face different choice sets have the same preference distribution. The second restricts the shape of this distribution. The generic finding is partial identification of preferences. This implies partial prediction of tax revenue under proposed policies and partial knowledge of the welfare function for utilitarian policy evaluation.
Do Clinical Psychologists Extend the Bereavement Exclusion for Major Depression to Other Stressful Life Events?

Background. In assessing potential cases of major depressive disorder (MDD), to what extent do clinicians interpret symptoms within the explanatory context of major life stressors? Past research suggests that when clinicians know a plausible life event cause for a person’s disordered symptoms, they generally judge that person to be less abnormal than if the cause was unknown. However, the current, fourth edition of the Diagnostic and Statistical Manual of Mental Disorders specifies that only bereavement-related life events exclude a client from a diagnosis of MDD, and the upcoming fifth edition of the manual (DSM-V) is currently slated to eliminate this bereavement clause altogether. Objective. To systematically examine whether clinicians’ judgments reflect agreement with either of these formal DSM specifications. Method. In a controlled experiment, 72 practicing, licensed clinical psychologists made judgments about realistic MDD vignettes that included a bereavement event, stressful non-bereavement event, neutral event, or no event. Results. Bonferroni-corrected paired comparisons revealed that both bereavement and non-bereavement life events led MDD symptoms to be rated as significantly less indicative of a depression diagnosis, less abnormal, less rare, and less culturally unacceptable (all P ≤ 0.001) relative to control conditions. Limitations. Clinicians made judgments of realistic, controlled vignettes rather than patients. Conclusions. The results suggest that practicing clinical psychologists assess symptoms within the explanatory context of bereavement and non-bereavement life stressors, indicating a departure from the DSM’s recommendations, both current and proposed. Implications for diagnostic decision making and the clinical utility of the DSM’s recommendations are discussed.
Quantification of Head Movement Predictability and Implications for Suppression of Vestibular Input during Locomotion

Achieved motor movement can be estimated using both sensory and motor signals. The value of motor signals for estimating movement should depend critically on the stereotypy or predictability of the resulting actions. As predictability increases, motor signals become more reliable indicators of achieved movement, so weight attributed to sensory signals should decrease accordingly. Here we describe a method to quantify this predictability for head movement during human locomotion by measuring head motion with an inertial measurement unit (IMU), and calculating the variance explained by the mean movement over one stride, i.e., a metric similar to the coefficient of determination. Predictability exhibits differences across activities, being most predictable during running, and changes over the course of a stride, being least predictable around the time of heel-strike and toe-off. In addition to quantifying predictability, we relate this metric to sensory-motor weighting via a statistically optimal model based on two key assumptions: (1) average head movement provides a conservative estimate of the efference copy prediction, and (2) noise on sensory signals scales with signal magnitude. The model suggests that differences in predictability should lead to changes in the weight attributed to vestibular sensory signals for estimating head movement. In agreement with the model, prior research reports that vestibular perturbations have greatest impact at the time points and during activities where high vestibular weight is predicted. Thus, we propose a unified explanation for time-and activity-dependent modulation of vestibular effects that was lacking previously. Furthermore, the proposed predictability metric constitutes a convenient general method for quantifying any kind of kinematic variability. The probabilistic model is also general; it applies to any situation in which achieved movement is estimated from both motor signals and zero-mean sensory signals with signal-dependent noise.
Cardiovascular disease in patients with hemophilia

Summary. Mortality due to ischemic heart disease in hemophilia patients is lower as compared to the general male population. Differences in the prevalence of cardiovascular risk factors cannot explain this finding. The hypocoagulable state of hemophilia patients might have a protective effect on thrombus formation, which precipitates infarction. It remains unclear whether the deficiency of coagulation factor VIII or IX exerts a protective effect on the development of atherosclerosis. Despite the relative protection against cardiovascular events, the incidence of ischemic cardiovascular disease in hemophilia patients is increasing, because life expectancy of these patients now approaches that of the general population. This review focuses on what is currently known about cardiovascular risk factors, atherosclerosis, arterial thrombosis and ischemic cardiovascular disease in hemophilia patients.
Effect of perinatal lead treatment on morphine dependence in the adult rat.

The effect of perinatal lead exposure (at 300 and 1000 ppm in the maternal drinking water from conception to postnatal day 14) on the opioid withdrawal syndrome in adult offspring has been studied to assess if lead produces long term disruption of opioid systems manifested as altered morphine dependence. Dependence was induced in 50 day old rats by administration of morphine in osmotic mini-pumps implanted subcutaneously and delivering 5, 15 or 40 mg/kg/day. At postnatal day 55 an opioid withdrawal syndrome was precipitated by administration of naloxone (4 mg/kg i.p) and withdrawal behaviour scored over the next 30 min. Both objective (jumping, weight loss, weight of excreta, wet dog shakes, mouthing and face washing) and subjective (teeth chatter, ptosis, diarrhoea, irritability) measures were scored. 60 min after naloxone animals were killed and plasma corticosterone measured as a biochemical index of withdrawal. Morphine withdrawal scores and plasma corticosterone exhibited a clear dose relationship and there were no significant differences between 0 and 300 ppm lead-exposed groups. However withdrawal scores in 1000 ppm lead-exposed animals were lower in 15 and 40 mg/kg morphine treated rats, predominantly associated with lower weight loss, wet dog shakes and mouthing responses. Paradoxically corticosterone levels were elevated in the 40 mg/kg morphine dose group. The results support other evidence that perinatal lead exposure can induce disruption in opioid functioning which persists to adulthood and suggest a possible link between lead and opioid addiction.
Phylogenetic placement and characterization of a new alpha-2 proteobacterium isolated from a patient with sepsis

An alpha-2 proteobacterium, previously unknown as determined by its phylogenetic characteristics and the DNA sequence of its 16S rRNA gene, was isolated from a patient who presented an unusual clinical picture, including high remitting fever and multiorgan involvement. The bacterium was detected in multiple plasma samples, obtained during the acute phase of the disease, after cocultivation in cell culture media. Electron microscopy of the organism showed a three-layer laminar cell wall and electron-dense granules within the cytoplasm, as well as a polar flagellum. By means of PCR followed by sequencing of amplified 16S ribosomal DNA fragments, the bacterium was found to differ from all species for which ribosomal sequence information is available. It is here provisionally named the Rasbo bacterium. At a subsequent relapse, the bacterium was identified in pericardial fluid both by PCR/sequencing and by direct electron microscopy. At a second relapse, it was again cultured from plasma. After in vitro adaptation to solid media, the MICs of various antibiotics could be determined. A transient immunoglobulin M (IgM) but no IgG response to the bacterium was found by an indirect immunofluorescence test, as well as by an immobilization test during the acute phase of the disease.
Intraoperative Epidural Analgesia Combined with Ketamine Provides Effective Preventive Analgesia in Patients Undergoing Major Digestive Surgery

Background: As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context. Methods: In a randomized, double-blinded trial, 85 patients scheduled to undergo neoplastic colonic resection were included. All the patients received a thoracic epidural catheter, systemic ketamine at a antihyperalgesic dose, and general anesthesia. Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery. Patients were allocated to four groups to receive intraoperative intravenous lidocaine–sufentanil–clonidine or epidural bupivacaine–sufentanil–clonidine followed postoperatively by either intravenous (lidocaine–morphine–clonidine) or epidural (bupivacaine–sufentanil–clonidine) patient-controlled analgesia. Postoperative pain scores (visual analog scale), analgesic consumption, wound area of punctuate hyperalgesia, residual pain, and analgesics needed from 2 weeks until 12 months were recorded. Results: Analgesic requirements, visual analog scale scores, and area of hyperalgesia were significantly higher in the intravenous treatment group (intravenous–intravenous), and more patients reported residual pain from 2 weeks until 1 yr (28%). Although postoperative pain measurements did not differ, postoperative epidural treatment (intravenous–epidural) was less effective to prevent residual pain at 1 yr (11%; P = 0.2 with intravenous–intravenous group) than intraoperative one (epidural–epidural and epidural–intravenous groups) (0%; P = 0.01 with intravenous–intravenous group). Conclusion: Combined with an antihyperalgesic dose of ketamine, intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery.
Consumer Heterogeneity and Pricing Strategies:A Quality-Price Competition Model

We consider duopoly quality-price competition in a market with two types of consumers: price-sensitive consumers and quality-sensitive consumers.The characteristics of consumers are reflected by both the price sensitivity and the quality sensitivity.We first establish the utility function for each type of consumers and derive the demand function for every firm based on Hotelling model.Then,we analyze the duopoly quality-price competition under two pricing strategies: uniform pricing sand discriminatory pricing.The results show that under price discrimination the quality is higher than that under the uniform pricing strategy;firms set lower prices for price-sensitive consumers and higher price for quality-sensitive consumers.By comparisons,we conclude that the firms may carry out discriminatory pricing when consumer's transportation cost is high,and adopt uniform pricing when consumer's transportation cost is low.Additionally,the proportion of different types of consumers has significant impact on equilibrium prices and qualities.
A Putative Polypeptide N-Acetylgalactosaminyltransferase/Williams-Beuren Syndrome Chromosome Region 17 (WBSCR17) Regulates Lamellipodium Formation and Macropinocytosis*

Background: WBSCR17 is a potential polypeptide N-acetylgalactosaminyltransferase with unknown function. Results: WBSCR17, induced with N-acetylglucosamine, regulated O-glycosylation, lamellipodium formation, and macropinocytosis. Conclusion: Mucin-type O-glycosylation may be involved in lamellipodium formation and membrane trafficking through macropinocytosis. Significance: The data suggest that mucin-type O-glycosylation modulates the dynamic membrane transport of the cell and may be involved in the control of nutrient uptake. We previously identified a novel polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) gene, which is designated Williams-Beuren syndrome chromosome region 17 (WBSCR17) because it is located in the chromosomal flanking region of the Williams-Beuren syndrome deletion. Recent genome-scale analysis of HEK293T cells treated with a high concentration of N-acetylglucosamine (GlcNAc) demonstrated that WBSCR17 was one of the up-regulated genes possibly involved in endocytosis (Lau, K. S., Khan, S., and Dennis, J. W. (2008) Genome-scale identification of UDP-GlcNAc-dependent pathways. Proteomics 8, 3294–3302). To assess its roles, we first expressed recombinant WBSCR17 in COS7 cells and demonstrated that it was N-glycosylated and localized mainly in the Golgi apparatus, as is the case for the other GalNAc-Ts. Assay of recombinant WBSCR17 expressed in insect cells showed very low activity toward typical mucin peptide substrates. We then suppressed the expression of endogenous WBSCR17 in HEK293T cells using siRNAs and observed phenotypic changes of the knockdown cells with reduced lamellipodium formation, altered O-glycan profiles, and unusual accumulation of glycoconjugates in the late endosomes/lysosomes. Analyses of endocytic pathways revealed that macropinocytosis, but neither clathrin- nor caveolin-dependent endocytosis, was elevated in the knockdown cells. This was further supported by the findings that the overexpression of recombinant WBSCR17 stimulated lamellipodium formation, altered O-glycosylation, and inhibited macropinocytosis. WBSCR17 therefore plays important roles in lamellipodium formation and the regulation of macropinocytosis as well as lysosomes. Our study suggests that a subset of O-glycosylation produced by WBSCR17 controls dynamic membrane trafficking, probably between the cell surface and the late endosomes through macropinocytosis, in response to the nutrient concentration as exemplified by environmental GlcNAc.
Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid/Chondroitin Sulfate Instillation for Interstitial Cystitis/Painful Bladder Syndrome

Background/Aims: To assess the efficacy of intravesical hyaluronic acid (HA) and HA/chondroitin sulfate (CS) instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis. Methods: A systematic literature search was performed using the keywords: ‘interstitial cystitis' or ‘painful bladder syndrome' or ‘bladder pain syndrome' and ‘hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS). Secondary outcomes were the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), frequency, nocturia, bladder volume, and voided urine volume. Results: Ten articles involving 390 patients were retrieved and assessed in analysis. A significant improvement in mean VAS on fixed-effect and random-effect models (mean difference [MD] -3.654, 95% confidence interval [CI] -3.814 to -3.495, and MD -3.206, 95% CI -4.156 to -2.257, respectively) was found. Significant improvements were found in the ICSI (MD -3.223, 95% CI -4.132 to -2.315) and ICPI (MD -2.941, 95% CI -3.767 to -2.116). Similarly, the other outcomes were significantly improved. Conclusion: Intravesical HA and HA/CS instillation improved pain symptom, quality of life, and other outcomes and could be included as therapeutic modality of interstitial cystitis/painful bladder syndrome.
Prosody Aware Word-Level Encoder Based on BLSTM-RNNs for DNN-Based Speech Synthesis

Recent studies have shown the effectiveness of the use of word vectors in DNN-based speech synthesis. However, these word vectors trained from a large amount of text generally carry not prosodic information, which is important information for speech synthesis, but semantic information. Therefore, if word vectors that take prosodic information into account can be obtained, it would be expected to improve the quality of synthesized speech. In this paper, to obtain word-level vectors that take prosodic information into account, we propose a novel prosody aware word-level encoder. A novel point of the proposed technique is to train a word-level encoder by using a large speech corpus constructed for automatic speech recognition. A word-level encoder that estimates the F0 contour for each word from the input word sequence is trained. The outputs of the bottleneck layer in the trained encoder are used as the word-level vector. By training the relationship between words and their prosodic information by using large speech corpus, the outputs of the bottleneck layer would be expected to contain prosodic information. The results of objective and subjective experiments indicate the proposed technique can synthesize speech with improved naturalness.