Miracle-dz/UniFAR-FTUs huggingface dataset:
A Genome-Wide Association Study of Optic Disc Parameters

The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72×10−19) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67×10−33) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15×10−11) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93×10−10) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.
Gender and endogenous levels of estradiol do not influence adult hippocampal neurogenesis in mice

In several species, including rat and vole, the proliferation of new neurons in the adult dentate gyrus (DG) subgranular zone (SGZ) is influenced by both gender and endogenous levels of the gonadotropic steroid hormone estradiol. However, little is known about how adult neurogenesis is regulated by these factors in the mouse. We report here that adult C57BL/6 mice do not have gender differences in hippocampal proliferation or neurogenesis. In addition, the production of new SGZ cells in female mice was not influenced by estrous cycle or after ovariectomy, suggesting that fluctuations in endogenous estradiol levels do not alter adult neurogenesis in the mouse. Both male and female mice had a greater number of BrdU‐immunoreactive SGZ cells following chronic treatment with fluoxetine. This demonstrates a parallel proliferation response in both genders, and opens avenues for addressing the neurogenesis hypothesis of depression in female rodents. These findings underscore a distinct regulation of adult neurogenesis in mice vs. other rodents, and are discussed in regard to their implications for the study of adult hippocampal neurogenesis. © 2007 Wiley‐Liss, Inc.
Inherited ichthyosis: Non‐syndromic forms

Inherited ichthyoses are a group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, and often associated with erythroderma. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses consist of non‐syndromic ichthyoses and ichthyosis syndromes. Non‐syndromic ichthyoses are characterized by the phenotypic expression of the disorder being seen only in the skin. Non‐syndromic ichthyoses include ichthyosis vulgaris, recessive X‐linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis and other forms. This review focuses on updates for each type of non‐syndromic ichthyosis, highlighting molecular mechanisms and phenotype/genotype correlations. Included in autosomal recessive congenital ichthyosis are three of the major phenotypes (harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma) and three of the minor subtypes (self‐healing collodion baby, acral self‐healing collodion baby and bathing suit ichthyosis). Keratinopathic ichthyosis is proposed as an umbrella term for ichthyoses caused by mutations in keratin genes. Next‐generation sequencing technologies have become powerful tools for the diagnosis of inherited ichthyoses and the discovery of their genetic causes. This article reviews the current understanding of molecular pathomechanisms for non‐syndromic ichthyoses and explores future perspectives.
A Bayesian approach to Nested Clade Analysis

The purpose of this study is to identify genetically distinct clusters of individuals based on related characteristic traits (namely phenotypic data) or geographical locations (namely phylogeographic data). There are 2 main steps to this process: inferring the genetic history of the sequences under study, and subsequently identifying significant clusters according to the phenotypic/phylogeographic measurements. Based on an evolutionary model and an appropriate model for the distribution of the phenotype, such inference is possible in a number of different ways. However, due to the multiple level uncertainty and the complexity of the models, it is essential that the methods avoid stepwise optimization in order to give statistically reliable conclusions. The main methods currently used for analysis of this type are called Nested Clade Analysis (NCA) and Nested Clade Phylogeographic Analysis (NCPA) for phenotypic and phylogeographic data respectively. In short, they rely on finding the optimal genetic history based on a simplified evolutionary model, and identifying significantly different clusters for the phenotype/geography (assuming the inferred genetic history as fixed) by using Nested Analysis of Variance and permutation tests. Such methods do not allow for the uncertainty of each step to fully propagate through the model and have been shown by simulations often to lead to false conclusions. Here we describe a coherent statistical framework for NCA/NCPA by taking a (Reversible Jump) Markov chain Monte Carlo approach to the genetic clustering problem. By considering a general evolutionary model and clustering constructions using haplotype trees for the phenotypic and phylogeographic analysis respectively, we construct a holistic method in order to obtain the global optimum of the parameters of interest. Several challenges arise in this process. The presence of homoplasy (representing convergent evolution, usually through back mutations) can obscure the analysis, increasing the number of possible histories that underly the data. This leads to intractable likelihoods and normalisation constants. Here we use Approximate Bayesian Computation to address these issues. In addition, the parameter space of clusterings is vast, so we employ adaptive methods and efficient proposals to ensure mixing and convergence. Lastly, we address inherent issues of similar clustering and phylogenetic inference problems such as label-switching (for the cluster parameters) and representation of trees (essential for convergence assessment). We implement our method for 3 datasets and discuss the results in relation to NCA and NCPA.
Substructural Regularization With Data-Sensitive Granularity for Sequence Transfer Learning

Sequence transfer learning is of interest in both academia and industry with the emergence of numerous new text domains from Twitter and other social media tools. In this paper, we put forward the data-sensitive granularity for transfer learning, and then, a novel substructural regularization transfer learning model (STLM) is proposed to preserve target domain features at substructural granularity in the light of the condition of labeled data set size. Our model is underpinned by hidden Markov model and regularization theory, where the substructural representation can be integrated as a penalty after measuring the dissimilarity of substructures between target domain and STLM with relative entropy. STLM can achieve the competing goals of preserving the target domain substructure and utilizing the observations from both the target and source domains simultaneously. The estimation of STLM is very efficient since an analytical solution can be derived as a necessary and sufficient condition. The relative usability of substructures to act as regularization parameters and the time complexity of STLM are also analyzed and discussed. Comprehensive experiments of part-of-speech tagging with both Brown and Twitter corpora fully justify that our model can make improvements on all the combinations of source and target domains.
Selective Breeding for High Anxiety Introduces a Synonymous SNP That Increases Neuropeptide S Receptor Activity

Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behavior (HAB) versus low anxiety-related behavior, and, thereafter, determined the effect of central NPS administration on anxiety- and fear-related behavior. The HAB phenotype was accompanied by lower basal NPS receptor (Npsr1) expression, which we could confirm via in vitro dual luciferase promoter assays. Assessment of shorter Npsr1 promoter constructs containing a sequence mutation that introduces a glucocorticoid receptor transcription factor binding site, confirmed via oligonucleotide pull-down assays, revealed increased HAB promoter activity—an effect that was prevented by dexamethasone. Analogous to the human NPSR1 risk isoform, functional analysis of a synonymous single nucleotide polymorphism in the coding region of HAB rodents revealed that it caused a higher cAMP response to NPS stimulation. Assessment of the behavioral consequence of these differences revealed that intracerebroventricular NPS reversed the hyperanxiety of HAB rodents as well as the impaired cued-fear extinction in HAB rats and the enhanced fear expression in HAB mice, respectively. These results suggest that alterations in the NPS system, conserved across rodents and humans, contribute to innate anxiety and fear, and that HAB rodents are particularly suited to resolve the apparent discrepancy between the preclinical and clinical findings to date.
After inspection in special schools: action planning and making progress

As a high proportion of special schools ‘fail’ their inspections, the DfEE commissioned researchers from the University of the West of England (UWE) to examine post-inspection improvement. Can other schools learn from the ‘best practice’ identified? John Dwyfor Davies, John Lee, Keith Postlethwaite, Jane Tarr and Wan Ching Yee (all of whom lecture and research at UWE) and Gary Thomas, now Chair of Education at Oxford Brookes University, report on their findings, which point strongly to the need for good target-setting and monitoring, together with strong support.
The compositional adjustment of amino acid substitution matrices

Amino acid substitution matrices are central to protein-comparison methods. In most commonly used matrices, the substitution scores take a log-odds form, involving the ratio of “target” to “background” frequencies derived from large, carefully curated sets of protein alignments. However, such matrices often are used to compare protein sequences with amino acid compositions that differ markedly from the background frequencies used for the construction of the matrices. Of course, the target frequencies should be adjusted in such cases, but the lack of an appropriate way to do this has been a long-standing problem. This article shows that if one demands consistency between target and background frequencies, then a log-odds substitution matrix implies a unique set of target and background frequencies as well as a unique scale. Standard substitution matrices therefore are truly appropriate only for the comparison of proteins with standard amino acid composition. Accordingly, we present and evaluate a rationale for transforming the target frequencies implicit in a standard matrix to frequencies appropriate for a nonstandard context. This rationale yields asymmetric matrices for the comparison of proteins with divergent compositions. Earlier approaches are unable to deal with this case in a fully consistent manner. Composition-specific substitution matrix adjustment is shown to be of utility for comparing compositionally biased proteins, including those of organisms with nucleotide-biased, and therefore codon-biased, genomes or isochores.
Infectivity and Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1 Variants Isolated during Primary Infection

ABSTRACT It is believed that replication capacity is an important determinant of human immunodeficiency virus type 1 (HIV-1) pathogenicity and transmissibility. To explore this, we conducted a comprehensive analysis of the replication properties of nine drug-resistant and nine drug-susceptible viral isolates derived from patients with primary HIV-1 infection. Viral isolates were tested for single-cycle infectivity in the GHOST cell line. The infectivity of isolates carrying resistance-associated mutations was significantly higher than that of drug-susceptible isolates. Additionally, the growth kinetics of these isolates were determined in CD4+ T lymphocytes. Drug-resistant isolates replicated as well as drug-susceptible viruses. Insertion of the resistance-conferring regions into an NL4-3-based molecular background resulted in chimeras that displayed a modest but significant reduction in replication capacity compared to the drug-susceptible chimeric viruses. Of note, two multidrug-resistant isolates and one protease inhibitor-resistant isolate displayed higher rates of infectivity and growth kinetics than the other drug-resistant or drug-susceptible isolates. These distinct replicative features, however, were not seen in the corresponding chimeras, indicating that changes within the C-terminal region of Gag as well as within the protease and reverse transcriptase genes contribute to but are not sufficient for the level of compensatory adaptation observed. These findings suggest that some drug-resistant viruses isolated during primary infection possess unique adaptive changes that allow for both high viral replication capacity and resistance to one or more classes of antiretroviral drugs. Further studies are needed to elucidate the precise regions that are essential for these characteristics.
An energy-efficient enhanced virtual resource provision middleware in clouds

In the past few years, cloud computing has emerged as a promising paradigm for delivering IT-infrastructures, platforms, applications and services. The consolidation of this new paradigm in both commercial business and academic research requires that the underlying resources should be economically managed. In this paper, we present a resource provision framework, which is aiming at improving the energy-efficiency of cloud-based data centres. The proposed framework is implemented as a lightweight middleware, which consists of three novel services that enable cloud providers to up/down scale their virtual resource pool in an efficient manner. Extensive experiments are conducted to evaluate the effectiveness and the performance of the proposed middleware in real-world cloud platform. The results indicate that it can significantly improving the energy-efficiency in virtualised clouds without significantly degradation on application performance.
Posture stabilization of a 3-link nonholonomic manipulator – two control approaches

The paper presents two different control approaches, which allow to solve difficult posture stabilization task for a 3−link nonholonomic planar manipulator. Difficulties arise from nonintegrable motion constraints imposed on a system evolution and less number of control inputs in comparison to a state dimension. Presented solutions belong to one of two general stabilization approaches: time-varying or discontinuous one. Control performances of both stabilization strategies have been illustrated by simulation results.
Profitability of Contrarian Strategies in the Chinese Stock Market

This paper reexamines the profitability of loser, winner and contrarian portfolios in the Chinese stock market using monthly data of all stocks traded on the Shanghai Stock Exchange and Shenzhen Stock Exchange covering the period from January 1997 to December 2012. We find evidence of short-term and long-term contrarian profitability in the whole sample period when the estimation and holding horizons are 1 month or longer than 12 months and the annualized return of contrarian portfolios increases with the estimation and holding horizons. We perform subperiod analysis and find that the long-term contrarian effect is significant in both bullish and bearish states, while the short-term contrarian effect disappears in bullish states. We compare the performance of contrarian portfolios based on different grouping manners in the estimation period and unveil that decile grouping outperforms quintile grouping and tertile grouping, which is more evident and robust in the long run. Generally, loser portfolios and winner portfolios have positive returns and loser portfolios perform much better than winner portfolios. Both loser and winner portfolios in bullish states perform better than those in the whole sample period. In contrast, loser and winner portfolios have smaller returns in bearish states, in which loser portfolio returns are significant only in the long term and winner portfolio returns become insignificant. These results are robust to the one-month skipping between the estimation and holding periods and for the two stock exchanges. Our findings show that the Chinese stock market is not efficient in the weak form. These findings also have obvious practical implications for financial practitioners.
Unique Effects of Mycophenolate Mofetil on Cord Blood T Cells: Implications for GVHD Prophylaxis

Background Hematopoietic stem cell transplantation (HSCT) is a common treatment for hematological diseases. Cord blood (CB) is increasingly used as a source of stem cells for HSCT. Prophylactic drugs, such as mycophenolate mofetil (MMF) and cyclosporine A (CsA), are often used together after HSCT to prevent graft-versus-host disease (GvHD), but so far little is known about their effects on CB mononuclear cells (CBMCs). As CB and peripheral blood (PB) have different cell compositions and characteristics, it was hypothesized that MMF and CsA might have different effects on CB and PB T cells. Methods Using a combination of flow cytometry, ELISA, and quantitative PCR, the effects of MMF, CsA, and the combination of both drugs were studied on resting and activated CBMCs and peripheral blood mononuclear cells. Results MMF had a stronger effect on activated PB T cells than on activated CB T cells, which was consistent with the lower level of IMPDH2 mRNA expressed by PB T cells. Interestingly, only MMF could preserve the activated CB regulatory T-cell population. Activated CB T cells were more sensitive to CsA than activated PB T cells, which might be explained by the lower NFATc1 expression and cytokine secretion. These results may explain the lower GvHD incidence observed in recipients of CB transplants. Conclusion This study provides valuable insight into the effects of immunosuppressive drugs used after HSCT on resting and activated T-cell subsets from PB but especially from CB.
Shape from Shading with a Linear Triangular Element Surface Model

The authors propose to combine a triangular element surface model with a linearized reflectance map to formulate the shape-from-shading problem. The main idea is to approximate a smooth surface by the union of triangular surface patches called triangular elements and express the approximating surface as a linear combination of a set of nodal basis functions. Since the surface normal of a triangular element is uniquely determined by the heights of its three vertices (or nodes), image brightness can be directly related to nodal heights using the linearized reflectance map. The surface height can then be determined by minimizing a quadratic cost functional corresponding to the squares of brightness errors and solved effectively with the multigrid computational technique. The proposed method does not require any integrability constraint or artificial assumptions on boundary conditions. Simulation results for synthetic and real images are presented to illustrate the performance and efficiency of the method. >
The Wireless Sensor Network and Local Computational Unit in the Neighbourhood Area Network of the Smart Grid

The Smart Grid intends to provide good power quality, energy cost reduction and improve the reliability of the electricity Grid. Electricity Grids exist across a wide hierarchy of voltages and spatial scales. In this paper we particularly investigate the deployment of monitoring systems in the urban environment, specifically in a university campus that is embedded in a city. Monitoring at this level of the Grid is very underdeveloped, since most current Grids are controlled centrally and the response of the neighbourhood area is not generally monitored or actively controlled. We develop a communications architecture that can integrate sensor network applications. We provide both for sensors that directly measure the electricity activity of the network and also sensors that measure the environment (e.g. temperature) since these provide information that can be used to anticipate demand and improve control actions. Energy efficiency is a major design driver for our architecture. Finally we analyse the optimal number of clusters in a wireless sensor network for collecting and transmitting data to the local control unit for applying finer-grained control.
Indian aspects of drug information resources and impact of drug information centre on community

Drug information centre refer to facility specially set aside for, and specializing in the provision of drug information and related issues. The purpose of drug information center is to provide authentic individualized, accurate, relevant and unbiased drug information to the consumers and healthcare professionals regarding medication related inquiries to the nation for health care and drug safety aspects by answering their call regarding the all critical problems on drug information, their uses and their side effects. Apart from that the center also provides in-depth, impartial source of crucial drug information to meet the needs of the practicing physicians, pharmacists and other health care professionals to safeguard the health, financial and legal interests of the patient and to broaden the pharmacist role visible in the society and community. The service should include collecting, reviewing, evaluating, indexing and distributing information on drugs to health workers. Drug and poisons information centers are best established within major teaching hospitals. This allows access to clinical experience, libraries, research facilities and educational activities. Information present in the current paper will not only enlighten the role of drug information center but also focused on the rational use of drug.