Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards an accurate prediction of the thermal stability of homologous proteins

Protein thermostability has been the focus of growing research interests in the last decades since its understanding and control play important roles in the optimization of a wide series of bioprocesses of academic and industrial importance. The complexity of this issue is rooted in the fact that the mechanisms ensuring thermal resistance are not unique and specific, but rather family- or even protein-dependent. Therefore, and despite the amount of research already accomplished, obtaining fast and precise thermal stability predictions is still a challenge, especially on a large scale. This article deepens the study of protein thermal stability and is focused on the prediction of its best descriptor, the melting temperature Tm. The relations between Tm and a series of factors that are expected to influence the protein stability are analyzed and discussed. Different Tm-prediction methods that utilize these factors, sometimes with additional information about homologous proteins, are introduced, and their individual performances are evaluated. The best methods are based on temperature-dependent statistical potentials, on the environmental temperature of the host organism, on the fraction of charged residues, and on the number of residues. They are combined to build an improved prediction method with significantly increased score. The root mean square deviation between the computed and experimental Tm-values for 45 proteins of known structure from 11 families is about 7°C in cross-validation and decreases to 5°C when 10% outliers are removed. The associated linear correlation coefficients are equal to . 91 and . 95, respectively.
Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing

Broadly neutralizing antibodies to HIV with similar specificities can be found in multiple HIV-infected individuals. Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1–infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.
Novel CIPK1-Associated Proteins in Arabidopsis Contain an Evolutionarily Conserved C-Terminal Region That Mediates Nuclear Localization1

Environmental stimuli, including light, pathogens, hormones, and abiotic stresses, elicit changes in the cytosolic Ca2+ signatures of plant cells. However, little is known about the molecular mechanisms by which plants sense and transmit the specific cytoplasmic Ca2+ signal into the nucleus, where gene regulation occurs to respond appropriately to the stress. In this study, we have identified two novel Arabidopsis (Arabidopsis thaliana) proteins specifically associated with Calcineurin B-Like-Interacting Protein Kinase1 (CIPK1), a member of Ser/Thr protein kinases that interact with the calcineurin B-like Ca2+-binding proteins. These two proteins contain a very similar C-terminal region (180 amino acids in length, 81% similarity), which is required and sufficient for both interaction with CIPK1 and translocation to the nucleus. Interestingly, the conserved C-terminal region was also found in many proteins from various eukaryotic organisms, including humans. However, none of them have been characterized so far. Taken together, these findings suggest that the two proteins containing the evolutionarily conserved C-terminal region (ECT1 and ECT2) may play a critical role in relaying the cytosolic Ca2+ signals to the nucleus, thereby regulating gene expression.
On the relation between stock prices and exchange rates: a review article

Purpose - – While changes in stock prices are said to affect exchange rates, exchange rate changes are also said to affect stock prices. The purpose of this paper is threefold. First, the authors review all empirical literature by dividing them into two groups of univariate and multivariate studies. Second, a table which summarizes the main features of each study is provided to help future researchers to have easy access to summary of each study. Finally, a new direction for future research is proposed. This new direction relies upon non-linear ARDL approach and shows how to investigate symmetric vs asymmetric effects of exchange rate changes on stock prices. Design/methodology/approach - – The paper reviews existing published work and provides suggestions for future research. Findings - – The paper reviews existing published work and provides suggestions for future research. An application reveals that exchange rate changes have asymmetric effect on stock prices. Originality/value - – This is the first review paper on the relation between exchange rates and stock prices.
The influence of high performance work systems on voluntary turnover of new hires in US state governments

Purpose – This article aims to examine factors associated with new employee turnover in US state governments, where turnover is often highest in organizations. Building on existing studies of high performance work systems (HPWS) turnover, this article develops a set of hypotheses to explain new hire turnover.Design/methodology/approach – The proposed model has been analyzed with a sample of 42 of the 50 US state governments.Findings – Practices associated with HPWS influence turnover of new hires. State governments that operate centralized college recruiting programs, pay higher salaries, offer pay for performance incentives, award group bonuses, invest more in training, and allow job rotation lose significantly fewer new hires.Research limitations/implications – This study is limited to specific variables collected in an online survey of states' central human resource departments. Future research may want to focus on other levels of government, include additional practices associated with HPWS, and exami.
Amphipathic α-Helix AH2 Is a Major Determinant for the Oligomerization of Hepatitis C Virus Nonstructural Protein 4B

ABSTRACT Nonstructural protein 4B (NS4B) is a key organizer of hepatitis C virus (HCV) replication complex formation. It induces a specific membrane rearrangement, designated membranous web, that serves as a scaffold for the HCV replication complex. However, the mechanisms underlying membranous web formation are poorly understood. Based on fluorescence resonance energy transfer (FRET) and confirmatory coimmunoprecipitation analyses, we provide evidence for an oligomerization of NS4B in the membrane environment of intact cells. Several conserved determinants were found to be involved in NS4B oligomerization, through homotypic and heterotypic interactions. N-terminal amphipathic α-helix AH2, comprising amino acids 42 to 66, was identified as a major determinant for NS4B oligomerization. Mutations that affected the oligomerization of NS4B disrupted membranous web formation and HCV RNA replication, implying that oligomerization of NS4B is required for the creation of a functional replication complex. These findings enhance our understanding of the functional architecture of the HCV replication complex and may provide new angles for therapeutic intervention. At the same time, they expand the list of positive-strand RNA virus replicase components acting as oligomers.
Stochastic Dominance with Ordinal Variables: Conditions and a Test

A re-emerging literature on robustness in multidimensional welfare and poverty comparisons has revived interest in multidimensional stochastic dominance. Considering the widespread use of ordinal variables in wellbeing measurement, and particularly in composite indices, I derive multivariate stochastic dominance conditions for ordinal variables. These are the analogues of the conditions for continuous variables (e.g., Bawa, 1975, and Atkinson and Bourguignon, 1982). The article also derives mixed-order-of-dominance conditions for any type of variable. Then I propose an extension of Anderson's nonparametric test in order to test these conditions for ordinal variables. In addition, I propose the use of vectors and matrices of positions in order to handle multivariate, multinomial distributions. An empirical application to multidimensional wellbeing in Peru illustrates these tests.
Contract Length and Salaries Compensating Wage Differentials in Major League Baseball

This study investigates the relationship between free agent salaries and contract length in Major League Baseball (MLB) to examine whether players trade-off returns to performance for additional job security. This study is the first to conduct a comprehensive, multiperiod study of salary determination for all MLB position players who were free agents and signed contracts between 1984-1994 and 2003-2006. The authors use the same technique and variables in all models so that comparisons across time are possible. The empirical results of this study indicate that free agent position players appear willing to trade monetary returns to performance for the security of a longer guaranteed contract. The results are not sensitive to the definition of salary used but are sensitive to the productivity measure employed. The results are least compelling for 1990-1994, a result that is different from the finding of Krautmann and Oppenheimer.
Filling is Believing…?

Sensation is an essential aspect of fecal continence. We aimed to correlate manovolumetric and radiologic changes at successive levels of rectal filling sensation. Combined anorectal manometry and proctography were performed in nine volunteers. Images, volumes, and pressures were analyzed at the start of the test, at 20 s before first sensation, and at first, constant, urge, and maximum tolerable sensation. Consecutive levels of rectal filling sensation were associated with progressive opening and dilation of the upper anal canal (up to 44 mm) and sliding down of the rectal contents (14 mm), which had already started before the first sensation. This coincided initially with a pressure decrease in the proximal anal canal (from 94 to 42 mm Hg). With constant sensation and particularly with urge sensation, rectal pressure increase appeared to be responsible for further proximal anal dilation. This was accompanied by a significant increase of proximal anal pressure (up to 133 mm Hg) and sharpening of the angle between the anal axis and the horizontal reference line. The proximal anal canal or its surrounding structures plays an important role in the desire-to-defecate sensation. They can be activated by a progressive buildup of rectal reservoir pressure in the presence of a competent distal anal sphincter barrier.
Product and process innovation in Malaysian manufacturing: The role of government, organizational innovation and exports

Abstract Using firm level data while controlling firm heterogeneity, we examine the importance of the government’s role, organizational innovation and export incidence for product and process innovation. The empirical results show that government incentives, organizational innovation and export are significant in explaining innovative activities among firms. By separating innovation into product and process categories, the empirical evidence reveals that organizational innovation and export incidence are important for both types of innovation while government incentives are significant only for process innovation. Hence, government indirect supports via tax and non-tax incentives such as government technological support is found to have no effect on product innovation suggesting policy redesign to improve the capability of indigenous product development. This study also suggests policy implications for manufacturing firms with regard to sustaining technological upgrading and innovation.
Fire Loss Reduction: Fire Detectors vs. Fire Stations

This paper develops a method for comparing the cost effectiveness of two ways of improving the fire protection in a community: the installation of detection-alarm systems DAS in dwellings and the addition of fire companies. The method is developed from a number of relatively simple models and assumptions. One is a relationship that predicts average travel time from the number of “covered” fire stations and the size of the area being served. A second is a set of regressions of the percentage of the property value destroyed vs. response time for five classes of fires in one-and two-family homes. And a third is the effect of installing detection-alarm systems on the distribution of fires among the five classes at the time of detection. Adding fire companies increases the number of covered stations, thus reducing response time, and thence expected loss. Installing detectors increases the proportion of fires in the less serious classes, thus reducing expected loss. The method was applied to data from Calgary, Canada. The results for this case show that, from a base case with no DAS and 16 fire stations, adding detectors would be more cost effective than adding fire stations to reduce fire losses if a DAS for a one-or two-family home costs less than $2500 to install and $1700 a year to maintain or the equivalent cost mix using present values. The methodology can be extended to other types of occupancies e.g., high-rise buildings and commercial properties, and to other types of losses e.g., indirect and life. It could then become a useful tool in helping to choose fire protection levels for a community, as well as determining how to allocate a given amount of resources among different means of fire protection.
Robust Discovery of Genetic Associations Incorporating Gene-Environment Interaction and Independence

This article considers the detection and evaluation of genetic effects incorporating gene-environment interaction and independence. Whereas ordinary logistic regression cannot exploit the assumption of gene-environment independence, the proposed approach makes explicit use of the independence assumption to improve estimation efficiency. This method, which uses both cases and controls, fits a constrained retrospective regression in which the genetic variant plays the role of the response variable, and the disease indicator and the environmental exposure are the independent variables. The regression model constrains the association of the environmental exposure with the genetic variant among the controls to be null, thus explicitly encoding the gene-environment independence assumption, which yields substantial gain in accuracy in the evaluation of genetic effects. The proposed retrospective regression approach has several advantages. It is easy to implement with standard software, and it readily accounts for multiple environmental exposures of a polytomous or of a continuous nature, while easily incorporating extraneous covariates. Unlike the profile likelihood approach of Chatterjee and Carroll (Biometrika. 2005;92:399–418), the proposed method does not require a model for the association of a polytomous or continuous exposure with the disease outcome, and, therefore, it is agnostic to the functional form of such a model and completely robust to its possible misspecification.
D-4F Decreases White Matter Damage After Stroke in Mice

Background and Purpose— Stroke-induced neuroinflammation and white matter damage are associated with neurological deficits. Whether D-4F, an apolipoprotein A-I mimetic peptide, treatment of stroke decreases neuroinflammation and white matter damage and improves functional outcome has not been investigated. Methods— Adult male C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (MCAo) and were orally administered saline as a vehicle control and different doses of D-4F (2, 4, 8, 16, or 32 mg/kg) starting at 2 h after MCAo and daily until euthanized at 7 days after MCAo. D-4F treatment did not alter the blood levels of high-density lipoprotein, total cholesterol, triglyceride, blood–brain barrier leakage, and infarction volume compared with control group. Results— D-4F (16 mg/kg) treatment of stroke significantly improved functional outcome, increased the white matter density and the number of oligodendrocyte progenitor cells in the ischemic boundary zone of the ipsilateral striatum, and increased myelin basic protein, insulin-like growth factor-1 (IGF1), but decreased inflammatory factor Toll-like receptor-4 and tumor necrosis factor-&agr; expression in the ischemic brain 7 days after MCAo (P<0.05, n=11/group). The neurite/axonal outgrowth in primary cultured neurons was significantly increased when treated with D-4F (100 ng/mL) and IGF1 (100 ng/mL) compared with the nontreatment control. Inhibition of IGF1 significantly attenuated D-4F or IGF1 treatment–induced axonal outgrowth. D-4F-treatment did not increase oligodendrocyte–progenitor cell proliferation but decreased oligodendrocyte–progenitor cell death. Conclusions— D-4F treatment initiated 2 h after MCAo decreases neuroinflammation and white matter damage and improves functional outcome after stroke. D-4F-induced increase in IGF1 may contribute to D-4F–induced neurite/axonal outgrowth after stroke.
Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity

Prostaglandin (PG) E2 acts via four functionally antagonistic E‐prostanoid (EP) receptors that are expressed on multiple cell types in the nervous system; these are designated EP1–4. We showed previously that EP2 null mice are protected from CD14‐dependent neuronal damage in vivo following intracerebroventricular (ICV) injection of lipopolysaccharide (LPS). Clear interpretation of this neuroprotective outcome is limited because EP2 is expressed on glia and neurons. We tested the hypothesis that microglial EP2 is required for paracrine neurotoxicity following activation of innate immunity, using primary murine microglia and neuron co‐cultures. We demonstrated that microglial EP2 was necessary for lipopolysaccharide (LPS)‐activated microglia‐mediated neurotoxicity, as well as induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‐2). Genetic deletion of microglial iNOS, pharmacological suppression of COX‐2 activity, or addition of exogenous superoxide dismutase (SOD) and catalase in the presence of EP2 also abolished neurotoxicity. This loss of paracrine neurotoxicity by EP2−/− microglia occurred in the absence of reduced cytokine levels. We conclude that microglial EP2 is critical to innate immunity‐mediated paracrine damage to neurons involving COX‐2 and iNOS. EP2 should be considered as a therapeutic target for suppression of microglial innate immunity‐mediated damage in neurodegenerative diseases. © 2005 Wiley‐Liss, Inc.
Crosstalk reduction for large scale photonic integrated circuits

The fundamental crosstalk characteristics related to design of highly compact optical and RF signal lines has been studied in this work. The systematic investigation of the crosstalk of parallel waveguides are carried out by modal analysis and the beam propagation analysis. The new idea of crosstalk mitigation in PIC by using uniform air gap along the longitudinal structure has been proposed. The crosstalk mitigation up to - 40dB by using air gap can successfully achieve, which results in reduction of spacing between signal lines.
Determining Factors of E-government Development: A Worldwide National Approach

ABSTRACT The implementation of e-government aims at simplifying and improving the relationships and transactions between public administrations and their users or customers. In this vein, the objective of this work is to analyze the factors that promote the development of e-government in the national governments of 192 countries worldwide, differentiating between developed and developing countries. Our findings emphasize that the development of e-government requires that countries have a degree of economic development that enables their citizens to have a certain standard of living, both economic and cultural, as well as important internal government reforms which promote administrative effectiveness. Once these essential factors are fulfilled, the national government's online presence is favored by governments that rule with a majority in their parliaments and with an important fiscal capacity.
Prospective memory in schizophrenia and schizotypy

Introduction. Most evidence suggests that schizophrenia is associated with pervasive prospective memory (PM) impairment that does not vary as a function of task demands. However, a central tenet of the Multiprocess Framework is that PM involves both automatic and strategic processes, and that their relative prominence varies as a function of PM task characteristics, such as target–cue saliency. Methods. Participants with schizophrenia (n=30), matched controls (n=29), low schizotypes (n=35), and high schizotypes (n=36) were administered a PM measure in which saliency was manipulated. To further clarify the relationship between PM and schizotypy, high and low schizotypies were additionally assessed on Virtual Week, a laboratory measure which has documented sensitivity to schizophrenia-related impairment. Results Relative to controls, participants with schizophrenia exhibited PM difficulties, but the magnitude of this deficit did not vary as a function of target–cue saliency. High and low schizotypes did not differ on any PM test parameter. Conclusions These data are consistent with other evidence showing that schizophrenia is characterised by generalised PM impairment. However, the absence of any schizotypy effects on PM does not support the recent suggestion that PM may represent an endophenotype for schizophrenia.
How to measure the comparability of financial statements

Since 2005, listed EU companies apply IFRS to prepare their consolidated financial statements. Users might get the impression that these financial statements are comparable now. However, differences in application of IFRS still exist. These differences can have a negative impact on the comparability of the financial statements. Therefore, the implementation of IFRS has not eliminated the need for research concerning the comparability of financial statements. The purpose of this article is to assist researchers in choosing the most appropriate method to measure this comparability. First the article discusses the concept of comparability. Second, important properties of measurement methods are discussed. Next, the H, C, I, V and T index and three statistical models are analysed. Finally, the article gives an illustration of choosing a method to measure the comparability of the consolidated financial statements of the EU listed companies.