Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic Dissection of the Pre-existing Conformational Equilibrium in the Trypsin Fold*

Background: The pre-existing equilibrium between open (E*) and closed (E) conformations is a defining feature of the trypsin fold, but its kinetic signatures remain elusive. Results: Kinetics of the E*-E interconversion are determined for protease and zymogen. Conclusion: Protease and zymogen differ in the relative distribution of E* and E. Significance: The role of the E*-E equilibrium in the trypsin fold is elucidated. Structural biology has recently documented the conformational plasticity of the trypsin fold for both the protease and zymogen in terms of a pre-existing equilibrium between closed (E*) and open (E) forms of the active site region. How such plasticity is manifested in solution and affects ligand recognition by the protease and zymogen is poorly understood in quantitative terms. Here we dissect the E*-E equilibrium with stopped-flow kinetics in the presence of excess ligand or macromolecule. Using the clotting protease thrombin and its zymogen precursor prethrombin-2 as relevant models we resolve the relative distribution of the E* and E forms and the underlying kinetic rates for their interconversion. In the case of thrombin, the E* and E forms are distributed in a 1:4 ratio and interconvert on a time scale of 45 ms. In the case of prethrombin-2, the equilibrium is shifted strongly (10:1 ratio) in favor of the closed E* form and unfolds over a faster time scale of 4.5 ms. The distribution of E* and E forms observed for thrombin and prethrombin-2 indicates that zymogen activation is linked to a significant shift in the pre-existing equilibrium between closed and open conformations that facilitates ligand binding to the active site. These findings broaden our mechanistic understanding of how conformational transitions control ligand recognition by thrombin and its zymogen precursor prethrombin-2 and have direct relevance to other members of the trypsin fold.
In Vivo 3D Digital Atlas Database of the Adult C57BL/6J Mouse Brain by Magnetic Resonance Microscopy

In this study, a 3D digital atlas of the live mouse brain based on magnetic resonance microscopy (MRM) is presented. C57BL/6J adult mouse brains were imaged in vivo on a 9.4 Tesla MR instrument at an isotropic spatial resolution of 100 μm. With sufficient signal-to-noise (SNR) and contrast-to-noise ratio (CNR), 20 brain regions were identified. Several atlases were constructed including 12 individual brain atlases, an average atlas, a probabilistic atlas and average geometrical deformation maps. We also investigated the feasibility of using lower spatial resolution images to improve time efficiency for future morphological phenotyping. All of the new in vivo data were compared to previous published in vitro C57BL/6J mouse brain atlases and the morphological differences were characterized. Our analyses revealed significant volumetric as well as unexpected geometrical differences between the in vivo and in vitro brain groups which in some instances were predictable (e.g. collapsed and smaller ventricles in vitro) but not in other instances. Based on these findings we conclude that although in vitro datasets, compared to in vivo images, offer higher spatial resolutions, superior SNR and CNR, leading to improved image segmentation, in vivo atlases are likely to be an overall better geometric match for in vivo studies, which are necessary for longitudinal examinations of the same animals and for functional brain activation studies. Thus the new in vivo mouse brain atlas dataset presented here is a valuable complement to the current mouse brain atlas collection and will be accessible to the neuroscience community on our public domain mouse brain atlas website.
Trigram Timmies and Bayesian Johnnies: Probabilistic Models of Personality in Dominion

Probabilistic models were fit to logs of player actions in the card game Dominion in an attempt to find evidence of personality types that could be used to classify player behavior as well as generate probabilistic bot behavior. Expectation Maximization seeded with players' self-assessments for their motivations was run for two different model types — Naive Bayes and a trigram model — to uncover three clusters each. For both model structures, most players were classified as belonging to a single large cluster that combined the goals of splashy plays, clever combos, and effective play, cross-cutting the original categories — a cautionary tale for research that assumes players can be classified into one category or another. However, subjects qualitatively report that the different model structures play very differently, with the Naive Bayes model more creatively combining cards.
Crystallization of Newcastle disease virus hemagglutinin-neuraminidase glycoprotein.

The hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus was isolated by cleaving HN (cHN) from reconstituted virosome with chymotrypsin. N-terminal sequence analysis of the purified cHN showed that chymotrypsin cleavage had occurred at amino acid 123, freeing the C-terminal 454 amino acids. The purified cHN retained its neuraminidase and receptor binding activities and reacted with specific monoclonal antibodies, showing that the isolated cHN was biologically and antigenically functional. The crystals of the cHN were obtained in acetate buffer (pH 4.6) containing polyethylene glycol 3350 and ammonium sulfate and belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell dimension of approximately a = 72 A, b = 78 A, and c = 198 A. Crystals of cHN grown in the presence of sialic acid (Neu5Ac) were grown in HEPES buffer (pH 6.2) containing polyethylene glycol 3350 and belong to the hexagonal space groups P6(1) or P6(5) with unit cell dimensions of a = b = 137.5 A and c = 116.6A. The orthorhombic crystals produced in this study diffract X rays to at least 2.0-A resolution, thereby setting the stage for the solution of the three-dimensional structure of the HN glycoprotein of a paramyxovirus.
The ETT2 Gene Cluster, Encoding a Second Type III Secretion System from Escherichia coli, Is Present in the Majority of Strains but Has Undergone Widespread Mutational Attrition

ABSTRACT ETT2 is a second cryptic type III secretion system in Escherichia coli which was first discovered through the analysis of genome sequences of enterohemorrhagic E. coli O157:H7. Comparative analyses of Escherichia and Shigella genome sequences revealed that the ETT2 gene cluster is larger than was previously thought, encompassing homologues of genes from the Spi-1, Spi-2, and Spi-3 Salmonella pathogenicity islands. ETT2-associated genes, including regulators and chaperones, were found at the same chromosomal location in the majority of genome-sequenced strains, including the laboratory strain K-12. Using a PCR-based approach, we constructed a complete tiling path through the ETT2 gene cluster for 79 strains, including the well-characterized E. coli reference collection supplemented with additional pathotypes. The ETT2 gene cluster was found to be present in whole or in part in the majority of E. coli strains, whether pathogenic or commensal, with patterns of distribution and deletion mirroring the known phylogenetic structure of the species. In almost all strains, including enterohemorrhagic E. coli O157:H7, ETT2 has been subjected to varying degrees of mutational attrition that render it unable to encode a functioning secretion system. A second type III secretion system-associated locus that likely encodes the ETT2 translocation apparatus was found in some E. coli strains. Intact versions of both ETT2-related clusters are apparently present in enteroaggregative E. coli strain O42.
Design implications for task-specific search utilities for retrieval and re-engineering of code

ABSTRACT The importance of information retrieval systems is unquestionable in the modern society and both individuals as well as enterprises recognise the benefits of being able to find information effectively. Current code-focused information retrieval systems such as Google Code Search, Codeplex or Koders produce results based on specific keywords. However, these systems do not take into account developers’ context such as development language, technology framework, goal of the project, project complexity and developer’s domain expertise. They also impose additional cognitive burden on users in switching between different interfaces and clicking through to find the relevant code. Hence, they are not used by software developers. In this paper, we discuss how software engineers interact with information and general-purpose information retrieval systems (e.g. Google, Yahoo! ) and investigate to what extent domain-specific search and recommendation utilities can be developed in order to support their work-related activities. In order to investigate this, we conducted a user study and found that software engineers followed many identifiable and repeatable work tasks and behaviours. These behaviours can be used to develop implicit relevance feedback-based systems based on the observed retention actions. Moreover, we discuss the implications for the development of task-specific search and collaborative recommendation utilities embedded with the Google standard search engine and Microsoft IntelliSense for retrieval and re-engineering of code. Based on implicit relevance feedback, we have implemented a prototype of the proposed collaborative recommendation system, which was evaluated in a controlled environment simulating the real-world situation of professional software engineers. The evaluation has achieved promising initial results on the precision and recall performance of the system.
Pain in acquired inflammatory demyelinating polyneuropathies

Acquired inflammatory demyelinating neuropathies are a heterogeneous group of autoimmune conditions that share common sensory, motor, autonomic, clinical, laboratory, and electrodiagnostic features. They exist in both acute and chronic forms, with variable levels of cell-mediated and humoral immune dysfunction. Pain is an increasingly recognized problem in many of these conditions. This topical review describes the types of pain associated with commonly encountered acquired inflammatory demyelinating polyneuropathies (Table 1; additional conditions presented in electronic supplement Table 1e, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A250).
Pulse rate analysis in case of central sleep apnea: A new algorithm for cardiac rate estimation

This paper first describes the AM-FM demodulation of an arterial pressure signal. Although it is known to be efficient on signals modulated by breathing, we demonstrate that in case of lack of respiratory modulation (real or simulated central sleep apnea), the AM-FM algorithm doesn’t perform well in heart rate extraction. We introduce then a new algorithm based on Singular Spectrum Analysis eigen values which performs better cardiac frequency estimation in this context. Respiratory estimation is possible but is beyond the scope of this paper. The error for cardiac frequency estimation is around 0.2 BPM (Beats Per Minute) versus 5.5 BPM for the AM-FM demodulation. Further experimentations will be performed (with this time both cardiac and respiratory assessments) and will deal with real sleep apnea cases.
The yeast Ty3 retrotransposon contains a 5′–3′ bipartite primer‐binding site and encodes nucleocapsid protein NCp9 functionally homologous to HIV‐1 NCp7

Retroviruses, including HIV‐1 and the distantly related yeast retroelement Ty3, all encode a nucleoprotein required for virion structure and replication. During an in vitro comparison of HIV‐1 and Ty3 nucleoprotein function in RNA dimerization and cDNA synthesis, we discovered a bipartite primer‐binding site (PBS) for Ty3 composed of sequences located at opposite ends of the genome. Ty3 cDNA synthesis requires the 3′ PBS for primer tRNAiMet annealing to the genomic RNA, and the 5′ PBS, in cis or in trans, as the reverse transcription start site. Ty3 RNA alone is unable to dimerize, but formation of dimeric tRNAiMet bound to the PBS was found to direct dimerization of Ty3 RNA–tRNAiMet. Interestingly, HIV‐1 nucleocapsid protein NCp7 and Ty3 NCp9 were interchangeable using HIV‐1 and Ty3 RNA template–primer systems. Our findings impact on the understanding of non‐canonical reverse transcription as well as on the use of Ty3 systems to screen for anti‐NCp7 drugs.
Maximal strength and power, muscle mass, endurance and serum hormones in weightlifters and road cyclists

Maximal strength, power, muscle cross-sectional area, maximal and submaximal cycling endurance characteristics and serum hormone concentrations of testosterone, free testosterone and cortisol were examined in three groups of men: weightlifters (n = 11), amateur road cyclists (n = 18) and age-matched controls (n = 12). Weightlifters showed 45–55% higher power values than road cyclists and controls, whereas the differences in maximal strength and muscle mass were only 15% and 20%, respectively. These differences were maintained when average power output was expressed relative to body mass or relative to muscle cross-sectional area. Road cyclists recorded 44% higher maximal workloads, whereas submaximal blood lactate concentration was 50–55% lower with increasing workload than in controls and weightlifters. In road cyclists, workloads associated with blood lactate concentrations of 2 and 4 mmol · l−1 were 50–60% higher and occurred at a higher percentage of maximal workload than in weightlifters or controls. Basal serum total testosterone and free testosterone concentrations were lower in elite amateur cyclists than in age-matched weightlifters or untrained individuals. Significant negative correlations were noted between the individual values of maximal workload, workloads at 2 and 4 mmol · l−1 and the individual values of muscle power output (r = −0.37 to −0.49), as well as the individual basal values of serum total testosterone and free testosterone (r = −0.39 to −0.41). These results indicate that the specific status of the participants with respect to training, resistance or endurance is important for the magnitude of the neuromuscular, physiological and performance differences observed between weightlifters and road cyclists. The results suggest that, in cycling, long-term endurance training may interfere more with the development of muscle power than with the development of maximal strength, probably mediated by long-term cycling-related impairment in anabolic hormonal status.
Employee turnover and perception of incentive: A cross-cultural comparison between China and Australia

Turnover is one of the most studied behaviors in human resource management. Hofstede's framework for assessing culture is one of the most influential and frequently quoted ones. In this research, we applied Hofstede's cultural dimensions theory in human resource management problems and analyzed the cultural influences on the employee turnover and perception of incentive between China and Australia. Generally, results showed that the Chinese employees had lower turnover intention than the Australian employees. Compared with the Australian employees, alternative job opportunities had less impact on turnover intention of Chinese employees. Chinese employees regarded career prospect as more important motivating factor, while Australian employees believe that the work itself motivated them better. This empirical research supported three dimensions of Hofstede's cultural dimensions theory.
Reactive Metal Bonding of Carbon Nanotube Arrays for Thermal Interface Applications

Vertically aligned carbon nanotube (CNT) arrays can offer an attractive combination of high thermal conductance and mechanical compliance for thermal interface applications. These arrays require a reliable, thermally conductive bonding technique to enable integration into devices. This paper examines the use of a reactive metal bonding layer to attach and transfer CNT arrays to metal-coated substrates, and the thermal performance is compared with CNT arrays bonded with indium solder. Infrared microscopy is used to simultaneously measure the intrinsic thermal conductivity of the CNT array and the thermal boundary resistance of both the bonded and growth CNT interfaces over a range of applied compressive stresses. A coarse-grained molecular simulation is used to model the effects of compressive pressure on the CNT array thermal conductivity. Reactive metal bonding reduces the thermal boundary resistance to as low as 27 mm2 · K · W-1, which is more than an order of magnitude less than the nonbonded contact.
Absence of Association Between Polymorphisms in the Hemostatic Factor Pathway Genes and Carotid Intimal Medial Thickness: The Framingham Heart Study

Background and Purpose— Fibrinogen, plasminogen activator inhibitor-1, and other key proteins in the coagulation cascade have been implicated in the origin of cardiovascular disease. Polymorphisms in genes encoding these proteins have been associated with variability in plasma levels of these proteins. Carotid intimal medial thickness (IMT) is a heritable, quantitative measure of atherosclerosis that is predictive of subsequent myocardial infarction and stroke. We sought to test whether carotid IMT is associated with polymorphisms in several well-characterized genes in the hemostatic factor pathways. Methods— Here, 867 men and 911 women (mean age, 57 years) in the Framingham offspring cohort underwent B-mode carotid ultrasonography to determine the mean internal (ICA) and common carotid artery (CCA) IMT. Age-, sex-, and multivariable-adjusted linear regression was used to estimate the association of the following variants with log-transformed CCA and ICA IMT: factor V Leiden, factor VII Arg/Gln, fibrinogen Hin dIII &bgr;-148, plasminogen activator inhibitor-1 4G/5G, and the glycoprotein IIIa P lA2 polymorphism. Results— Mean ICA IMT was 0.58 mm; mean CCA IMT was 0.60 mm. There were no differences in ICA or CCA IMT by genotype for any of the candidate genes in unadjusted, age- or sex-adjusted, and multivariable-adjusted models. Conclusions— There is no evidence for an association between well-studied polymorphisms in the hemostatic factor genes and carotid IMT. Whether other common genetic variants in hemostatic factor genes are associated with subclinical atherosclerosis remains to be determined.
Folates and Cardiovascular Disease

&NA; It is increasingly recognized that folates may play a role in the prevention of cardiovascular disease. Over the last few years, several studies have reported beneficial effects of folates on endothelial function, a surrogate end point for cardiovascular risk. Consistently, observational studies have demonstrated an association between folate levels and cardiovascular morbidity and mortality. The exact mechanisms underlying the ameliorative effects of folates on the endothelium remain to be elucidated. Thus far, most studies have focused on the homocysteine‐lowering effects of folates. However, recently, benefits of folates independent of homocysteine lowering have also been reported. Potential mechanisms include antioxidant actions, effects on cofactor availability, or direct interactions with the enzyme endothelial NO synthase. Obviously, beneficial effects of folates on cardiovascular risk would have important clinical and dietary consequences. However, for definite conclusions, the completion of ongoing randomized controlled trials will have to be awaited.
Minimal Interconnection Topology in Distributed Control Design

We propose and partially analyze a new model for determining the influence of a controller’s interconnection graph on closed-loop performance in distributed control design problems. Given a plant composed of dynamically uncoupled subsystems, we investigate the existence and properties of an optimal structured controller, when one of the weight matrices of a classical LQR cost function is topology-dependent. We also give some theoretical results as to the existence of "critical prices" at which adding supplementary edges becomes detrimental to closed-loop performance.
Nontechnological issues in software engineering

A panel discussion is reported. Three nontechnological problems were selected which each serve to cluster several lower-level elements. First, the software engineering profession has not produced a cadre of capable/competent managers. Second, software development is largely practiced as an individual creative activity, rather than a team effort. Third, the software engineering community has not taken positive action to reduce the performance (e.g., productivity and quality) differences among individuals (or across teams). Much of the potential impact of technological advances may be blocked by these factors. The panelists offer a wealth of experience, insight, and international perspectives on these nontechnological issues. The panelists address both the problems and steps for their resolution. <<ETX>>
World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders

Abstract Objectives. This 2013 update of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal has been to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. The guidelines are intended for use by all physicians seeing and treating patients with these conditions. Methods. The 2013 update was conducted by a systematic update literature search and appraisal. All recommendations were approved by the Guidelines Task Force. Results. This first part of the guidelines (Part 1) covers disease definition, classification, epidemiology, and course of unipolar depressive disorders, as well as the management of the acute and continuation phase treatment. It is primarily concerned with the biological treatment (including antidepressants, other psychopharmacological medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of adults. Conclusions. To date, there is a variety of evidence-based antidepressant treatment options available. Nevertheless there is still a substantial proportion of patients not achieving full remission. In addition, somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated. Therefore, further high-quality informative randomized controlled trials are urgently needed.
Demonstration of an analog heterodyne interferometric phase-modulated (HIPM) link

We present results from a proof-of-concept demonstration of a heterodyne interferometric phase-modulated (HIPM) link we have previously proposed and analyzed. The HIPM link uses a novel frequency shifter/phase modulator and a phase discriminator receiver. The experimental HIPM link demonstrated suppression of third-order intermodulation products (IMPs) by as much as 23 dB as compared to a conventional externally modulated AM link, corresponding to an increase in spurious-free dynamic range of 7.7 dB. We compare experimental performance and theoretical predictions, and consider practical implementations of the link. <<ETX>>