Miracle-dz/UniFAR-FTUs huggingface dataset:
Perioperative MI: Is there a clot or not?

Those of us in clinical cardiology know that among the most frequent inpatient consultation requests are those for the evaluation of an elevated troponin. Despite claims that the troponin assay is both highly sensitive and highly specific for myocardial infarction (MI) [1], we now know that troponin is a nonspecific marker of myocardial injury that may be elevated in a host of conditions (Table I). When ordered on patients with a low pretest probability of MI, a positive troponin has a low positive predictive value [2]. Unfortunately, when up to half of all admitted patients receive troponin testing [3], the inevitable result is a plethora of false positives. Even when patients meet the additional clinical or ECG criteria satisfying the requirements for MI, it is often unclear whether the etiology of the infarction is a thrombotic acute coronary syndrome (ACS, Type 1 MI) or a supply/demand mismatch (Type 2 MI) (Fig. 1). This distinction has important implications for the continued evaluation and ultimate treatment of these patients. Patients with Type 1 MI would be expected to benefit most from anticoagulation and urgent percutaneous coronary intervention, whereas patients with Type 2 MI from chronic coronary artery disease or demand ischemia would benefit more from fluid resuscitation, blood transfusion, and control of arrhythmias or blood pressure. Nowhere is this distinction more critical than in postoperative patients, where antithrombotic agents may be particularly hazardous. Differentiating between Type 1 and Type 2 MI currently relies on the presence of clinical factors (i.e., anemia, hypotension, hypertension, arrhythmias) that would tend to increase demand. Unfortunately, many of these factors are frequently present in postsurgical patients or even more confounding, may result from a MI, so their discriminatory power is limited. Hanson et al. [4], in this issue of Catheterization and Cardiovascular Interventions, make a unique and critical contribution by describing the clinical and angiographic differences in patients with Type 1 versus Type 2 MI. From a population of 226 perioperative MI (PMI) at their institution over 10 years, the authors analyzed 54 patients who received angiograms. They TABLE I. Common non-ACS Causes for elevated troponin
Crystal Structure of Bacillus sp. GL1 Xanthan Lyase, Which Acts on the Side Chains of Xanthan*

Xanthan lyase, a member of polysaccharide lyase family 8, is a key enzyme for complete depolymerization of a bacterial heteropolysaccharide, xanthan, in Bacillus sp. GL1. The enzyme acts exolytically on the side chains of the polysaccharide. The x-ray crystallographic structure of xanthan lyase was determined by the multiple isomorphous replacement method. The crystal structures of xanthan lyase and its complex with the product (pyruvylated mannose) were refined at 2.3 and 2.4 Å resolution with finalR-factors of 17.5 and 16.9%, respectively. The refined structure of the product-free enzyme comprises 752 amino acid residues, 248 water molecules, and one calcium ion. The enzyme consists of N-terminal α-helical and C-terminal β-sheet domains, which constitute incomplete α5/α5-barrel and anti-parallel β-sheet structures, respectively. A deep cleft is located in the N-terminal α-helical domain facing the interface between the two domains. Although the overall structure of the enzyme is basically the same as that of the family 8 lyases for hyaluronate and chondroitin AC, significant differences were observed in the loop structure over the cleft. The crystal structure of the xanthan lyase complexed with pyruvylated mannose indicates that the sugar-binding site is located in the deep cleft, where aromatic and positively charged amino acid residues are involved in the binding. The Arg313 and Tyr315 residues in the loop from the N-terminal domain and the Arg612 residue in the loop from the C-terminal domain directly bind to the pyruvate moiety of the product through the formation of hydrogen bonds, thus determining the substrate specificity of the enzyme.
Special Issue: Analytical methods in phylogeography and genetic structure

Over the last few years, the field of molecular ecology has changed drastically. With the advent of new molecular data such as mitochondrial DNA sequences or microsatellites, scientists have first been able to examine the levels of genetic diversity in their model organism, compare its extent within and among populations as well as between species (genetic structure), test if the observed pattern was congruent with geography (phylogeography), estimate divergence times, recognize isolated or small populations, get rough estimates of gene flow between populations, or find evidence for past bottlenecks, demographic or range expansions. Having collected this basic information, more and more scientists have begun to refine their questions. Now scientists want to use molecular data to gain an insight into mating systems: do some individuals reproduce more than others? How far do individuals (or gametes) go to reproduce? Is there sex-biased dispersal? Given two similar populations, scientists want to distinguish between recent common ancestry and large amounts of gene flow. They want to recognize the presence of admixed individuals or recent immigrants in a population and find their population of origin. They want to estimate the demographic history of a population, time the date of past bottlenecks or growth events, estimate the relative size of ancestral populations, find the geographical location of refuge areas or the geographical origin of a species. They would also like to distinguish the loci that could be subject to some form of selection, or detect populations subject to local adaptations, and somehow see the potential influence of environmental constraints on patterns of genetic diversity. For all these very relevant questions, new methodological tools have had to be developed (and more are still under development), population models had to be refined and made more realistic, and new statistical methods had to be designed. In this special issue of Molecular Ecology , several of these new developments are presented. While the present papers are not an exhaustive list of the latest developments, they are representative and important contributions to the field, addressing or reviewing a series of important questions related to the points mentioned above, in a variety of organisms ranging from viruses to humans. It is also our hope that these papers will contribute to enhancing the necessary communication between theoreticians and molecular ecologists, showing not only the limitations and the power of some approaches, but also that new analyses can be tailored to particular applied problems. This requires not only communication but a real collaboration between statisticians, population geneticists, and molecular ecologists. Several contributions of this special issue are representative of this collaborative effort, showing that specific models incorporating non-genetic information can be built to estimate genetic and demographic parameters. For many scientists this will be both good and bad news. The good news is that more precise information can be retrieved from
NRGsuite: a PyMOL plugin to perform docking simulations in real time using FlexAID

Ligand protein docking simulations play a fundamental role in understanding molecular recognition. Herein we introduce the NRGsuite, a PyMOL plugin that permits the detection of surface cavities in proteins, their refinements, calculation of volume and use, individually or jointly, as target binding-sites for docking simulations with FlexAID. The NRGsuite offers the users control over a large number of important parameters in docking simulations including the assignment of flexible side-chains and definition of geometric constraints. Furthermore, the NRGsuite permits the visualization of the docking simulation in real time. The NRGsuite give access to powerful docking simulations that can be used in structure-guided drug design as well as an educational tool. The NRGsuite is implemented in Python and C/C++ with an easy to use package installer. The NRGsuite is available for Windows, Linux and MacOS. Availability and implementation: http://bcb.med.usherbrooke.ca/flexaid. Contact: rafael.najmanovich@usherbroke.ca Supplementary information: Supplementary data are available at Bioinformatics online.
A sparse support vector machine approach to region-based image categorization

Automatic image categorization using low-level features is a challenging research topic in computer vision. In this paper, we formulate the image categorization problem as a multiple-instance learning (MIL) problem by viewing an image as a bag of instances, each corresponding to a region obtained from image segmentation. We propose a new solution to the resulting MIL problem. Unlike many existing MIL approaches that rely on the diverse density framework, our approach performs an effective feature mapping through a chosen metric distance function. Thus the MIL problem becomes solvable by a regular classification algorithm. Sparse SVM is adopted to dramatically reduce the regions that are needed to classify images. The selected regions by a sparse SVM approximate to the target concepts in the traditional diverse density framework. The proposed approach is a lot more efficient in computation and less sensitive to the class label uncertainty. Experimental results are included to demonstrate the effectiveness and robustness of the proposed method.
Dissection of a Complex Phenotype by Functional Genomics Reveals Roles for the Yeast Cyclin-Dependent Protein Kinase Pho85 in Stress Adaptation and Cell Integrity

ABSTRACT Cyclin-dependent kinases (Cdks) are key regulators of the cell division cycle. Pho85 is a multifunctional Cdk in budding yeast involved in aspects of metabolism, the cell cycle, cell polarity, and gene expression. Consistent with a broad spectrum of functions, Pho85 associates with a family of 10 cyclins and deletion of PHO85 causes a pleiotropic phenotype. Discovering the physiological substrates of protein kinases is a major challenge, and we have pursued a number of genomics approaches to reveal the processes regulated by Pho85 and to understand the root cause of reduced cellular fitness in pho85Δ mutant strains. We used a functional-genomics approach called synthetic genetic array (SGA) analysis to systematically identify strain backgrounds in which PHO85 is required for viability. In parallel, we used DNA microarrays to examine the genome-wide transcriptional consequences of deleting PHO85 or members of the Pho85 cyclin family. Using this pairwise approach coupled with phenotypic tests, we uncovered clear roles for Pho85 in cell integrity and the response to adverse growth conditions. Importantly, our combined approach allowed us to ascribe new aspects of the complex pho85 phenotype to particular cyclins; our data highlight a cell integrity function for the Pcl1,2 subgroup of Pho85 Cdks that is independent of a role for the Pho80-Pho85 kinase in the response to stress. Using a modification of the SGA technique to screen for suppressors of pho85Δ strain growth defects, we found that deletion of putative vacuole protein gene VTC4 suppressed the sensitivity of the pho85Δ strain to elevated CaCl2 and many other stress conditions. Expression of VTC4 is regulated by Pho4, a transcription factor that is inhibited by the Pho80-Pho85 kinase. Genetic tests and electron microscopy experiments suggest that VTC4 is a key target of Pho4 and that Pho80-Pho85-mediated regulation of VTC4 expression is required for proper vacuole function and for yeast cell survival under a variety of suboptimal conditions. The integration of multiple genomics approaches is likely to be a generally useful strategy for extracting functional information from pleiotropic mutant phenotypes.
Economics, Governance, and Law: Essays on Theory and Policy (review)

reception of Keynesianism as it crossed the Atlantic, and, perhaps most valuable of all, of how this generation now interprets these episodes given both hindsight and more or less active engagement with the modern literature. Consumers—or should that be epicures? —of gossip will also not be disappointed: old rifts continue, between the nonmonetary and monetary hypotheses, not least with the counterfactual potentialities of the Fed’s monetary policy. Newer vintage disagreements are also given succor. Names are deliberately not named here by this reviewer, though, so as to encourage a wide readership for this admirable volume.
Default Logic, Propositional Logic, and Constraints

We present a mapping from a class of default theories to sentences in propositional logic, such that each model of the latter corresponds to an extension of the former. Using this mapping we show that many properties of default theories can be determined by solving propositional satisfiability. In particular, we show how CSP techniques can be used to identify, analyze and solve tractable subsets of Reiter's default logic.
Arsenite is a cocarcinogen with solar ultraviolet radiation for mouse skin: an animal model for arsenic carcinogenesis.

Although epidemiological evidence shows an association between arsenic in drinking water and increased risk of skin, lung, and bladder cancers, arsenic compounds are not animal carcinogens. The lack of animal models has hindered mechanistic studies of arsenic carcinogenesis. Previously, this laboratory found that low concentrations of arsenite (the likely environmental carcinogen) which are not mutagenic can enhance the mutagenicity of other agents, including ultraviolet radiation (UVR). This enhancing effect appears to result from inhibition of DNA repair by arsenite. Recently we found that low concentrations of arsenite disrupted p53 function and upregulated cyclin D1. These results suggest that the failure to find an animal model for arsenic carcinogenesis is because arsenite is not a carcinogen per se, but rather acts as an enhancing agent (cocarcinogen) with a genotoxic partner. We tested this hypothesis with solar UVR as carcinogenic stimulus in hairless Skh1 mice. Mice given 10 mg/l sodium arsenite in drinking water for 26 weeks had a 2.4-fold increase in yield of tumors after 1.7 KJ/m(2) UVR three times weekly compared with mice given UVR alone. No tumors appeared in mice given arsenite alone. The tumors were mostly squamous cell carcinomas, and those occurring in mice given UVR plus arsenite appeared earlier and were much larger and more invasive than in mice given UVR alone. These results are consistent with the hypothesis that arsenic acts as a cocarcinogen with a second (genotoxic) agent by inhibiting DNA repair and/or enhancing positive growth signaling.
Simultaneous magnetic and chemical order-disorder phenomena in Fe3Ni, FeNi, and FeNi3.

We study the magnetic and chemical order-disorder transitions in face-centered-cubic ${\mathrm{FeNi}}_{3}$, FeNi, and ${\mathrm{Fe}}_{3}$Ni, by Monte Carlo (MC) simulations using the Ising approximation. The calculations are done: (1) with magnetic interactions only, assuming fixed preset degrees of chemical order, (2) with chemical interactions only, and (3) with both magnetic and chemical interactions acting simultaneously. As expected and known from measurements, the degree of chemical order is found to have a large influence on the magnetic transitions. On the other hand, although one might expect the effects of magnetism on the chemical ordering processes to be small (because the chemical bond energies are much larger than the magnetic exchange bond energies), one finds that the latter effects are also large. Several new features arise that are not predicted by mean-field theory or MC simulations with chemical interactions only. For example: (1) chemical order can be induced where using chemical interactions only leads to the prediction of no chemical order, (2) chemical segregation can be induced where using chemical interactions only leads to the prediction of no chemical segregation, (3) ${\mathrm{FeNi}}_{3}$ and ${\mathrm{Fe}}_{3}$Ni are found to have significantly different chemical ordering temperatures where chemical interactions only lead to equal ordering temperatures, (4) chemical ordering temperatures are significantly shifted from their chemical interactions only values, even when the chemical ordering temperature is larger than the magnetic ordering temperature (or Curie point), (5) abrupt steps can occur in the spontaneous magnetization at the chemical ordering temperature, when the latter is smaller than the magnetic ordering temperature, and (6) nonlinear relations arise between the chemical ordering temperature and the usual differential bonding parameter U\ensuremath{\equiv}2${\mathit{U}}_{\mathrm{FeNi}}$-${\mathit{U}}_{\mathrm{FeFe}}$-${\mathit{U}}_{\mathrm{NiNi}}$, where the ${\mathit{U}}_{\mathit{ij}}$'s are the near-neighbor pair-wise chemical bonds. \textcopyright{} 1996 The American Physical Society.
Neurotransmitter receptor and time dependence of the synaptic plasticity disrupting actions of Alzheimer's disease Aβ in vivo

Many endogenous factors influence the time course and extent of the detrimental effects of amyloid β-protein (Aβ) on synaptic function. Here, we assessed the impact of varying endogenous glutamatergic and cholinergic transmission by pharmacological means on the disruption of plasticity at hippocampal CA3-to-CA1 synapses in the anaesthetized rat. NMDA receptors (NMDARs) are considered critical in mediating Aβ-induced inhibition of long-term potentiation (LTP). However, intracerebroventricular injection of Aβ1–42 inhibited not only NMDAR-dependent LTP but also voltage-activated Ca2+-dependent LTP induced by strong conditioning stimulation during NMDAR blockade. On the other hand, another form of NMDAR-independent synaptic plasticity, endogenous acetylcholine-induced muscarinic receptor-dependent long-term enhancement, was not hindered by Aβ1–42. Interestingly, augmenting endogenous acetylcholine activation of nicotinic receptors prior to the injection of Aβ1–42 prevented the inhibition of NMDAR-dependent LTP, whereas the same intervention when introduced after the infusion of Aβ was ineffective. We also examined the duration of action of Aβ, including water soluble Aβ from Alzheimer's disease (AD) brain. Remarkably, the inhibition of LTP induction caused by a single injection of sodium dodecyl sulfate-stable Aβ dimer-containing AD brain extract persisted for at least a week. These findings highlight the need to increase our understanding of non-NMDAR mechanisms and of developing novel means of overcoming, rather than just preventing, the deleterious synaptic actions of Aβ.
GreenMeter: a tool for assessing the quality and recommending tags for web 2.0 applications

We present GreenMeter, a tool for assessing the quality and recommending tags for Web 2.0 content. Its goal is to improve tag quality and the effectiveness of various information services (e.g., search, content recommendation) that rely on tags as data sources. We demonstrate an implementation of GreenMeter for the popular Last.fm application.
General practice encounters for young patients with autism spectrum disorder in Australia

This study compared the patient demographics and reasons for encounter in general practice for patients <25 years with and without an autism spectrum disorder identified as a reason for encounter and/or problem managed. The Bettering the Evaluation and Care of Health programme collected information about clinical activities in Australian general practice. Each year, the programme recruited a random sample of 1000 general practitioners, each of whom collected data for 100 consecutive consultations (encounters). Encounters with patients <25 years, where at least one autism spectrum disorder was recorded as a reason for encounter and/or a problem managed (n = 579), were compared with all other encounters (n = 281,473) from April 2000 to March 2014 inclusive. Data were age–sex standardised. Patients at autism spectrum disorder encounters (compared to non-autism spectrum disorder encounters) were more likely to be younger and male. There was a dramatic rise in the number of general practitioner consultations at autism spectrum disorder encounters from 2000 to 2013. More reasons for encounter were recorded at autism spectrum disorder encounters than at non-autism spectrum disorder encounters (156.4 (95% confidence interval: 144.0–168.8) and 140.5 (95% confidence interval: 140.0–141.0), respectively). At autism spectrum disorder (vs non-autism spectrum disorder) encounters, there were more psychological, general and unspecified, and social reasons for encounter and fewer preventive and acute health reasons for encounter. People with an autism spectrum disorder have complex health care needs that require a skilled general practice workforce.
Quantification of clusterin in paired cerebrospinal fluid and plasma samples

Background Clusterin (ApoJ) is an amyloid-associated protein and plays an important role in Alzheimer’s disease (AD) pathology. Recent genome-wide association studies have indicated that certain genetic variants increase the risk of developing AD. To determine if the expression of clusterin is different in AD patients, both systemically and locally in the brain, differs between (subgroups of) AD patients and non-AD cases, an assay available that detects clusterin in both plasma and cerebrospinal fluid (CSF) with equal sensitivity would be helpful. Methods We compared four different commercially available antibodies in their ability to detect recombinant clusterin and immune-purified human clusterin. Specificity was tested on western blot and in ELISA systems, and selection was based on the ability to detect clusterin in CSF and plasma. A sandwich ELISA was developed and validated with monoclonal antibody G7 as capture, and rabbit polyclonal (Alexis) antibodies for detection. Results Our ELISA measured clusterin concentrations in plasma and CSF with dynamic ranges of 2–70 mg/L and 0.5–40 mg/L, respectively. The assays showed 99.8% recovery in CSF and 97% recovery in plasma. Intra-assay coefficient of variation was 1.4% and inter-assay 8.8%. The assay shows no cross-reactivity with related apolipoproteins. Clusterin quantification is dependent on the type of storage for plasma samples. A single freeze/thaw cycle caused fluctuations of clusterin concentrations in plasma, while clusterin in CSF is stable for up to five cycles. Conclusions We have successfully developed a clusterin ELISA that reliably measures CSF and plasma clusterin concentrations. In a pilot study, all samples gave results that were well within the dynamic range of the assay, with low variations. Freshly stored plasma samples are crucial for accurate clusterin quantification.
Effect of protein A on staphylococcal opsonization

To study the effect of wall protein A on bacterial opsonization, phagocytosis of 10 strains of Staphylococcus aureus with high and low protein A contents was measured. Those strains that contained the highest concentrations of protein A were phagocytized by human neutrophils at a slower rate than strains with little or no protein A when normal human serum and purified immunoglobulin G (IgG) were used as opsonic sources. When IgG-deficient serum was used as an source, however, protein A-rich strains were phagocytized more rapidly than protein A-deficient strains. Extracellular (purified) protein A decrease the opsonic activity of all sera tested including IgG-deficient serum. It is proposed that when IgG is not present in the opsonic medium, cell wall protein A is capable of activating complement at the bacterial surface and thereby opsonization is promoted.