Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanoenergetics of the Negative Inotropism of Isoflurane in the Canine Left Ventricle: No O2 Wasting Effect

Background: The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross‐circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure‐volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2). Methods: Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane. Results: Emax, PVA, and VO2 dose‐dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05). Conclusions: These mechanoenergetic findings suggest that the primary method by which isoflurane decreases contractility is not by decreasing Ca sup 2+ sensitivity of contractile proteins but mainly by decreasing Ca2+ handling in the excitation‐contraction coupling without myocardial oxygen wasting effect.
Multivariate Analysis of Rehabilitation Services Needs of People with Disability at Zhabei District in Shanghai

Objective To provide the advice on how to optimize the allocation of resources and make other policy through the analysis factors affecting rehabilitation services needs of people with disability at Zhabei district in Shanghai.MethodsThe factors affecting rehabilitation services needs such as types of disability,disability levels,education,employment,marital status,age and sex were analyzed with Logistic analysis.ResultsThe factors affecting primary rehabilitation services were types of disability,education,employment situation,marital status and sex.And people with disability had the characters of female,hearing disability,retired returned to more primary rehabilitation services,with OR values being 1.219,1.544 and 1.533 respectively compared with itself controls.And the high educational disable people' will,returning to primary rehabilitation services,was weaker compared with low educational disable people.The factors affecting special rehabilitation services were types of disability and employment situation.And people with disability had the characters of hearing disability,unemployment returned to more special rehabilitation services,with OR values being 2.380 and 1.310 respectively compared with itself controls.ConclusionThe rehabilitation needs are different among different groups people with disability,so the factors affecting rehabilitation services needs such as types of disability,education,employment situation,marital status and sex should be taken into consideration while activating primary rehabilitation services,while the types of disability and employment situation should be taken into more consideration while activating special rehabilitation services.
Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers

Currently, there is no single test for multiple sclerosis (MS). Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI), and analysis of cerebrospinal fluid (CSF) chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation.
PTF10ops – a subluminous, normal-width light curve Type Ia supernova in the middle of nowhere

PTF10ops is a Type Ia supernova (SN Ia), whose light curve and spectral properties place it outside the current SN Ia subtype classifications. Its spectra display the characteristic lines of subluminous SNe Ia, but it has a normal-width light curve with a long rise time, typical of normal-luminosity SNe Ia. The early-time optical spectra of PTF10ops were modelled using a spectral fitting code and found to have all the lines typically seen in subluminous SNe Ia, without the need to invoke more uncommon elements. The host galaxy environment of PTF10ops is also unusual with no galaxy detected at the position of the SN down to an absolute limiting magnitude of r≥−12.0 mag, but a very massive galaxy is present at a separation of ∼148 kpc and at the same redshift as suggested by the SN spectral features. The progenitor of PTF10ops is most likely a very old star, possibly in a low-metallicity environment, which affects its explosion mechanism and observational characteristics. PTF10ops does not easily fit into any of the current models of either subluminous or normal SN Ia progenitor channels.
A Deep Bag-of-Features Model for Music Auto-Tagging

Feature learning and deep learning have drawn great attention in recent years as a way of transforming input data into more effective representations using learning algorithms. Such interest has grown in the area of music information retrieval (MIR) as well, particularly in music audio classification tasks such as auto-tagging. In this paper, we present a two-stage learning model to effectively predict multiple labels from music audio. The first stage learns to project local spectral patterns of an audio track onto a high-dimensional sparse space in an unsupervised manner and summarizes the audio track as a bag-of-features. The second stage successively performs the unsupervised learning on the bag-of-features in a layer-by-layer manner to initialize a deep neural network and finally fine-tunes it with the tag labels. Through the experiment, we rigorously examine training choices and tuning parameters, and show that the model achieves high performance on Magnatagatune, a popularly used dataset in music auto-tagging.
On the implementation of minimum-redundancy prefix codes

Minimum-redundancy coding (also known as Huffman (1952) coding) is one of the enduring techniques of data compression. We examine how best minimum-redundancy coding can be implemented, with particular emphasis on the situation when n is large, perhaps of the order of 10/sup 6/. We review techniques for devising minimum-redundancy codes, and consider in detail how encoding and decoding should be accomplished. In particular, we describe a modified decoding method that allows improved decoding throughput, requiring just a few machine operations per output symbol (rather than for each decoded bit), and uses just a few hundred bytes of memory above and beyond the space required to store an enumeration of the source alphabet. We review methods for calculating codeword lengths, show how those codeword lengths should be used to derive a minimum-redundancy code that has the alphabetic sequence property, and describes a memory-compact method for decoding such canonical codes. An improved method for decoding canonical codes is also presented.
Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus

ABSTRACT Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV; Poxviridae). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV-like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC/CTGV-like viruses, and Dryvax strain. IMPORTANCE First-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV. Therefore, the search for new-generation smallpox vaccines that combine low pathogenicity, immune protection, and genetic homogeneity is extremely important. In addition, the phylogenetic relationships and origins of VACV strains are quite nebulous. We show the characterization of two clones of VACV-IOC, a unique smallpox vaccine strain that contributed to smallpox eradication in Brazil. The immunogenicity and reduced virulence make the IOC clones good options for alternative second-generation smallpox vaccines. More importantly, this study reveals the phylogenetic relationship between VACV-IOC, feral VACV established in nature, and the ancestor-like horsepox virus. Our data expand the discussion on the origins and evolutionary connections of VACV lineages.
Peripheral neuropathy in colorectal cancer survivors: The influence of oxaliplatin administration. Results from the population-based PROFILES registry

Abstract Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of oxaliplatin which can negatively influence quality of life. We aimed to study the influence of cumulative dose, dose schedule and dose reductions of adjuvant oxaliplatin on long-term severity and prevalence of CIPN among colorectal cancer (CRC) survivors. Material and methods. In total 207 patients, diagnosed with CRC between 2000 and 2009 who underwent adjuvant treatment with oxaliplatin, were included. They completed the EORTC QLQ-CIPN20 2–11 years after diagnosis. Data on oxaliplatin administration and acute neuropathy during treatment were extracted from the medical files. Subscales were analyzed with analysis of covariance and neuropathy symptoms with logistic regression analysis. Results. Patients who received cumulative oxaliplatin dose of ≥ 842 mg/m2 had a significantly worse EORTC QLQ-CIPN20 sensory score compared to those who received a low cumulative dose of < 421 mg/m2 (mean 19 vs. 8; p = 0.02). They more often reported tingling toes/feet (13% vs. 2%, respectively; p = 0.01). Dose intensity and time delay did not influence the occurrence of CIPN. Patients receiving a dose reduction because of neuropathy (N = 50) reported a significantly worse sensory score at very similar cumulative doses, than those who did not receive a dose reduction because of neuropathy (N = 96) (mean 21 vs. 15; p = 0.01). Conclusion. Cumulative dose of oxaliplatin is associated with long-term CIPN. The risk of developing long-term CIPN could only be reduced by decreasing the cumulative dose, whereas delay probably is not beneficial. Patients receiving a dose reduction because of acute neuropathy are still at risk of developing long-term CIPN. Future studies should focus on identifying patients who are at risk of developing CIPN.
Structural Features of the Glutamate Binding Site in Recombinant NR1/NR2A N-Methyl-d-aspartate Receptors Determined by Site-Directed Mutagenesis and Molecular Modeling

We have used site-directed mutagenesis of amino acids located within the S1 and S2 ligand binding domains of the NR2A N-methyl-d-aspartate (NMDA) receptor subunit to explore the nature of ligand binding. Wild-type or mutated NR1/NR2A NMDA receptors were expressed in Xenopus laevis oocytes and studied using two electrode voltage clamp. We investigated the effects of mutations in the S1 and S2 regions on the potencies of the agonists l-glutamate, l-aspartate, (R,S)-tetrazol-5yl-glycine, and NMDA. Mutation of each of the corresponding residues found in the NR2A receptor subunit, suggested to be contact residues in the GluR2 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit, caused a rightward shift in the concentration-response curve for each agonist examined. None of the mutations examined altered the efficacy of glutamate as assessed by methanethiosulfonate ethylammonium potentiation of agonist-evoked currents. In addition, none of the mutations altered the potency of glycine. Homology modeling and molecular dynamics were used to evaluate molecular details of ligand binding of both wild-type and mutant receptors, as well as to explore potential explanations for agonist selectivity between glutamate receptor subtypes. The modeling studies support our interpretation of the mutagenesis data and indicate a similar binding strategy for l-glutamate and NMDA when they occupy the binding site in NMDA receptors, as has been proposed for glutamate binding to the GluR2 AMPA receptor subunit. Furthermore, we offer an explanation as to why “charge conserving” mutations of two residues in the binding pocket result in nonfunctional receptor channels and suggest a contributing molecular determinant for why NMDA is not an agonist at AMPA receptors.
Classification and filtering of laser data

A strategy for the classification of raw LIDAR data as terrain, buildings and vegetation is presented. Its main features are a preliminary classification of grid data based on a geometric and topological description and a final filtering of raw data, guided by the previous classification. After raw data have been interpolated to a grid and segmented in connected regions bordered by a step edge, the topology of these regions is built up. Noise, vegetation and data gaps are classified first, mainly based on size and region fragmentation. Then, regions enclosing terrain and building points are labelled analysing their relationships with adjacent regions. Since regions may enclose more than one instance of different classes, a first check is made on grid data looking for consistency of gradient orientation with class characteristics. Finally, a local analysis is performed on each grid cell to label raw data point, based on the information on the surroundings inferred by the classification. Results obtained with Toposys and Optech systems on datasets with different ground point density gathered over the town of Pavia are shown to illustrate the effectiveness of the procedure.
Plasma proANP and SDMA and microRNAs are associated with chronic mitral regurgitation in a pig model

Objective Non-ischemic mitral regurgitation (MR) is primarily caused by myxomatous mitral valve (MV) disease leading to adaptive remodeling, enlargement, and dysfunction of the left ventricle. The aim of this study was to examine the regulation of plasma markers and several cardiac key genes in a novel porcine model of non-ischemic MR. Methods and results Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20–50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR ≤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (P<0.05). The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05). Conclusions Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model.
Intrinsic Adaptation in Autonomous Recurrent Neural Networks

Abstract A massively recurrent neural network responds on one side to input stimuli and is autonomously active, on the other side, in the absence of sensory inputs. Stimuli and information processing depend crucially on the qualia of the autonomous-state dynamics of the ongoing neural activity. This default neural activity may be dynamically structured in time and space, showing regular, synchronized, bursting, or chaotic activity patterns. We study the influence of nonsynaptic plasticity on the default dynamical state of recurrent neural networks. The nonsynaptic adaption considered acts on intrinsic neural parameters, such as the threshold and the gain, and is driven by the optimization of the information entropy. We observe, in the presence of the intrinsic adaptation processes, three distinct and globally attracting dynamical regimes: a regular synchronized, an overall chaotic, and an intermittent bursting regime. The intermittent bursting regime is characterized by intervals of regular flows, which are quite insensitive to external stimuli, interceded by chaotic bursts that respond sensitively to input signals. We discuss these findings in the context of self-organized information processing and critical brain dynamics.
Genetic modifications of pigs for medicine and agriculture

Genetically modified swine hold great promise in the fields of agriculture and medicine. Currently, these swine are being used to optimize production of quality meat, to improve our understanding of the biology of disease resistance, and to reduced waste. In the field of biomedicine, swine are anatomically and physiologically analogous to humans. Alterations of key swine genes in disease pathways provide model animals to improve our understanding of the causes and potential treatments of many human genetic disorders. The completed sequencing of the swine genome will significantly enhance the specificity of genetic modifications, and allow for more accurate representations of human disease based on syntenic genes between the two species. Improvements in both methods of gene alteration and efficiency of model animal production are key to enabling routine use of these swine models in medicine and agriculture. Mol. Reprod. Dev. 78:879–891, 2011. © 2011 Wiley Periodicals, Inc.
Structure of the human 26S proteasome at a resolution of 3.9 Å

Significance The 26S proteasome is a giant protease assembled from at least 32 different canonical subunits. In eukaryotic cells it is responsible for the regulated degradation of proteins marked for destruction by polyubiquitin tags. Mainly because of the conformational heterogeneity of the 26S holocomplex, its structure determination has been challenging. Using cryo-electron microscopy single-particle analysis we were able to obtain a high-resolution structure of the human 26S proteasome allowing us to put forward an essentially complete atomic model. This model provides insights into the proteasome’s mechanism of operation and could serve as a basis for structure-based drug discovery. Protein degradation in eukaryotic cells is performed by the Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex consists of a core particle (CP) that proteolytically degrades polyubiquitylated proteins, and a regulatory particle (RP) containing the AAA-ATPase module. This module controls access to the proteolytic chamber inside the CP and is surrounded by non-ATPase subunits (Rpns) that recognize substrates and deubiquitylate them before unfolding and degradation. The architecture of the 26S holocomplex is highly conserved between yeast and humans. The structure of the human 26S holocomplex described here reveals previously unidentified features of the AAA-ATPase heterohexamer. One subunit, Rpt6, has ADP bound, whereas the other five have ATP in their binding pockets. Rpt6 is structurally distinct from the other five Rpt subunits, most notably in its pore loop region. For Rpns, the map reveals two main, previously undetected, features: the C terminus of Rpn3 protrudes into the mouth of the ATPase ring; and Rpn1 and Rpn2, the largest proteasome subunits, are linked by an extended connection. The structural features of the 26S proteasome observed in this study are likely to be important for coordinating the proteasomal subunits during substrate processing.
Comparison of the effects of propofol and pentobarbital on hydrogen peroxide-stimulated hepatic SNU761 cells

Background Propofol and barbiturates are both known to protect cells of several organs against ischemia/reperfusion injury, but there are few reports on any possible protective effects on human hepatocytes. We investigated the activities of both agents on human hepatic SNU761 cells under hydrogen peroxide (H2O2)-induced oxidative stress. Methods To determine whether propofol and pentobarbital protect hepatocytes from H2O2-induced toxicity, we used SNU761 cells, a human hepatocellular carcinoma (HCC) cell line. Cells were pretreated with different dosages (1, 10, 50 µM) of propofol or pentobarbital (1, 10, 50, 100, 400 µM) 30 min before H2O2 application. Lactate dehydrogenase (LDH) was measured to assess and quantify cell death. To determine the nature of cell death, treated hepatocytes were doubly stained with fluorescein isothiocyanate (FITC)-labeled Annexin V and propidium iodide (PI), and analyzed by flow cytometry. Results Pretreatment with propofol, but not pentobarbital, suppressed H2O2-induced LDH release. In Annexin V-FITC/PI binding analysis, propofol decreased the number of necrotic and late apoptotic cells, but no significant decreases in such cell numbers were seen when pentobarbital was used. Conclusions Unlike pentobarbital, propofol, at clinical concentrations, protected SNU-761 HCC cells against oxidative stress.