Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Modeling Method of Electro-Thermo-Mechanical Degradation in IGBT Modules

A degradation model investigating the electro-thermo-mechanical fatigue, experienced by insulated gate bipolar transistors modules, is presented. To illustrate the concept, a specific case of power modules subjected to active power cycling which induce failure through bond wire lift-off is considered. Bond wire lift-off is believed to be due to thermally induced stress arising from a mismatch in the coefficients of thermal expansion between the wires and the given substrate. Overall, the theoretical evaluation is based on determining the thermo-mechanical stress around the bond wire/substrate interface through multiphysics-based models. The simulation detail and included equations are specified according to the region of interest and their complexity. In common, however, is the use of the finite element method combined with empirical equations. The final result is a numerical approach to evaluate the damage accumulated by a given load which may be used for prediction of lifetime or optimization of work points and module geometry.
Profiling glycoprotein N‐linked oligosaccharide by capillary electrophoresis

A method for analysis of N‐linked oligosaccharides derived from glycoproteins including sialic acid‐containing species is presented. It is based on the combination of specific chemical and enzymatic conversions coupled with capillary electrophoretic (CE) separation and laser‐induced fluorescence (LIF) detection. Glycoproteins were heat‐denatured in the presence of a reducing agent and the N‐linked oligosaccharides were released by peptide N‐glycosidase (PNGase F; EC3.5.1.52)‐catalyzed hydrolysis. The released N‐linked oligosaccharides were derivatized with 8‐aminopyrene‐1,3,6‐trisulfonate (APTS) under mild reductive amination conditions in which desialylation and loss of fucose residues are minimized. A model N‐linked oligosaccharide, desialylated, galactosylated biantennary, core‐substituted with fucose (A2F) was tested for APTS‐based derivatization chemistry with excellent recovery of the adduct without losing fucose and neuraminic acid residues. The profiles of heavily sialylated N‐linked oligosaccharides derived from fetuin, recombinant human erythropoietin and kallikrein are reported and the data show that the present method produces a high resoluton of the N‐linked oligosaccharide profile for fingerprinting glycans derived from glycoproteins.
Information-based dichotomization: A method for multiclass Support Vector Machines

Approaches for solving a multiclass classification problem by support vector machines (SVMs) are typically to consider the problem as combination of two-class classification problems. Previous approaches have some limitations in classification accuracy and evaluation time. This paper proposes a novel method that employs information-based dichotomization for constructing a binary classification tree. Each node of the tree is a binary SVM with the minimum entropy. Our method can reduce the number of binary SVMs used in the classification to the logarithm of the number of classes which is lower than previous methods. The experimental results show that the proposed method takes lower evaluation time while it maintains accuracy compared to other methods.
Prediction of transition to psychosis in patients with a clinical high risk for psychosis: a systematic review of methodology and reporting

Background To enhance indicated prevention in patients with a clinical high risk (CHR) for psychosis, recent research efforts have been increasingly directed towards estimating the risk of developing psychosis on an individual level using multivariable clinical prediction models. The aim of this study was to systematically review the methodological quality and reporting of studies developing or validating such models. Method A systematic literature search was carried out (up to 14 March 2016) to find all studies that developed or validated a clinical prediction model predicting the transition to psychosis in CHR patients. Data were extracted using a comprehensive item list which was based on current methodological recommendations. Results A total of 91 studies met the inclusion criteria. None of the retrieved studies performed a true external validation of an existing model. Only three studies (3.5%) had an event per variable ratio of at least 10, which is the recommended minimum to avoid overfitting. Internal validation was performed in only 14 studies (15%) and seven of these used biased internal validation strategies. Other frequently observed modeling approaches not recommended by methodologists included univariable screening of candidate predictors, stepwise variable selection, categorization of continuous variables, and poor handling and reporting of missing data. Conclusions Our systematic review revealed that poor methods and reporting are widespread in prediction of psychosis research. Since most studies relied on small sample sizes, did not perform internal or external cross-validation, and used poor model development strategies, most published models are probably overfitted and their reported predictive accuracy is likely to be overoptimistic.
Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes.

AIM To study the effects of tumor necrosis factor-alpha (TNF-alpha) on calcium movement in rat ventricular myocytes. METHODS Intracellular free Ca2+ concentration was measured with calcium fluorescent probe Fluo-3/AM and laser confocal microscope. L-type calcium current (ICa,L) was recorded with the whole-cell configuration of the patch-clamp techniques. RESULTS At 2, 20 and 200 microg/L, TNF-alpha was found to increase intracellular free Ca2+ concentration in a dose-dependent manner illustrated by the increment of calcium fluorescence density with laser confocal microscope. Nicardipine 0.5 micromol/L slightly attenuated TNF-alpha-induced response. When the cardiac myocytes were exposed to caffeine (100 mmol/L) for 30 min, TNF-alpha failed to induce any change of intracellular free calcium. However, it was found that TNF-alpha inhibited I(Ca,L) in whole-cell patch-clamp experiments. At 2, 20, and 200 microg/L, TNF-alpha decreased peak I(Ca,L) by 3.9 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.9 pA/pF+/-0.2 pA/pF, n=9, P>0.05), 15.7 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.3 pA/pF+/-0.3 pA/pF, n=9, P<0.05) and 19.6 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.1 pA/pF+/-0.4 pA/pF, n=9, P<0.01), respectively. It shifted the steady-state inactivation curve of I(Ca,L) to the left (V1/2 shifted from -28.7 mV+/-0.3 mV to -37.8 mV+/-1.4 mV, n=7, P<0.05), while it took no effects on steady-state activation and recovery from inactivation. CONCLUSION TNF-alpha inhibited I(Ca,L) in rat ventricular myocytes, while increasing the intercellular free Ca2+ level due to the release of Ca2+ from intracellular stores.
Assessment of Morbidity Over Time in Predicting Health Outcomes

Background:Administratively derived morbidity measures are often used in observational studies as predictors of outcomes. These typically reflect a limited time period before an index event; some outcomes may be affected by rate of morbidity change over longer preindex periods. Objectives:The aim of the study was to develop statistical models representing the trajectory of individual morbidity over time and to evaluate the performance of trajectory versus other summary morbidity measures in predicting a range of health outcomes. Methods:From a retrospective cohort study of integrated health system members aged 65 years or older with 3 or more common chronic medical conditions, we used available diagnoses for up to 10 years to examine associations between variations of the Charlson Comorbidity Index (CCI, Quan adaptation) and health outcomes. A linear mixed effects model was used to estimate the trajectory of individual CCI over time; estimated parameters describing individual trajectories were used as predictors for health outcomes. Other variations of CCI were: a “snapshot” measure, a cumulative measure, and actual baseline and rate of change. Models were developed in an initial cohort for whom we had survey data, and verified in a larger cohort. Results:Among 961 surveyed members and 13,163 members of a secondary cohort, cumulative and snapshot measures provided best fit and predictive ability for utilization outcomes. Incorporating trajectory resulted in a slightly better model for self-reported health status. Conclusions:Modeling longitudinal morbidity trajectories did not add substantially to the association between morbidity and utilization or mortality. Standard snapshot morbidity measures likely sufficiently capture multimorbidity in assessing these outcomes.
Logical modelling and analysis of cellular regulatory networks with GINsim 3.0

The logical formalism is well adapted to model large cellular networks, for which detailed kinetic data are scarce. This tutorial focuses on this well-established qualitative framework. Relying on GINsim (release 3.0), a software implementing this formalism, we guide the reader step by step towards the definition, the analysis and the simulation of a four-node model of the mammalian p53-Mdm2 network.
Testing for qualitative heterogeneity: An application to composite endpoints in survival analysis

Composite endpoints are frequently used in clinical outcome trials to provide more endpoints, thereby increasing statistical power. A key requirement for a composite endpoint to be meaningful is the absence of the so-called qualitative heterogeneity to ensure a valid overall interpretation of any treatment effect identified. Qualitative heterogeneity occurs when individual components of a composite endpoint exhibit differences in the direction of a treatment effect. In this paper, we develop a general statistical method to test for qualitative heterogeneity, that is to test whether a given set of parameters share the same sign. This method is based on the intersection–union principle and, provided that the sample size is large, is valid whatever the model used for parameters estimation. We propose two versions of our testing procedure, one based on a random sampling from a Gaussian distribution and another version based on bootstrapping. Our work covers both the case of completely observed data and the case where some observations are censored which is an important issue in many clinical trials. We evaluated the size and power of our proposed tests by carrying out some extensive Monte Carlo simulations in the case of multivariate time to event data. The simulations were designed under a variety of conditions on dimensionality, censoring rate, sample size and correlation structure. Our testing procedure showed very good performances in terms of statistical power and type I error. The proposed test was applied to a data set from a single-center, randomized, double-blind controlled trial in the area of Alzheimer’s disease.
Positive fragile X microsatellite associations point to a common mechanism of dynamic mutation evolution.

We recently reported that the size of fragile X gene (FMR1) triplet repeats and two nearby microsatellites show positive allele-size associations. The larger alleles of microsatellite DXS548, located {approximately}150 kb proximal to the FMR1 CGG repeat, and of FRAXAC1 (AC1), located 7 kb proximal to the FMR1 CGG repeat, tend to occur together, and smaller alleles also tend to occur together. Also, fragile X chromosomes are more commonly found on the larger combined microsatellite-allele haplotypes. We now have extended these observations to include two other nearby repeats, FRAXAC2 (AC2), a complex three-part polymorphism located 12 kb distal, and the FRAXE triplet repeat, located 600 kb distal. We divided the chromosomes into controls with FMR1 repeats of =}60, since FMR1 alleles with repeats {>=}60 show high intergenerational instability. In the 133 controls, previously analyzed for AGG interspersions, and in 119 fragile X chromosomes, we found that these repeats show nonrandom size associations. To describe this numerically, we calculated correlation coefficients for the repeat lengths. These repeats showed significantly positive correlations with each other. Although FRAXE alleles showed no correlation with the control repeats, they did have positive correlations with fragile X chromosome microsatellites (AC1more » and AC2 but not DXS548), which may reflect the larger recombinational distances involved and the possibly more recent origin of the fragile X mutations. The correlations tended to be higher for the number of 3{prime} pure CGGs than for total FMR1 repeats in controls. These findings strengthen our hypothesis that there may be a common underlying mutational mechanism that simultaneously affects these repeat loci. 13 refs., 1 tab. « less
Complete Genome of the Cellulolytic Ruminal Bacterium Ruminococcus albus 7

ABSTRACT Ruminococcus albus 7 is a highly cellulolytic ruminal bacterium that is a member of the phylum Firmicutes. Here, we describe the complete genome of this microbe. This genome will be useful for rumen microbiology and cellulosome biology and in biofuel production, as one of its major fermentation products is ethanol.
Proteolytic Cleavage of Ataxin-7 by Caspase-7 Modulates Cellular Toxicity and Transcriptional Dysregulation*

Spinocerebellar ataxia type 7 (SCA7) is a polyglutamine (polyQ) disorder characterized by specific degeneration of cerebellar, brainstem, and retinal neurons. Although they share little sequence homology, proteins implicated in polyQ disorders have common properties beyond their characteristic polyQ tract. These include the production of proteolytic fragments, nuclear accumulation, and processing by caspases. Here we report that ataxin-7 is cleaved by caspase-7, and we map two putative caspase-7 cleavage sites to Asp residues at positions 266 and 344 of the ataxin-7 protein. Site-directed mutagenesis of these two caspase-7 cleavage sites in the polyQ-expanded form of ataxin-7 produces an ataxin-7 D266N/D344N protein that is resistant to caspase cleavage. Although ataxin-7 displays toxicity, forms nuclear aggregates, and represses transcription in human embryonic kidney 293T cells in a polyQ length-dependent manner, expression of the non-cleavable D266N/D344N form of polyQ-expanded ataxin-7 attenuated cell death, aggregate formation, and transcriptional interference. Expression of the caspase-7 truncation product of ataxin-7-69Q or -92Q, which removes the putative nuclear export signal and nuclear localization signals of ataxin-7, showed increased cellular toxicity. We also detected N-terminal polyQ-expanded ataxin-7 cleavage products in SCA7 transgenic mice similar in size to those generated by caspase-7 cleavage. In a SCA7 transgenic mouse model, recruitment of caspase-7 into the nucleus by polyQ-expanded ataxin-7 correlated with its activation. Our results, thus, suggest that proteolytic processing of ataxin-7 by caspase-7 may contribute to SCA7 disease pathogenesis.
Tat acetylation modulates assembly of a viral-host RNA–protein transcription complex

HIV-1 Tat enhances viral transcription elongation by forming a ribonucleoprotein complex with transactivating responsive (TAR) RNA and P-TEFb, an elongation factor composed of cyclin T1 (CycT1) and Cdk9 that phosphorylates the C-terminal domain of RNA polymerase II. Previous studies have shown that Lys-28 in the activation domain (AD) of Tat is essential for HIV-1 transcription and replication and is acetylated by p300/CBP-associated factor (PCAF), but the mechanistic basis of the Lys-28 requirement is unknown. Here, we show that Lys-28 acetylation modulates the affinity and stability of HIV-1 Tat–CycT1–TAR complexes by enhancing an interaction with the CycT1 Tat–TAR recognition motif. High-affinity assembly correlates strongly with stimulation of transcription elongation in vitro and Tat activation in vivo. In marked contrast, bovine lentiviral Tat proteins have evolved a high-affinity TAR interaction that does not require PCAF-mediated acetylation of the Tat AD or CycT1 for RNA binding, whereas HIV-2 Tat has evolved an intermediate mechanism that uses a duplicated TAR element and CycT1 to enhance RNA affinity and consequently transcription activation. The coevolution of Tat acetylation, CycT1 dependence, and TAR binding affinity is seen in viral replication assays using Tat proteins that rely on CycT1 for TAR binding but are acetylation deficient, where compensatory mutations rapidly accrue in TAR to generate high-affinity, CycT1-independent complexes reminiscent of the bovine viruses. Thus, lysine acetylation can be used to modulate and evolve the strength of a viral-host RNA–protein complex, thereby tuning the levels of transcription elongation.
A new algorithm for controlling building evacuation by feedback on hazard level and crowd distribution

This paper proposes an integrated macroscopic approach for controlling crowd evacuation from buildings. An efficient planning is always based on the knowledge of all variables characterizing the hazard and people motion, as described by the dynamic severity matrix. The possibility to use a feedback from the real scenario would be of enormous utility for the evacuation strategy, but still associated with a high computational load, as stated in the literature. This paper introduces a new algorithm, which uses online the entire severity matrix. A feedback from the system is also provided to simultaneously achieve a number of objectives, which are usually treated separately: to evacuate the maximum number of people and to do it in the shortest time by online updating the more suitable escape routes. To this aim, a route will be more or less suitable based on the crowd and the hazard levels. Simulation performed on randomly generated data showed the effectiveness of the new proposed approach.
Cell based clustering scheme considering dynamic network topology in wireless sensor networks

A routing protocol is one of key technical issues for wireless sensor networks (WSN), and various protocols have been proposed. Some protocols use cell based clustering; however, few of them can be applied to the dynamic network topology. In this paper, we refine HGAF (Hierarchical Geographical Adaptive Fidelity), which has been proposed for the static network topology, and apply it to the dynamic one. When HGAF is applied to the sensor network which consists of mobile nodes, there is the problem that some cluster heads go out of their staying cell and no cluster head exists in a cell. Our proposed scheme selects the node with the longest staying period in a cell as the cluster head in the cell. Furthermore, this scheme dynamically changes the cell in which the cluster head node is selected. By computer simulations, we show the effectiveness of the proposed scheme with respect to the packet delivery ratio.
Cardiac Na+ ‐Ca2+ Exchange System in Giant Membrane Patches

This article presents an overview of recent work on cardiac Na-Ca exchange in giant, excised membrane patches. ' The need to develop this experimental model became pressing in the period of 1985-87. On the one hand, many properties of Na-Ca exchange currents in cardiac m y ~ c y t e s ~ . ~ were consistent with previous data from cardiac vesicles (for review, see Reeves & Philipson3 and converged neatly with data from intact t i~sue .~ Current densities of the inward exchange current, for example, fit remarkably well with rates of sodium-dependent calcium efflux measured during the late action potential.6 On the other hand, many questions about the catalytic cycle of the exchanger remained unanswered and new enigmas emerged (for overview, see Hilgemann'). The exchanger in intact cells appeared to be regulated secondarily by cytoplasmic calcium and ATP,* similar to the squid axon system. Ion dependencies of the exchanger in intact cells appeared to be asymmetrical (Kimura et al. 3; more recently, Li & Kimura9), similar to the axon exchanger and in contrast to conclusions from cardiac vesicle studies. Although internal perfusion of cardiac myocytes'O represented a great improvement over previous electrophysiological myocyte techniques, control of the cytoplasmic environment remained inadequate for many purposes.
Social networks and the spread of Salmonella in a sleepy lizard population

Although theoretical models consider social networks as pathways for disease transmission, strong empirical support, particularly for indirectly transmitted parasites, is lacking for many wildlife populations. We found multiple genetic strains of the enteric bacterium Salmonella enterica within a population of Australian sleepy lizards (Tiliqua rugosa), and we found that pairs of lizards that shared bacterial genotypes were more strongly connected in the social network than were pairs of lizards that did not. In contrast, there was no significant association between spatial proximity of lizard pairs and shared bacterial genotypes. These results provide strong correlative evidence that these bacteria are transmitted from host to host around the social network, rather than that adjacent lizards are picking up the same bacterial genotype from some common source.
An Algorithm for the Solution of Fixed-Point Equations for Infinite Words

— The solutions offixed-point équations for generalized (infinité) mords have previously been obtained asfrontiers of infinité trees. An algorithm is given which computes an explicit solution using a shuffle opération on words. This solution can be proven equal to the previous one so that the structure of the frontier s of infinité trees is completely analyzedfor those context-free grammars which contain exactly one production rulefor each syntactic variable.
Muscle Architecture and Optimum Angle of the Knee Flexors and Extensors: A Comparison Between Cyclists and Australian Rules Football Players

Brughelli, M, Cronin, J, and Nosaka, K. Muscle architecture and optimum angle of the knee flexors and extensors: a comparison between cyclists and Australian Rules football players. J Strength Cond Res 24(3): 717-721, 2010-The purpose of this study was to investigate differences in optimum angle of peak torque (knee extensors and flexors) and muscle architecture (vastus lateralis) between 9 cyclists and 9 Australian Rules football (ARF) players. The angles of peak torque of the ARF players were significantly (p < 0.05) greater during knee extension (70.8 ± 3.5 vs. 66.6 ± 5.9°) and smaller during knee flexion (26.2 ± 2.9 vs. 32.3 ± 3.8°) compared with the cyclists. The ARF players had significantly (p < 0.05) smaller pennation angles (19.3 ± 2.0 vs. 24.9 ± 2.5°) and longer fascicle lengths (7.9 ± 0.7 vs. 6.2 ± 0.8 cm) in comparison with the cyclists. There were no significant differences between groups regarding muscle thickness or peak torque ratios between the quadriceps and hamstrings. Muscle architectural changes associated with resistance strength training need to be investigated so that the effects of training on architecture and functional performance can be determined.
In vivo identification of morphologic retinal abnormalities in neuromyelitis optica

Editors' Note: In reference to the article “In vivo identification of morphologic retinal abnormalities in neuromyelitis optica,” Dr. Borruat reports his own experience in diagnosing microcystic macular edema in patients with noninflammatory optic neuropathies, supporting the hypothesis of retrograde transsynaptic degeneration of inner retinal cells as etiology. Dr. Khoo espouses the benefits of Sniffin’ Sticks, an inexpensive, noninvasive test of olfactory dysfunction, in diagnosing idiopathic intracranial hypertension. Authors Kunte et al. explain the drawbacks of this approach. —Megan Alcauskas, MD, and Robert C. Griggs, MD Sotirchos et al.1 used optical coherence tomography (OCT) …