Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/− murine hearts modelling the Brugada syndrome

Brugada syndrome (BrS) is associated with a loss of Na+ channel function and an increased incidence of rapid polymorphic ventricular tachycardia (VT) and sudden cardiac death. A programmed electrical stimulation (PES) technique assessed arrhythmic tendency in Langendorff‐perfused wild‐type (WT) and genetically modified (Scn5a+/−) ‘loss‐of‐function’ murine hearts in the presence and absence of flecainide and quinidine, and the extent to which Scn5a+/− hearts model the human BrS. Extra‐stimuli (S2), applied to the right ventricular epicardium, followed trains of pacing stimuli (S1) at progressively reduced S1–S2 intervals. These triggered VT in 16 out of 29 untreated Scn5a+/− and zero out of 31 WT hearts. VT occurred in 11 out of 16 (10 μm) flecainide‐treated WT and nine out of the 13 initially non‐arrhythmogenic Scn5a+/− hearts treated with (1.0 μm) flecainide. Quinidine (10 μm) prevented VT in six out of six flecainide‐treated WT and 13 out of the 16 arrhythmogenic Scn5a+/− hearts in parallel with its clinical effects. Paced electrogram fractionation analysis demonstrated increased electrogram durations, expressed as electrogram duration (EGD) ratios, with shortening S1–S2 intervals in arrhythmogenic Scn5a+/− hearts, and prolonged ventricular effective refractory periods (VERPs) in non‐arrhythmogenic Scn5a+/− hearts. Flecainide increased EGD ratios in WT (at 10 μm) and non‐arrhythmogenic Scn5a+/− hearts (at 1.0 μm), whereas quinidine (10 μm) reduced EGD ratios and prolonged VERPs in WT and arrhythmogenic Scn5a+/− hearts. However, epicardial and endocardial monophasic action potential recordings consistently demonstrated positive gradients of repolarization in WT, arrhythmogenic and non‐arrhythmogenic Scn5a+/− hearts under all pharmacological conditions. Together, these findings demonstrate proarrhythmic effects of flecainide in WT and Scn5a+/− murine hearts that recapitulate its clinical effects. They further attribute the arrhythmogenic phenomena observed here to re‐entrant substrates resulting from delayed epicardial activation despite an absence of transmural heterogeneities of repolarization, in sharp contrast to recent characterizations in ‘gain‐of‐function’Scn5a+/Δ murine hearts modelling the long‐QT(3) syndrome.
Genetics of early neurogenesis in Drosophila melanogaster.

Cells of the neurogenic ectoderm of insects must decide between two alternative fates, the neurogenic and the epidermogenic. In the last few years several genes have been identified in Drosophila which are involved in controlling this decision. The analysis of mutations in these genes has led to hypotheses about the commitment of the neurogenic ectoderm and of the neural progenitors.
Filtrage collaboratif sensible au contexte - Une approche basée sur LDA

Les systemes de recommandations visent a proposer aux utilisateurs des items en lien avec leur consultation en cours et qui peuvent retenir leur interet. L'interet des utilisateurs depend du contexte dans lequel ils se trouvent. Dans ce travail, nous proposons un systeme hybride CBCF (Contex-aware Based Collaborative Filtering) qui combine le systeme de recommandations sensibles aux contextes et le filtrage collaboratif. Le contexte est ici defini comme l'objectif ou l'intention de l'utilisateur. Nous le modelisons par une approche LDA (Latent Dirichlet Allocation) qui genere un modele de themes pour chaque intention. Nous avons evalue notre approche sur la collection Book-Crossing et montrons sa superiorite par rapport a plusieurs methodes etat de l'art.
Microarchitecture Configurations and Floorplanning Co-Optimization

Microarchitecture configurations and floorplanning are keys to boost throughput, and they are strongly related. In this paper, we propose a new method to optimize them simultaneously. We first concentrate on floorplanning under given microarchitecture configurations. In addition to the objectives of conventional floorplanning methods, we minimize the throughput degradation caused by pipelined global interconnects based on efficient yet accurate models for microarchitecture throughput over pipeline stages of global interconnects. Our results show that an accurate trajectory piecewise-linear (TPWL) model incurs more offline setup time to obtain 13% better throughput than a rough access ratio-based model, and both models lead to much better throughput (up to 64% higher) compared with conventional floorplanning methods. We then build a unified throughput model parameterized for pipelined global interconnects and microarchitecture configurations based on the TPWL method and apply this model to efficiently explore over one million microarchitecture configurations and corresponding floorplan variations. We obtain microarchitecture configurations and floorplans with throughput 26.9% better than manually chosen microarchitecture followed by automatic floorplanning in a very recent paper.
K-Sample Anderson–Darling Tests

Abstract Two k-sample versions of an Anderson–Darling rank statistic are proposed for testing the homogeneity of samples. Their asymptotic null distributions are derived for the continuous as well as the discrete case. In the continuous case the asymptotic distributions coincide with the (k – 1)-fold convolution of the asymptotic distribution for the Anderson–Darling one-sample statistic. The quality of this large sample approximation is investigated for small samples through Monte Carlo simulation. This is done for both versions of the statistic under various degrees of data rounding and sample size imbalances. Tables for carrying out these tests are provided, and their usage in combining independent one- or k-sample Anderson–Darling tests is pointed out. The test statistics are essentially based on a doubly weighted sum of integrated squared differences between the empirical distribution functions of the individual samples and that of the pooled sample. One weighting adjusts for the possibly different s.
Comparison of Single‐Biphasic Versus Sequential‐Biphasic Shocks on Defibrillation Threshold in Pigs

Current generation implantable cacdioverter defibrillators use monophasic, biphasic, or sequential pulse shocks, most of which truncate after a given time, dumping the remaining charge on the capacitor through an internal resistor. We hypothesized that having an additional current pathway, and delivering the majority of the remaining charge on a single capacitor to the two pathways using additional shock phases, would improve defibrillotion efficacy. This hypothesis was tested by comparing DFTs using a simulated single capacitor, single‐biphasic shock (two 5‐ms pulses separated by 0.2 ms), delivered to coupled pairs of electrodes, to those using a sequential‐biphasic shock (four 5‐ms pulses separated by 0.2 ms) delivered to separate opposing electrodes, delivered from the same electrodes for both woveforms. In eight open‐chest anesthetized pigs, four mesh electrodes (Medtronic TX‐7. 6.5 cm2), were sutured on the epicardium of the anterior and posterior surfaces of each ventricle. Shocks were delivered from a 200‐μF capacitor bank. Triplicate DFTs were obtained using each waveform in a randomized crossover design. Initial leading edge voltage (mean ± SEM: 420 ± 33 V vs 497 ± 34 V; P < 0.05). initial peak current (4.8 ± 0.4 Avs 13 ± 1.1 A: P < 0.001). and delivered energy (16.9 ± 2.6 J vs 30.4 ± 5.3 f; P < 0.05) at the DFT were all significantly lower using sequential‐biphasic shocks than those using single‐biphasic shocks, respectivelv. We conclude that for direct heart defibrillation, it is worthwhile to combine sequential capability to biphasic shocks and deliver the remaining charge on the capacitor to the two different pathways.
Population Genetics of Soilborne Fungal Plant Pathogens The Population Genetics of Fungi : Tools and Techniques

Over the last 10 years plant pathologists have begun to realize that more knowledge about the genetic structure of populations of plant pathogens is needed to implement effective control strategies (48). Research on the genetic structure of fungal populations has mushroomed, and review papers that summarize these studies are numerous (7,27,33,34,38). Although the number of fungal studies has increased greatly, the most comprehensive work has focused on a small number of plant-pathogenic fungi. The majority of these fungi can be recognized easily by their fruiting bodies or disease symptoms on aboveground plant parts. It has proven more difficult to assess the genetic structure of fungal populations that exist mainly belowground, because the distribution of individuals cannot be visualized directly and appropriate sampling procedures are less obvious and more cumbersome. Nevertheless, substantial progress has been made in interpreting the population genetic structure of some soilborne fungi (1,17). The purpose of this paper is to provide an overview of the tools and techniques of fungal population genetics. I will try to emphasize approaches that may be applied to studies of soilborne fungi. Instead of providing detailed methods, I will cite recent references where appropriate. There are many opinions regarding which techniques and tools are best suited to studies of fungal populations. I will give a personal and biased viewpoint, which I believe will be most useful to those who are just entering the field.
Sex‐biased genetic component distribution among populations: additive genetic and maternal contributions to phenotypic differences among populations of Chinook salmon

An approach frequently used to demonstrate a genetic basis for population‐level phenotypic differences is to employ common garden rearing designs, where observed differences are assumed to be attributable to primarily additive genetic effects. Here, in two common garden experiments, we employed factorial breeding designs between wild and domestic, and among wild populations of Chinook salmon (Oncorhynchus tshawytscha). We measured the contribution of additive (VA) and maternal (VM) effects to the observed population differences for 17 life history and fitness‐related traits. Our results show that, in general, maternal effects contribute more to phenotypic differences among populations than additive genetic effects. These results suggest that maternal effects are important in population phenotypic differentiation and also signify that the inclusion of the maternal source of variation is critical when employing models to test population differences in salmon, such as in local adaptation studies.
Evaluating Density Forecasts with Applications to Financial Risk Management

Density forecasting is increasingly more important and commonplace, for example in financial risk management, yet little attention has been given to the evaluation of density forecasts. The authors develop a simple and operational framework for density forecast evaluation. They illustrate the framework with a detailed application to density forecasting of asset returns in environments with time-varying volatility. Finally, the authors discuss several extensions. Copyright 1998 by Economics Department of the University of Pennsylvania and the Osaka University Institute of Social and Economic Research Association.
Role of Metastasis in Hypertabastic Survival Analysis of Breast Cancer: Interaction with Clinical and Gene Expression Variables

This paper analyzes the survival of breast cancer patients, exploring the role of a metastasis variable in combination with clinical and gene expression variables. We use the hypertabastic model in a detailed analysis of 295 breast cancer patients from the Netherlands Cancer Institute given in.1 In comparison to Cox regression the increase in accuracy is complemented by the ability to analyze the time course of the disease progression using the explicitly described hazard and survival curves. We also demonstrate the ability to compute deciles for survival and probability of survival to a given time. Our primary concern in this article is the introduction of a variable representing the existence of metastasis and the effects on the other clinical and gene expression variables. In addition to making a quantitative assessment of the impact of metastasis on the prospects for survival, we are able to look at its interactions with the other prognostic variables. The estrogen receptor status increase in importance, while the significance of the gene expression variables used in the combined model diminishes. When considering only the subgroup of patients who experienced metastasis, the covariates in the model are only the clinical variables for estrogen receptor status and tumor grade.
Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion

Summary. In high endemic areas of hepatitis B virus (HBV) infection, the vast majority of infection is acquired perinatally or during early childhood. The age of the patient is, therefore, almost equivalent to the duration of HBV infection. The natural history of chronic HBV infection consists of three chronological phases: immune tolerance, immune clearance and low replicative phases. The prevalence of hepatitis B e antigen (HBeAg) in asymptomatic HBV carriers is around 90% before 15 years of age, and decreases remarkably to less than 10% after 40 years of age. The immune clearance phase is characterized by a series of hepatitis flares and remissions. These will be followed eventually by HBeAg seroconversion, which is usually accompanied by remission of liver disease and confers favourable outcome. However, patients with persistent HBeAg seropositivity over 40 years of age are associated with a significantly higher risk for progression to cirrhosis than those with HBeAg seroconversion before 40 years of age, and thus should be considered as patients with ‘delayed’ HBeAg seroconversion. Antiviral or immunomodulatory therapy should be considered seriously for these patients.
Toward Printed Integrated Circuits based on Unipolar or Ambipolar Polymer Semiconductors

For at least the past ten years printed electronics has promised to revolutionize our daily life by making cost‐effective electronic circuits and sensors available through mass production techniques, for their ubiquitous applications in wearable components, rollable and conformable devices, and point‐of‐care applications. While passive components, such as conductors, resistors and capacitors, had already been fabricated by printing techniques at industrial scale, printing processes have been struggling to meet the requirements for mass‐produced electronics and optoelectronics applications despite their great potential. In the case of logic integrated circuits (ICs), which constitute the focus of this Progress Report, the main limitations have been represented by the need of suitable functional inks, mainly high‐mobility printable semiconductors and low sintering temperature conducting inks, and evoluted printing tools capable of higher resolution, registration and uniformity than needed in the conventional graphic arts printing sector.
Trade‐offs between land and water requirements for large‐scale bioenergy production

Bioenergy is expected to play an important role in the future energy mix as it can substitute fossil fuels and contribute to climate change mitigation. However, large‐scale bioenergy cultivation may put substantial pressure on land and water resources. While irrigated bioenergy production can reduce the pressure on land due to higher yields, associated irrigation water requirements may lead to degradation of freshwater ecosystems and to conflicts with other potential users. In this article, we investigate the trade‐offs between land and water requirements of large‐scale bioenergy production. To this end, we adopt an exogenous demand trajectory for bioenergy from dedicated energy crops, targeted at limiting greenhouse gas emissions in the energy sector to 1100 Gt carbon dioxide equivalent until 2095. We then use the spatially explicit global land‐ and water‐use allocation model MAgPIE to project the implications of this bioenergy target for global land and water resources. We find that producing 300 EJ yr−1 of bioenergy in 2095 from dedicated bioenergy crops is likely to double agricultural water withdrawals if no explicit water protection policies are implemented. Since current human water withdrawals are dominated by agriculture and already lead to ecosystem degradation and biodiversity loss, such a doubling will pose a severe threat to freshwater ecosystems. If irrigated bioenergy production is prohibited to prevent negative impacts of bioenergy cultivation on water resources, bioenergy land requirements for meeting a 300 EJ yr−1 bioenergy target increase substantially (+ 41%) – mainly at the expense of pasture areas and tropical forests. Thus, avoiding negative environmental impacts of large‐scale bioenergy production will require policies that balance associated water and land requirements.
Multi-state Markov model in outcome of mild cognitive impairments among community elderly residents in Mainland China

ABSTRACT Background: Although knowledge of established risk factors for Alzheimer's disease (AD) can logically contribute to the search for predictors of the progression of cognitive impairment, it has not yet been firmly established where in the cognitive impairment process these risk factors exert their effects and how to predict quantitatively for the progression of mild cognitive impairments (MCI) to AD. This study aimed to determine whether known risk factors increased the risk of progression from MCI to AD and to make prediction based on transition probabilities. Methods: Based on ten examinations of 600 community-dwelling MCI residents and cognitive assessments to classify individuals into MCI, global impairment, and AD, a multi-state Markov Cox's regression model was used and the hazard ratios with their confidence intervals and transition probabilities were estimated. Results: Multivariate analysis showed that gender, age, and hypertension were statistically significant predictors of transition from MCI to global impairment; age, education, and reading statistically influenced transition from global impairment to MCI; gender, age, hypertension, diabetes, and apolipoprotein E geneε4 status were statistically associated with transition from global impairment to AD. Subjects at MCI were more likely (67%) to remain in that cognitive state at the next cognitive assessment than to transition to cognitive deterioration. For global impairment, probability of remaining in the same state was only 18% and that of forward transition was three times more likely than that of backward transition. Conclusions: Known risk factors influenced differently for different transitions. Transition from global impairment was more likely to worsen to severe cognitive deterioration than transition from MCI.
Assessment of Peritoneal Fibrosis by Conventional Light Microscopy and Hydroxyproline Measurements

Peritoneal fibrosis may develop during long-term peritoneal dialysis (PD), probably as a result of chronic exposure to dialysis fluids (1,2). Fibrosis has not only been described in PD patients but has also been induced in chronic peritoneal exposure models in the rat (3,4). Scoring of fibrosis in these studies has been assessed using semiquantitative methods, on either parietal peritoneum or omentum. Also, measurements of the thickness of the submesothelial compact zone of the parietal peritoneum have been performed (5). These methods are not objective and are very time consuming. The hydroxyproline content in tissue specimens has been considered a characteristic biochemical marker for the amount of fibrosis (6). The aim of this study was to compare the semiquantitative scoring of fibrosis to the peritoneal hydroxyproline content in peritoneal tissues of rats chronically exposed to dialysis solutions.
Calculation and Adjustment Limitation of Four-Parameter TRV in High Power Testing Circuits and Their Comparison

This paper presents a method for analysis and calculation of 4-parameter transient recovery voltage (TRV) and its adjustment limitation and two sets of formulae for determination of electrical component parameters, relying on nondimensional presentation of TRV requirements and circuit parameters, to obtain accurate TRV waveforms complying with IEC standard in three kinds of testing circuits used in high-power laboratories. The results show that choosing suitable testing circuit and adopting some applicable measures could greatly save the capacitive energy needed in Weil-synthetic testing circuits and increase the injection-current frequencies, which are imperative at UHV levels.
HLA and eye disease: a synopsis

Human leukocyte antigen (HLA) gene products have been implicated in the pathogenesis of an increasing number of eye diseases, mainly inflammatory in nature. This perspective reviews the current hypotheses for why HLA polymorphisms are associated with specific eye diseases. Statistical problems in studies involving HLA associations are discussed, and possible solutions outlined. The relevance of HLA testing in routine ophthalmic practice, its practical and cost implications is also assessed.
Reproducibility of the measurement of knee joint proprioception in patients with osteoarthritis of the knee.

OBJECTIVE To estimate the inter- and intrarater reliability and agreement of instrumented knee joint proprioception measurement in subjects with knee osteoarthritis (OA) and healthy subjects; to assess the effect of variations in the measurement procedure on agreement parameters. METHODS Proprioception was measured by a computer-controlled knee angular motion-detecting device in a movement-detecting task. The angular displacement between the starting position and the position at the instant of movement detection by the subject was recorded. Two raters independently assessed knee joint proprioception. After 14 days the assessment was repeated. Complete data were obtained from 24 subjects with knee OA and 26 healthy subjects. The inter- and intrarater reliability coefficients (intraclass correlation coefficients [ICC]) and inter- and intrarater agreement measures (standard error of measurement [SEM] and minimal detectable difference [MDD]) were calculated. Additionally, the effect of changing the velocity of angular displacement and applying headphone music during the measurement on the absolute error (i.e., SEM and MDD) was estimated at the second occasion. RESULTS Interrater reliability was good in subjects with knee OA and healthy subjects (ICC 0.91 and 0.89, respectively). Interrater agreement was higher in subjects with knee OA than in healthy subjects (SEM 2.13 degrees versus 0.43 degrees , MDD 5.90 degrees versus 1.19 degrees ). Intrarater reliability was good in subjects with knee OA and healthy subjects (ICC 0.91 and 0.86, respectively). Intrarater agreement (SEM and MDD) was 2.26 degrees and 6.26 degrees in subjects with knee OA and 0.39 degrees and 1.08 degrees in healthy subjects. The original measurement and the 2 variations in measurement showed comparable measurement errors for subjects with knee OA and healthy subjects. CONCLUSION In knee OA subjects and healthy subjects, knee proprioception measurement shows adequate intra- and interreliability. However, the absolute measurement error is rather high. Therefore, this measurement has limited value in the assessment of individual subjects, but can be recommended for scientific research in groups of individuals.