Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep GDashboard: Visualizing and Understanding Genomic Sequences Using Deep Neural Networks

Deep neural network (DNN) models have recently obtained state-of-the-art prediction accuracy for the transcription factor binding (TFBS) site classification task. However, it remains unclear how these approaches identify meaningful DNA sequence signals and give insights as to why TFs bind to certain locations. In this paper, we propose a toolkit called the Deep Genomic Dashboard (Deep GDashboard) which provides a suite of visualization strategies to extract motifs, or sequence patterns from deep neural network models for TFBS classification. We demonstrate how to visualize and understand three important DNN models: convolutional, recurrent, and convolutional-recurrent networks. Our first visualization method is finding a test sequence’s saliency map which uses first-order derivatives to describe the importance of each nucleotide in making the final prediction. Second, considering recurrent models make predictions in a temporal manner (from one end of a TFBS sequence to the other), we introduce temporal output values, indicating the prediction score of a model over time for a sequential input. Lastly, a class-specific visualization strategy finds the optimal input sequence for a given TFBS positive class via stochastic gradient optimization. Our experimental results indicate that a convolutional-recurrent architecture performs the best among the three architectures. The visualization techniques indicate that CNN-RNN makes predictions by modeling both motifs as well as dependencies among them.
Tomographic and functional findings in severe COPD: comparison between the wood smoke-related and smoking-related disease *

OBJECTIVE: Wood smoke exposure is a risk factor for COPD. For a given degree of airway obstruction, the reduction in DLCO is smaller in individuals with wood smoke-related COPD than in those with smoking-related COPD, suggesting that there is less emphysema in the former. The objective of this study was to compare HRCT findings between women with wood smoke-related COPD and women with smoking-related COPD. METHODS: Twenty-two women with severe COPD (FEV1/FVC ratio < 70% and FEV1 < 50%) were divided into two groups: those with wood smoke-related COPD (n = 12) and those with smoking-related COPD (n = 10). The two groups were compared regarding emphysema scores and airway involvement (as determined by HRCT); and functional abnormalities-spirometry results, DLCO, alveolar volume (VA), the DLCO/VA ratio, lung volumes, and specific airway resistance (sRaw). RESULTS: There were no significant differences between the two groups in terms of FEV1, sRaw, or lung hyperinflation. Decreases in DLCO and in the DLCO/VA ratio were greater in the smoking-related COPD group subjects, who also had higher emphysema scores, in comparison with the wood smoke-related COPD group subjects. In the wood smoke-related COPD group, HRCT scans showed no significant emphysema, the main findings being peribronchial thickening, bronchial dilation, and subsegmental atelectasis. CONCLUSIONS: Female patients with severe wood smoke-related COPD do not appear to develop emphysema, although they do show severe airway involvement. The reduction in DLCO and VA, with a normal DLCO/VA ratio, is probably due to severe bronchial obstruction and incomplete mixing of inspired gas during the determination of single-breath DLCO.
Antibodies against Native and Oxidized Cardiolipin and Phosphatidylserine and Phosphorylcholine in Atherosclerosis Development

Background Antibodies against cardiolipin and phosphatidylserine (anti-CL and anti-PS) are associated with thrombosis. In contrast, we determined that IgM antibodies against oxidized CL and PS (OxCL and OxPS) and phosphorylcholine (anti-PC) could be protection markers for cardiovascular disease (CVD). Methods 226 individuals with established hypertension (diastolic pressure>95 mmHg) from the European Lacidipine Study on Atherosclerosis. Antibodies were tested by ELISA. As a surrogate measure of atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of inclusion and 4 years following inclusion. Results Increases in IMT measures at follow-up were significantly less common in subjects which at baseline had high IgM anti-OxPS and anti-PC at above 75th percentile: OR 0,45, CI (0,23–0,86) and OR 0.37, CI (0,19–0,71), p = 0.0137 respectively and above 90th percentile: OR 0.32, CI (0,12–0,84) and OR 0.39, CI (0,15–1.00), p = 0.050 and OR 0,22, CI (0,08–0,59) p = 0,0029. IgM anti-OxCL was negatively associated with IMT increases (OR, 0.32, CI (0,12–0,84), p = 0231). There were no associations for IgM anti-PS or anti-CL. Anti-PC, as determined herein by a commercial ELISA, was strongly associated with data from our previously published in house ELISA (R = 0,87; p<0,0001). ) Anti-PC was also a risk marker at low levels (below 25th percentile; OR = 2,37 (1,16–4,82), p = 0,0177). Conclusions High levels of IgM anti-OxPS and anti-OxCL, but not traditional anti-phospholipid antibodies (anti-PS and anti-CL), are associated with protection against atherosclerosis development. In addition, low IgM anti-PC was a risk marker but high a protection marker.
Heat Equation with Dynamical Boundary Conditions of Reactive Type

The aim of this paper is to study the initial boundary problem where Ω is a bounded regular open domain in ℝN (N ≥ 1), Γ = ∂Ω, ν is the outward normal to Ω, and k < 0. In particular we prove that the problem is ill-posed when N ≥ 2, while it is well-posed in dimension N = 1. Moreover we carefully study the case when Ω is a ball in ℝN. As a byproduct we give several results on the elliptic eigenvalue problem
Dissection of regenerating T-Cell responses against tuberculosis in HIV-infected adults sensitized by Mycobacterium tuberculosis.

RATIONALE Combination antiretroviral treatment (cART) reduces the risk of tuberculosis in HIV-infected people. Therefore a novel approach to gain insight into protection against tuberculosis is to analyze the T cells that expand in people sensitized by Mycobacterium tuberculosis (MTB) during cART. OBJECTIVES To longitudinally analyze CD4 T-cell subsets during the first year of cART, from the time of starting cART (Day 0), in 19 HIV-infected, MTB-sensitized adults. METHODS Peripheral blood mononuclear cells were obtained on Day 0, Weeks 2, 4, 12, 24, 36, and 48 of cART and were stimulated with purified protein derivative (PPD) followed by flow cytometry to analyze surface markers and intracellular cytokines. MEASUREMENTS AND MAIN RESULTS CD4(+) T cells significantly increased during follow-up and the viral load fell to undetectable levels in each patient, indicating successful immune restoration. Central memory CD27(+)CD45RA(-) and CD27(+)CCR5(-) CD4(+) cells expanded by 12 weeks (P < 0.02) followed by naive CD27(+)CD45RA(+) cells at 36 weeks (P = 0.02). Terminally differentiated effector CD4(+)CD27(-)CCR7(-) cells decreased by 12 weeks (P = 0.02), paralleled by a proportional decline of PPD-specific CD4(+)IFN-gamma(+) cells (P = 0.02). However, the absolute numbers of PPD-specific IFN-gamma-producing cells, determined by enzyme-linked immunospot assay, increased (P = 0.02). CONCLUSIONS Rapid effector responses are often measured when evaluating immunity. We show that although cART is associated with an absolute increase in effector function, the proportional response decreased and the strongest correlate of increased cART-mediated immunity in this study was the central memory response.
Bandwidth Extension of Telephone Speech Using a Neural Network and a Filter Bank Implementation for Highband Mel Spectrum

The limited audio bandwidth used in narrowband telephone systems degrades both the quality and the intelligibility of speech. This paper presents a new method for the bandwidth extension of telephone speech. Frequency components are added to the frequency band 4-8 kHz using only the information in the narrowband speech. A neural network is used to estimate the mel spectrum in the extension band in short time frames based on features calculated from the narrowband speech. A wideband excitation signal is generated by spectral folding from the narrowband linear prediction residual and a filter bank is utilized to divide the excitation into four sub-bands that cover the extension band. These sub-bands are weighted such that the estimated mel spectrum is realized. Bandwidth-extended speech is obtained by summing the weighted sub-bands and the original narrowband signal. Listening tests show that this new method improves speech quality compared with narrowband telephone speech and with a previously published bandwidth extension method.
Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for genetic skeletal diseases

Mutant matrilin-3 (V194D) forms non-native disulphide bonded aggregates in the rER of chondrocytes from cell and mouse models of multiple epiphyseal dysplasia (MED). Intracellular retention of mutant matrilin-3 causes endoplasmic reticulum (ER) stress and induces an unfolded protein response (UPR) including the upregulation of two genes recently implicated in ER stress: Armet and Creld2. Nothing is known about the role of Armet and Creld2 in human genetic diseases. In this study, we used a variety of cell and mouse models of chondrodysplasia to determine the genotype-specific expression profiles of Armet and Creld2. We also studied their interactions with various mutant proteins and investigated their potential roles as protein disulphide isomerases (PDIs). Armet and Creld2 were up-regulated in cell and/or mouse models of chondrodysplasias caused by mutations in Matn3 and Col10a1, but not Comp. Intriguingly, both Armet and Creld2 were also secreted into the ECM of these disease models following ER stress. Armet and Creld2 interacted with mutant matrilin-3, but not with COMP, thereby validating the genotype-specific expression. Substrate-trapping experiments confirmed Creld2 processed PDI-like activity, thus identifying a putative functional role. Finally, alanine substitution of the two terminal cysteine residues from the A-domain of V194D matrilin-3 prevented aggregation, promoted mutant protein secretion and reduced the levels of Armet and Creld2 in a cell culture model. We demonstrate that Armet and Creld2 are genotype-specific ER stress response proteins with substrate specificities, and that aggregation of mutant matrilin-3 is a key disease trigger in MED that could be exploited as a potential therapeutic target.
Atmospheric Chemistry and Physics Discussions Interactive comment on “ Aerosols ’ influence on the interplay between condensation , evaporation and rain in warm cumulus cloud ”

The manuscript presents modelling study about the effect of aerosol particle concentration on cloud droplet and precipitation formation, as well as cloud lifetime of warm cumulus cloud. The results presented are interesting and closely related to other recent studies, and give some new information about the complex interactions between aerosols, clouds and precipitation. Conclusions are well argumented and clear. Overall, the manuscript is well written with clear structure, but slightly too concise at some points.
The Chandra Deep Field-North Survey. XVII. Evolution of Magnetic Activity in Old Late-Type Stars

The extremely sensitive Chandra Deep Field-North (CDF-N) pencil-beam X-ray survey is used to identify and characterize the X-ray emission from old high-latitude main-sequence Galactic stars. Our principal goal is to investigate the expected long-term decay of magnetic activity of late-type stars due to the gradual spin-down of stellar rotation from a magnetized stellar wind. Thirteen X-ray sources are associated with late-type stars; 11 of these constitute a well-defined sample for statistical analysis. This sample consists of two G, two K0-K4, and seven M2-M5 stars with median V-band magnitude around 19 and median distance around 300 pc. X-ray luminosities are typically log LX ≃ 27 ergs s-1 but are substantially higher in two cases. The combination of large-amplitude variations on timescales of hours and plasma temperatures around 5-30 MK indicates that the observed X-ray emission is dominated by magnetic reconnection flares rather than quiescent coronal emission. These X-ray properties are quantitatively similar to those seen in the active contemporary Sun. The CDF-N stellar sample is compared to simulations based on convolution of X-ray luminosity functions (XLFs) with the known spatial distribution of old-disk stars. The model indicates that the CDF-N stars are the most magnetically active old-disk stars. A substantial decline in X-ray luminosities over the 1 Gyr < t < 11 Gyr age interval is required: 39 rather than 11 stars should have been detected if the XLF does not evolve over this time interval. This is a clear demonstration that the coronal and flaring components of stellar magnetic activity—and presumably the interior magnetic dynamos responsible for the reconnecting fields at the stellar surface—exhibit long-term decay over the age of the Galactic disk. The model that best fits the magnitudes, spectral types, and X-ray luminosities of the sample has LX ∝ t-2 ergs s-1, which is faster than the t-1 decay rate predicted from widely accepted rotational spin-down rates and X-ray-activity relations.
Fetal Hemodynamic Adaptive Changes Related to Intrauterine Growth: The Generation R Study

Background— It has been suggested that an adverse fetal environment increases susceptibility to hypertension and cardiovascular disease in adult life. This increased risk may result from suboptimal development of the heart and main arteries in utero and from adaptive cardiovascular changes in conditions of reduced fetal growth. The aim of the present study was to evaluate whether reduced fetal growth is associated with fetal circulatory changes and cardiac dysfunction. Methods and Results— This study was embedded in a population-based, prospective cohort study starting in early fetal life. Fetal growth characteristics and fetal circulation variables were assessed with ultrasound and Doppler examinations in 1215 healthy women. The fetal circulation was examined in relation to estimated fetal weight. Higher placental resistance indices were strongly associated with decreased fetal growth. Cerebral resistance showed a gradual decline with reduced fetal growth. Cardiac output, peak systolic velocity of the outflow tracts, and cardiac compliance showed a gradual reduction with diminished fetal growth, whereas intraventricular pressure gradually increased. Conclusions— Decreased fetal growth is associated with adaptive fetal cardiovascular changes. Cardiac remodeling and cardiac output changes are consistent with a gradual increase in afterload and compromised arterial compliance in conditions of decreased fetal growth. These changes have already begun to occur before the stage of clinically apparent fetal growth restriction and may contribute to the increased risk of cardiovascular disease in later life.
Limited-Memory Fast Gradient Descent Method for Graph Regularized Nonnegative Matrix Factorization

Graph regularized nonnegative matrix factorization (GNMF) decomposes a nonnegative data matrix to the product of two lower-rank nonnegative factor matrices, i.e., and () and aims to preserve the local geometric structure of the dataset by minimizing squared Euclidean distance or Kullback-Leibler (KL) divergence between X and WH. The multiplicative update rule (MUR) is usually applied to optimize GNMF, but it suffers from the drawback of slow-convergence because it intrinsically advances one step along the rescaled negative gradient direction with a non-optimal step size. Recently, a multiple step-sizes fast gradient descent (MFGD) method has been proposed for optimizing NMF which accelerates MUR by searching the optimal step-size along the rescaled negative gradient direction with Newton's method. However, the computational cost of MFGD is high because 1) the high-dimensional Hessian matrix is dense and costs too much memory; and 2) the Hessian inverse operator and its multiplication with gradient cost too much time. To overcome these deficiencies of MFGD, we propose an efficient limited-memory FGD (L-FGD) method for optimizing GNMF. In particular, we apply the limited-memory BFGS (L-BFGS) method to directly approximate the multiplication of the inverse Hessian and the gradient for searching the optimal step size in MFGD. The preliminary results on real-world datasets show that L-FGD is more efficient than both MFGD and MUR. To evaluate the effectiveness of L-FGD, we validate its clustering performance for optimizing KL-divergence based GNMF on two popular face image datasets including ORL and PIE and two text corpora including Reuters and TDT2. The experimental results confirm the effectiveness of L-FGD by comparing it with the representative GNMF solvers.
Research on Dynamic Effects of Employability of Vocational College Students in Taiwan

This study used the dynamic scenario simulation of system dynamics to perform simulation on the effects of education policies, trend of employment demand, and employability qualities of vocational college graduates on the development of employment demand in Taiwan’s technology industry. According to the research results, dynamic situational simulation of system dynamics can be used to simulate the effect of changes in education policy system with time on the development and trend of employment demand in technology industry. The simulation results of policy scenario showed that the talent shortage in technology industry should be overcome by improving education policy. The problem of talent shortage cannot be effectively alleviated until the matching rate between education policy and employment demand reaches 90%. The simulation results of this study can be provided as reference for education policy planners to improve the employability of vocational college students. It is intended to provide valuable suggestions to reduce the unemployment rate of vocational college graduates and to substantially reduce the gap between industries and academia, in order to further enhance Taiwan’s competitiveness in the global economic system.
Prevalence of Virulence Determinants and Antimicrobial Resistance among Commensal Escherichia coli Derived from Dairy and Beef Cattle

Cattle is a reservoir of potentially pathogenic E. coli, bacteria that can represent a significant threat to public health, hence it is crucial to monitor the prevalence of the genetic determinants of virulence and antimicrobial resistance among the E. coli population. The aim of this study was the analysis of the phylogenetic structure, distribution of virulence factors (VFs) and prevalence of antimicrobial resistance among E. coli isolated from two groups of healthy cattle: 50 cows housed in the conventional barn (147 isolates) and 42 cows living on the ecological pasture (118 isolates). The phylogenetic analysis, identification of VFs and antimicrobial resistance genes were based on either multiplex or simplex PCR. The antimicrobial susceptibilities of E. coli were examined using the broth microdilution method. Two statistical approaches were used to analyse the results obtained for two groups of cattle. The relations between the dependent (VFs profiles, antibiotics) and the independent variables were described using the two models. The mixed logit model was used to characterise the prevalence of the analysed factors in the sets of isolates. The univariate logistic regression model was used to characterise the prevalence of these factors in particular animals. Given each model, the odds ratio (OR) and the 95% confidence interval for the population were estimated. The phylogroup B1 was predominant among isolates from beef cattle, while the phylogroups A, B1 and D occurred with equal frequency among isolates from dairy cattle. The frequency of VFs-positive isolates was significantly higher among isolates from beef cattle. E. coli from dairy cattle revealed significantly higher resistance to antibiotics. Some of the tested resistance genes were present among isolates from dairy cattle. Our study showed that the habitat and diet may affect the genetic diversity of commensal E. coli in the cattle. The results suggest that the ecological pasture habitat is related to the increased spreading rate of the VFs, while the barn habitat is characterised by the higher levels of antimicrobial resistance among E. coli.
Preliminary Effects of Oral Uridine on the Ocular Surface in Dry Eye Patients

We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes.
Racial Differences in the Prevalence and Outcomes of Atrial Fibrillation Among Patients Hospitalized With Heart Failure

Background The intersection of heart failure (HF) and atrial fibrillation (AF) is common, but the burden of AF among black patients with HF is poorly characterized. We sought to determine the prevalence of AF, characteristics, in‐hospital outcomes, and warfarin use associated with AF in patients hospitalized with HF as a function of race. Methods and Results We analyzed data on 135 494 hospitalizations from January 2006 through January 2012 at 276 hospitals participating in the American Heart Association's Get With The Guidelines HF Program. Multivariable logistic regression models using generalized estimating equations approach for risk‐adjusted comparison of AF prevalence, in‐hospital outcomes, and warfarin use. In this HF population, 53 389 (39.4%) had AF. Black patients had markedly less AF than white patients (20.8% versus 44.8%, P<0.001). Adjusting for risk factors and hospital characteristics, black race was associated with significantly lower odds of AF (adjusted odds ratio 0.52, 95% CI 0.48 to 0.55, P<0.0001). There were no racial differences in in‐hospital mortality; however, black patients had a longer length of stay relative to white patients. Black patients compared with white patients with AF were less likely to be discharged on warfarin (adjusted odds ratio 0.76, 95% CI 0.69 to 0.85, P<0.001). Conclusions Despite having many risk factors for AF, black patients, relative to white patients hospitalized for HF, had a lower prevalence of AF and lower prescription of guideline‐recommended warfarin therapy.