Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes

Cysteine S-nitrosation is a reversible post-translational modification mediated by nitric oxide (•NO)-derived agents. S-Nitrosation participates in cellular signaling and is associated with several diseases such as cancer, cardiovascular diseases, and neuronal disorders. Despite the physiological importance of this nonclassical •NO-signaling pathway, little is understood about how much S-nitrosation affects protein function. Moreover, identifying physiologically relevant targets of S-nitrosation is difficult because of the dynamics of transnitrosation and a limited understanding of the physiological mechanisms leading to selective protein S-nitrosation. To identify proteins whose activities are modulated by S-nitrosation, we performed a metabolomics study comparing WT and endothelial nitric-oxide synthase knockout mice. We integrated our results with those of a previous proteomics study that identified physiologically relevant S-nitrosated cysteines, and we found that the activity of at least 21 metabolic enzymes might be regulated by S-nitrosation. We cloned, expressed, and purified four of these enzymes and observed that S-nitrosation inhibits the metabolic enzymes 6-phosphogluconate dehydrogenase, Δ1-pyrroline-5-carboxylate dehydrogenase, catechol-O-methyltransferase, and d-3-phosphoglycerate dehydrogenase. Furthermore, using site-directed mutagenesis, we identified the predominant cysteine residue influencing the observed activity changes in each enzyme. In summary, using an integrated metabolomics approach, we have identified several physiologically relevant S-nitrosation targets, including metabolic enzymes, which are inhibited by this modification, and we have found the cysteines modified by S-nitrosation in each enzyme.
Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

Abstract Background: Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Purpose: Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. Methods: EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Results and discussion: Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. Conclusion: EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site.
Teacher Improves Learning by Selecting a Training Subset

We call a learner super-teachable if a teacher can trim down an iid training set while making the learner learn even better. We provide sharp super-teaching guarantees on two learners: the maximum likelihood estimator for the mean of a Gaussian, and the large margin classifier in 1D. For general learners, we provide a mixed-integer nonlinear programming-based algorithm to find a super teaching set. Empirical experiments show that our algorithm is able to find good super-teaching sets for both regression and classification problems.
The analysis of terminal endpoint events in stepped wedge designs

The stepped wedge design is a unique clinical trial design that allows for a sequential introduction of an intervention. However, the statistical analysis is unclear when this design is applied in survival data. The time‐dependent introduction of the intervention in combination with terminal endpoints and interval censoring makes the analysis more complicated. In this paper, a time‐on‐study scale discrete survival model was constructed. Simulations were conducted primarily to study the performance of our model for different settings of the stepped wedge design. Secondary, we compared our approach to continuous Cox proportional hazard model. The results show that the discrete survival model estimates the intervention effects unbiasedly. If the length of the censoring interval is increased, the precision of the estimates is decreased. Without left truncation and late entry, the number of steps improves the precision of the estimates, whereas in combination of left truncation and late entry, the number of steps decreases the precision. Given the same number of participants and clusters, a parallel group design has higher precision than a stepped wedge design. Copyright © 2016 John Wiley & Sons, Ltd.
MiR-128 reverses the gefitinib resistance of the lung cancer stem cells by inhibiting the c-met/PI3K/AKT pathway

Gefitinib is a first line anti-tumor drug used for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, the drug resistance to gefitinib limits its clinical application. Here, we observed the CSCs of PC9 are obviously resistant to gefitinib compared with the non-CSCs. Furthermore, we found the gefitinib failed to suppress the PI3K/AKT pathway in the PC9-CSCs. Mechanically, we showed significant down-regulation of miR-128 in the PC9-CSCs compared with the non-CSCs. Overexpression of miR-128 significantly increased the sensitivity of PC9-CSCs to gefitinib-induced apoptosis. In addition, the gene of c-met was proved to be directly inhibited by miR-128. Enforced expression of c-met could “rescue” the miR-128 promoted apoptosis and cleavage of caspases in PC9-CSCs treated with gefitinib. Thus, these results indicate that the miR-128/c-met pathway enhances the gefitinib sensitivity of the lung cancer stem cells by suppressing the PI3K/AKT pathway.
Prevalence of overweight, obesity, underweight and normal weight in French youth from 2009 to 2013

Abstract Objective To determine the prevalence of underweight, overweight and obesity in French youth from 2009 to 2013 and to determine if there are differences in weight categories according to socio-economic status. Design Cross-sectional study performed in different regions of France. Physical measures included weight, height and BMI. Underweight, overweight and obesity were defined according to age- and sex-specific BMI cut-off points from the International Obesity Task Force. Setting France. Subjects Children and adolescents (n 9670; 4836 boys, 4834 girls) from the French national BOUGE Program between 2009 and 2013. Results The prevalence of obesity was higher in boys than girls (P<0·05). In contrast, underweight was more prevalent in girls (P<0·05). Although there were no significant changes in overweight or underweight boys or girls from 2009 to 2013, there was a significant increase in obesity in boys and girls (P<0·05) during the same time period. The prevalence of underweight increased in girls from 12·0 to 16·7 % (P >0·05) and remained unchanged in boys (7·1–7·3 %) between 2009 and 2013. Overweight and obesity were higher in low socio-economic families (P<0·0001). Conclusions Findings suggest that the prevalence of overweight was stable although high in French children and adolescents, while the prevalence of obesity increased significantly. Changes in underweight, although not significant, were high in girls and merit further attention. Improving public health interventions, especially in high-risk low socio-economic populations, may help to modify the behaviour that contributes to underweight, overweight and obesity in young boys and girls.
Biomarkers and Functional Decline in Prodromal Alzheimer's Disease.

BACKGROUND Little is known of possible associations between Alzheimer's disease (AD) biomarkers and instrumental activities of daily living (IADL) change over time. OBJECTIVE The present study seeks to identify relationships between baseline imaging and fluid biomarker profiles, and decline in IADL utilizing data collated from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. METHODS Generalized estimating equations analysis, adjusted for cognitive deterioration, was applied to a cohort of 509 individuals from all stages of ADNI, including 156 healthy controls, 189 early mild cognitive impairment (MCI) patients and 164 MCI patients. RESULTS A significant correlation was found between baseline biomarkers, specifically CSF Aβ and FDG PET, and IADL change over a 3-year period in individuals with MCI. Importantly, comparable correlations between presence of pathological biomarker levels and temporal decline in both functional and cognitive performance were also noted. DISCUSSION We show that distinct baseline biomarkers may predict latent changes in IADL. Our results necessitate a revision of the commonly held view upholding cognitive changes as the predominant endpoint measure associated with presence of abnormal baseline biomarkers.
Language Code Switching in Web Corpora

One of the challenges in building and using web corpora is their rather high content of “noise”, most notably having the form of foreign-language text fragments within otherwise monolingual text. Our paper presents an approach trying to cope with this problem by means of “exhaustive” stop-word lists provided by morphosyntactic taggers. As a side effect of the procedure, a problem of tagging text with missing diacritics is also addressed.
An Analysis of the Abstracts Presented at the Annual Meetings of the Society for Neuroscience from 2001 to 2006

Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001–2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain.
AGAROSE DROPLET MICROFLUIDICS FOR HIGHLY PARALLEL SINGLE MOLECULE EMULSION RT-PCR

A microfluidic device for generating uniform agarose droplets for highly parallel single molecule emulsion reverse transcription PCR (eRT-PCR) is presented. The device mixed RNA template and RT-PCR reagents, in agarose solution, immediately prior to mono-disperse droplet generation to ensure uniform concentration and distribution of components. After eRTPCR, the agarose droplets were solidified by cooling to form stable beads enabling downstream processing whilst maintaining monoclonality. Stochastic data were then obtained using fluorescence flow cytometry to demonstrate detection of single copy number RNA within agarose droplets. This method allows highly efficient, high throughput, eRT-PCR suitable for gene expression studies, and other applications.
Molecular characterization and functional analysis of a piscidin gene in large yellow croaker (Larimichthys crocea)

The piscidin family, which includes potent antimicrobial peptides with broad-spectrum activity, plays an important role in the innate immune system of fish. In this study, we cloned piscidin-5-like type 3 (Lcpis5lt3) in large yellow croaker (Larimichthys crocea). Multiple alignments with other known piscidins revealed amino acid conservation throughout the fish, especially at the signal peptide (22 amino acids). The phylogenetic tree confirmed that Lcpis5lt3 and large yellow croaker piscidin-5-like proteins were grouped together to form a branch. Quantitative real-time PCR revealed that Lcpis5lt3 was expressed in a wide range of tissues, including the brain, muscle, gill, head kidney, intestine, kidney, liver, and spleen. The highest mRNA expression level of Lcpis5lt3 was found in the spleen. After Vibrio alginolyticus infection, mRNA expression was rapidly upregulated in the liver, head kidney, gill, kidney, and intestine at 4, 8, 12, and 24 h post infection (hpi), whereas there were no significant changes in the spleen. The antimicrobial spectrum showed that the synthetic mature peptide of Lcpis5lt3 exhibited different activity in vitro against various bacteria, such as Aeromonas hydrophila, V. anguillarum, V. alginolyticus, V. parahaemolyticus, Staphylococcus aureus, and Listeria monocytogenes. In addition, survival rates from the in vivo assay indicated that the synthetic peptide of Lcpis5lt3 increased the survival rate of large yellow croaker after V. alginolyticus challenge, resulting in a decline in bacterial burden and mRNA expression levels of interleukin-1β, interleukin-10, and tumor necrosis factor-α. These data suggest that Lcpis5lt3 plays an important role in innate immunity in large yellow croaker and might represent a potential therapeutic agent against pathogen invasion.
A novel dual-phase-shift control strategy for dual-active-bridge DC-DC converter

There is power circulating flow in dual-active-bridge(DAB) dc-dc converter under the traditional single-phase-shift(SPS) control, and this is the main factor contributing to larger current stress and larger converter loss. In order to eliminate the power circulating flow and reduce the current stress, this paper proposes a novel dual-phase-shift(DPS)control method. By analyzing the operating principle of the DAB converter under the proposed DPS control method, the steady-state power model and small-signal equivalent mathematical model, as well as the constraint condition of eliminating the power circulating flow, are derived and established, on the basis of which the closed-loop controller is then designed. The simulation and experimental results verify the correctness and excellent performance of the proposed DPS control method.
Goserelin promotes the apoptosis of epithelial ovarian cancer cells by upregulating forkhead box O1 through the PI3K/AKT signaling pathway

Gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), are conducive to the growth of ovarian cancer based on the ‘gonadotropin theory’ and are regulated by gonadotropin-releasing hormone (GnRH). The present study was carried out to investigate the effect of goserelin, a GnRH agonist, on the apoptosis of epithelial ovarian cancer (EOC) cells and the underlying in vitro and in vivo mechanisms. Through flow cytometry, Hoechst staining and TUNEL staining, we demonstrated that goserelin promoted the apoptosis of EOC cells both in vitro and in vivo. Through human apoptosis gene PCR array, we verified that the promotion of EOC cell apoptosis by goserelin was linked to the upregulation of members of the tumor necrosis factor (TNF) and TNF receptor superfamilies, which have been identified as downstream targets of forkhead box O1 (FOXO1). Goserelin enhanced FOXO1 expression, and siRNA-mediated knockdown of FOXO1 abrogated the induction of apoptosis by goserelin. Moreover, goserelin decreased AKT activity, and FOXO1 upregulation by goserelin was dependent on the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In vivo, the expression of key factors in the PI3K/AKT/FOXO1 pathway was consistent with that observed in vitro. In conclusion, our data suggested that goserelin may promote EOC cell apoptosis by upregulating FOXO1 through the PI3K/AKT signaling pathway. We believe that GnRH agonists may be potential antitumor agents, and key factors in the PI3K/AKT-FOXO1 pathway may also be novel therapeutic targets for the treatment of EOC.
exting while driving , executive function , and impulsivity in ollege students

The purpose of the present study was to investigate the cognitive processes underlying texting while driving. A sample of 120 college students completed a survey to assess how frequently they send and read a text message while driving. Based on this information, students were assigned to one of two groups: 20 students who frequently text while driving and 20 matched-control students who infrequently text while driving but were similar in gender, age, years of education, and years driving. The groups were compared on the extent to which they differed in self-reported measures of executive function and impulsivity. The groups were also compared on a behavioral measure of impulsivity: the extent to which they discounted hypothetical monetary rewards as a function of the delay. For this measure, the students made repeated choices between smaller monetary rewards available immediately and larger rewards available after
Testing Cyber-Physical Systems through Bayesian Optimization

Many problems in the design and analysis of cyber-physical systems (CPS) reduce to the following optimization problem: given a CPS which transforms continuous-time input traces in Rm to continuous-time output traces in Rn and a cost function over output traces, find an input trace which minimizes the cost. Cyber-physical systems are typically so complex that solving the optimization problem analytically by examining the system dynamics is not feasible. We consider a black-box approach, where the optimization is performed by testing the input-output behaviour of the CPS. We provide a unified, tool-supported methodology for CPS testing and optimization. Our tool is the first CPS testing tool that supports Bayesian optimization. It is also the first to employ fully automated dimensionality reduction techniques. We demonstrate the potential of our tool by running experiments on multiple industrial case studies. We compare the effectiveness of Bayesian optimization to state-of-the-art testing techniques based on CMA-ES and Simulated Annealing.
Illumination Variation-Resistant Video-Based Heart Rate Measurement Using Joint Blind Source Separation and Ensemble Empirical Mode Decomposition

Recent studies have demonstrated that heart rate (HR) could be estimated using video data [e.g., exploring human facial regions of interest (ROIs)] under well-controlled conditions. However, in practice, the pulse signals may be contaminated by motions and illumination variations. In this paper, tackling the illumination variation challenge, we propose an illumination-robust framework using joint blind source separation (JBSS) and ensemble empirical mode decomposition (EEMD) to effectively evaluate HR from webcam videos. The framework takes the hypotheses that both facial ROI and background ROI have similar illumination variations. The background ROI is then considered as a noise reference sensor to denoise the facial signals by using the JBSS technique to extract the underlying illumination variation sources. Further, the reconstructed illumination-resisted green channel of the facial ROI is detrended and decomposed into a number of intrinsic mode functions using EEMD to estimate the HR. Experimental results demonstrated that the proposed framework could estimate HR more accurately than the state-of-the-art methods. The Bland–Altman plots showed that it led to better agreement with HR ground truth with the mean bias 1.15 beats/min (bpm), with 95% limits from $-$15.43 to 17.73 bpm, and the correlation coefficient 0.53. This study provides a promising solution for realistic noncontact and robust HR measurement applications.
Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir‐experienced, NS5A treatment‐naïve patients: Findings from two randomized trials

We report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF‐based, non‐NS5A inhibitor‐containing regimens.
Dreyfus and Dreyfus and Indicators of Behavioral Performance: A Study of Measurement Convergence

Introduction: Assessment of efficacy of continuous professional development is an important part of continuing professional development programing as one of its goals is to increase the performance of the clinicians that serve the community. A frequently used and researched classification system for skill mastery is the Dreyfus and Dreyfus Model of Skill Acquisition. An alternative approach is the core competency framework that informs the assessment of residents and forms the foundation of the American Board of Medical Specialties Program for Maintenance of Certification. There are a number of methods of assessment of each competence. One of the most broadly employed and researched methods is a multisource assessment (360°) methodology. Methods: Three hundred sixty-degree data were collected from 264 raters of physicians holding supervisory roles. Raters included the physicians' leaders, peers, and support/reports. The scale items were taken from an instrument developed for the assessment of interpersonal and communications skills, professionalism, and system-based practice. The Dreyfus scale was purposely built for this application. Results: The Dreyfus scale was reduced to a single dimension, and raters assigned their score on that dimension as the indicator of their assessment of the physician's level of mastery. Results of a multivariate analysis of variance indicated a significant relationship between Dreyfus mastery score and competency items (P < .0001). Discussion: These findings demonstrate a relationship between a measure of Dreyfus skill acquisition and measures based on the American Board of Medical Specialties/Accreditation Council for Graduate Medical Education six core competency framework. Results have implication for continuing professional development design and assessment.