Miracle-dz/UniFAR-FTUs huggingface dataset:
Post-translational Mechanisms Regulating NK Cell Activating Receptors and Their Ligands in Cancer: Potential Targets for Therapeutic Intervention

Efficient clearance of transformed cells by Natural Killer (NK) cells is regulated by several activating receptors, including NKG2D, NCRs, and DNAM-1. Expression of these receptors as well as their specific “induced self” ligands is finely regulated during malignant transformation through the integration of different mechanisms acting on transcriptional, post-transcriptional, and post-translational levels. Among post-translational mechanisms, the release of activating ligands in the extracellular milieu through protease-mediated cleavage or by extracellular vesicle secretion represents some relevant cancer immune escape processes. Moreover, covalent modifications including ubiquitination and SUMOylation also contribute to negative regulation of NKG2D and DNAM-1 ligand surface expression resulting either in ligand intracellular retention and/or ligand degradation. All these mechanisms greatly impact on NK cell mediated recognition and killing of cancer cells and may be targeted to potentiate NK cell surveillance against tumors. Our mini review summarizes the main post-translational mechanisms regulating the expression of activating receptors and their ligands with particular emphasis on the contribution of ligand shedding and of ubiquitin and ubiquitin-like modifications in reducing target cell susceptibility to NK cell-mediated killing. Strategies aimed at inhibiting shedding of activating ligands and their modifications in order to preserve ligand expression on cancer cells will be also discussed.
Identification of a Contact-Dependent Growth Inhibition (CDI) System That Reduces Biofilm Formation and Host Cell Adhesion of Acinetobacter baumannii DSM30011 Strain

Acinetobacter baumannii is a multidrug-resistant nosocomial opportunistic pathogen that is becoming a major health threat worldwide. In this study, we have focused on the A. baumannii DSM30011 strain, an environmental isolate that retains many virulence-associated traits. We found that its genome contains two loci encoding for contact-dependent growth inhibition (CDI) systems. These systems serve to kill or inhibit the growth of non-sibling bacteria by delivering toxins into the cytoplasm of target cells, thereby conferring the host strain a significant competitive advantage. We show that one of the two toxins functions as a DNA-damaging enzyme, capable of inducing DNA double-stranded breaks to the chromosome of Escherichia coli strain. The second toxin has unknown catalytic activity but stops the growth of E. coli without bactericidal effect. In our conditions, only one of the CDI systems was highly expressed in the A. baumannii DSM30011 strain and was found to mediate interbacterial competition. Surprisingly, the absence of this CDI system promotes adhesion of A. baumannii DSM30011 to both abiotic and biotic surfaces, a phenotype that differs from previously described CDI systems. Our results suggest that a specific regulation mediated by this A. baumannii DSM30011 CDI system may result in changes in bacterial physiology that repress host cell adhesion and biofilm formation.
A Dynamic Transcriptional Analysis Reveals IL-6 Axis as a Prominent Mediator of Surgical Acute Response in Non-ischemic Mouse Heart

Background Ischemic heart diseases are a major cause of death worldwide. Different animal models, including cardiac surgery, have been developed over time. Unfortunately, the surgery models have been reported to trigger an important inflammatory response that might be an effect modifier, where involved molecular processes have not been fully elucidated yet. Objective We sought to perform a thorough characterization of the sham effect in the myocardium and identify the interfering inflammatory reaction in order to avoid misinterpretation of the data via systems biology approaches. Methods and Results We combined a comprehensive analytical pipeline of mRNAseq dataset and systems biology analysis to characterize the acute phase response of mouse myocardium at 0 min, 45 min, and 24 h after surgery to better characterize the molecular processes inadvertently induced in sham animals. Our analysis showed that the surgical intervention induced 1209 differentially expressed transcripts (DETs). The clustering of positively co-regulated transcript modules at 45 min fingerprinted the activation of signalization pathways, while positively co-regulated genes at 24 h identified the recruitment of neutrophils and the differentiation of macrophages. In addition, we combined the prediction of transcription factors (TF) regulating DETs with protein-protein interaction networks built from these TFs to predict the molecular network which have induced the DETs. By mean of this retro-analysis of processes upstream gene transcription, we revealed a major role of the Il-6 pathway and further confirmed a significant increase in circulating IL-6 at 45 min after surgery. Conclusion This study suggests that a strong induction of the IL-6 axis occurs in sham animals over the first 24 h and leads to the induction of inflammation and tissues’ homeostasis processes.
Cytokines and Abnormal Glucose and Lipid Metabolism

Clear evidence indicates that cytokines, for instance, adipokines, hepatokines, inflammatory cytokines, myokines, and osteokines, contribute substantially to the development of abnormal glucose and lipid metabolism. Some cytokines play a positive role in metabolism action, while others have a negative metabolic role linking to the induction of metabolic dysfunction. The mechanisms involved are not fully understood, but are associated with lipid accumulation in organs and tissues, especially in the adipose and liver tissue, changes in energy metabolism, and inflammatory signals derived from various cell types, including immune cells. In this review, we describe the roles of certain cytokines in the regulation of metabolism and inter-organ signaling in regard to the pathophysiological aspects. Given the disease-related changes in circulating levels of relevant cytokines, these factors may serve as biomarkers for the early detection of metabolic disorders. Moreover, based on preclinical studies, certain cytokines that can induce improvements in glucose and lipid metabolism and immune response may emerge as novel targets of broader and more efficacious treatments and prevention of metabolic disease.
Functional Analysis of Pepper F-box Protein CaDIF1 and Its Interacting Partner CaDIS1: Modulation of ABA Signaling and Drought Stress Response

Plant adaptive responses to environmental stress are coordinated by inhibition of plant growth and development. Abscisic acid (ABA) is a major phytohormone that regulates the stress response, and its sensitivity determines stress tolerance levels. In this study, we report the identification and functional role of a novel F-box protein, CaDIF1 (Capsicum annuum Drought-Induced F-box Protein 1). The expression of CaDIF1 in pepper leaves was induced by ABA, drought, H2O2, and NaCl treatments. In comparison with wild-type pepper plants, CaDIF1-silenced pepper plants exhibited a drought-sensitive phenotype, whereas CaDIF1-overexpressing (OX) plants exhibited ABA-sensitive and drought-tolerant phenotypes. Using a yeast two-hybrid assay, we identified CaDIS1 (C. annuum DIF1-Interacting SKP 1), which interacts with CaDIF1 in the cytoplasm and nucleus. Consistent with CaDIF1-silenced pepper plants, CaDIS1-silenced pepper plants displayed ABA insensitivity and reduced drought tolerance, and these were characterized by larger stomatal apertures and greater transpirational water loss. Taken together, our results indicate that CaDIF1 and its interacting partner CaDIS1 synergistically regulate the ABA-dependent defence signaling response to drought stress.
Validity and Reliability of a New Specific Parkour Test: Physiological and Performance Responses

Main aim of this study was examining validity and reliability of using a new specific Parkour repeated sprint ability test (SPRSA) for assessing repeated sprint ability while facing obstacles and establishing between-day reliability and sensitivity of SPRSA related to its physiological and performance responses. Thirteen high-level traceurs (three females) performed in random order and twice eight tests for assessing a total of 23 variables: SPRSA (a typical maximal-speed shuttle run interspersed with four Parkour competition-common fundamentals) and seven established fitness tests, core stability, hand-grip, vertical-jump, long-jump, pull-up, 300-m shuttle run (as a field test for anaerobic capacity), and Leger test. Except for muscular elasticity index of vertical jump test (intra-class Correlation Coefficient model 3,1 [ICC3,1] = 0.54 [fair]), fitness tests’ ICC3,1s resulted excellent (ICC3,1: 0.93–1.00). SPRSA total time and time of its fastest sprint (SPRSA peak time) were significantly correlated with the majority of core stability (r: −0.79 to 0.59; P < 0.01–0.05), jumping (r: −0.78 to 0.67; P < 0.01–0.05), pull-up tests (r: −0.86; P < 0.01), 300-m shuttle run test total time (r: 0.77–0.82; P < 0.01), and Leger test-estimated VO2 max (r: −0.78; P < 0.01). Principal component analysis (PCA) of the 23 variables led to extraction of four significant components (each due to different variables’ combinations), which explained 90.2% of 23 variables’ total variance. SPRSA (i.e., total and peak time) showed high reliability (ICC3,1: 0.991–0.998 and standard-error-of-measurement %: 0.07–0.32). Finally, SPRSA showed high sensitivity (smallest-worthwhile-change %: 0.29–0.68). Considering its excellent logical and strong ecological validity, SPRSA may serve as a valid specific field test for Parkour sport. In addition, thanks to its high reliability and sensitivity, this test is suitable for monitoring, evaluating, and programming training processes for Parkour practitioners in repeated sprint ability involving crossing obstacles.
Measurement of Thromboxane Biosynthesis in Health and Disease

Thromboxane (TX) A2 is a chemically unstable lipid mediator involved in several pathophysiologic processes, including primary hemostasis, atherothrombosis, inflammation, and cancer. In human platelets, TXA2 is the major arachidonic acid derivative via the cyclooxygenase (COX)-1 pathway. Assessment of platelet TXA2 biosynthesis can be performed ex vivo through measurement of serum TXB2, an index of platelet COX-1 activity, as well as in vivo through measurement of urinary enzymatic metabolites, a non-invasive index of platelet activation. This article reviews the main findings of four decades of clinical investigation based on these analytical approaches, focusing on the measurement of TXA2 metabolites to characterize the pathophysiologic role of transiently or persistently enhanced platelet activation and to describe the clinical pharmacology of COX-1 inhibition in health and disease.
Mental Imagery and Brain Regulation—New Links Between Psychotherapy and Neuroscience

Mental imagery is a promising tool and mechanism of psychological interventions, particularly for mood and anxiety disorders. In parallel developments, neuromodulation techniques have shown promise as add-on therapies in psychiatry, particularly non-invasive brain stimulation for depression. However, these techniques have not yet been combined in a systematic manner. One novel technology that may be able to achieve this is neurofeedback, which entails the self-regulation of activation in specific brain areas or networks (or the self-modulation of distributed activation patterns) by the patients themselves, through real-time feedback of brain activation (for example, from functional magnetic resonance imaging). One of the key mechanisms by which patients learn such self-regulation is mental imagery. Here, we will first review the main mental imagery approaches in psychotherapy and the implicated brain networks. We will then discuss how these networks can be targeted with neuromodulation (neurofeedback or non-invasive or invasive brain stimulation). We will review the clinical evidence for neurofeedback and discuss possible ways of enhancing it through systematic combination with psychological interventions, with a focus on depression, anxiety disorders, and addiction. The overarching aim of this perspective paper will be to open a debate on new ways of developing neuropsychotherapies.
Nationwide Earthquake Risk Model for Wood-Frame Houses in Canada

Quantitative seismic risk assessments involve hazard characterization, exposure database, vulnerability assessment, and uncertainty modelling, and promote consistent risk management actions, when conducted systematically across a country. This study implements a performance-based earthquake engineering methodology to develop a nationwide earthquake risk model for Canadian wood-frame houses by integrating probabilistic seismic hazard analysis results provided by the Geological Survey of Canada and seismic fragility functions derived from incremental dynamic analysis. To facilitate the implementation of the seismic risk analysis method, an in-house probabilistic seismic hazard analysis tool for Canada is developed and used to verify the accuracy of the adopted approach of approximating the upper tail of the seismic intensity measure distribution and to generate detailed seismic disaggregation results for ground motion record selection and seismic fragility modelling purposes. By integrating the preceding two elements via Monte Carlo methods, a full seismic risk curve can be obtained in a computationally efficient manner. The approach is applied to 1,620 representative locations used for the 2016 Canadian Census and thus facilitates the development of seismic risk maps of key risk metrics that are derived from exceedance probability curves in terms of earthquake damage/loss ratio. The developed seismic risk maps serve as valuable decision-support tools to implement risk-based management strategies consistently across Canada.
Hierarchically Structured CeO2 Catalyst Particles From Nanocellulose/Alginate Templates for Upgrading of Fast Pyrolysis Vapors

Hierarchically structured porous materials often exhibit advantageous functionality for many applications including catalysts, adsorbents, and filtration systems. In this study, we report a facile approach to achieve hierarchically structured, porous cerium oxide (CeO2) catalyst particles using a templating method based on nanocellulose, a class of renewable, plant-derived nanomaterials. We demonstrate the catalyst performance benefits provided by this templating method in the context of Catalytic Fast Pyrolysis (CFP) which is a promising conversion technology to produce renewable fuel and chemical products from biomass and other types of organic waste. We show that variations in the porous structures imparted by this templating method may be achieved by modifying the content of cellulose nanofibrils, cellulose nanocrystals, and alginate in the templating suspensions. Nitrogen physisorption reveals that nearly 10-fold increases in surface area can be achieved using this method with respect to commercially available cerium oxide powder. Multiscale electron microscopy further verifies that bio-derived templating can alter the morphology of the catalyst nanostructure and tune the distribution of meso- and macro-porosity within the catalyst particles while maintaining CeO2 crystal structure. CFP experiments demonstrate that the templated catalysts display substantially higher activity on a gravimetric basis than their non-templated counterpart, and that variations in the catalyst architecture can impact the distribution of upgraded pyrolysis products. Finally, we demonstrate that the templating method described here may be extended to other materials derived from metal chlorides to achieve 3-dimensional networks of hierarchical porosity.
The Role of Social and Ability Belonging in Men’s and Women’s pSTEM Persistence

The benefits of belonging for academic performance and persistence have been examined primarily in terms of subjective perceptions of social belonging, but feeling ability belonging, or fit with one’s peers intellectually, is likely also important for academic success. This may particularly be the case in male-dominated fields, where inherent genius and natural talent are viewed as prerequisites for success. We tested the hypothesis that social and ability belonging each explain intentions to persist in physical science, technology, engineering, and math (pSTEM). We further explore whether women experience lower social and ability belonging than men on average in pSTEM and whether belonging more strongly relates to intentions to persist for women. At three time points throughout a semester, we assessed undergraduate pSTEM majors enrolled in a foundational calculus or physics course. Women reported lower pSTEM ability belonging and self-efficacy than men but higher identification with pSTEM. End-of-semester social belonging, ability belonging, and identification predicted intentions to persist in pSTEM, with a stronger relationship between social belonging and intentions to persist in pSTEM for women than men. These findings held after controlling for prior and current academic performance, as well as two conventional psychological predictors of academic success.
From Big Scholarly Data to Solution-Oriented Knowledge Repository

The volume of scientific articles grow rapidly, producing a scientific basis for understanding and identifying the research problems and the state-of-the-art solutions. Despite the considerable significance of the problem-solving information, existing scholarly recommending systems lack the ability to retrieve this information from the scientific articles for generating knowledge repositories and providing problem-solving recommendations. To address this issue, this paper proposes a novel framework to build solution-oriented knowledge repositories and provide recommendations to solve given research problems. The framework consists of three modules: a semantics based information extraction module mining research problems and solutions from massive academic papers; a knowledge assessment module based on the heterogeneous bibliometric graph and a ranking algorithm; and a knowledge repository generation module to produce solution-oriented maps with recommendations. Based on the framework, a prototype scholarly solution support system is implemented. A case study is carried out in the research field of intrusion detection, and the results demonstrate the effectiveness and efficiency of the proposed method.
Toll-Like Receptor-Mediated Activation of CD39 Internalization in BMDCs Leads to Extracellular ATP Accumulation and Facilitates P2X7 Receptor Activation

Toll-like receptors (TLRs) trigger innate immune responses through their recognition of conserved molecular ligands of either endogenous or microbial origin. Although activation, function, and signaling pathways of TLRs were already well-studied, their precise function in specific cell types, especially innate immune cells, needs to be further clarified. In this study, we showed that when significantly decreased amounts of membrane CD39, an adenosine triphosphate (ATP)-degrading enzyme, were detected in lipopolysaccharide (LPS)-treated bone marrow-derived dendritic cells (BMDCs), Cd39 mRNA expression, and whole-cell CD39 expression were at the same levels as those in untreated BMDCs. Further experiments demonstrated that the downregulation of membrane CD39 expression in LPS-treated BMDCs was mediated by endocytosis, leading to membrane-exposed CD39 downregulation, which was positively associated with decreased enzymatic activity in ATP metabolism and increased extracellular ATP accumulation. The accumulated ATP promoted intracellular calcium accumulation and IL-1β production in BMDCs through P2X7 signaling activation. Further research revealed that not only LPS but also other TLR ligands, excluding polyI:C, induced CD39 internalization in BMDCs and that the MyD88 pathway was critical in this process. The results suggested that the activation of CD39 internalization in DCs induced by a TLR ligand caused increased ATP accumulation, leading to P2X7 receptor activation that mediated a proinflammatory effect. Considering the strong modulatory effect of extracellular ATP accumulation on the immune response and inflammation, the manipulation of membrane CD39 expression on DCs may have implications on the regulation and treatment of inflammatory responses.
1 . 1 Algorithms for Lasso and Dantzig Selector : Fixing the Gap in Performance

We consider a class of linear-programming based estimators in reconstructing a sparse signal from linear measurements. Specific formulations of the reconstruction problem considered here include Dantzig selector, basis pursuit (for the case in which the measurements contain no errors), and the fused Dantzig selector (for the case in which the underlying signal is piecewise constant). In spite of being estimators central to sparse signal processing and machine learning, solving these linear programming problems for large scale instances remains a challenging task, thereby limiting their usage in practice. We show that classic constraintand column-generation techniques from large scale linear programming, when used in conjunction with a commercial implementation of the simplex method, and initialized with the solution from a closely-related Lasso formulation, yields solutions with high efficiency in many settings.
The Prediction of Multimodal Public Transportation Sharing Rate Based on Data

Accurate prediction of multimodal public transportation sharing rate is of great significance in coordinating traffic management, increasing public transport efficiency and allocating resources properly. The daily number of trips by subway, bus and ferry of pubic transport is calculated through data reduction and data mining, and the data of main factors affecting the fluctuation of public transportation sharing rate, i.e. holidays (or not), weather and air temperature, is collected in this paper based on big data on swiping public transportation IC cards in Shanghai. In addition, the sharing rates of subway, bus and ferry are predicted by using deep learning model based on historical data on daily number of trips and main influence factors, setting characteristic data and label data, and selecting activation function, loss function and gradient descent algorithm. The results show that the prediction error is less than 2.9%.
Comparison between CNA Estimators and WGS technology based on the Refinement of Breakpoints using the Confidence Masks

Alterations in some sections of genomes are commonly related with genetic disorders, which are well known as Structural Aberrations (SAs). The SAs are usually best known as Copy Number Alteration (CNA), and the identifications of this aberrations is essential to diagnose a diseases and to provide an specific treatment. Many algorithms have been developed to estimate the breakpoints and segmental levels of CNAs with the minimum error using the data obtained by modern technologies of hybridization. In spite of recent advances in high resolution data, the breakpoints estimated of CNAs are regularly inconsistent by two principal causes: an extensive variability of measurements and the different designs of the algorithms. Although the estimation of the CNAs is extremely important, still much less attention is given to the estimation accuracy and it is difficult to select the best estimator. In this work, we propose to use the confidence masks based on asymmetric exponential power distribution (AEP) to remove the breakpoints estimated from Ovarian Cancer samples using the CBS and PELT algorithms at a specific probability. Next, the refined breakpoints are compared with a reference obtained by the Whole Genome Sequencing (WGS) technology. Finally, the effectiveness of each estimator is registered by the F1 test, Area Under Curve (AUC) and Youden's J statistic to determine the best algorithm.