Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrative analysis of transcriptomic and metabolomic data via sparse canonical correlation analysis with incorporation of biological information

Integrative analysis of high dimensional omics data is becoming increasingly popular. At the same time, incorporating known functional relationships among variables in analysis of omics data has been shown to help elucidate underlying mechanisms for complex diseases. In this article, our goal is to assess association between transcriptomic and metabolomic data from a Predictive Health Institute (PHI) study that includes healthy adults at a high risk of developing cardiovascular diseases. Adopting a strategy that is both data‐driven and knowledge‐based, we develop statistical methods for sparse canonical correlation analysis (CCA) with incorporation of known biological information. Our proposed methods use prior network structural information among genes and among metabolites to guide selection of relevant genes and metabolites in sparse CCA, providing insight on the molecular underpinning of cardiovascular disease. Our simulations demonstrate that the structured sparse CCA methods outperform several existing sparse CCA methods in selecting relevant genes and metabolites when structural information is informative and are robust to mis‐specified structural information. Our analysis of the PHI study reveals that a number of gene and metabolic pathways including some known to be associated with cardiovascular diseases are enriched in the set of genes and metabolites selected by our proposed approach.
Chemo-Mechanical Micromodel for Alkali-Silica Reaction

This paper presents a two-stage numerical model for alkali-silica reaction (ASR)/stress analysis in concrete. The coupled analytical chemo-mechanical model developed by Suwito et al. was modified to include the effects of internal moisture and ion concentration on the transport properties of concrete. A finite difference model was used to simulate the coupled diffusion of alkali into concrete and subsequent ASR gel into pores surrounding the aggregates. A finite element model was then subsequently used to perform a nonlinear analysis. This model is invoked from the master finite difference model, resulting in a coupled chemo-mechanical simulation of ASR-affected concrete with aggregates of different shapes and sizes. Throughout this analysis, the authors keep track of the vertical and lateral expansions of the concrete with time which, in turn, are transformed into equivalent anisotropic coefficients of ASR expansion. Finally, the accuracy of the model is assessed through comparison with simulated laboratory tests.
Large-Scale Flow Experiments for Managing River Systems

Experimental manipulations of streamflow have been used globally in recent decades to mitigate the impacts of dam operations on river systems. Rivers are challenging subjects for experimentation, because they are open systems that cannot be isolated from their social context. We identify principles to address the challenges of conducting effective large-scale flow experiments. Flow experiments have both scientific and social value when they help to resolve specific questions about the ecological action of flow with a clear nexus to water policies and decisions. Water managers must integrate new information into operating policies for large-scale experiments to be effective. Modeling and monitoring can be integrated with experiments to analyze long-term ecological responses. Experimental design should include spatially extensive observations and well-defined, repeated treatments. Large-scale flow manipulations are only a part of dam operations that affect river systems. Scientists can ensure that experimental manipulations continue to be a valuable approach for the scientifically based management of river systems.
Phthalate induced toxicity in prostate cancer cell lines and effects of alpha lipoic acid.

OBJECTIVE The effects of dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate were investigated on human prostate cancer cell lines DU145 and PC3 in vitro. MATERIALS AND METHODS Standards of dimethyl phthalate, diethyl phthalate, di-isobutyl phthalate, dibutyl phthalate, benzyl butyl phthalate, and di-ethyl hexyl phthalate were used. Alpha lipoic acid was used as antioxidant compound. DU145 and PC3 human prostate carcinoma cells were used. MTT assay were used for cytotoxicity assay. RESULTS A low dose proliferative effect of phthalates in vitro was observed. With the hypothesis of the inhibition of aerobic glycolysis activity in cancer treatment, α-lipoic acid was applied to cells; where as a contrary to previous studies, no change in the cell proliferation was observed. In combination with ALA, at IC50 and lower doses, an increase of the cytotoxic effect was found for DIBP, DBP and BBP; while for DMP, DEP and DEHP, a decrease was observed for DU145 cells. In PC3 cells, a decrease was observed for DMP, DEP and DBPs; while no significant difference were observed for DEHP, DIBP and BBP. CONCLUSSION The present study demonstrates preliminary information regarding the low dose proliferative effects of phthalates in prostate cancer in vitro (Tab. 2, Fig. 2, Ref. 65).
The Effects of a Deicing Agent on the Absorption and Permeability of Various Concretes

The ultimate goal of this research is the development of test methods for the prediction of the frost durability of concrete. The absorption and permeability properties of three different precast concrete paving slabs andfive laboratory fabricated slabs were investigated using water and three different concentrations (2, 4, and 10 percent) of sodium chloride in water. Concrete parameters investigated included water/cement ratio, air entrainment, and method of slab manufacture. The absorptivity and permeability of the various concrete slabs appeared to be more affected by the water/cement ratio of the concretes than by either the salt solution concentration or air entrainment.
Characterization of clinical features and outcome for human-to-human transmitted severe fever with thrombocytopenia syndrome

Abstract Background: Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease identified in 2009. SFTS is mainly transmitted by contact with ticks or animals; however, sporadic reports suggested that SFTS could be transmitted among humans. Objectives: We aimed to comprehensively characterize clinical features and disease progression of SFTS acquired by human-to-human transmission. Study design: A retrospective study of 90 SFTS patients was performed in a tertiary hospital of Nanjing, China, from October 2010 to October 2016. Seven cases of secondary SFTS were identified based on their epidemic timeline. Their clinical presentations, dynamic laboratory results and clinical outcome were analyzed. Results: First, 20 out of 83 primary SFTS patients were deceased, leading to a case-fatality ratio of 24.1%, while all secondary patients survived, suggesting a superior clinical outcome for secondary infection. Moreover, clinical symptoms and laboratory tests in primary and secondary SFTS patients were analyzed, respectively. Secondary SFTS patients developed milder clinical manifestation in the absence of neurological disorder and multiple organ failure. Further, clinical laboratory tests revealed that secondary patients had less disturbed key laboratory parameters, compared to those in primary SFTS patients. During day 7–13 post illness onset, most of the clinical laboratory results of secondary patients went back to normal range. They also had significantly lower level of viral load than primary patients. Conclusions: Secondary SFTS acquired through human-to-human transmission leads to milder clinical representations and superior prognoses compared to primary SFTS, suggesting that the transmission route makes a difference in disease progression and clinical outcome of SFTS disease.
A randomized controlled trial of self‐regulated modified constraint‐induced movement therapy in sub‐acute stroke patients

Emerging research suggests the use of self‐regulation (SR) for improving functional regain in patients post stroke. SR is proposed to produce an added effect to effective modified constraint‐induced movement therapy (mCIMT). This study aimed to examine the effect of a self‐regulated mCIMT programme (SR‐mCIMT) for functional regain in patients with sub‐acute stroke.
Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK

Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the up‐ and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC‐1α, SIRT‐1, and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes. Further, RA treatment increased the glucose uptake and decreased the phosphorylation of serine IRS‐1 while increasing the translocation of GLUT 4. Together, our findings evidenced that RA treatment significantly inhibit insulin resistance in skeletal muscle cells by enhancing mitochondrial biogenesis. J. Cell. Biochem. 118: 1839–1848, 2017. © 2017 Wiley Periodicals, Inc.
EBNA3C Attenuates the Function of p53 through Interaction with Inhibitor of Growth Family Proteins 4 and 5

ABSTRACT Epstein-Barr virus (EBV)-encoded EBNA3C is one of the latent proteins essential for the efficient transformation of human primary B lymphocytes into continuously proliferating lymphoblastoid cell lines (LCLs) in vitro through manipulation of a number of major cellular pathways. Although it does not have direct DNA-binding activity, EBNA3C plays a central role in the transcriptional modulation of a wide range of both viral and cellular genes during latent infection. Recently, we showed that EBNA3C can directly bind to the tumor suppressor protein p53 and repress its functions, in part by blocking its transcriptional activity as well as facilitating its degradation through stabilization of its negative regulator, Mdm2. In this study, we further showed that EBNA3C can negatively regulate p53-mediated functions by interacting with its regulatory proteins, the inhibitor of growth family proteins ING4 and ING5, shown to be frequently deregulated in different cancers. Functional mapping revealed that both ING4 and ING5 bound to N-terminal domain residues 129 to 200 of EBNA3C, which was previously demonstrated to associate with p53 and is also essential for LCL growth. In addition, we showed that a conserved domain of either ING4 or ING5 bound to both p53 and EBNA3C in a competitive manner, suggesting a potential role for EBNA3C whereby the ING4 or -5/p53 pathway is modulated in EBV-infected cells. Subsequently, we demonstrated that EBNA3C significantly suppresses both the ING4- and ING5-mediated regulation of p53 transcriptional activity in a dose-dependent manner. A colony formation assay as well as an apoptosis assay showed that EBNA3C nullified the negative regulatory effects on cell proliferation induced by coupled expression of p53 in the presence of either ING4 or ING5 in Saos-2 (p53−/−) cells. This report demonstrates a possible role for the candidate tumor suppressor ING genes in the biology of EBV-associated cancers.
Structure Analysis of a New Psychrophilic Marine Protease

A new psychrophilic marine protease was found from a marine bacterium Flavobacterium YS-80 in the Chinese Yellow Sea. The protease is about 49 kD with an isoelectric point about 4.5. It consists of 480 amino acids and is homologous to a psychrophilic alkaline protease (PAP) from an Antarctic Pseudomonas species. The protein was purified from the natural bacterium fermented and crystallized. Its crystal structure (PDB ID 3U1R) was solved at 2.0 Å by Molecular Replacement using a model based on PAP, and was refined to a crystallographic Rwork of 0.16 and an Rfree of 0.21. The marine protease consists of a two domain structure with an N-terminal domain including residues 37–264 and a C-terminal domain including residues 265–480. Similar to PAP, the N-terminal domain is responsible for proteolysis and the C-terminal is for stability. His186, His190, His196 and Tyr226 are ligands for the Zn2+ ion in the catalytic center. The enzyme's Tyr226 is closer to the Zn2+ ion than in PAP and it shows a stronger Zn2+―Tyr-OH bond. There are eight calcium ions in the marine protease molecule and they have significantly shorter bond distances to their ligands compared to their counterparts in all three crystal forms of PAP. On the other hand, the loops in the marine protease are more compact than in PAP. This makes the total structure stable and less flexible, resulting in higher thermo stability. These properties are consistent with the respective environments of the proteases. The structural analysis of this new marine protease provides new information for the study of psychrophilic proteases and is helpful for elucidating the structure-environment adaptation of these enzymes.
Digital poly-victimization: The increasing importance of online crime and harassment to the burden of victimization

ABSTRACT Many forms of victimization, including bullying and property crime, are increasingly moving online, but most studies of poly-victimization still primarily focus on in-person crime and violence. Few studies have examined the importance of incorporating technology-based victimizations for assessing the true burden of violence. The purpose of this study is to explore whether digital poly-victimization contributes to post-traumatic stress and anxiety/dysphoria symptoms after controlling for in-person poly-victimization. Given that technology use and technology-based victimization are changing rapidly, a mixed methods approach was adopted. In the first two phases, focus groups and cognitive interviews (89 total participants) were used to identify the range of digital victimization and develop the Digital Poly-Victimization Scale. In the third phase, the new measure was included in a community survey (n = 478, 57.5% female; 62.6% earning under $50,000 per year) in a rural Southern region, along with measures of in-person poly-victimization, posttraumatic stress and anxiety/dysphoria symptoms, and other outcomes and personal characteristics. A comprehensive measure of digital poly-victimization indicated that almost 3 in 4 participants (72.3%) had experienced at least one form of digital victimization. The results indicated that digital poly-victimization contributed unique variance to post-traumatic stress and anxiety/dysphoria symptoms (p < .001), health-related quality of life (p < .01), and subjective and family well-being (both p < .001), even after controlling for demographics and in-person poly-victimization. Digital victimization often presents fewer risks to perpetrators and can be expected to represent an increasing share of the societal burden of violence. Future research on poly-victimization should pay more attention to the role of digital victimization.
Reactance of hollow, solid, and hemispherical-cap cylindrical posts in rectangular waveguide

An accurate experimental technique is employed to determine the reactance of three commonly used symmetrical waveguide discontinuities: cylindrical posts with hollow, solid, and hemispherical-cap ends, and a useful data set is presented. Length adjustment factors are derived for the case of symmetrical excitation that relate the reactance of each post form. When used in conjunction with an existing analysis, it is shown that very accurate results can be predicted for the reactance of solid and hemispherical-cap posts.
Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease

Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co‐existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio‐incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom.
Reported traumatic injuries among West Coast Dungeness crab fishermen, 2002-2014.

BACKGROUND Commercial fishing is a high-risk occupation. The West Coast Dungeness crab fishery has a high fatality rate; however, nonfatal injuries have not been previously studied. The purpose of this report was to describe the characteristics of fatal and nonfatal traumatic occupational injuries and associated hazards in this fleet during 2002-2014. MATERIALS AND METHODS Data on fatal injuries were obtained from a surveillance system managed by the National Institute for Occupational Safety and Health. Data on nonfatal injuries were manually abstracted from Coast Guard investigation reports and entered into a study database. Descriptive statistics were used to characterise demographics, injury characteristics, and work processes performed. RESULTS Twenty-eight fatal and 45 nonfatal injuries were reported between 2002 and 2014 in the Dungeness crab fleet. Most fatalities were due to vessel disasters, and many nonfatal injuries occurred on-deck when fishermen were working with gear, particularly when hauling the gear (47%). The most frequently reported injuries affected the upper extremities (48%), and fractures were the most commonly reported injury type (40%). The overall fatality rate during this time period was 209 per 100,000 full-time equivalent workers and the rate of nonfatal injury was 3.4 per 1,000 full-time equivalent workers. CONCLUSIONS Dungeness crab fishermen are at relatively high risk for fatal injuries. Nonfatal injuries were limited to reported information, which hampers efforts to accurately estimate nonfatal injury risk and understand fishing hazards. Further research is needed to identify work tasks and other hazards that cause nonfatal injuries in this fleet. Engaging fishermen directly may help develop approaches for injury prevention.
Time-Dependent Effects of POT1 Knockdown on Proliferation, Tumorigenicity, and HDACi Response of SK-OV3 Ovarian Cancer Cells

The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot. The relative telomerase activity levels were detected using qTRAP; cell proliferation was assessed using cumulative population doubling (cPD) experiments. Cell tumorigenicity was evaluated by anchorage-independent cell growth assays, and cell response to HDACi was determined by luminescence cell viability assays. Results indicate that lenti-shRNA-mediated POT1-KD significantly reduced POT1 mRNA and protein expression. POT1-KD immediately downregulated c-Myc expression, which led to the inhibition of cell proliferation, tumorigenesis, and HDACi response. However, after brief suppression, c-Myc expression increased in the medium term, which resulted in enhanced cell proliferation, tumorigenesis, and HDACi response in the POT1-KD cells. Furthermore, we discovered that c-Myc regulated cell proliferation and tumorigenesis via hTERT/telomerase/telomere pathway.
Thinning or thickening? Multiple rheological regimes in dense suspensions of soft particles

The shear rheology of dense colloidal and granular suspensions is strongly nonlinear, as these materials exhibit shear-thinning and shear-thickening, depending on multiple physical parameters. We numerically study the rheology of a simple model of soft repulsive particles at large densities, and show that nonlinear flow curves reminiscent of experiments on real suspensions can be obtained. By using dimensional analysis and basic elements of kinetic theory, we rationalize these multiple rheological regimes and disentangle the relative impact of thermal fluctuations, glass and jamming transitions, inertia and particle softness on the flow curves. We characterize more specifically the shear-thickening regime and show that both particle softness and the emergence of a yield stress at the jamming transition compete with the inertial effects responsible for the observed thickening behaviour. This allows us to construct a dynamic state diagram, which can be used to analyze experiments.
17β‐Estradiol Protects Skeletal Myoblasts From Apoptosis Through p53, Bcl‐2, and FoxO Families

17β‐Estradiol (E2) protects several nonreproductive tissues from apoptosis, including skeletal muscle. Previously, we showed that E2 at physiological concentrations prevented apoptosis induced by H2O2 in skeletal myoblasts, reverting PKCδ, JNK, and p66Shc activation and exerting a beneficial action over mitochondria. Since genomic actions underlying the regulation of nuclear gene transcription are a common property of this steroid, the present work characterizes the transcriptional activity modulated by E2 to exert its antiapoptotic effect. We report that E2 protects skeletal myoblasts against apoptosis induced by H2O2 modulating p53 and FoxO transcription factors and then their target genes Bcl‐2, Bim, Puma, PERP, and MDM2, without affecting Noxa gene. The results presented in this work support the notion that the transcription factors FoxO and p53 coordinate apoptosis in C2C12 cells, and deepens our knowledge about a putative molecular mechanism by which E2 exerts beneficial effects against oxidative stress in skeletal myoblasts. J. Cell. Biochem. 118: 104–115, 2017. © 2016 Wiley Periodicals, Inc.