Miracle-dz/UniFAR-FTUs huggingface dataset:
The HSP70 Molecular Chaperone Is Not Beneficial in a Mouse Model of α-synucleinopathy

Background Aggregation and misfolded α-synuclein is thought to be central in the pathogenesis of Parkinson's disease (PD). Heat-shock proteins (HSPs) that are involved in refolding and degradation processes could lower the aggregate load of α-synuclein and thus be beneficial in α-synucleinopathies. Methodology/Principal Findings We co-overexpressed human A53T point-mutated α-synuclein and human HSP70 in mice, both under the control of Thy1 regulatory sequences. Behavior read-outs showed no beneficial effect of HSP70 expression in mice. In contrast, motor coordination, grip strength and weight were even worse in the α-synucleinopathy model in the presence of HSP70 overexpression. Biochemical analyses revealed no differences in α-synuclein oligomers/aggregates, truncations and phosphorylation levels and α-synuclein localization was unchanged in immunostainings. Conclusion/Significance Overexpressing HSP70 in a mouse model of α-synucleinopathy did not lower the toxic load of α-synuclein species and had no beneficial effect on α-synuclein-related motor deficits.
Acetaminophen ingestion improves repeated sprint cycling performance in females: a randomized crossover trial

The aim of this study is to investigate the effect of acute acetaminophen (ACT) ingestion on eight maximal 30-second cycling bouts, interspersed with two-minute rests. Seven recreationally active females (N=7, 22.8Â±6.7 years of age, with a stature of 163.4Â±5.8 cm, and body mass of 58.9Â±5.9 kg) participated in a placebo-controlled, randomized crossover design. Pain perception, heart rate, and power profiles were analyzed using a time x condition repeated measures ANOVA. Blood lactate after the eighth bout and total work done were analyzed using the paired samples t-test. Participants achieved a significantly greater (p=.007, =.725) peak power output during the ACT trials (402.9Â±73.8 W, 95% CI=334.6â€“471.1 W) when compared to the placebo (PLA) trials (378.7Â±64.6 W, 95% CI=319.0â€“438.4 W). Supplementation of ACT had no effect on mean power output, blood lactate accumulation, pain perception, or total work done after eigth bouts (p>.05). Data presented here suggest females can improve peak power output during repeated Wingate tests with ACT ingestion. It is proposed that the altered afferent feedback may have caused these alterations in power output.
Common clinical conditions – age, low BMI, ritonavir use, mild renal impairment – affect tenofovir pharmacokinetics in a large cohort of HIV-infected women

Objective:Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown. Design:Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIV-infected women over 24 h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration–time curves (AUCs)] identified. Methods:HIV-infected women (n = 101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures. Results:The median (range) of tenofovir AUCs was 3350 (1031–13 911) ng × h/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P = 0.002), increasing age (1.21-fold increase per decade, P = 0.0007), and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increase when pre-tenofovir GFR <70 ml/min, P = 0.0075). Conclusion:Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.
Observations of green fluorescent protein as a fusion partner in genetically engineered Escherichia coli: monitoring protein expression and solubility.

We have constructed three plasmid vectors for the expression of green fluorescent protein (GFP) fusion proteins using the following motif: (His)(6)-GFP-EK-X, where X represents chloramphenicol acetyl-transferase (CAT), human interleukin-2 (hIL-2), and organophosphorous hydrolase (OPH), respectively, (His)(6) represents a histidine affinity ligand for purification, and EK represents an enterokinase cleavage site for recovering the protein-of-interest from the fusion. The CAT and OPH fusion products ( approximately 63 kDa GFP/CAT and approximately 70 kDa GFP/OPH) were expressed at 4.85 microg/mL (19.9 microg/mg-total protein) and 1.42 microg/mL (4.2 microg/mg-total protein) in the cell lysis supernatant, and, in both cases, enzymatic activity was retained while coupled to GFP. In the case of hIL-2 fusion ( approximately 52 kDa), however, the GFP fluorescence was significantly reduced and most of the fusion was retained in the cell pellet. Linear relationships between GFP fluorescence and CAT or OPH concentration, and with enzymatic activity of CAT or OPH, indicated, for the first time, that in vivo noninvasive quantification of proteins-of-interest, was made possible by simple measurement of GFP fluorescence intensity. The utility of GFP as a reporter was not realized without disadvantages however, in particular, an incremental metabolic cost of GFP was found. This could be offset by many benefits foreseen in expression and purification efficiencies.
UCP 2 regulates energy metabolism and differentiation potential of human pluripotent stem cells

Jin Zhang, Ivan Khvorostov, Jason S Hong, Yavuz Oktay, Laurent Vergnes, Esther Nuebel, Paulin N Wahjudi, Kiyoko Setoguchi, Geng Wang, Anna Do, Hea-Jin Jung, J Michael McCaffery, Irwin J Kurland, Karen Reue, Wai-Nang P Lee, Carla M Koehler* and Michael A Teitell* Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA, Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA, Department of Human Genetics, University of California, Los Angeles, CA, USA, Department of Pediatrics, LA Biomedical Research Institute, Torrance, CA, USA, Department of Biology, Integrated Imaging Center, Johns Hopkins University, Baltimore, MD, USA, Department of Medicine, Stable Isotopes and Metabolomics Core Facility, Albert Einstein College of Medicine Diabetes Center, Bronx, NY, USA, Molecular Biology Institute, University of California, Los Angeles, CA, USA and Broad Stem Cell Research Center, Jonsson Comprehensive Cancer Center, Center for Cell Control, and California NanoSystems Institute, University of California, Los Angeles, CA, USA
Active Transfer Learning for Cross-System Recommendation

Recommender systems, especially the newly launched ones, have to deal with the data-sparsity issue, where little existing rating information is available. Recently, transfer learning has been proposed to address this problem by leveraging the knowledge from related recommender systems where rich collaborative data are available. However, most previous transfer learning models assume that entity-correspondences across different systems are given as input, which means that for any entity (e.g., a user or an item) in a target system, its corresponding entity in a source system is known. This assumption can hardly be satisfied in real-world scenarios where entity-correspondences across systems are usually unknown, and the cost of identifying them can be expensive. For example, it is extremely difficult to identify whether a user A from Facebook and a user B from Twitter are the same person. In this paper, we propose a framework to construct entity correspondence with limited budget by using active learning to facilitate knowledge transfer across recommender systems. Specifically, for the purpose of maximizing knowledge transfer, we first iteratively select entities in the target system based on our proposed criterion to query their correspondences in the source system. We then plug the actively constructed entity-correspondence mapping into a general transferred collaborative-filtering model to improve recommendation quality. We perform extensive experiments on real world datasets to verify the effectiveness of our proposed framework for this cross-system recommendation problem.
Numerical Approach at Flat Plate for Predicting the Film Cooling Effectiveness Part A: Effect Blowing Ratio

Film cooling is vital for gas turbine blades to protect them from thermal stresses and high temperatures due to the hot gas flow in the blade surface. Film cooling is applied to almost all external surfaces associated with aerodynamic profiles that are exposed to hot combustion gases such as main bodies, end-walls, blade tips and leading edges. In a review of the literature, it was found that there are strong effects of free-stream turbulence, surface curvature and hole shape on film cooling performance also blowing ratio. The performance of the film cooling is difficult to predict due to the inherent complex flow fields along the surfaces of the airfoil components in the turbine engines. From all what we introducing the film cooling is reviewed through a discussion of the analyses methodologies, a physical description, and the various influences on film-cooling performance. Initially Computational analysis was done on a flat plate with hole inclined at 55° to the surface plate. This study focuses on the efficient computation of film cooling flows with three blowing ratio. The numerical results show the effectiveness cooling and heat transfer behavior with increasing injection blowing ratio M (0.5, 1, and 1.5). The influence of increased blade film cooling can be assessed via the values of Nusselt number in terms of reduced heat transfer to the blade. Predictions of film effectiveness are compared with experimental results for a circular jet at blowing ratios ranging from 0.5, 1.0 and 1.5. The present results are obtained at a free stream turbulence of 10%, which are the typical conditions upstream of the effectiveness is generally lower for a large stream-wise angle of 55°.
Therapy with Interleukin-22 Alleviates Hepatic Injury and Hemostasis Dysregulation in Rat Model of Acute Liver Failure

The therapeutic efficacy of interleukin-22 (IL-22) on liver injury and hematological disturbances was studied in rat model of acute liver failure (ALF) induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS). The following parameters were investigated: (1) survival rate, (2) serum levels of liver function enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), total bilirubin (TBILI), and total albumen (ALB), (3) blood clotting tests (prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level (FIB)) and white blood cells (WBCs), red blood cells (RBCs), and platelet counts, (4) hepatic levels of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), and (5) liver histopathology. After 48 hours of D-GalN/LPS, the rats exhibited 20% mortality, significant increases in AST, ALT, ALP, TBILI, PT, and aPTT, TNF-α, and COX-2 and significant decreases in FIB, WBCs, and RBCs. By contrast, therapy with IL-22 prevented the lethal effect of D-GalN/LPS by 100% and efficiently alleviated all the biochemical and hematological abnormalities that were observed in ALF untreated group. Furthermore, IL-22 treatment decreased the hepatic contents of TNF-α and COX-2. The histopathological findings also supported the hepatoprotective effect of IL-22. Taken together, therapy with IL-22 can represent a promising therapeutic tool against liver injury and its associated hemostasis disturbances.
Early and Differential Diagnosis of Dementia and Mild Cognitive Impairment

Background: The German Dementia Competence Network (DCN) has established procedures for standardized multicenter acquisition of clinical, biological and imaging data, for centralized data management, and for the evaluation of new treatments. Methods: A longitudinal cohort study was set up for patients with mild cognitive impairment (MCI), patients with mild dementia and control subjects. The aims were to establish the diagnostic, differential diagnostic and prognostic power of a range of clinical, laboratory and imaging methods. Furthermore, 2 clinical trials were conducted with patients suffering from MCI and mild to moderate Alzheimer’s Disease (AD). These trials aimed at evaluating the efficacy and safety of the combination of galantamine and memantine versus galantamine alone. Results: Here, we report on the scope and projects of the DCN, the methods that were employed, the composition and flow within the diverse groups of patients and control persons and on the clinical and neuropsychological baseline characteristics of the group of 2,113 subjects who participated in the observational and clinical trials. Conclusion: These data have an impact on the procedures for the early and differential clinical diagnosis of dementias, the current standard treatment of AD as well as on future clinical trials in AD.
Velocity oscillations in actin-based motility

We present a simple and generic theoretical description of actin-based motility, where polymerization of filaments maintains propulsion. The dynamics is driven by polymerization kinetics at the filaments' free ends, crosslinking of the actin network, attachment and detachment of filaments to the obstacle interface and entropic forces. We show that spontaneous oscillations in the velocity emerge due to a push–pull mechanism in a broad range of parameter values, and compare our findings with experiments.
Hormone Therapy and Cardiovascular Risk : Why the New Focus on Perimenopausal Women ?

he results of 2 large randomized trials involving postmenopausal hormone therapy (HT) recently have transformed long-standing beliefs about the efficacy and safety of such therapy in lowering cardiovascular (CV) risk. Most significantly, the landmark Women’s Health Initiative (WHI) study reported in 2002 that healthy women assigned to estrogen with progestin had a possible increase in coronary heart disease (CHD) compared with women taking placebo. The risks of stroke and pulHormone Therapy and Cardiovascular Risk: Why the New Focus on Perimenopausal Women?
Biofunctionalization of biomaterials for nitric oxide delivery: potential applications in regenerative medicine

*These authors contributed equally to this work Introduction: Mimicking physiological functions of nitric oxide (NO) has applications in regenerative medicine. However, few NO delivery systems have progressed to clinical trials owing to limitations in delivery. Materials and methods: A novel NO delivery system was explored by integrating S-nitroN-acetylpenicillamine-functionalized long-chain aliphatic hydrocarbons (LCAHs) into a polyurethane-based polymer. Results and discussion: Contact angle analysis determined the novel delivery system to be significantly more hydrophobic than control. Chemilluminscence showed a four-phase NO release profile of the delivery system with more stable and prolong NO release than control. Conclusion: LCAHs can optimize the duration and rate of NO delivery and present a viable option for use in surgical implants and biomedical applications.
Extracellular Recombinant Annexin II Confers UVC-Radiation Resistance and Increases the Bcl-xL to Bax Protein Ratios in Human UVC-Radiation-Sensitive Cells

In this study, we found that refractoriness to ultraviolet (UVC) light-induced cell death was increased in UVC-radiation-sensitive cells derived from Cockayne syndrome patients when the cells were precultured in medium supplemented with recombinant annexin II (rANX II). In CS3BES cells, an immortal cell line derived from Cockayne syndrome patients, the rANX II supplementation-induced UVC-radiation resistance was suppressed by treatment with an anti-annexin II antibody and EGTA. The amount of biotinylated annexin II on the cell surface increased in the rANX II-supplemented cells but did not increase in the cells that were cotreated with rANX II and EGTA. The capacity to remove UVC-radiation-damaged DNA, (6-4) photoproducts and cyclobutane pyrimidine dimers, was the same in cells that were precultured with rANX II and in control cells that did not receive rANX II supplementation. The rANX II supplementation-induced UVC-radiation resistance was also observed in nucleotide excision repair-deficient cells and xeroderma pigmentosum group A-downregulated cells. The Bcl-xL to Bax protein ratios, an index of survival activity in cells exposed to lethal stresses, were increased in the cells that had been precultured in rANX II for 24 h prior to UVC irradiation. Treatment with a phosphatidylinositol 3-kinase inhibitor suppressed the increased UVC-radiation resistance and Bcl-xL to Bax ratios in the cells with rANX II supplementation. Furthermore, downregulation of Bcl-xL by siRNA transfection also suppressed the UVC-radiation resistance that was induced by rANX II supplementation. These results suggest that the increase in the Bcl-xL to Bax ratios may be associated with enhanced resistance to UVC-radiation-induced cell death.
The stability of hollow nanoparticles and the simulation temperature ramp

Hollow nanoparticles (hNPs) are of interest because their large cavities and small thickness give rise to a large surface to volume ratio. However, in general they are not in equilibrium and far from their global energy minimum, which often makes them unstable against perturbations. In fact, a temperature increase can induce a structural collapse into a nanoparticle, and consequently a loss of their unique properties. This problem has been studied by means of molecular dynamics (MD) simulations, but without emphasis on the speed of the temperature increase. Here we explore how the temperature variation, and the rate at which it is varied in MD simulations, determines the final conformation of the hNPs. In particular, we show how different temperature ramps determine the final shape of Pt hNPs that initially have an external radius between 0.7 and 24 nm, and an internal radius between 0.19 and 2.4 nm. In addition, we also perform the simulations of other similar metals like Ag and Au. Our results indicate that the temperature ramp strongly modifies the final hNP shape, even at ambient temperature. In fact, a rapid temperature increase leads to the formation of stacking faults and twin boundaries which are not generated by a slower temperature increase. Quantitative criteria are established and they indicate that the stacking fault energy is the dominant parameter.
THE EFFECTS OF THE LOCAL ENVIRONMENT AND STELLAR MASS ON GALAXY QUENCHING TO z ∼ 3

We study the effects of the local environment and stellar mass on galaxy properties using a mass complete sample of quiescent and star-forming systems in the COSMOS field at . We show that at the median star formation rate (SFR) and specific SFR (sSFR) of all galaxies depend on the environment, but they become independent of the environment at z ≳ 1. However, we find that only for star-forming galaxies, the median SFR and sSFR are similar in different environments regardless of redshift and stellar mass. We find that the quiescent fraction depends on the environment at z ≲ 1 and on stellar mass out to z ∼ 3. We show that at z ≲ 1 galaxies become quiescent faster in denser environments and that the overall environmental quenching efficiency increases with cosmic time. Environmental and mass quenching processes depend on each other. At z ≲ 1 denser environments more efficiently quench galaxies with higher masses (log( ) ≳ 10.7), possibly due to a higher merger rate of massive galaxies in denser environments. We also show that mass quenching is more efficient in denser regions. We show that the overall mass quenching efficiency ( ) for more massive galaxies (log( ) ≳ 10.2) rises with cosmic time until z ∼ 1 and then flattens out. However, for less massive galaxies, the rise in continues to the present time. Our results suggest that environmental quenching is only relevant at z ≲ 1 and is likely a fast process, whereas mass quenching is the dominant mechanism at z ≳ 1 with a possible stellar feedback physics.
Perceptions of Statin Discontinuation among Patients with Life-Limiting Illness.

BACKGROUND Optimal management of chronic medications for patients with life-limiting illness is uncertain. Medication deprescribing may improve outcomes in this population, but patient concerns regarding deprescribing are unclear. OBJECTIVE The aim of this study was to quantify the perceived benefits and concerns of statin discontinuation among patients with life-limiting illness. DESIGN Baseline data from a multicenter, pragmatic clinical trial of statin discontinuation were used. SETTING/SUBJECTS Cognitively intact participants with a life expectancy of 1-12 months receiving statin medications for primary or secondary prevention were enrolled. MEASUREMENTS Responses to a 9-item questionnaire addressing patient concerns about discontinuing statins were collected. We used Pearson chi-square tests to compare responses by primary life-limiting diagnosis (cancer, cardiovascular disease, other). RESULTS Of 297 eligible participants, 58% had cancer, 8% had cardiovascular disease, and 30% other primary diagnoses. Mean (standard deviation) age was 72 (11) years. Fewer than 5% of participants expressed concern that statin deprescribing indicated physician abandonment. About one in five participants reported being told to take statins for the rest of their life (18%) or feeling that discontinuation represented prior wasted effort (18%). Many participants reported benefits of stopping statins, including spending less money on medications (63%), potentially stopping other medications (34%), and having a better quality of life (25%). More participants with cardiovascular disease as a primary diagnosis perceived that quality-of-life benefits related to statin discontinuation (52%) than participants with cancer (27%) or noncardiovascular disease diagnoses (27%) [p = 0.034]. CONCLUSION Few participants expressed concerns about discontinuing statins; many perceived potential benefits. Cardiovascular disease patients perceived greater potential positive impact from statin discontinuation.
Keyphrase Extraction Using Deep Recurrent Neural Networks on Twitter

Keyphrases can provide highly condensed and valuable information that allows users to quickly acquire the main ideas. The task of automatically extracting them have received considerable attention in recent decades. Different from previous studies, which are usually focused on automatically extracting keyphrases from documents or articles, in this study, we considered the problem of automatically extracting keyphrases from tweets. Because of the length limitations of Twitter-like sites, the performances of existing methods usually drop sharply. We proposed a novel deep recurrent neural network (RNN) model to combine keywords and context information to perform this problem. To evaluate the proposed method, we also constructed a large-scale dataset collected from Twitter. The experimental results showed that the proposed method performs signiﬁcantly better than previous methods.