Revealing the variation mechanism of ON 231 via the two-components shock-in-jet model

The variation mechanism of blazars is a long-standing unresolved problem. In this work, we present a scenario to explain diverse variation phenomena for ON 231, where the jet emissions are composed of the flaring and the less variable components (most probably from the post-flaring blobs), and the variation is dominated by shock-in-jet instead of the Doppler effect. We perform correlation analysis for the multiwavelength light curves and find no significant correlations. For optical band, ON 231 exhibits a harder when brighter (HWB) trend, and the trend seems to shift at different periods. Correspondingly, the correlation between polarization degree and flux exhibits a V-shaped behavior, and a similar translation relation during different periods is also found. These phenomena could be understood via the superposition of the flaring component and slowly varying background component. We also find that the slopes of HWB trend become smaller at higher flux levels, which indicates the energy-dependent acceleration processes of the radiative particles. For X-ray, we discover a trend transition from HWB to softer when brighter (SWB) to HWB. We consider that the X-ray emission is composed of both the synchrotron tail and the Synchrotron Self-Compton components, which could be described by two log-parabolic functions. By varying the peak frequency, we reproduce the observed trend transition in a quantitative manner. For $\gamma$-ray, we find the SWB trend, which could be explained naturally if a very-high-energy $\gamma$-ray background component exists. Our study elucidates the variation mechanism of intermediate synchrotron-peaked BL Lac objects.Comment: 19 pages, 12 figures, 5 tables. Accepted for publication in The Astrophysical Journa

Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis

Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). While ω-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both ω-3 and ω-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C ω-3 LCPUFA (and ω-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPARα-/-mice and augmented ω-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic ω-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPARα. Fenofibrate augmented the overall protective effects of ω-3 LCPUFAs on neovascular eye diseases

Dihydroartemisinin Enhances Apo2L/TRAIL-Mediated Apoptosis in Pancreatic Cancer Cells via ROS-Mediated Up-Regulation of Death Receptor 5

BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded as a promising anticancer agent, but chemoresistance affects its efficacy as a treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL has not been well documented, and the mechanisms involved remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that DHA enhances the efficacy of Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was mediated through the generation of reactive oxygen species, the induction of death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small interfering RNA also significantly reduced the amount of apoptosis induced by DHA and Apo2L/TRAIL. CONCLUSIONS/SIGNIFICANCE: These results suggest that DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through reactive oxygen species-mediated up-regulation of DR5

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

Prior Antiplatelet Therapy, Excluding Phosphodiesterase Inhibitor Is Associated with Poor Outcome in Patients with Spontaneous Intracerebral Haemorrhage.

“This is a post-peer-review, pre-copyedit version of an article published in Translational Stroke Research. The final authenticated version is available online at: https://doi.org/10.1007/s12975-019-00722-x”.There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.Chang Gung Memorial Hospital (CMRPG3H1061, CMRPG3G1002

Open X-Embodiment:Robotic learning datasets and RT-X models

Large, high-capacity models trained on diverse datasets have shown remarkable successes on efficiently tackling downstream applications. In domains from NLP to Computer Vision, this has led to a consolidation of pretrained models, with general pretrained backbones serving as a starting point for many applications. Can such a consolidation happen in robotics? Conventionally, robotic learning methods train a separate model for every application, every robot, and even every environment. Can we instead train "generalist" X-robot policy that can be adapted efficiently to new robots, tasks, and environments? In this paper, we provide datasets in standardized data formats and models to make it possible to explore this possibility in the context of robotic manipulation, alongside experimental results that provide an example of effective X-robot policies. We assemble a dataset from 22 different robots collected through a collaboration between 21 institutions, demonstrating 527 skills (160266 tasks). We show that a high-capacity model trained on this data, which we call RT-X, exhibits positive transfer and improves the capabilities of multiple robots by leveraging experience from other platforms. The project website is robotics-transformer-x.github.io

Sleep problems during COVID-19 pandemic and its’ association to psychological distress: a systematic review and meta-analysis

Background: The emerging novel coronavirus disease 2019 (COVID-19) has become one of the leading cause of deaths worldwide in 2020. The present systematic review and meta-analysis estimated the magnitude of sleep problems during the COVID-19 pandemic and its relationship with psychological distress. Methods: Five academic databases (Scopus, PubMed Central, ProQuest, ISI Web of Knowledge, and Embase) were searched. Observational studies including case-control studies and cross-sectional studies were included if relevant data relationships were reported (i.e., sleep assessed utilizing the Pittsburgh Sleep Quality Index or Insomnia Severity Index). All the studies were English, peer-reviewed papers published between December 2019 and February 2021. PROSPERO registration number: CRD42020181644. Findings: 168 cross-sectional, four case-control, and five longitudinal design papers comprising 345,270 participants from 39 countries were identified. The corrected pooled estimated prevalence of sleep problems were 31% among healthcare professionals, 18% among the general population, and 57% among COVID-19 patients (all p-values < 0.05). Sleep problems were associated with depression among healthcare professionals, the general population, and COVID-19 patients, with Fisher's Z scores of -0.28, -0.30, and -0.36, respectively. Sleep problems were positively (and moderately) associated with anxiety among healthcare professionals, the general population, and COVID-19 patients, with Fisher's z scores of 0.55, 0.48, and 0.49, respectively. Interpretation: Sleep problems appear to have been common during the ongoing COVID-19 pandemic. Moreover, sleep problems were found to be associated with higher levels of psychological distress. With the use of effective programs treating sleep problems, psychological distress may be reduced. Vice versa, the use of effective programs treating psychological distress, sleep problems may be reduced