Weak Signal Inclusion Under Dependence and Applications in Genome-wide Association Study

Motivated by the inquiries of weak signals in underpowered genome-wide association studies (GWASs), we consider the problem of retaining true signals that are not strong enough to be individually separable from a large amount of noise. We address the challenge from the perspective of false negative control and present false negative control (FNC) screening, a data-driven method to efficiently regulate false negative proportion at a user-specified level. FNC screening is developed in a realistic setting with arbitrary covariance dependence between variables. We calibrate the overall dependence through a parameter whose scale is compatible with the existing phase diagram in high-dimensional sparse inference. Utilizing the new calibration, we asymptotically explicate the joint effect of covariance dependence, signal sparsity, and signal intensity on the proposed method. We interpret the results using a new phase diagram, which shows that FNC screening can efficiently select a set of candidate variables to retain a high proportion of signals even when the signals are not individually separable from noise. Finite sample performance of FNC screening is compared to those of several existing methods in simulation studies. The proposed method outperforms the others in adapting to a user-specified false negative control level. We implement FNC screening to empower a two-stage GWAS procedure, which demonstrates substantial power gain when working with limited sample sizes in real applications.Comment: arXiv admin note: text overlap with arXiv:2006.1566

Early evidence and predictors of mental distress of adults one month in the COVID-19 epidemic in Brazil

Objective: We aim to provide early evidence of mental distress and its associated predictors among adults one month into the COVID-19 crisis in Brazil. Methods: We conducted an online survey of 638 adults in Brazil on March 25–28, 2020, about one month (32 days) cross-sectionally after the first COVID-19 case in South America was confirmed in São Paulo. The 638 adults were in 25 states out of the 26 Brazilian states, with the only exception being Roraima, the least populated state in the Amazon. Of all the participating adults, 24%, 20%, and 18% of them were located in Rio de Janeiro state, Santa Catarina state, and São Paulo state respectively. Results: In Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less reported higher levels of distress. Each individual's distance from the Brazilian epicenter of São Paulo interacted with age and workplace attendance to predict the level of distress. The “typhoon eye effect” was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey. Conclusion: Identifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis

First study on mental distress in Brazil during the COVID-19 crisis

Objective: We aim to provide the first evidence of mental distress and its associated predictors among adults in the ongoing COVID-19 crisis in Brazil. Methods: We conducted a primary survey of 638 adults in Brazil on March 25-28, 2020, about one month (32 days) after the first COVID-19 case in South America was confirmed in Sao Paulo. Results: In Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less report-ed higher levels of distress. The distance from the Brazilian epicenter of Sao Paulo inter-acted with age and workplace attendance to predict the level of distress. The typhoon eye effect was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey. Conclusion: Identifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis

Open charm production in sNN\sqrt{s_{NN}}=200 GeV Au+Au collisions

We report on the measurement of D meson production from the analysis of their hadronic ($D^0\to K\pi$) and semileptonic ($D\to \mu+X$, $D\to e+X$) decays in $\sqrt{s_{NN}}$=200 GeV Au+Au collisions. The transverse momentum ($p_T$) spectra and the nuclear modification factors for $D^0$ and for electron/muon from charm semileptonic decays will be presented. The differential cross section $d\sigma/dy$ is found to be consistent with the number of binary scaling. The blast-wave fit suggests that the charm hadron freeze out earlier than other light flavor hadrons.Comment: 4 pages, 2 figures, presentation at Strangeness in Quark Matter 2006, accepted for publication by Journal of Physics

GPU-based Iterative Cone Beam CT Reconstruction Using Tight Frame Regularization

X-ray imaging dose from serial cone-beam CT (CBCT) scans raises a clinical concern in most image guided radiation therapy procedures. It is the goal of this paper to develop a fast GPU-based algorithm to reconstruct high quality CBCT images from undersampled and noisy projection data so as to lower the imaging dose. For this purpose, we have developed an iterative tight frame (TF) based CBCT reconstruction algorithm. A condition that a real CBCT image has a sparse representation under a TF basis is imposed in the iteration process as regularization to the solution. To speed up the computation, a multi-grid method is employed. Our GPU implementation has achieved high computational efficiency and a CBCT image of resolution 512\times512\times70 can be reconstructed in ~5 min. We have tested our algorithm on a digital NCAT phantom and a physical Catphan phantom. It is found that our TF-based algorithm is able to reconstrct CBCT in the context of undersampling and low mAs levels. We have also quantitatively analyzed the reconstructed CBCT image quality in terms of modulation-transfer-function and contrast-to-noise ratio under various scanning conditions. The results confirm the high CBCT image quality obtained from our TF algorithm. Moreover, our algorithm has also been validated in a real clinical context using a head-and-neck patient case. Comparisons of the developed TF algorithm and the current state-of-the-art TV algorithm have also been made in various cases studied in terms of reconstructed image quality and computation efficiency.Comment: 24 pages, 8 figures, accepted by Phys. Med. Bio

3D meso-scale modelling of concrete material in spall tests

Tensile strength is one of the key factors of concrete material that need be accurately defined in analysis of concrete structures subjected to high-speed impact loads. Dynamic tensile strength of concrete material is usually obtained by conducting laboratory tests such as direct tensile test, Brazilian splitting test and spall test. Concrete is a heterogeneous material with different components, but is conventionally assumed to be homogeneous, i.e., cement mortar only, in most previous experimental or numerical studies. The aggregates in concrete material are usually neglected owing to testing limitation and numerical simplification. It has been well acknowledged that neglecting coarse aggregates might not necessarily give accurate concrete dynamic material properties. In the present study, a 3D meso-scale model of concrete specimen with consideration of cement mortar and aggregates is developed to simulate spall tests and investigate the behaviour of concrete material under high strain rate. The commercial software LS-DYNA is used to perform the numerical simulations of spall tests. The mesh size sensitivity is examined by conducting mesh convergence tests. The reliability of the numerical model in simulating the spall tests is verified by comparing the numerical results with the experimental data from the literature. The influence of coarse aggregates on the experimental test results is studied. The wave attenuation in concrete specimen is analysed, and empirical equations are proposed for quick assessment of the test data to determine the true dynamic tensile strength of concrete material. The contributions of aggregates to dynamic strength in spall tests are quantified for modifying the test results based on mortar material in the literature

Copper Selenide Nanosnakes: Bovine Serum Albumin-Assisted Room Temperature Controllable Synthesis and Characterization

Herein we firstly reported a simple, environment-friendly, controllable synthetic method of CuSe nanosnakes at room temperature using copper salts and sodium selenosulfate as the reactants, and bovine serum albumin (BSA) as foaming agent. As the amounts of selenide ions (Se2−) released from Na2SeSO3 in the solution increased, the cubic and snake-like CuSe nanostructures were formed gradually, the cubic nanostructures were captured by the CuSe nanosnakes, the CuSe nanosnakes grew wider and longer as the reaction time increased. Finally, the cubic CuSe nanostructures were completely replaced by BSA–CuSe nanosnakes. The prepared BSA–CuSe nanosnakes exhibited enhanced biocompatibility than the CuSe nanocrystals, which highly suggest that as-prepared BSA–CuSe nanosnakes have great potentials in applications such as biomedical engineering

Linker-extended native cyanovirin-N facilitates PEGylation and potently inhibits HIV-1 by targeting the glycan ligand

Cyanovirin-N (CVN) potently inhibits human immunodeficiency virus type 1 (HIV-1) infection, but both cytotoxicity and immunogenicity have hindered the translation of this protein into a viable therapeutic. A molecular docking analysis suggested that up to 12 residues were involved in the interaction of the reverse parallel CVN dimer with the oligosaccharide targets, among which Leu-1 was the most prominent hot spot residue. This finding provided a possible explanation for the lack of anti-HIV-1 activity observed with N-terminal PEGylated CVN. Therefore, linker-CVN (LCVN) was designed as a CVN derivative with a flexible and hydrophilic linker (Gly4Ser)3 at the N-terminus. The N-terminal α-amine of LCVN was PEGylated to create 10 K PEG-aldehyde (ALD)-LCVN. LCVN and 10 K PEG-ALD-LCVN retained the specificity and affinity of CVN for high mannose N-glycans. Moreover, LCVN exhibited significant anti-HIV-1 activity with attenuated cytotoxicity in the HaCaT keratinocyte cell line and MT-4 T lymphocyte cell lines. 10 K PEG-ALD-LCVN also efficiently inactivated HIV-1 with remarkably decreased cytotoxicity and pronounced cell-to-cell fusion inhibitory activity in vitro. The linker-extended CVN and the mono-PEGylated derivative were determined to be promising candidates for the development of an anti-HIV-1 agent. This derivatization approach provided a model for the PEGylation of biologic candidates without introducing point mutations. © 2014 Chen et al

Inhibition of Endothelin-1-Mediated Contraction of Hepatic Stellate Cells by FXR Ligand

Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands