Penalized regression approaches to testing for quantitative trait-rare variant association

In statistical data analysis, penalized regression is considered an attractive approachfor its ability of simultaneous variable selection and parameter estimation. Althoughpenalized regression methods have shown many advantages in variable selection andoutcome prediction over other approaches for high-dimensional data, there is a relativepaucity of the literature on their applications to hypothesis testing, e.g. in geneticassociation analysis. In this study, we apply several new penalized regression methodswith a novel penalty, called Truncated L1-penalty (TLP) (Shen et al. 2012), foreither variable selection, or both variable selection and parameter grouping, in a dataadaptiveway to test for association between a quantitative trait and a group of rarevariants. The performance of the new methods are compared with some existing tests,including some recently proposed global tests and penalized regression-based methods,via simulations and an application to the real sequence data of the Genetic AnalysisWorkshop 17 (GAW17). Although our proposed penalized methods can improve oversome existing penalized methods, often they do not outperform some existing globalassociation tests. Some possible problems with utilizing penalized regression methodsin genetic hypothesis testing are discussed. Given the capability of penalized regressionin selecting causal variants and its sometimes promising performance, further studiesare warranted

The Reaction of CO absorption in MEA(monoethanolamine) aqueous Solution: A Theoretical Study on the Effect of Neighboring Molecules

Objectives CO2 is one of the greenhouse gases that cause the global warming. Alkanolamine aqueous solutions are frequently used as a chemical absorption solvent for post combustion capture process. The reaction of CO2 and MEA(monoethanolamine) was studied by theoretical analysis to describe the effect of neighboring molecules. Methods The reaction of CO2 absorption in MEA aqueous solution was investigated using DFT (density functional theory) method. The 14 reaction models were designed according to the arrangement of reactant and neighboring molecules. Results and Discussion The structures of reactant, TS (transition state) and product were analyzed in perspective of the geometry, thermodynamics and kinetics. The neighboring molecules stabilized the structures of reactant complex due to increasing intermolecular interaction (hydrogen bond) between reactants and these molecules. The structures of reactant complex were change to the arrangement that MEA can easily react with CO2 . However, the neighboring molecules would slightly affect the reaction pathway of the structures of TS and product. The activation energy and TS structure were differed according to the type of hydrogen atom transfer, not the effect of neighboring molecules. The neighboring molecules seems to work slightly in the aspect of chemical kinetics of the reaction between CO2 and MEA in aqueous solution

Predictive Factors of Patient Satisfaction with Pharmacy Services in South Korea: A Cross-Sectional Study of National Level Data

Objectives Patient satisfaction has emerged as a prerequisite to improving patients’ health behaviors leading to better health care outcomes. This study was to identify predictive determinants for patient satisfaction with pharmacy services using national-level data. Methods A cross-sectional evaluation was conducted using 2008 Korean National Health and Nutrition Examination Survey (KNHANES) data. To assess the predictive factors for patient satisfaction with pharmacy services, an ordinal logistic regression model was conducted adjusting for patient characteristics, clinical comorbidities, and perception of health. Results A total of 9,744 people, a representative sample of 48.2 million Koreans, participated in the 2008 KNHANES, of whom 2,188 (23.6%) reported visits to pharmacy within the last 2 weeks prior to the survey. Of the patients who visited the pharmacy, 74.6% reported to be either “very satisfied” or “satisfied,” and 25.4%responded as being “neutral,” “dissatisfied,” or “very dissatisfied.” A multivariate ordinal logistic regression analysis with weighted observations revealed that patients with fair perception of health (adjusted OR 1.32; 95% CI 1.01–1.74; p\u3c0.05) and those with middle to low family incomes (adjusted OR 1.34; 95% CI 1.02–1.76; p\u3c0.05) were more likely to be satisfied with pharmacy services, and employment- based insurers were less likely to be satisfied with pharmacy services (adjusted OR 0.80; 95% CI 0.65–0.97; p\u3c0.05). Conclusion Our findings indicated that three out of four patients expressed satisfaction toward pharmacy services. Middle to low family incomes, fair perception of health, and employee insured individuals were significant predictors of patient satisfaction with pharmacy services

Single oxygen vacancies of (TiO2)35 as a prototype of reduced nanoparticle: implication for photocatalytic activity

Titanium dioxide (TiO2), as a semiconductor metal oxide, has been one of the most popular materials studied in the field of photocatalysis. In the present study, the properties of single oxygen vacancies of (TiO2)35, a prototype of an anatase nanoparticle, were investigated by DFT calculations. (TiO2)35 is the minimum sized model (∼2 nm) for a bipyramidal nanoparticle with anatase phase and eight {101} facets. All the available oxygen vacancies at various sites according to position, coordination number, and distance from the center atom were examined. The geometric, energetic and electronic properties of the reduced TiO2 clusters were analyzed by hybrid DFT functionals with different Hartree-Fock exchange ratios (0, 12.5 and 25%). It was found that the structure of pristine (TiO2)35 is somewhat different from the bulk lattice, with a relatively high surface to volume ratio. Moreover, the particular highly (three)-coordinated oxygen atom is energetically the most favorable for oxygen vacancy formation from the nanoparticle mainly due to its substantially high relaxation energy. TiO2 nanoparticles have low oxygen vacancy formation energy and narrow band gap because of their defect states, and can be utilized as an efficient photocatalyst material

The nano gold rush: Graphynes as atomic sieves for coinage and Pt-group transition metals

Graphyne two-dimensional materials have been envisaged as potential useful membranes for applications such as gases separation and water desalination with very high salt rejection rates. The graphyne acetylenic linkages length defines its acetylenic holes size, thus offering a way of tuning their membrane permeability. The present study evaluates, based on density functional theory simulations, the possible use of γ-graphyne, the graphyne with the smallest acetylenic hole, to sieve Transition Metal (TM) atoms. The systematic study comprises obtaining adsorption minima for the 30 3d, 4d, and 5d TMs along with transition states for the diffusion across the γ-graphyne layer. The study reveals very small penetration barriers, below 0.5 eV, for late 3d, Pt-group, and coinage metals, whereas water molecules are found to display high penetration energy barriers above 5 eV, even when accounting for possible γ-graphyne out-of-plane deformations facilitating the water trespassing. The adsorption energy distribution of the adsorbed TMs shows that Pd and Au sieving by γ-graphyne would be specially enhanced versus their anchoring on the γ-graphyne carbon framework, thus pointing γ-graphyne as a possible effective membrane to sieve, particularly, late transition metals

Fabrication of n-type nanotube transistors with large-work-function electrodes

The authors found experimentally that carbon nanotube field-effect transistors (CNFETs) could exhibit n -type characteristics even though their electrodes consist of a large-work-function metal such as Co. To explain their result, which is contrary to the general belief that CNFETs with large-work-function electrodes always lead to p -type characteristics, ab initio electronic structure calculation for the metal-carbon nanotube junction was performed, which showed that the Fermi level alignment at the junction could sensitively depend on microscopic structures of the metal-carbon nanotube junction. This suggests that deposition method of electrodes as well as the metal type could be utilized to obtain n -type CNFETs.open121

Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development

Functionalization of γ-graphyne by transition metal adatoms

Transition Metal (TM) atom adsorption on γ-graphyne is here studied to unravel the electronic and magnetic properties tuning of this 2D carbon allotrope, with possible repercussions on molecular storage, sensing, and catalytic properties. A thorough density functional theory study, including dispersion, of the structural, energetic, diffusivity, magnetic, and doping properties for all 3d, 4d, and 5d TM adatoms adsorbed on γ-graphyne is provided. Overall, TMs strongly chemisorb on γ-graphyne acetylenic rings, except d10 group XII TMs which physisorb. Diffusion energy barriers span 0.5-3.5 eV and adatom height with respect the γ-graphyne sheet seems to be governed by TM atomic radius. All TMs are found to give n-doped γ-graphyne, where charge transfer decays along d series due to the increasing electronegativity of TMs. Middle TMs infer noticeable magnetism to γ-graphyne, yet magnetism is heavily quenched for early and late TMs. The large adsorption energies close to parent TM bulk cohesive energies, the high diffusion energy barriers, and the coulombic repulsion between positively charged TM adatoms provide a good environment for TMs to disperse over the graphyne

RBFOX3 regulates Claudin-1 expression in human lung tissue via attenuation of proteasomal degradation

RBFOX3, a nuclear RNA-binding protein, is well known as a regulator of alternative pre-mRNA splicing during neuronal development. However, other functions of RBFOX3 are poorly understood. Here, we investigated the function of RBFOX3 in the cytoplasm with respect to regulation of Claudin-1 expression. In human lung tissue, Claudin-1 is higher in RBFOX3-positive cells than in RBFOX3-negative cells. Immunostaining and mRNA quantification revealed that protein levels, but not mRNA levels, of Claudin-1 are increased by RBFOX3. In addition, cycloheximide treatment of human lung cancer cells revealed that RB-FOX3 increases the stability of Claudin-1 through attenuation of its ubiquitination. Our study provides insights into the molecular mechanisms by which RBFOX3 regulates Claudin-1 expression in human lung tissue