Testing gene-environment interactions for rare and/or common variants in sequencing association studies.

The risk of many complex diseases is determined by a complex interplay of genetic and environmental factors. Advanced next generation sequencing technology makes identification of gene-environment (GE) interactions for both common and rare variants possible. However, most existing methods focus on testing the main effects of common and/or rare genetic variants. There are limited methods developed to test the effects of GE interactions for rare variants only or rare and common variants simultaneously. In this study, we develop novel approaches to test the effects of GE interactions of rare and/or common risk, and/or protective variants in sequencing association studies. We propose two approaches: 1) testing the effects of an optimally weighted combination of GE interactions for rare variants (TOW-GE); 2) testing the effects of a weighted combination of GE interactions for both rare and common variants (variable weight TOW-GE, VW-TOW-GE). Extensive simulation studies based on the Genetic Analysis Workshop 17 data show that the type I error rates of the proposed methods are well controlled. Compared to the existing interaction sequence kernel association test (ISKAT), TOW-GE is more powerful when there are GE interactions\u27 effects for rare risk and/or protective variants; VW-TOW-GE is more powerful when there are GE interactions\u27 effects for both rare and common risk and protective variants. Both TOW-GE and VW-TOW-GE are robust to the directions of effects of causal GE interactions. We demonstrate the applications of TOW-GE and VW-TOW-GE using an imputed data from the COPDGene Study

Internal kinematics of groups of galaxies in the Sloan Digital Sky Survey data release 7

We present measurements of the velocity dispersion profile (VDP) for galaxy groups in the final data release of the Sloan Digital Sky Survey (SDSS). For groups of given mass we estimate the redshift-space cross-correlation function (CCF) with respect to a reference galaxy sample, xi(r_p, pi), the projected CCF, w_p(r_p), and the real-space CCF, xi(r). The VDP is then extracted from the redshift distortion in xi(r_p, pi), by comparing xi(r_p, pi) with xi(r). We find that the velocity dispersion (VD) within virial radius (R_200) shows a roughly flat profile, with a slight increase at radii below ~0.3 R_200 for high mass systems. The average VD within the virial radius, sigma_v, is a strongly increasing function of central galaxy mass. We apply the same methodology to N-body simulations with the concordance Lambda cold dark matter cosmology but different values of the density fluctuation parameter sigma_8, and we compare the results to the SDSS results. We show that the sigma_v-M_* relation from the data provides stringent constraints on both sigma_8 and sigma_ms, the dispersion in log M_* of central galaxies at fixed halo mass. Our best-fitting model suggests sigma_8 = 0.86 +/- 0.03 and sigma_ms = 0.16 +/- 0.03. The slightly higher value of sigma_8 compared to the WMAP7 result might be due to a smaller matter density parameter assumed in our simulations. Our VD measurements also provide a direct measure of the dark matter halo mass for central galaxies of different luminosities and masses, in good agreement with the results obtained by Mandelbaum et al. (2006) from stacking the gravitational lensing signals of the SDSS galaxies.Comment: 17 pages, 10 figures, 1 table, accepted for publication in ApJ, text slightly changed, abstract substantially shortened, two new panels added to Figs. 2 and 3 showing w_p and VDP as functions of r_p/R_200 instead of r_

Identification and Characterization of Two Novel Compounds: Heterozygous Variants of Lipoprotein Lipase in Two Pedigrees With Type I Hyperlipoproteinemia

BackgroundType I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis.ObjectiveThis study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia.MethodsWe conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium.ResultsProband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 ± 9.46% (p<0.01) and 54.60 ± 9.03% (p<0.01), respectively, compared with the control. In vitro studies showed a substantial reduction in the expression or enzyme activity of LPL in the LPL variants.ConclusionsTwo novel compound heterozygous variants of LPL induced defects in the expression and function of LPL and caused type I hyperlipoproteinemia. The functional characterization of these variants was in keeping with the postulated LPL mutant activity

Design of functions in Smart TV : A survey study of user acceptance on Smart TV functions

This paper is defined as a qualitative study and mainly uses a survey, interview and previous reports and papers as methodology. We research which functions in the Smart TV that are widely used and what functions of the Smart TV do people need, and if people accept the design of the functions in the Smart TV.Through the investigation we got three conclusions: firstly, we have discovered the top four popular functions of Smart TV based on the questionnaire, secondly, the precautions the developers should pay attention to when they design the product, lastly we have said that people do not accept these intelligent functions in the Smart TV, and after the study we give the future direction andsuggestion for how to make well designed functions for the Smart TV

A review of environment problems in the coastal sea of South China

The coastal sea of South China provided an important habitat for protection and propagation of marine organisms. Rapid economic development and human activities, such as wastewater discharge, reclamation, overfishing and aquaculture in the South China Sea had already resulted in environmental degradation, and thus caused sharp contradictions between exploitation and protection of the coastal sea of South China. In this present article, the main environment problems and degradation trends were reviewed based on literatures and other sources of information, which mainly referenced nutrient pollution, persistent organic pollution and metal pollution, decrease of biodiversity, reduction of marine habitat and frequent natural and ecological disasters. The current efforts in China on protecting the environment in the coastal sea of South China were discussed, which included improving legislation by formulating a series of laws and regulations at national or local level, setting up natural reserves, and supporting research projects. There were many challenges regarding policy, management and science research to protect and sustain the coastal sea of South China, such as imperfect legal and administrative systems, lack of public participation, poor financial support and lack of monitoring and evaluation. Finally, some recommendations were put forward for the sake of the sustainable use of the environment in the coastal sea of South China, including reinforcing the planning of marine resource exploitation and use through integrated coastal zone management, strengthening the marine environment and protection awareness of the public, and scientifically establishing the fishery spawning spots and aquatic reserves.The coastal sea of South China provided an important habitat for protection and propagation of marine organisms. Rapid economic development and human activities, such as wastewater discharge, reclamation, overfishing and aquaculture in the South China Sea had already resulted in environmental degradation, and thus caused sharp contradictions between exploitation and protection of the coastal sea of South China. In this present article, the main environment problems and degradation trends were reviewed based on literatures and other sources of information, which mainly referenced nutrient pollution, persistent organic pollution and metal pollution, decrease of biodiversity, reduction of marine habitat and frequent natural and ecological disasters. The current efforts in China on protecting the environment in the coastal sea of South China were discussed, which included improving legislation by formulating a series of laws and regulations at national or local level, setting up natural reserves, and supporting research projects. There were many challenges regarding policy, management and science research to protect and sustain the coastal sea of South China, such as imperfect legal and administrative systems, lack of public participation, poor financial support and lack of monitoring and evaluation. Finally, some recommendations were put forward for the sake of the sustainable use of the environment in the coastal sea of South China, including reinforcing the planning of marine resource exploitation and use through integrated coastal zone management, strengthening the marine environment and protection awareness of the public, and scientifically establishing the fishery spawning spots and aquatic reserves

Applicable Conditions of Room-and-Pillar Mining Goaf Treatment Methods under a Traffic Load

The disturbance depth of traffic load has a direct impact on the stability of a room-and-pillar mining goaf. To quantitatively calculate the relationship between the traffic load disturbance depth and influencing factors, 49 groups of horizontal combinations of different influencing parameters are designed in this study, based on the orthogonal experimental design method. Midas GTS is used to simulate and obtain the corresponding traffic load disturbance depth data. A multivariate linear regression analysis of the traffic load disturbance depth is conducted, and a regression formula for calculating the traffic load disturbance depth is established. According to the traffic load disturbance depth, goaf depth, and the stability of the roof, coal pillar, and base plate under traffic load conditions, a judgment flow of the room-and-pillar mining goaf treatment method under traffic load conditions is established, and it is applied to the reconstruction and expansion project of the Jixi section of the Dan-A national highway. The results show that a geogrid can be used for treatment purposes when the traffic load disturbance depth is 1.5 times lower than the depth of the room-and-pillar mining goaf, or when the traffic load disturbance depth is 1.5 times greater than the depth of the room-and-pillar mining goaf but the roof, coal pillar, and base plate are stable. Additionally, grouting is needed for treatment in other cases. The results of this study can provide a scientific basis for the selection of treatment methods for room-and-pillar mining goafs underlying highways in the future. The results are of great significance in the field of engineering for the safety measures concerning highway room-and-pillar mining goafs