Gene- or region-based association study via kernel principal component analysis.

BACKGROUND: In genetic association study, especially in GWAS, gene- or region-based methods have been more popular to detect the association between multiple SNPs and diseases (or traits). Kernel principal component analysis combined with logistic regression test (KPCA-LRT) has been successfully used in classifying gene expression data. Nevertheless, the purpose of association study is to detect the correlation between genetic variations and disease rather than to classify the sample, and the genomic data is categorical rather than numerical. Recently, although the kernel-based logistic regression model in association study has been proposed by projecting the nonlinear original SNPs data into a linear feature space, it is still impacted by multicolinearity between the projections, which may lead to loss of power. We, therefore, proposed a KPCA-LRT model to avoid the multicolinearity. RESULTS: Simulation results showed that KPCA-LRT was always more powerful than principal component analysis combined with logistic regression test (PCA-LRT) at different sample sizes, different significant levels and different relative risks, especially at the genewide level (1E-5) and lower relative risks (RR = 1.2, 1.3). Application to the four gene regions of rheumatoid arthritis (RA) data from Genetic Analysis Workshop16 (GAW16) indicated that KPCA-LRT had better performance than single-locus test and PCA-LRT. CONCLUSIONS: KPCA-LRT is a valid and powerful gene- or region-based method for the analysis of GWAS data set, especially under lower relative risks and lower significant levels.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Structural characteristics and pyrolysis behavior of low-rank coal with different vitrinite/inertinite ratio

Pyrolysis is the basis of clean coal technologies such as coal liquefaction and gasification, especially for the low-rank coal. To further investigate the pyrolysis characteristics of low-rank coals, a series of different vitrinite/inertinite ratio ZJZ, MTH, and DT coals (V/I: 0.1, 0.76, and 1.76 respectively) are used as the research objects. The chemical structure of the sample was analyzed with Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction technology (XRD). The pyrolysis process and gas release behavior of coal samples at 30−900 °C was checked by TG-MS. The results show that the chemical structure content of low-rank coals with different V/I is quite different. Compared with the inertinite-rich ZJZ coals, the vitrinite-rich coals have relatively rich aliphatic structures, long aliphatic chains, and oxygen functional groups. Especially for DT coal, it has more C—O content. The corresponding aromatic structure content decreases with the increase of the mirror-inert ratio. With the increase of V/I in the coal, the aromatic layer spacing d002, the ratio of the aromatic layer size to the aromatic layer stacking height (La/Lc) increase, and Lc, La and the number of stacking layers (N) decrease. The weight loss ratio of DT, MTH, and ZJZ coal during pyrolysis is 36.4%, 32.2%, and 28.9% respectively. As the V/I decreases, the final pyrolysis gaseous product yield and the maximum pyrolysis rate decrease accordingly. During the pyrolysis process, the small molecular gas, such as H2, H2O, CH4, CO, CO2, are released; In addition, the content of released gas is closely related to the maceral composition. The mass of small molecules produced by inertinite-rich coal is almost lower than that produced by vitrinite-rich coal. Because the vitrinite in coal contains more aliphatic structures, and the polycondensation capacity between the aromatic layers is stronger, the free radicals fragment are easily formed during the thermal process and then combined into gas

The combustion characteristics and kinetic analysis of low-rank coals with different vitrinite/inertinite ratio

To explain the effect of maceral composition on the combustion characteristics of coal, a series of low-rank coals with different vitrinite/inertinite ratio were collected as the research object, and the combustion characteristics, heat change process and gas escape behavior of the samples under air atmosphere were investigated using thermoanalytical methods (TG-MS-DTA). The results show that the maceral content has little effect on the temperature of the maximum reaction rate. However, it has an effect on the value of the maximum reaction rate, and the maximum reaction rate of the inertinite-rich coal is larger. Meanwhile, higher minerals in coal allow the reaction to reach its maximum rate at a higher temperature. The combustion process shows two obvious stages. The first stage (before 400 ℃) is exothermic slowly, corresponding to the devolatilization process, and the second stage (after 400 ℃) is exothermic rapidly, corresponding to the fixed-carbon combustion process. The exothermic characteristics of coal combustion show a slow to fast exothermic transition. Coal with different vitrinite/inertinite ratio mainly release CO2, CO, H2O during the combustion process, however, the relative content of the released gas is different. In the devolatilization stage, there is less CO2 and CO released, while more H2O release. In the fixed-carbon combustion stage, a large amount of CO2 is released, the amount of CO released is slightly lower, and H2O is the lowest. Among them, the inertinite-rich coal releases relatively more CO2 during the combustion process and burns more completely under the same conditions. In addition, the kinetic calculation of the coal combustion process is carried out with the Coats-Redfern method, and the trend of reaction activation energy increases as the vitrinite/inertinite ratio decreases. However, it does not affect the inertinite-rich coal in the fixed-carbon combustion stage. The ability to burn rapidly may be due to the cell lumen structure formed by a large number of fusinites, which enlarges the contact area between the surface of coal particles and O2, and the combustion reaction is sufficient

Research progress on preparation and physicochemical properties of coal-based graphene quantum dots

Graphene quantum dots (GQDs) have attracted great research interest due to their remarkable quantum confinement and edge effects. In addition to exhibiting stable photoluminescence, it also has many advantages such as low cytotoxicity, good solubility and chemical inertness, making it widely used in bioimaging, photocatalysts and sensors. The industrial development of GQDs has been seriously hampered by the expensive raw materials and tedious operation of traditional preparation methods. Coal and its derivatives not only possess the characteristics of low price and abundant reserves, but also show greater advantages than graphite, graphene, graphite oxide and other carbon materials in the preparation of GQDs due to its inherent internal disorder structure and small crystal domain. GQDs can be prepared by simply stripping the aromatic ring clusters inside the coal and its derivatives through physical, chemical or electrochemical methods. This review first summarizes the “top-down” synthesis method of coal-based graphene quantum dots (C-GQDs) and its pros and cons. Then the structural morphology, chemical composition, fluorescence properties of C-GQDs and their influencing factors are analyzed. Further, we describe the progress in applications of C-GQDs in fields such as sensors, bioimaging and energy Finally, the future development of C-GQDs is discussed from the perspectives of preparation methods, carbon source selection and research directions, and the following experimental schemes are proposed: (1) Experiment with H2O2 as oxidizer and thermally altered coals as carbon sources； (2) Experiments other than oxidation with sulfuric acid and nitric acid using superhigh organic sulfur coals as carbon sources； (3) Experiment on coal macerals as a carbon sources. In addition, the combination of experimentally derived basic data and computer simulation technology can solve the problems of current research such as single fluorescence color and low quantum yield. The goals of clean utilization of coal resources and green development of GQDs have been achieved

SYNERGISTIC EFFECT OF RADIATION AND TRADITIONAL CHINESE MEDICINE RHIZOMA TYPHONII ETHANOL EXTRACTS DEPENDS ON P53 EXPRESSION IN TREATMENT OF LEWIS MOUSE LUNG CANCER CELLS

Background: Lung cancer is the leading cause of cancer-related death, and it is the most common cancer in terms of both incidence and mortality. There is an urgent need on novel therapeutic strategies for lung cancer. Traditional Chinese herbal medicines (CHM) have potential valuable for cancer treatment. Materials and Methods: Lewis mouse lung cancer cell line and Lewis cells tumors xenograft were used in this experiment. MTT assay was used to detect cell proliferation, flow cytometry (FCM) analysis and Western blotting to detect cell apoptosis, and colony formation assay to evaluate the effect of combined therapy of RT+IR. Results: Our data showed that Rhizoma typhonii (RT) obviously inhibited the proliferations of Lewis cells in time and dose dependent manners by MTT assay and enhanced radiosensitivity by colony formation assay. The effects of RT to Ionizing radiation (IR) therapy were demonstrated radiosensitivity on tumors xenograft experiment. In our study, RT induced apoptotic in Lewis cells directly and enhanced the pro-apoptotic effect of IR by regulating the expression of p53. Conclusions: These data suggested that RT may be a great potential anti-tumor medicine and the combination of RT and IR may provide a new therapeutic strategy for the treatment of Lewis lung cancer

Association of lncRNA H19 polymorphisms with cancer susceptibility: An updated meta-analysis based on 53 studies

The association between polymorphisms in lncRNA H19 and cancer susceptibility remains to be inconsistent. This study aimed to provide a more precise estimation of the relationship between lncRNA H19 polymorphisms and the risk of cancer based on all available published studies. 53 studies encompassing 32,376 cases and 43,659 controls were included in our meta-analysis by searching the Pubmed, Embase, Web of Science, WanFang, and China National Knowledge Infrastructure databases. Pooled ORs and their 95% CIs were used to estimate the strength between the SNPs in H19 (rs217727, rs2839698, rs2107425, rs3024270, rs2735971, rs3741216, and rs3741219) and cancer susceptibility. The results showed that H19 rs2839698 polymorphism was associated with increased cancer risk in all participants under three genetic models. However, no significant association was identified between the other six SNPs as well as an overall cancer risk. Stratification by ethnicity showed that rs2839698 mutation indicated to be an important hazardous factor for the Asian population. While rs2107425 mutation had a protective effect on the Caucasian population. Stratification by cancer type identified that rs217727 mutation was linked to increased susceptibility to oral squamous cell carcinoma, lung cancer, and hepatocellular carcinoma; whereas rs2839698 mutation was associated with an elevated risk of hematological tumor and digestive system tumor (p < 0.05). Besides, the rs2735971 mutation was connected with the digestive system tumor. In summary, the rs217727, rs2839698, rs2107425 and rs2735971 polymorphisms in H19 have associations with cancer susceptibility

Genome-Wide Association and Mechanistic Studies Indicate That Immune Response Contributes to Alzheimer’s Disease Development

Alzheimer’s disease (AD) is the most common cause of dementia. Although genome-wide association study (GWAS) have reported hundreds of single-nucleotide polymorphisms (SNPs) and genes linked to AD, the mechanisms about how these SNPs modulate the development of AD remain largely unknown. In this study, we performed GWAS for three traits in cerebrospinal fluid (CSF) and one clinical trait in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Our analysis identified five most significant AD related SNPs (FDR < 0.05) within or proximal to APOE, APOC1, and TOMM40. One of the SNPs was co-inherited with APOE allele 4, which is the most important genetic risk factor for AD. Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptor-related 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). The altered regulation of PVRL2 may increase the susceptibility AD patients to HSV and other virus infections of the brain. Our work suggests that AD is a type of immune disorder driven by viral or microbial infections of the brain during aging

Vomiting and wasting disease associated with hemagglutinating encephalomyelitis viruses infection in piglets in jilin, china

One coronavirus strain was isolated from brain tissues of ten piglets with evident clinical manifestations of vomiting, diarrhea and dyskinesia in Jilin province in China. Antigenic and genomic characterizations of the virus (isolate PHEV-JLsp09) were based on multiplex PCR and negative staining electron microscopy and sequence analysis of the Hemagglutinin-esterase (HE) gene. These piglets were diagnosed with Porcine hemagglutinating encephalomyelitis virus (PHEV)