Region-based and pathway-based QTL mapping using a p-value combination method

Quantitative trait locus (QTL) mapping using deep DNA sequencing data is a challenging task. In this study we performed region-based and pathway-based QTL mappings using a p-value combination method to analyze the simulated quantitative traits Q1 and Q4 and the exome sequencing data. The aims were to evaluate the performance of the QTL mapping approaches that were used and to suggest plausible strategies for QTL mapping of DNA sequencing data. We conducted single-locus QTL mappings using a linear regression model with adjustments for age and smoking status, and we also conducted region-based and pathway-based QTL mappings using a truncated product method for combining p-values from the single-locus QTL mapping. To account for the features of rare variants and common single-nucleotide polymorphisms (SNPs), we considered independently rare-variant-only, common-SNP-only, and combined analyses. An analysis of 200 simulated replications showed that the three region-based methods reasonably controlled type I error, whereas the combined analysis yielded the greatest statistical power. Rare-variant-only, common-SNP-only, and combined analyses were also applied to pathway-based QTL mappings. We found that pathway-based QTL mappings had a power of approximately 100% when the significance of the vascular endothelial growth factor pathway was evaluated, but type I errors were slightly inflated. Our approach complements single-locus QTL mapping. An integrated approach using single-locus, combined region-based, and combined pathway-based analyses should yield promising results for QTL mapping of DNA sequencing data

ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population

Kawasaki disease (KD) is characterized by systemic vasculitis with unknown etiology. Previous studies from Japan indicated that a gene polymorphism of ITPKC (rs28493229) is responsible for susceptibility to KD. We collected DNA samples from 1,531 Taiwanese subjects (341 KD patients and 1,190 controls) for genotyping ITPKC. In this study, no significant association was noted for the ITPKC polymorphism (rs28493229) between the controls and KD patients, although the CC genotype was overrepresented. We further combined our data with previously published case/control KD studies in the Taiwanese population and performed a meta-analysis. A significant association between rs28493229 and KD was found (Odds Ratio:1.36, 95% Confidence Interval 1.12–1.66). Importantly, a significant association was obtained between rs28493229 and KD patients with aneurysm formation (P = 0.001, under the recessive model). Taken together, our results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population

Using Neural Networks for Relation Extraction from Biomedical Literature

Using different sources of information to support automated extracting of relations between biomedical concepts contributes to the development of our understanding of biological systems. The primary comprehensive source of these relations is biomedical literature. Several relation extraction approaches have been proposed to identify relations between concepts in biomedical literature, namely, using neural networks algorithms. The use of multichannel architectures composed of multiple data representations, as in deep neural networks, is leading to state-of-the-art results. The right combination of data representations can eventually lead us to even higher evaluation scores in relation extraction tasks. Thus, biomedical ontologies play a fundamental role by providing semantic and ancestry information about an entity. The incorporation of biomedical ontologies has already been proved to enhance previous state-of-the-art results.Comment: Artificial Neural Networks book (Springer) - Chapter 1

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

Linear Confinement for Mesons and Nucleons in AdS/QCD

By using a new parametrization of the dilaton field and including a cubic term in the bulk scalar potential, we realize linear confinement in both meson and nucleon sectors within the framework of soft-wall AdS/QCD. At the same time this model also correctly incorporate chiral symmetry breaking. We compare our resulting mass spectra with experimental data and find good agreement between them.Comment: 14 pages, published version in JHE

Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

The Galaxy Structure-Redshift Relationship

There exists a gradual, but persistent, evolutionary effect in the galaxy population such that galaxy structure and morphology change with redshift. This galaxy structure-redshift relationship is such that an increasingly large fraction of all bright and massive galaxies at redshifts 2 < z < 3 are morphologically peculiar at wavelengths from rest-frame ultraviolet to rest-frame optical. There are however examples of morphologically selected spirals and ellipticals at all redshifts up to z ~ 3. At lower redshift, the bright galaxy population smoothly transforms into normal ellipticals and spirals. The rate of this transformation strongly depends on redshift, with the swiftest evolution occurring between 1 < z < 2. This review characterizes the galaxy structure-redshift relationship, discusses its various physical causes, and how these are revealing the mechanisms responsible for galaxy formation.Comment: 20 pages, 8 figures. Invited Review to appear in "Penetrating Bars Through Masks of Cosmic Dust: The Hubble Tuning Fork Strikes A New Note", ed. D. Block et a

Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

<p>Abstract</p> <p>Background</p> <p>To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>The <it>Aurora B </it>and <it>Aurora A </it>mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the <it>p53 </it>and <it>β-catenin </it>genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of <it>p53 </it>and exon 3 of <it>β-catenin</it>. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines.</p> <p>Results</p> <p><it>Aurora B </it>was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of <it>Aurora B </it>was associated with <it>Aurora A </it>overexpression (<it>P </it>= 0.0003) and <it>p53 </it>mutation (<it>P </it>= 0.002) and was inversely associated with <it>β</it>-<it>catenin </it>mutation (<it>P </it>= 0.002). <it>Aurora B </it>overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that <it>Aurora B </it>overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of <it>p53 </it>and <it>β</it>-<it>catenin</it>. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis.</p> <p>Conclusion</p> <p><it>Aurora B </it>overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.</p