The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Real Time Burning Image Classification Using Support Vector Machine

Burning image classification is critical and attempted problems in medical image processing. This paper has proposed the real time image classification for burning image to automatically identify the degrees of burns in three levels: II, III, and IV. The proposed model uses the multi-colour channels extraction and binary based on adaptive threshold. The proposed model uses One-class Support Vector Machine instead of traditional Support Vector Machine (SVM) because of unbalanced degrees of burns images database. The classifying precision 77.78% shows the feasibility of our proposed model

Improved electrical property of Sb-doped SnO 2 nanonets as measured by contact and non-contact approaches

10.1039/c2ra20973jRSC Advances2259590-959

Extracting kinetic freeze-out temperature and radial flow velocity from an improved Tsallis distribution

We analyze the transverse momentum ($p_T$) spectra of identified particles ($\pi^{\pm}$, $K^{\pm}$, $p$, and $\bar p$) produced in gold-gold (Au-Au) and lead-lead (Pb-Pb) collisions over a $\sqrt{s_{NN}}$ (center-of-mass energy per nucleon pair) range from 14.5 GeV [one of the Relativistic Heavy Ion Collider (RHIC) energies] to 2.76 TeV [one of the Large Hadron Collider (LHC) energies]. For the spectra with a narrow $p_T$ range, an improved Tsallis distribution which is in fact the Tsallis distribution with radial flow is used. For the spectra with a wide $p_T$ range, a superposition of the improved Tsallis distribution and an inverse power-law is used. Both the extracted kinetic freeze-out temperature ($T_0$) and radial flow velocity ($\beta_T$) increase with the increase of $\sqrt{s_{NN}}$, which indicates a higher excitation and larger expansion of the interesting system at the LHC. Both the values of $T_0$ and $\beta_T$ in central collisions are slightly larger than those in peripheral collisions, and they are independent of isospin and slightly dependent on mass.Comment: We have corrected the pseudorapidity ranges of the data quoted in this paper. The PHENIX data should be in the pseudorapidity range $|\eta|<0.35$, but not the rapidity range $|y|<0.5$; and the ALICE data should be in $|\eta|<0.8$ for high transverse momentum region and $|y|<0.5$ for low transverse momentum region, but not only $|y|<0.5$. These do not affect the results of the publicatio

TRAIL Recombinant Adenovirus Triggers Robust Apoptosis in Multidrug-Resistant HL-60/Vinc Cells Preferentially Through Death Receptor DR5

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic because of its highly selective apoptosis-inducing action on neoplastic versus normal cells. However, some cancer cells express resistance to recombinant soluble TRAIL. To overcome this problem, we used a TRAIL adenovirus (Ad5/35-TRAIL) to induce apoptosis in a drug-sensitive and multidrug-resistant variant of HL-60 leukemia cells and determined the molecular mechanisms of Ad5/35-TRAIL-induced apoptosis. Ad5/35-TRAIL did not induce apoptosis in normal human lymphocytes, but caused massive apoptosis in acute myelocytic leukemia cells. It triggered more efficient apoptosis in drug-resistant HL-60/Vinc cells than in HL-60 cells. Treating the cells with anti-DR4 and anti-DR5 neutralizing antibodies (particularly anti-DR5) reduced, whereas anti-DcR1 antibody enhanced, the apoptosis triggered by Ad5/35-TRAIL. Whereas Ad5/35-TRAIL induced apoptosis in both cell lines through activation of caspase-3 and caspase-10, known to link the cell death receptor pathway to the mitochondrial pathway, it triggered increased mitochondrial membrane potential change (Δψm) only in HL-60/Vinc cells. Ad5/35-TRAIL also increased the production of reactive oxygen species, which play an important role in apoptosis. Therefore, using Ad5/35-TRAIL may be an effective therapeutic strategy for eliminating TRAIL-resistant malignant cells and these studies may provide clues to treat and eradicate acute myelocytic leukemias

Increased fatty acid synthase as a potential therapeutic target in multiple myeloma*

Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma (MM patients) and peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy donors. In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPMI8226. U266 cells were treated with cerulenin at various concentrations (5 to 320 µg/ml) for 24 h, and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Apoptosis was evaluated by dual Annexin V/PI (propidium iodide) labeling and flow cytometry (FCM) in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results: By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPMI8226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPMI8226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 µg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V+/PI− cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V+/PI+ cells. Conclusion: Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma