| 1. |
|
|
| 2. |
- McCarthy, Shane, et al.
(författare)
-
A reference panel of 64,976 haplotypes for genotype imputation
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
|
|
| 3. |
- Sarwar, Martuza, et al.
(författare)
-
Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells
- 2016
-
Ingår i: Oncotarget. - : Impact Journals. - 1949-2553. ; 7:39, s. 63065-63081
-
Tidskriftsartikel (refereegranskat)abstract
- One mechanism of resistance of prostate cancer (PCa) to enzalutamide (MDV3100) treatment is the increased expression of AR variants lacking the ligand binding-domain, the best characterized of which is AR-V7. We have previously reported that Phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), is a lipid kinase that links to CDK1 and AR pathways. The discovery of PIP5Kα inhibitor highlight the potential of PIP5K1α as a drug target in PCa. In this study, we show that AR-V7 expression positively correlates with PIP5K1α in tumor specimens from PCa patients. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. PIP5K1α is a key co-factor for both AR-V7 and AR, which are present as protein-protein complexes predominantly in the nucleus of PCa cells. In addition, PIP5K1α and CDK1 influence AR-V7 expression also through AKT-associated mechanism dependent on PTEN-status. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice. Our study suggests that combination of enzalutamide and PIP5K1α may have a significant impact on refining therapeutic strategies to circumvent resistance to antiandrogen therapies
|
|
| 4. |
- Wang, Chenglong, et al.
(författare)
-
Experimental and numerical investigation of outlet guide vane and endwall heat transfer with various inlet flow angles
- 2016
-
Ingår i: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 95, s. 355-367
-
Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the heat transfer on the outlet guide vane (OGV) surface and its endwall region. The Reynolds number is fixed at 300,000 and the flow is subsonic. The inlet flow angle is varied from +25 degrees (on-design), to +40 degrees and -25 degrees (off-design). Experiments were conducted in a linear cascade test facility using thermochromic liquid crystal technique. Numerical simulations using RANS were carried out with three turbulence models, i.e., standard k-omega model (k-omega), baseline k-omega model (BSL), and shear stress transport k-omega model (SST). Both the experimental and numerical results are provided and compared. On the OGV surface, boundary layer transition and separation affect the heat transfer significantly and they vary with the inlet flow angle. The abilities of the three models to predict these heat transfer behaviors are revealed. For the on-design case, both BSL and SST models capture the main feature of the heat transfer variations due to transition, but the k-omega model fails. For off-design cases where separation occurs, there are discrepancies found between the calculations and experimental data. On the endwall region, the effects of a horseshoe vortex (HV) on the heat transfer are clearly noticed at the leading edge (LE). The three models perform well to simulate the pitchwise averaged Nusselt number while they always over-predict the strength and size of the HV, which leads to higher heat transfer there compared to the measurements. For off-design conditions, the HV becomes more energetic than that of the on design condition and the pressure side leg departs from the OGV at the inlet flow angle alpha = -25 degrees
|
|
