| 1. |
- McKay, James D., et al.
(författare)
-
A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
|
|
| 2. |
- Shen, Yong-Feng, et al.
(författare)
-
Deformation mechanisms of a 20Mn TWIP steel investigated by in situ neutron diffraction and TEM
- 2013
-
Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 61:16, s. 6093-6106
-
Tidskriftsartikel (refereegranskat)abstract
- The deformation mechanisms and associated microstructure changes during tensile loading of an annealed twinning-induced plasticity steel with chemical composition Fe-20Mn-3Si-3Al-0.045C (wt.%) were systematically investigated using in situ time-of-flight neutron diffraction in combination with post mortem transmission electron microscopy (TEM). The initial microstructure of the investigated alloy consists of equiaxed gamma grains with the initial alpha'-phase of similar to 7% in volume. In addition to dislocation slip, twinning and two types of martensitic transformations from the austenite to alpha'- and epsilon-martensites were observed as the main deformation modes during the tensile deformation. In situ neutron diffraction provides a powerful tool for establishing the deformation mode map for elucidating the role of different deformation modes in different strain regions. The critical stress is 520 MPa for the martensitic transformation from austenite to alpha'-martensite, whereas a higher stress (>600 MPa) is required for actuating the deformation twin and/or the martensitic transformation from austenite to epsilon-martensite. Both epsilon- and alpha'-martensites act as hard phases, whereas mechanical twinning contributes to both the strength and the ductility of the studied steel. TEM observations confirmed that the twinning process was facilitated by the parent grains oriented with < 1 1 1 > or < 1 1 0 > parallel to the loading direction. The nucleation and growth of twins are attributed to the pole and self-generation formation mechanisms, as well as the stair-rod cross-slip mechanism.
|
|
| 3. |
- Zhang, Mei, et al.
(författare)
-
Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement
- 2012
-
Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 3:4, s. 317-321
-
Tidskriftsartikel (refereegranskat)abstract
- A series of 1-phenyl-3-(1-phenylethyl)urea derivatives were identified as novel and potent complement inhibitors through structural modification of the original compound from high-throughput screening. Various analogues (7 and 13-15) were synthesized and identified as complement inhibitors, with the introduction of a five- or six-carbon chain (7c, 7d, 7k, 7I, and 7o) greatly improving their activity. Optimized compound 7I has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7I inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.
|
|
