Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1

High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers

Understanding morphological variation in the extant koala as a framework for identification of species boundaries in extinct koalas (Phascolarctidae; Marsupialia)

We document morphological variation (both geographical and sexual) in the dentition of the extant koala, Phascolarctos cinereus, in order to facilitate discrimination of species boundaries in extinct phascolarctids. Considerable variation is evident in dental structures previously used to diagnose several phascolarctid fossil species. Consistent patterns of morphological variation are not evident between sexes or geographic regions, with variation as great between samples as within them. Metric variation is evident between the sexes in upper molar dimensions with Victorian (southern) males significantly larger than Victorian females, although this is not reflected in lower molar dimensions or in the Queensland (northern) sample. Male koalas from southern populations generally display significantly larger molars than their northern counterparts; however this trend is not evident in female upper molar dimensions. In both males and females, some, but not all, lower molar dimensions are larger in southern populations than northern. In light of these results, a systematic revision of species of Litokoala suggests L. dicktedfordi' is a junior synonym of L. kutjamarpensis, and the poorly known L. thurmerae is regarded to be a nomen dubium. Further, we describe a partial cranium of a new species of koala from Early Miocene sediments in the Riversleigh World Heritage Area, northern Australia. Litokoala dicksmithi sp. nov. is the fifth koala species recorded from the diverse rainforest assemblages of Riversleigh and the third species referred to the Oligo-Miocene genus Litokoala. Aspects of cranial morphology, including a shortened robust rostrum and broad, irregular nasal aperture, confirm placement of Litokoala as sister taxon to the modern genus Phascolarctos. Relatively large orbits and small body size suggest the possibility that L. dicksmithi was nocturnal, had enhanced visual acuity, and was a more agile arboreal species than the relatively sedentary extant koala

Evolution of microstructure and crystallographic texture during dissimilar friction stir welding of duplex stainless steel to low carbon-manganese structural steel

Electron backscattered diffraction (EBSD) was used to analyze the evolution of microstructure and crystallographic texture during friction stir welding of dissimilar type 2205 duplex stainless steel (DSS) to type S275 low carbon-manganese structural steel. The results of microstructural analyses show that the temperature in the center of stirred zone reached temperatures between Ac 1 and Ac 3 during welding, resulting in a minor ferrite-to-austenite phase transformation in the S275 steel, and no changes in the fractions of ferrite and austenite in the DSS. Temperatures in the thermomechanically affected and shoulder-affected zones of both materials, in particular toward the root of the weld, did not exceed the Ac 1 of S275 steel. The shear generated by the friction between the material and the rotating probe occurred in austenitic/ferritic phase field of the S275 and DSS. In the former, the transformed austenite regions of the microstructure were transformed to acicular ferrite, on cooling, while the dual-phase austenitic/ferritic structure of the latter was retained. Studying the development of crystallographic textures with regard to shear flow lines generated by the probe tool showed the dominance of simple shear components across the whole weld in both materials. The ferrite texture in S275 steel was dominated by D 1, D 2, E, E¯ , and F, where the fraction of acicular ferrite formed on cooling showed a negligible deviation from the texture for the ideal shear texture components of bcc metals. The ferrite texture in DSS was dominated by D 1, D 2, I, I¯ , and F, and that of austenite was dominated by the A, A¯ , B, and B¯ of the ideal shear texture components for bcc and fcc metals, respectively. While D 1, D 2, and F components of the ideal shear texture are common between the ferrite in S275 steel and that of dual-phase DSS, the preferential partitioning of strain into the ferrite phase of DSS led to the development of I and I¯ components in DSS, as opposed to E and E¯ in the S275 steel. The formations of fine and ultrafine equiaxed grains were observed in different regions of both materials that are believed to be due to strain-induced continuous dynamic recrystallization (CDRX) in ferrite of both DSS and S275 steel, and discontinuous dynamic recrystallization (DDRX) in austenite phase of DSS

Foreign investment and migration Extensions of the basic model

With 8 figs.Bibliothek Weltwirtschaft Kiel C 152110 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

The Proof Is in the Process: A Preamble for a Philosophy of Computer-Assisted Mathematics

According to some well-known mathematicians well-versed in computer-assisted mathematics (CaM), “Computers are changing the way we are doing mathematics”. To what extent this is really true is still an open question. Indeed, even though some philosophers of math have taken up the challenge to think about CaM, it is unclear in what sense exactly a machine (can) affect(s) the so-called “queen of the sciences”. In fact, some have concluded that issues raised by the use of the computer in mathematics are not specific to the use of the computer per se. However, such findings seem precarious since a systematic study of computer-assisted mathematics is still lacking. In this paper I argue that in order to understand the impact of CaM, it is necessary to take more seriously the computer itself and how it is actually used in the process of doing mathematics. Within such an approach, one searches for characteristics that are specific to the use of the computer in mathematics. I will focus on a feature that is beyond any doubt inherently connected to the use of computing machinery, viz. mathematician-computer interactions. I will show how such interactions are fundamentally different from the usual interactions between mathematicians and non-human aids (a piece of paper, a blackboard etc) and how such interactions determine at least two more characteristics of CaM, viz. the significance of time and processes and the steady process of internalization of mathematical tools and knowledge into the machine. I will restrict myself to the use of the computer within so-called experimental mathematics since this is the main object of CaM within the philosophical literature