Structural and chemical embrittlement of grain boundaries by impurities: a general theory and first principles calculations for copper

First principles calculations of the Sigma 5 (310)[001] symmetric tilt grain boundary in Cu with Bi, Na, and Ag substitutional impurities provide evidence that in the phenomenon of Bi embrittlement of Cu grain boundaries electronic effects do not play a major role; on the contrary, the embrittlement is mostly a structural or "size" effect. Na is predicted to be nearly as good an embrittler as Bi, whereas Ag does not embrittle the boundary in agreement with experiment. While we reject the prevailing view that "electronic" effects (i.e., charge transfer) are responsible for embrittlement, we do not exclude the role of chemistry. However numerical results show a striking equivalence between the alkali metal Na and the semi metal Bi, small differences being accounted for by their contrasting "size" and "softness" (defined here). In order to separate structural and chemical effects unambiguously if not uniquely, we model the embrittlement process by taking the system of grain boundary and free surfaces through a sequence of precisely defined gedanken processes; each of these representing a putative mechanism. We thereby identify three mechanisms of embrittlement by substitutional impurities, two of which survive in the case of embrittlement or cohesion enhancement by interstitials. Two of the three are purely structural and the third contains both structural and chemical elements that by their very nature cannot be further unravelled. We are able to take the systems we study through each of these stages by explicit computer simulations and assess the contribution of each to the nett reduction in intergranular cohesion. The conclusion we reach is that embrittlement by both Bi and Na is almost exclusively structural in origin; that is, the embrittlement is a size effect.Comment: 13 pages, 5 figures; Accepted in Phys. Rev.

Raman spectra and calculated vibrational frequencies of size-selected C16, C18, and C20 clusters

The surface plasmon polariton-enhanced Raman spectra of size-selected C16, C18, and C20 clusters isolated in nitrogen matrices are presented along with the calculated vibrational frequencies for the ring and linear chain isomers. The Raman spectra, recorded at a range of excitation wavelengths from 457.9 to 670 nm, show strong resonance enhancement for the three clusters. The calculated vibrational frequencies for ring and linear chain isomers and the cage and bowl structures for C20 are compared to the experimental frequencies. Systematic shifts in the series of peaks in the 200 cm-1 region for C16, C18, and C20 suggest that the observed isomers have the same geometry, thereby ruling out the bowl and cage isomers for C20. The measured spectra appear to be most consistent with the linear chain isomer. This high-energy isomer may be produced during neutralization of the deposited cluster ions

Autoimmunity plays a role in the onset of diabetes after 40 years of age

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood

Autoimmunity plays a role in the onset of diabetes after 40 years of age

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood

Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores

Background & Aims: Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. Methods: We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5). Results: In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p = 0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p <10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p <0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p <10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ~90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p <10-5) and without cirrhosis (p <0.05). Conclusions: Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy of HCC detection and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings. Lay summary: By analyzing variations in genes that contribute to fatty liver disease, we developed two risk scores to help predict liver cancer in individuals with obesity-related metabolic complications. These risk scores can be easily tested in the clinic. We showed that the risk scores helped to identify the risk of liver cancer both in high-risk individuals and in the general population

ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?

We report on a high-statistics measurement of the basic double pionic fusion reaction $pn \to d\pi^0\pi^0$ over the energy region of the so-called ABC effect, a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The measurements were performed with the WASA detector setup at COSY. The data reveal the ABC effect to be associated with a Lorentzian shaped energy dependence in the integral cross section. The observables are consistent with a resonance with $I(J^P) =0(3^+)$ in both $pn$ and $\Delta\Delta$ systems. Necessary further tests of the resonance interpretation are discussed

Sequence Analysis of the Cloned mRNA Coding for Glyceraldehyde-3-Phosphate Dehydrogenase from Chicken Heart Muscle

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66279/1/j.1432-1033.1983.tb07239.x.pd

Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk

<p>Abstract</p> <p>Backgroud</p> <p>Patients with chronic inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer (CRC) and it is estimated that one in six persons diagnosed with IBD will develop CRC. This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers.</p> <p>Methods</p> <p>In order to test this hypothesis we investigated a series of polymorphisms in 6 genes (NOD2, DLG5, OCTN1, OCTN2, IL4, TNFα) associated with the inflammatory response on a group of 607 consecutive newly diagnosed colorectal cancer patients and compared the results to controls (350 consecutive newborns and 607 age, sex and geographically matched controls).</p> <p>Results</p> <p>Of the six genes only one polymorphism in TNFα(-1031T/T) showed any tendency to be associated with disease risk (64.9% for controls and 71.4% for CRC) which we further characterized on a larger cohort of CRC patients and found a more profound relationship between the TNFα -1031T/T genotype and disease (64.5% for controls vs 74.7% for CRC cases above 70 yrs). Then, we investigated this result and identified a suggestive tendency, linking the TNFα -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs).</p> <p>Conclusion</p> <p>The association of polymorphisms in genes involved in the inflammatory response and CRC onset suggest that there are genetic changes capable of influencing disease risk in older persons.</p

Climate Change and the Future of California's Endemic Flora

The flora of California, a global biodiversity hotspot, includes 2387 endemic plant taxa. With anticipated climate change, we project that up to 66% will experience >80% reductions in range size within a century. These results are comparable with other studies of fewer species or just samples of a region's endemics. Projected reductions depend on the magnitude of future emissions and on the ability of species to disperse from their current locations. California's varied terrain could cause species to move in very different directions, breaking up present-day floras. However, our projections also identify regions where species undergoing severe range reductions may persist. Protecting these potential future refugia and facilitating species dispersal will be essential to maintain biodiversity in the face of climate change