Characterization of Cu-Sn SLID interconnects for harsh environment applications

This paper reports on the results obtained from performing 'shake and bake' testing on demonstrator vehicles bonded using Cu-Sn SLID technique. The demonstrator vehicles were exposed concurrently to vibration and thermal loadings similar to those seen in aerospace and downhole applications. This work demonstrates that Cu-Sn SLID bonding process is ideal for packaging sensors and electronics to be used within harsh environments, especially those encountered in the aerospace and oil & gas industries

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer.The QIMR Berghofer groups were supported by a Rio Tinto Ride to Conquer Cancer (RTCC)/Weekend to End Women's Cancers (WEWC) Grant and NHMRC project grants 1058415 to SLE and 1031333 to ABS. ABS is supported by an NHMRC Senior Research Fellowship (1061779). DFE is a Principal Research Fellow of CR-UK.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Cell Press

Knockdown of SF-1 and RNF31 Affects Components of Steroidogenesis, TGFβ, and Wnt/β-catenin Signaling in Adrenocortical Carcinoma Cells

The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads. We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) genes. To further evaluate the role of SF-1 in the adrenal cortex and the involvement of RNF31 in SF-1-dependent pathways, we performed genome-wide gene-expression analysis of adrenocortical NCI-H295R cells where SF-1 or RNF31 had been knocked down using RNA interference. We find RNF31 to be deeply connected to cholesterol metabolism and steroid hormone synthesis, strengthening its role as an SF-1 coregulator. We also find intriguing evidence of negative crosstalk between SF-1 and both transforming growth factor (TGF) β and Wnt/β-catenin signaling. This crosstalk could be of importance for adrenogonadal development, maintenance of adrenocortical progenitor cells and the development of adrenocortical carcinoma. Finally, the SF-1 gene profile can be used to distinguish malignant from benign adrenocortical tumors, a finding that implicates SF-1 in the development of malignant adrenocortical carcinoma

CSR and related terms in SME owner-managers' mental models in six European countries: national context matters

As a contribution to the emerging field of corporate social responsibility (CSR) cognition, this article reports on the findings of an exploratory study that compares SME owner–managers’ mental models with regard to CSR and related concepts across six European countries (Belgium, Italy, Norway, France, UK, Spain). Utilising Repertory Grid Technique, we found that the SME owner–managers’ mental models show a few commonalities as well as a number of differences across the different country samples. We interpret those differences by linking individual cognition to macro-environmental variables, such as language, national traditions and dissemination mechanisms. The results of our exploratory study show that nationality matters but that classifications of countries as found in the comparative capitalism literature do not exactly mirror national differences in CSR cognition and that these classifications need further differentiation. The findings from our study raise questions on the universality of cognition of academic management concepts and warn that promotion of responsible business practice should not rely on the use of unmediated US American management terminology

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Qur’anic Ethics for Environmental Responsibility: Implications for Business Practice

Despite the growing interest in examining the role of religious beliefs as a guide towards environmental conscious actions, there is still a lack of research informed by an analysis of divine messages. This deficiency includes the extent to which ethics for environmental responsibility are promoted within textual divine messages; types of environmental themes promoted within the text of divine messages; and implications of such religious environmental ethics for business practice. The present study attempts to fill this gap by conducting a thorough content analysis of environmental themes within the divine message of Muslims (the Qur’an) focusing on their related ethical aspects and business implications. The analysis has revealed 675 verses in 84 chapters throughout all 30 parts of the Qur’an, with environmental content relating to the core components of the natural world, i.e. human beings, water, air, land, plants, animals, and other natural resources. This environmental content and its related ethics are grounded on the belief that humans are vicegerents of God on the earth and their behaviours and actions are motivated by earthly and heavenly rewards. Implications of these findings for different sectors/businesses are also highlighted

Identification of nine new susceptibility loci for endometrial cancer

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study

Identification of nine new susceptibility loci for endometrial cancer

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study

Development of prediction models for lymph node metastasis in endometrioid endometrial carcinoma

Background In endometrioid endometrial cancer (EEC), current clinical algorithms do not accurately predict patients with lymph node metastasis (LNM), leading to both under- and over-treatment. We aimed to develop models that integrate protein data with clinical information to identify patients requiring more aggressive surgery, including lymphadenectomy. Methods Protein expression profiles were generated for 399 patients using reverse-phase protein array. Three generalised linear models were built on proteins and clinical information (model 1), also with magnetic resonance imaging included (model 2), and on proteins only (model 3), using a training set, and tested in independent sets. Gene expression data from the tumours were used for confirmatory testing. Results LNM was predicted with area under the curve 0.72–0.89 and cyclin D1; fibronectin and grade were identified as important markers. High levels of fibronectin and cyclin D1 were associated with poor survival (p = 0.018), and with markers of tumour aggressiveness. Upregulation of both FN1 and CCND1 messenger RNA was related to cancer invasion and mesenchymal phenotype. Conclusions We demonstrate that data-driven prediction models, adding protein markers to clinical information, have potential to significantly improve preoperative identification of patients with LNM in EEC.publishedVersio