Statistical Physics Modeling of Disordered Metallic Alloys

The great majority of metallic alloys in use are disordered. The material property of a disordered alloy changes on exposure to thermal, chemical, or mechanical forcing; the changes are often irreversible. We present a new first principle method for modeling disordered metallic alloys suitable for predicting how the morphology, strength, and transport property would evolve under arbitrary forcing conditions. Such a predictive capability is critically important in designing new alloys for applications, such as in new-generation fission and fusion reactors, where unrelenting harsh thermal loading conditions exist. The protocol is developed for constructing a coarse-grained model that can be specialized for the evolution of thermophysical properties of an arbitrary disordered alloy under thermal, stress, nuclear, or chemical forcing scenarios. We model a disordered binary alloy as a randomly close-packed (RCP) assembly of constituent atoms at given composition. As such, a disordered alloy specimen is an admixture of nanocrystallites and glassy matter. For the present purpose, we first assert that interatomic interactions are by repulsion only, but the contributions from the attractive part of the interaction are restored by treating the nanocrystallites as nanoscale pieces of a single crystalline solid composed of the same constituent atoms. Implementation of the protocol is discussed for heating of disordered metals, and results are compared to the known melting point data

Epigenetic silencing of DSC3 is a common event in human breast cancer

INTRODUCTION: Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens. METHODS: We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines. RESULTS: DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure. CONCLUSION: These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure

Academic misconduct, misrepresentation and gaming: a reassessment

The motivation for this Special Issue is increasing concern not only with academic misconduct but also with less easily defined forms of misrepresentation and gaming. In an era of intense emphasis on measuring academic performance, there has been a proliferation of scandals, questionable behaviors and devious stratagems involving not just individuals but also organizations, including universities, editors and reviewers, journal publishers, and conference organizers. This introduction first reviews the literature on the prevalence of academic misconduct, misrepresentation and gaming (MMG). The core of the article is organized around a life-cycle model of the production and dissemination of research results. We synthesize the findings in the MMG literature at the level of the investigator or research team, emphasizing that misbehavior extends well beyond fabrication and falsification to include behaviors designed to exaggerate or to mislead readers as to the significance of research findings. MMG is next explored in the post-research review, publication, and post-publication realms. Moving from the individual researcher to the organizational level, we examine how MMG can be engaged in by either journals or organizations employing or funding the researchers. The changing institutional environment including the growth of research assessment exercises, increased quantitative output measurement and greater pressure to publish may all encourage MMG. In the final section, we summarize the main conclusions and offer suggestions both on how we might best address the problems and on topics for future research

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation