Modelling negative linear compressibility in tetragonal beam structures

Copyright © 2012 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Mechanics of Materials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Mechanics of Materials, Volume 46 (2012), DOI: 10.1016/j.mechmat.2011.12.007Most materials compress axially in all directions when loaded hydrostatically. Contrary to this, some materials have been discovered that exhibit negative linear compressibility and, as such, expand along a specific axis or plane. This paper analyses a fundamental mechanism by using a combination of finite element simulations and analytical derivations to show that negative linear compressibility can be found in a body-centred or face-centred tetragonal network of nodes connected by a network of beams. The magnitude and direction of this behaviour depends on the cross geometry in the network

Measurement of the atmospheric muon charge ratio at TeV energies with MINOS

The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray muon data since the beginning of August, 2003 at a depth of 2070 m.w.e. in the Soudan Underground Laboratory, Minnesota, USA. The data with both forward and reversed magnetic field running configurations were combined to minimize systematic errors in the determination of the underground muon charge ratio. When averaged, two independent analyses find the charge ratio underground to be N{sub {mu}}+/N{sub {mu}}-=1.374{+-}0.004(stat)-0.010{sup +0.012}(sys). Using the map of the Soudan rock overburden, the muon momenta as measured underground were projected to the corresponding values at the surface in the energy range 1-7 TeV. Within this range of energies at the surface, the MINOS data are consistent with the charge ratio being energy independent at the 2 standard deviation level. When the MINOS results are compared with measurements at lower energies, a clear rise in the charge ratio in the energy range 0.3-1.0 TeV is apparent. A qualitative model shows that the rise is consistent with an increasing contribution of kaon decays to the muon charge ratio

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting