Comparison of Mechanical Properties of Ni[sub]3Al Thin Films in Disordered FCC and Ordered L1[sub]2 Phases

We report the results of several experiments isolating the effect of long-range order on mechanical properties of intermetallic compounds. Kinetically disordered FCC Ni3Al (Ni 76%) thin films were produced by rapid solidification following pulsed laser melting. For comparison, compositionally and microstructurally identical films with ordered L12 structure were produced by subsequent annealing at 550 °C for 2 hours. These FCC and L12 Ni3Al thin films were tested by nanoindentation for hardness and Young’s modulus, and the critical strain to fracture was measured by straining the substrate under four-point bending. Ni3Al thin films in the disordered phase were found to have nearly twice the critical strain to fracture, more than three times the fracture toughness, and about 20% lower hardness than in the ordered counterpart. Blunter crack tips and crack bridging observed in the disordered phase also illustrate increased ductility. The increased plasticity of Ni3Al due to chemical disorder is manifested both within the grains and at the grain boundaries. Young’s moduli of the ordered and disordered materials were found to be indistinguishable.Engineering and Applied Science

Understanding your water test report (1995)

"New 7/93, Reprinted 4/95/5M.""Water Quality.""Focus area : drinking water.""Published by University Extension. University of Missouri-Columbia.""Reviewed and adapted for Missouri by Wanda Eubank, Jerry Carpenter, Bev Maltsberger, University of Missouri-Columbia, and Nix Anderson, Missouri Department of Health, from Understanding Your Water Test Report by Michael H. Bradshaw, Health and Safety Extension Specialist and G. Morgan Powell, Natural Resource Engineer, Kansas State University.

Simulation of ultrafast photodynamics of pyrrole with a multiconfigurational Ehrenfest method

We report the first results of ab initio multiconfigurational Ehrenfest simulations of pyrrole photodynamics. We note that, in addition to the two intersections of 11A2 and 11B1 states with the ground state 11A1, which are known to be responsible for N–H bond fission, another intersection between the 12A2 and 12B1 states of the resulting molecular radical becomes important after the departure of the H atom. This intersection, which is effectively between the two lowest electronic states of the pyrrolyl radical, may play a significant role in explaining the branching ratio between the two states observed experimentally. The exchange of population between the two states of pyrrolyl occurs on a longer scale than that of N–H bond fission

Chemoradiotherapy of locally-advanced non-small cell lung cancer: Analysis of radiation dose-response, chemotherapy and survival-limiting toxicity effects indicates a low alpha/beta ratio

Purpose To analyse changes in 2-year overall survival (OS2yr) with radiotherapy (RT) dose, dose-per-fraction, treatment duration and chemotherapy use, in data compiled from prospective trials of RT and chemo-RT (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC). Material and methods OS2yr data was analysed for 6957 patients treated on 68 trial arms (21 RT-only, 27 sequential CRT, 20 concurrent CRT) delivering doses-per-fraction ≤4.0 Gy. An initial model considering dose, dose-per-fraction and RT duration was fitted using maximum-likelihood techniques. Model extensions describing chemotherapy effects and survival-limiting toxicity at high doses were assessed using likelihood-ratio testing, the Akaike Information Criterion (AIC) and cross-validation. Results A model including chemotherapy effects and survival-limiting toxicity described the data significantly better than simpler models (p < 10−14), and had better AIC and cross-validation scores. The fitted α/β ratio for LA-NSCLC was 4.0 Gy (95%CI: 2.8–6.0 Gy), repopulation negated 0.38 (95%CI: 0.31–0.47) Gy EQD2/day beyond day 12 of RT, and concurrent CRT increased the effective tumour EQD2 by 23% (95%CI: 16–31%). For schedules delivered in 2 Gy fractions over 40 days, maximum modelled OS2yr for RT was 52% and 38% for stages IIIA and IIIB NSCLC respectively, rising to 59% and 42% for CRT. These survival rates required 80 and 87 Gy (RT or sequential CRT) and 67 and 73 Gy (concurrent CRT). Modelled OS2yr rates fell at higher doses. Conclusions Fitted dose–response curves indicate that gains of ~10% in OS2yr can be made by escalating RT and sequential CRT beyond 64 Gy, with smaller gains for concurrent CRT. Schedule acceleration achieved via hypofractionation potentially offers an additional 5–10% improvement in OS2yr. Further 10–20% OS2yr gains might be made, according to the model fit, if critical normal structures in which survival-limiting toxicities arise can be identified and selectively spared

Advances in MASELTOV – Serious Games in a Mobile Ecology of Services for Social Inclusion and Empowerment of Recent Immigrants

Immigration imposes a range of challenges with the risk of social exclusion from the information society (Halfman 1998), such as, getting into communication with the local society and understanding the culture of their host nation. Failure to address these challenges can lead to difficulties in the frame of integrating into the society of the host country, leading to fragmented communities and a range of social issues. As part of a comprehensive suite of services for immigrants, the European project seeks to provide both practical tools and learning services via mobile devices, providing a readily usable resource for immigrants. We introduce recent results, such as the game-based learning aspect of the MASELTOV project is introduced, with the rationale behind its design presented. In doing so, the benefits and implications of mobile platforms and emergent data capture techniques for game-based learning are discussed, as are methods for putting engaging gameplay at the forefront of the experience whilst relying on rich data capture and analysis to provide an effective learning solution

Endothelial Membrane Remodeling Is Obligate for Anti-Angiogenic Radiosensitization during Tumor Radiosurgery

While there is significant interest in combining anti-angiogenesis therapy with conventional anti-cancer treatment, clinical trials have as of yet yielded limited therapeutic gain, mainly because mechanisms of anti-angiogenic therapy remain to a large extent unknown. Currently, anti-angiogenic tumor therapy is conceptualized to either "normalize" dysfunctional tumor vasculature, or to prevent recruitment of circulating endothelial precursors into the tumor. An alternative biology, restricted to delivery of anti-angiogenics immediately prior to single dose radiotherapy (radiosurgery), is provided in the present study.Genetic data indicate an acute wave of ceramide-mediated endothelial apoptosis, initiated by acid sphingomyelinase (ASMase), regulates tumor stem cell response to single dose radiotherapy, obligatory for tumor cure. Here we show VEGF prevented radiation-induced ASMase activation in cultured endothelium, occurring within minutes after radiation exposure, consequently repressing apoptosis, an event reversible with exogenous C(16)-ceramide. Anti-VEGFR2 acts conversely, enhancing ceramide generation and apoptosis. In vivo, MCA/129 fibrosarcoma tumors were implanted in asmase(+/+) mice or asmase(-/-) littermates and irradiated in the presence or absence of anti-VEGFR2 DC101 or anti-VEGF G6-31 antibodies. These anti-angiogenic agents, only if delivered immediately prior to single dose radiotherapy, de-repressed radiation-induced ASMase activation, synergistically increasing the endothelial apoptotic component of tumor response and tumor cure. Anti-angiogenic radiosensitization was abrogated in tumors implanted in asmase(-/-) mice that provide apoptosis-resistant vasculature, or in wild-type littermates pre-treated with anti-ceramide antibody, indicating that ceramide is necessary for this effect.These studies show that angiogenic factors fail to suppress apoptosis if ceramide remains elevated while anti-angiogenic therapies fail without ceramide elevation, defining a ceramide rheostat that determines outcome of single dose radiotherapy. Understanding the temporal sequencing of anti-angiogenic drugs and radiation enables optimized radiosensitization and design of innovative radiosurgery clinical trials

A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells

Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground-based “simulated” microgravity induced changes on DNA methylation (5-methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations

DNA Specificity Determinants Associate with Distinct Transcription Factor Functions

To elucidate how genomic sequences build transcriptional control networks, we need to understand the connection between DNA sequence and transcription factor binding and function. Binding predictions based solely on consensus predictions are limited, because a single factor can use degenerate sequence motifs and because related transcription factors often prefer identical sequences. The ETS family transcription factor, ETS1, exemplifies these challenges. Unexpected, redundant occupancy of ETS1 and other ETS proteins is observed at promoters of housekeeping genes in T cells due to common sequence preferences and the presence of strong consensus motifs. However, ETS1 exhibits a specific function in T cell activation; thus, unique transcriptional targets are predicted. To uncover the sequence motifs that mediate specific functions of ETS1, a genome-wide approach, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), identified both promoter and enhancer binding events in Jurkat T cells. A comparison with DNase I sensitivity both validated the dataset and also improved accuracy. Redundant occupancy of ETS1 with the ETS protein GABPA occurred primarily in promoters of housekeeping genes, whereas ETS1 specific occupancy occurred in the enhancers of T cell–specific genes. Two routes to ETS1 specificity were identified: an intrinsic preference of ETS1 for a variant of the ETS family consensus sequence and the presence of a composite sequence that can support cooperative binding with a RUNX transcription factor. Genome-wide occupancy of RUNX factors corroborated the importance of this partnership. Furthermore, genome-wide occupancy of co-activator CBP indicated tight co-localization with ETS1 at specific enhancers, but not redundant promoters. The distinct sequences associated with redundant versus specific ETS1 occupancy were predictive of promoter or enhancer location and the ontology of nearby genes. These findings demonstrate that diversity of DNA binding motifs may enable variable transcription factor function at different genomic sites