Gamma-400 Science Objectives Built on the Current HE Gamma-Ray and CR Results

The main scientific interest of the Russian Gamma-400 team: Observe gamma-rays above approximately 50 GeV with excellent energy and angular resolution with the goals of: (1) Studying the fine spectral structure of the isotropic high-energy gamma-radiation, (2) Attempting to identify the many still-unidentified Fermi-LAT gamma-ray sources. Gamma-400 will likely be the only space-based gamma-ray observatory operating at the end of the decade. In our proposed Gamma-400-LE version, it will substantially improve upon the capabilities of Fermi LAT and AGILE in both LE and HE energy range. Measuring gamma-rays from approx 20 MeV to approx 1 TeV for at least 7 years, Gamma-400-LE will address the topics of dark matter, cosmic ray origin and propagation, neutron stars, flaring pulsars, black holes, AGNs, GRBs, and actively participate in multiwavelength campaigns

Modeling Materials: Design for Planetary Entry, Electric Aircraft, and Beyond

NASA missions push the limits of what is possible. The development of high-performance materials must keep pace with the agency's demanding, cutting-edge applications. Researchers at NASA's Ames Research Center are performing multiscale computational modeling to accelerate development times and further the design of next-generation aerospace materials. Multiscale modeling combines several computationally intensive techniques ranging from the atomic level to the macroscale, passing output from one level as input to the next level. These methods are applicable to a wide variety of materials systems. For example: (a) Ultra-high-temperature ceramics for hypersonic aircraft-we utilized the full range of multiscale modeling to characterize thermal protection materials for faster, safer air- and spacecraft, (b) Planetary entry heat shields for space vehicles-we computed thermal and mechanical properties of ablative composites by combining several methods, from atomistic simulations to macroscale computations, (c) Advanced batteries for electric aircraft-we performed large-scale molecular dynamics simulations of advanced electrolytes for ultra-high-energy capacity batteries to enable long-distance electric aircraft service; and (d) Shape-memory alloys for high-efficiency aircraft-we used high-fidelity electronic structure calculations to determine phase diagrams in shape-memory transformations. Advances in high-performance computing have been critical to the development of multiscale materials modeling. We used nearly one million processor hours on NASA's Pleiades supercomputer to characterize electrolytes with a fidelity that would be otherwise impossible. For this and other projects, Pleiades enables us to push the physics and accuracy of our calculations to new levels

Geospatial forecast model for tsetse-transmitted animal trypanosomosis in Ethiopia

The aims of this study were to develop a geographic information systems (GIS) forecast and risk assessment model for cyclically transmitted trypanosomosis in Ethiopia by matching features in the environment to available information on the preferences and limits of tolerance of the parasite and its vector, and validate and further develop the GIS model using data from current and historical prevalence survey data and habitat microenvironment studies from trypanosomosis endemic areas. Results indicate that GIS model developed for parasitic diseases based on growing degree day (GDD) concept can be applied to tsetse-transmitted trypanosomosis. GIS for animal trypanosomosis was created using Food and Agriculture Organization – Crop Production System Zones (FAO-CPSZ) database and Normalized Difference Vegetation Index (NDVI) and maximum temperature (Tmax) from the Global Land 1km dataset. The two datasets used to determine the risk of tsetse flies and consequently animal trypanosomosis in Ethiopia indicated the magnitude of the disease and possible expansion of the “fly belt” in the future. The GIS model indicated the distribution and importance of tsetse-transmitted trypanosomosis in Ethiopia. Spatial and statistical analysis verified the use of GDD concept and climate forecast system that was developed to determine the suitability of a given environment for the proliferation of a biotype, in this case tsetse and trypanosomes. Results presented here indicate the importance of GDD and the two climatic variables (NDVI and Tmax) in the development of forecast model for tsetse-transmitted trypanosomosis in Ethiopia. Key words/phrases: Ethiopia, GIS, NDVI, Tmax, trypanosomosis SINET: Ethiopian Journal of Science Vol.27(1) 2004: 1-

Onion gene expression in response to ethylene and 1-MCP

Onion is regarded as a non-climacteric vegetable. In onions, however, ethylene can suppress sprouting while the ethylene binding inhibitor, 1-MCP (1- methylcyclopropene) can also suppress sprout growth yet, it is unknown how ethylene and 1-MCP elicit the same response. In this study, onions were treated with 10 μL L-1 ethylene or 1 μL L-1 1-MCP individually or in combination for 24 h at 20°C before or after curing (six weeks) at 20 or 28°C then stored at 1°C. Following curing, a subset of these same onions was stored separately under continuous air or ethylene (10 μL L- 1) at 1°C Onions treated with ethylene and 1-MCP in combination after curing for 24 h had reduced sprout growth as compared with the control 25 weeks after harvest. Sprout growth following storage beyond 25 weeks was only reduced through continuous ethylene treatment. This observation was supported by a higher proportion of down-regulated genes characterised as being involved in photosynthesis measured using a newly developed onion microarray. Physiological and biochemical data suggested that ethylene was being perceived in the presence of 1-MCP since sprout growth was reduced in onions treated with 1-MCP and ethylene applied in combination but not when applied individually. A cluster of probes representing transcripts up-regulated by 1-MCP alone but down-regulated by ethylene alone or in the presence of 1-MCP support this suggestion. Ethylene and 1-MCP both down52 regulated a probe tentatively annotated as an ethylene receptor as well as EIN3, suggesting that both treatments down-regulate the perception and signalling events of ethylene

Deciphering the functions of O-GlcNAc glycosylation in the brain: The role of site-specific quantitative O-GlcNAcomics

The dynamic posttranslational modification O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain. Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease. Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins. However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy. Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed. Revealing sites that are dynamically altered by different stimuli or disease states will likely go a long way in this regard. Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo. We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites. These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins. By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases

Ab Initio Simulations of Phase Stability and Martensitic Transitions in NiTi

For NiTi based alloys, the shape memory effect is governed by a transition from a low-temperature martensite phase to a high-temperature austenite phase. Despite considerable experimental and computational work, basic questions regarding the stability of the phases and the martensitic phase transition remain unclear even for the simple case of binary, equiatomic NiTi. We perform ab initio molecular dynamics simulations to describe the temperature-dependent behavior of NiTi and resolve several of these outstanding issues. Structural correlation functions and finite temperature phonon spectra are evaluated to determine phase stability. We show that finite temperature, entropic effects stabilize the experimentally observed martensite (B19') and austenite (B2) phases while destabilizing the theoretically predicted (B33) phase. Free energy computations based on ab initio thermodynamic integration confirm these results and permit estimates of the transition temperature between the phases. In addition to the martensitic phase transition, we predict a new transition between the B33 and B19' phases. The role of defects in suppressing phase transformation temperatures is discussed

characteristics and outcomes in patients with venous thromboembolism taking concomitant anti platelet agents and anticoagulants in the amplify trial

AbstractThe double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ≥ 5 days] overlapped and followed by warfarin [international normalized ratio = 2.0–3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death; the principal safety outcome was major bleeding. Of 5,365 (apixaban, n = 2,676; enoxaparin/warfarin, n = 2,689) randomized patients, 813 (apixaban, n = 402 [15%]; enoxaparin/warfarin, n = 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0%; enoxaparin/warfarin: 3.0 and 2.6%; anti-platelet use: relative risk [RR], 1.23; 95% confidence interval [CI], 0.58–2.62; no anti-platelet use: RR, 0.77; 95% CI, 0.52–1.13); interaction p-value = 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4%; enoxaparin/warfarin: 4.1 and 1.4%; anti-platelet use: RR, 0.30; 95% CI, 0.11–0.81; no anti-platelet use: RR, 0.31; 95% CI, 0.15–0.63); interaction p-value = 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201

Computational Design of Materials: Planetary Entry to Electric Aircraft and Beyond

NASA's projects and missions push the bounds of what is possible. To support the agency's work, materials development must stay on the cutting edge in order to keep pace. Today, researchers at NASA Ames Research Center perform multiscale modeling to aid the development of new materials and provide insight into existing ones. Multiscale modeling enables researchers to determine micro- and macroscale properties by connecting computational methods ranging from the atomic level (density functional theory, molecular dynamics) to the macroscale (finite element method). The output of one level is passed on as input to the next level, creating a powerful predictive model

Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits.

INTRODUCTION: Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach. A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution. To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group. AIM: The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee. METHODS: Multi-layer scaffolds, consisting of a bone layer composed of type I collagen (bovine source) and hydroxyapatite (HA), an intermediate layer composed of type I and type II collagen and HA; and a superficial layer composed of type I and type II collagen (porcine source) and hyaluronic acid (HyA), were implanted into critical size (3 × 5 mm) osteochondral defects created in the medial femoral condyle of the knee joint of New Zealand white rabbits and compared to an empty control group. Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation. RESULTS: Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group. In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark. CONCLUSION: These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects. STATEMENT OF SIGNIFICANCE: Osteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury. While some treatment options are available, success is limited and patients often eventually require joint replacement. To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group. The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark

Changes in Body composition and Maintenance efficiency during periods of restricted and maintenance feeding in immature and mature sheep

Improvements in production and quality can occur, without the need for increased inputs, through the use of 'Compensatory growth' or by reducing the maintenance requirements during growth and at maturity. A series of studies were used to examine the changes in body composition that occurred during weight loss and realimentation in immature and mature sheep. The effect of variations in body composition, induced through manipulation of nutrition, on estimates for equilibrium maintenance efficiency of mature sheep was examined. Statistical methods developed, tested for seasonal cycles in body composition in an attempt to determine the impact that any endogenous pattern in tissue deposition has on estimates of efficiencies for growth and maintenance. ..... Seasonality After adjusting for differences in body composition attributable to growth using an allometric function, seasonal oscillations for total body fat and carcass muscle were apparent in growing sheep. The magnitude and phase of the sine oscillations for fat and carcass muscle suggested that seasonal cues affect the priorities for tissue deposition. Seasonal oscillations where present for mature sheep that had been fed at a constant feed level. However a more precise method of describing the patterns of change in body tissues using random effects models and cubic splines did not reveal the presence of any time based deviation in total fat, carcass muscle or visceral lean. Nevertheless, the possibility of oscillations in body composition must be considered when estimating the efficiency of growth and maintenance or when evaluating the effects of nutritional manipulation on tissue development in immature and mature sheep