Modeling and Simulation of Long-Term Performance of Near-Surface Barriers

Society has and will continue to generate hazardous wastes whose risks must be managed. For exceptionally toxic, long-lived, and feared waste, the solution is deep burial, e.g., deep geological disposal at Yucca Mtn. For some waste, recycle or destruction/treatment is possible. The alternative for other wastes is storage at or near the ground level (in someone’s back yard); most of these storage sites include a surface barrier (cap) to prevent migration of the waste due to infiltration of surface water. The design lifespan for such barriers ranges from 30 to 1000 years, depending on hazard and regulations. In light of historical performance, society needs a better basis for predicting barrier performance over long time periods and tools for optimizing maintenance of barriers while in service. We believe that, as in other industries, better understanding of the dynamics of barrier system degradation will enable improved barriers (cheaper, longer-lived, simpler, easier to maintain) and improved maintenance. We are focusing our research on earthen caps, especially those with evapo-transpiration and capillary breaks. Typical cap assessments treat the barrier’s structure as static prior to some defined lifetime. Environmental boundary conditions such as precipitation and temperature are treated as time dependent. However, other key elements of the barrier system are regarded as constant, including engineered inputs (e.g., fire management strategy, irrigation, vegetation control), surface ecology (critical to assessment of plant transpiration), capillary break interface, material properties, surface erosion rate, etc. Further, to be conservative, only harmful processes are typically considered. A more holistic examination of both harmful and beneficial processes will provide more realistic pre-service prediction and in-service assessment of performance as well as provide designers a tool to encourage beneficial processes while discouraging harmful processes. Thus, the INEEL started a new project on long-term barrier integrity in April 2002 that aims to catalyze a Barrier Improvement Cycle (iterative learning and application) and thus enable Remediation System Performance Management (doing the right maintenance neither too early nor too late, prior to system-level failure). This paper describes our computer simulation approach for better understanding the relationships and dynamics between the various components and management decisions in a cap. The simulation is designed to clarify the complex relationships between the various components within the cap system and the various management practices that affect the barrier performance. We have also conceptualized a time-dependent 3-D simulation with rigorous solution to unsaturated flow physics with complex surface boundary conditions

Achieving performance portability for a heat conduction solver mini-application on modern multi-core systems

Modernizing production-grade, often legacy applications to take advantage of modern multi-core and many-core architectures can be a difficult and costly undertaking. This is especially true currently, as it is unclear which architectures will dominate future systems. The complexity of these codes can mean that parallelisation for a given architecture requires significant re-engineering. One way to assess the benefit of such an exercise would be to use mini-Applications that are representative of the legacy programs.In this paper, we investigate different implementations of TeaLeaf, a mini-Application from the Mantevo suite that solves the linear heat conduction equation. TeaLeaf has been ported to use many parallel programming models, including OpenMP, CUDA and MPI among others. It has also been re-engineered to use the OPS embedded DSL and template libraries Kokkos and RAJA. We use these different implementations to assess the performance portability of each technique on modern multi-core systems.While manually parallelising the application targeting and optimizing for each platform gives the best performance, this has the obvious disadvantage that it requires the creation of different versions for each and every platform of interest. Frameworks such as OPS, Kokkos and RAJA can produce executables of the program automatically that achieve comparable portability. Based on a recently developed performance portability metric, our results show that OPS and RAJA achieve an application performance portability score of 71% and 77% respectively for this application

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Global prevalence and disease burden of vitamin D deficiency: a roadmap for action in low- and middle-income countries.

Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25-hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency-related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low- and middle-income countries have been hampered by limited availability of population-representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D 1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency-related conditions in vulnerable populations

Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia

Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing to microglia activation for synapse elimination in pathology are not fully understood. Here, using in vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) in genetically engineered mice in vivo, we report that at 24 hours after ischemia, microglia release brain-derived neurotrophic factor (BDNF) to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the cornu ammonis 1 (CA1) in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75 neurotrophin receptor (p75NTR) and tropomyosin receptor kinase B (TrkB) receptors, respectively. After MCAO, we report that in the peri-infarct area and in the corresponding contralateral hemisphere, similar neuroplasticity occurs through microglia activation and gephyrin phosphorylation at serine-268 and serine-270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point mutations protects against ischemic brain damage, neuroinflammation, and synapse downregulation after MCAO

Impact, regulation and health policy implications of physician migration in OECD countries

BACKGROUND: In the face of rising demand for medical services due to ageing populations, physician migration flows are increasingly affecting the supply of physicians in Organisation for Economic Co-operation and development (OECD) countries. This paper offers an integrated perspective on the impact of physician migration on home and host countries and discusses international regulation and policy approaches governing physician migration. METHODS: Information about migration flows, international regulation and policies governing physician migration were derived from two questionnaires sent to OECD countries, a secondary analysis of EUROSTAT Labour Force Surveys, a literature review and official policy documents of OECD countries. RESULTS: OECD countries increasingly perceive immigration of foreign physicians as a way of sustaining their physician workforce. As a result, countries have entered into international agreements regulating physician migration, although their success has been limited due to the imposition of licensing requirements and the protection of vested interests by domestic physicians. OECD countries have therefore adopted specific policies designed to stimulate the immigration of foreign physicians, whilst minimising its negative impact on the home country. Measures promoting immigration have included international recruitment campaigns, less strict immigration requirements and arrangements that foster shared learning between health care systems. Policies restricting the societal costs of physician emigration from developing countries such as good practice guidelines and taxes on host countries have not yet produced their expected effect or in some cases have not been established at all. CONCLUSIONS: Although OECD countries generally favour long-term policies of national self-sufficiency to sustain their physician workforce, such policies usually co-exist with short-term or medium-term policies to attract foreign physicians. As this is likely to continue, there is a need to create a global framework that enforces physician migration policies that confer benefits on home and host countries. In the long term, OECD countries need to put in place appropriate education and training policies rather than rely on physician migration to address their future needs

Microbial diversity and biogeography in Arctic soils

Microorganisms dominate terrestrial environments in the polar regions and Arctic soils are known to harbour significant microbial diversity, far more diverse and numerous in the region than was once thought. Furthermore, the geographic distribution and structure of Arctic microbial communities remains elusive, despite their important roles in both biogeochemical cycling and in the generation and decomposition of climate active gases. Critically, Arctic soils are estimated to store over 1500 Pg of carbon and thus, have the potential to generate positive feedback within the climate system. As the Arctic region is currently undergoing rapid change, the likelihood of faster release of greenhouse gases such as CO2 , CH4 and N2 O is increasing. Understanding the microbial communities in the region, in terms of their diversity, abundance and functional activity, is key to producing accurate models of greenhouse gas release. This review brings together existing data to determine what we know about microbial diversity and biogeography in Arctic soils

5′UTR Variants of Ribosomal Protein S19 Transcript Determine Translational Efficiency: Implications for Diamond-Blackfan Anemia and Tissue Variability

Background: Diamond-Blackfan anemia (DBA) is a lineage specific and congenital erythroblastopenia. The disease is associated with mutations in genes encoding ribosomal proteins resulting in perturbed ribosomal subunit biosynthesis. The RPS19 gene is mutated in approximately 25 % of DBA patients and a variety of coding mutations have been described, all presumably leading to haploinsufficiency. A subset of patients carries rare polymorphic sequence variants within the 59untranslated region (59UTR) of RPS19. The functional significance of these variants remains unclear. Methodology/Principal Findings: We analyzed the distribution of transcriptional start sites (TSS) for RPS19 mRNAs in testis and K562 cells. Twenty-nine novel RPS19 transcripts were identified with different 59UTR length. Quantification of expressed w.t. 59UTR variants revealed that a short 59UTR correlates with high levels of RPS19. The total levels of RPS19 transcripts showed a broad variation between tissues. We also expressed three polymorphic RPS19 59UTR variants identified in DBA patients. The sequence variants include two insertions (c.-147_-146insGCCA and c.-147_-146insAGCC) and one deletion (c.-144_-141delTTTC). The three 59UTR polymorphisms are associated with a 20–30 % reduction in RPS19 protein levels when compared to the wild-type (w.t.) 59UTR of corresponding length. Conclusions: The RPS19 gene uses a broad range of TSS and a short 59UTR is associated with increased levels of RPS19. Comparisons between tissues showed a broad variation in the total amount of RPS19 mRNA and in the distribution of TS

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants