The Computing and Data Grid Approach: Infrastructure for Distributed Science Applications

Grid technology has evolved over the past several years to provide the services and infrastructure needed for building ``virtual'' systems and organizations. With this Grid based infrastructure that provides for using and managing widely distributed computing and data resources in the science environment, there is now an opportunity to provide a standard, large-scale, computing, data, instrument, and collaboration environment for science that spans many different projects, institutions, and countries. We argue that Grid technology provides an excellent basis for the creation of the integrated environments that can combine the resources needed to support the large-scale science projects located at multiple laboratories and universities. We also present some science case studies that indicate that a paradigm shift in the process of science will come about as a result of Grids providing transparent and secure access to advanced and integrated information and technologies infrastructure: powerful computing systems, large-scale data archives, scientific instruments, and collaboration tools. These changes will be in the form of Grid based services that can be integrated with the user's work environment, and that enable uniform and highly capable access to these computers, data, and instruments, regardless of the location or exact nature of these resources. These services will integrate transient-use resources like computing systems, scientific instruments, and data caches (e.g., as they are needed to perform a simulation or analyze data from a single experiment); persistent-use resources, such as databases, data catalogues, and archives; and collaborators, whose involvement will continue for the lifetime of a project or longer. While we largely address large-scale science requirements in this paper, Grids, particularly when combined with Web Services, will address a broad spectrum of science scenarios, both large and small scale, as well as various commercial and cultural cyberinfrastructure applications

Consumer Willingness to Pay for Breads Marketed as "Low-Carbohydrate"

Bread producers are taking advantage of healthy feeding habits by developing new "low carbohydrate" products to entice customers. These low carbohydrate breads are generally more expensive than conventional types. This study tests the hypothesis that consumers are willing to pay higher premium for "low carbohydrate" breads at various locations and markets. We use retail data in a hedonic pricing framework to estimate the premium paid for the "low carbohydrate" attribute of bread. Results show that the implicit price of the "low carbohydrate" attribute of bread ranges from about 0.06¢ to 1.1¢ per gram, reflecting the amount consumers are willing to pay above the price of conventional bread.low carbohydrate bread, hedonic price, willingness to pay, Institutional and Behavioral Economics, D12,

Transcriptional Profiles of Leukocyte Populations Provide a Tool for Interpreting Gene Expression Patterns Associated with High Fat Diet in Mice

Microarray experiments in mice have shown that high fat diet can lead to elevated expression of genes that are disproportionately associated with immune functions. These effects of high fat (atherogenic) diet may be due to infiltration of tissues by leukocytes in coordination with inflammatory processes.The Novartis strain-diet-sex microarray database (GSE10493) was used to evaluate the hepatic effects of high fat diet (4 weeks) in 12 mouse strains and both genders. We develop and apply an algorithm that identifies "signature transcripts" for many different leukocyte populations (e.g., T cells, B cells, macrophages) and uses this information to derive an in silico "inflammation profile". Inflammation profiles highlighted monocytes, macrophages and dendritic cells as key drivers of gene expression patterns associated with high fat diet in liver. In some strains (e.g., NZB/BINJ, B6), we estimate that 50-60% of transcripts elevated by high fat diet might be due to hepatic infiltration by these cell types. Interestingly, DBA mice appeared to exhibit resistance to localized hepatic inflammation associated with atherogenic diet. A common characteristic of infiltrating cell populations was elevated expression of genes encoding components of the toll-like receptor signaling pathway (e.g., Irf5 and Myd88).High fat diet promotes infiltration of hepatic tissue by leukocytes, leading to elevated expression of immune-associated transcripts. The intensity of this effect is genetically controlled and sensitive to both strain and gender. The algorithm developed in this paper provides a framework for computational analysis of tissue remodeling processes and can be usefully applied to any in vivo setting in which inflammatory processes play a prominent role

Mutations in the E2 Glycoprotein of Venezuelan Equine Encephalitis Virus Confer Heparan Sulfate Interaction, Low Morbidity, and Rapid Clearance from Blood of Mice

AbstractThe arbovirus, Venezuelan equine encephalitis virus (VEE), causes disease in humans and equines during periodic outbreaks. A murine model, which closely mimics the encephalitic form of the disease, was used to study mechanisms of attenuation. Molecularly cloned VEE viruses were used: a virulent, epizootic, parental virus and eight site-specific glycoprotein mutants derived from the parental virus. Four of these mutants were selected in vitro for rapid binding and penetration, resulting in positive charge changes in the E2 glycoprotein from glutamic acid or threonine to lysine (N. L. Davis, N. Powell, G. F. Greenwald, L. V. Willis, B. J. Johnson, J. F. Smith, and R. E. Johnston, Virology 183, 20–31, 1991). Tissue culture adaptation also selected for the ability to bind heparan sulfate as evidenced by inhibition of plaque formation by heparin, decreased infectivity for CHO cells deficient for heparan sulfate, and tight binding to heparin–agarose beads. In contrast, the parental virus and three other mutants did not use heparan sulfate as a receptor. All eight mutants were partially or completely attenuated with respect to mortality in adult mice after a subcutaneous inoculation, and the five mutants that interacted with heparan sulfate in vitro had low morbidity (0–50%). These same five mutants were cleared rapidly from the blood after an intravenous inoculation. In contrast, the parental virus and the other three mutants were cleared very slowly. In summary, the five VEE viruses that contain tissue-culture-selected mutations interacted with cell surface heparan sulfate, and this interaction correlated with low morbidity and rapid clearance from the blood. We propose that one mechanism of attenuation is rapid viral clearance in vivo due to binding of the virus to ubiquitous heparan sulfate

Attenuation of Sindbis virus variants incorporating uncleaved PE2 glycoprotein is correlated with attachment to cell-surface heparan sulfate

Sindbis virus virions incorporating uncleaved precursor envelope protein PE2 bind efficiently to cell-surface heparan sulfate (HS) because the furin cleavage site (a consensus HS-binding domain) is retained in the mature virus particle. However, they are essentially nonviable. Resuscitating mutations selected in the E3 or E2 protein preserve the PE2 noncleaving phenotype and HS binding, but facilitate fusion, and thereby restore wild-type infectivity on cultured cells. Here, we have demonstrated that the resuscitated PE2 noncleaving virus was almost avirulent in vivo, but mutated during the infection. Mutants had increased virulence and cleavage of PE2, with reduced HS binding capacity. We hypothesize that HS binding leads to sequestration of PE2 noncleaving virus particles and suppression of serum viremia, thereby selecting for evolution of the virus into a PE2-cleaving, low HS-binding phenotype

Attenuation of Sindbis virus variants incorporating uncleaved PE2 glycoprotein is correlated with attachment to cell-surface heparan sulfate

Sindbis virus virions incorporating uncleaved precursor envelope protein PE2 bind efficiently to cell-surface heparan sulfate (HS) because the furin cleavage site (a consensus HS-binding domain) is retained in the mature virus particle. However, they are essentially nonviable. Resuscitating mutations selected in the E3 or E2 protein preserve the PE2 noncleaving phenotype and HS binding, but facilitate fusion, and thereby restore wild-type infectivity on cultured cells. Here, we have demonstrated that the resuscitated PE2 noncleaving virus was almost avirulent in vivo, but mutated during the infection. Mutants had increased virulence and cleavage of PE2, with reduced HS binding capacity. We hypothesize that HS binding leads to sequestration of PE2 noncleaving virus particles and suppression of serum viremia, thereby selecting for evolution of the virus into a PE2-cleaving, low HS-binding phenotype

Development of Composite Sandwich Bonded Longitudinal Joints for Space Launch Vehicle Structures

The NASA Composite Technology for Exploration (CTE) Project is developing and demonstrating critical composite technologies with a focus on composite bonded joints; incorporating materials, design/analysis, manufacturing, and tests that utilize NASAs expertise and capabilities. The project has goals of advancing composite technologies and providing lightweight structures to support future NASA exploration missions. In particular, the CTE project will demonstrate weight-saving, performance-enhancing composite bonded joint technology for Space Launch System (SLS)-scale composite hardware. Advancements from the CTE project may be incorporated as future block upgrades for SLS structural components. This paper discusses the details of the development of a composite sandwich bonded longitudinal joint for a generic space launch vehicle structure called the CTE Point Design. The paper includes details of the design, analysis, materials, manufacturing, and testing of sub-element joint test articles to test the capability of the joint design. The test results show that the composite longitudinal bonded joint design significantly exceeds the design loads with a 2.0 factor of safety. Analysis pre-test failure predictions for all sub-element bonded joint test coupons were all within 10% of the average test coupon failure load. This testing and analysis provides confidence in the potential use of composite bonded joints for future launch vehicle structures

Low-Cost Air Quality Monitoring Tools: From Research to Practice (A Workshop Summary).

In May 2017, a two-day workshop was held in Los Angeles (California, U.S.A.) to gather practitioners who work with low-cost sensors used to make air quality measurements. The community of practice included individuals from academia, industry, non-profit groups, community-based organizations, and regulatory agencies. The group gathered to share knowledge developed from a variety of pilot projects in hopes of advancing the collective knowledge about how best to use low-cost air quality sensors. Panel discussion topics included: (1) best practices for deployment and calibration of low-cost sensor systems, (2) data standardization efforts and database design, (3) advances in sensor calibration, data management, and data analysis and visualization, and (4) lessons learned from research/community partnerships to encourage purposeful use of sensors and create change/action. Panel discussions summarized knowledge advances and project successes while also highlighting the questions, unresolved issues, and technological limitations that still remain within the low-cost air quality sensor arena