Identification of hepatitis a virus mimotopes by phage display, antigenicity and immunogenicity

A phage-displayed peptide approach was used to identify ligands mimicking antigenic determinants of hepatitis A virus (HAV) for the first time. Bacteriophages displaying HAV mimotopes were isolated from a phage-display peptide library by affinity selection on serum antibodies from hepatitis A patients. Selected phage-peptides were screened for reactivity with sera from HAV infected patients and healthy controls. Four cloned peptides with different sequences were identified as mimotopes of HAV; three of them showed similarity in their amino acid sequences with at least one of the VP3 and VP1 antigenic proteins of HAV. One clone was recognised by 92% of the positive sera. The phagotopes competed effectively with HAV for absorption of anti-HAV-specific antibodies in human sera, as determined by ELISA. The four phage clones induced neutralising anti-HAV antibodies in immunised mice. These results demonstrate the potential of this method to elucidate the disease related epitopes of HAV and to use these mimotopes in diagnostic applications or in the development of a mimotope-based hepatitis A vaccine without the necessity of manipulation of the virus

Is adhesion superficial? Silicon wafers as a model system to study van der Waals interactions

Adhesion is a key issue for researchers of various fields, it is therefore of uppermost importance to understand the parameters that are involved. Commonly, only surface parameters are employed to determine the adhesive forces between materials. Yet, van der Waals forces act not only between atoms in the vicinity of the surface, but also between atoms in the bulk material. In this review, we describe the principles of van der Waals interactions and outline experimental and theoretical studies investigating the influence of the subsurface material on adhesion. In addition, we present a collection of data indicating that silicon wafers with native oxide layers are a good model substrate to study van der Waals interactions with coated materials

Soil carbon development in rejuvenated Indian coal mine spoil

The impact of mine spoil on the landscape is significant, as excavated rock-debris is commonly disposedin heaps that blanket the original land surface. Spoil heaps destroy the original soil habitat releasing soil-bound carbon, which is difficult to re-estate when mining operations cease and restoration begins. Thepresent work follows the development of vegetative cover on a coalmine spoil tip in India over a period of19 years following restoration. The potential of re-vegetated the mine spoil to imbibe carbon is examinedthrough the development of above- and below-ground biomass development. It was observed that the soilorganic carbon and microbial biomass carbon (MBC) significantly increased with re-vegetation age, withabove ground biomass increasing by 23 times, and belowground biomass increased by 26 times during theperiod of study. Soil organic carbon and MBC increased by 4× and 6.6× times, respectively. The averagecalculated annual carbon budget was 8.40 T/ha/year, of which 2.14 T/ha was allocated to above groundbiomass, 0.31 T/ha to belowground biomass, 2.88 T/ha to litter mass and 1.35 T/ha was sequestered intothe soil. This work has shown that the development of biomass following the restoration of mine spoilwas significant and that considerable quantities of carbon were stored in above and below ground plantmatter, and in the soil itself. It is concluded that appropriate restoration strategies can be used to rapidlyestablish a viable, healthy and sustainable ecosystem that imbibes carbon into former mine-impacted land

Portraying the nature of corruption: Using an explorative case-study design

What is the nature of corruption in Western democracies? To answer this research question, the authors study 10 Dutch corruption cases in depth, looking at confidential criminal files. The cases allow them to sketch a general profile of a corruption case. The authors offer nine propositions to portray the nature of corruption. They conclude that corruption usually takes place within enduring relationships, that the process of becoming corrupt can be characterized as a slippery slope, and that important motives for corruption, aside from material gain, include friendship or love, status, and the desire to impress others. The explorative multiple case study methodology helps to expand our understanding of the way in which officials become corrupt. © 2008 The American Society for Public Administration

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

Impact of different eddy covariance sensors, site set-up, and maintenance on the annual balance of CO2 and CH4 in the harsh Arctic environment

Improving year-round data coverage for CO2 and CH4 fluxes in the Arctic is critical for refining the global C budget but continuous measurements are very sparse due to the remote location limiting instrument maintenance, to low power availability, and to extreme weather conditions. The need for tailoring instrumentation, site set up, and maintenance at different sites can add uncertainty to estimates of annual C budgets from different ecosystems. In this study, we investigated the influence of different sensor combinations on fluxes of sensible heat, CO2, latent heat (LE), and CH4, and assessed the differences in annual CO2 and CH4 fluxes estimated with different instrumentation at the same sites. Using data from four sites across the North Slope of Alaska, we found that annual CO2 fluxes estimated with heated (7.5 ± 1.4 gC m−2 yr−1) and non-heated (7.9 ± 1.3 gC m−2 yr−1) anemometers were within uncertainty bounds. Similarly, despite elevated noise in 30-min flux data, we found that summer CO2 fluxes from open (−17.0 ± 1.1 gC m−2 yr−1) and close-path (−14.2 ± 1.7 gC m−2 yr−1) gas analyzers were not significantly different. Annual CH4 fluxes were also within uncertainty bounds when comparing both open (4.5 ± 0.31 gC m−2 yr−1) and closed-path (4.9 ± 0.27 gC m−2 yr−1) gas analyzers as well as heated (3.7 ± 0.26 gC m−2 yr−1) and non-heated (3.7 ± 0.28 gC m−2 yr−1) anemometers. A continuously heated anemometer increased data coverage (64%) relative to non-heated anemometers (47–52%). However, sensible heat fluxes were over-estimated by 12%, on average, with the heated anemometer, contributing to the overestimation of CO2, CH4, and LE fluxes (mean biases of −0.03 μmol m−2 s−1, −0.05 mgC m−2 h−1, and −3.77 W m−2, respectively). To circumvent this potential bias and reduce power consumption, we implemented an intermittent heating strategy whereby activation only occurred when ice or snow blockage of the transducers was detected. This resulted in comparable coverage (50%) during winter to the continuously heated anemometer (46%), while avoiding flux over-estimation. Closed and open-path analyzers showed good agreement, but data coverage was generally greater when using closed-path, especially during winter. Winter data coverage of 26–32% was obtained with closed-path devices, vs 10–14% for the open-path devices with unheated anemometers or up to 46% and 35% using closed and open-path analyzers, respectively with heated anemometers. Accurate estimation of LE remains difficult in the Arctic due to strong attenuation in closed-path systems, even when intake tubes are heated, and due to poor data coverage from open-path sensors in such a harsh environment

A History of Universalism: Conceptions of the Internationality of Science from the Enlightenment to the Cold War

That science is fundamentally universal has been proclaimed innumerable times. But the precise geographical meaning of this universality has changed historically. This article examines conceptions of scientific internationalism from the Enlightenment to the Cold War, and their varying relations to cosmopolitanism, nationalism, socialism, and 'the West'. These views are confronted with recent tendencies to cast science as a uniquely European product

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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