Ion Beams in Multi-Species Plasma

Argon and xenon ion velocity distribution functions are measured in Ar-He, Ar-Xe, and Xe-He expanding helicon plasmas to determine if ion beam velocity is enhanced by the presence of lighter ions. Contrary to observations in mixed gas sheath experiments, we find that adding a lighter ion does not increase the ion beam speed. The predominant effect is a reduction of ion beam velocity consistent with increased drag arising from increased gas pressure under all conditions: constant total gas pressure, equal plasma densities of different ions, and very different plasma densities of different ions. These results suggest that the physics responsible for the acceleration of multiple ion species in simple sheaths is not responsible for the ion acceleration observed in expanding helicon plasmas

Confocal Laser Induced Fluorescence with Comparable Spatial Localization to the Conventional Method

We present measurements of ion velocity distributions obtained by laser induced fluorescence (LIF) using a single viewport in an argon plasma. A patent pending design, which we refer to as the confocal fluorescence telescope, combines large objective lenses with a large central obscuration and a spatial filter to achieve high spatial localization along the laser injection direction. Models of the injection and collection optics of the two assemblies are used to provide a theoretical estimate of the spatial localization of the confocal arrangement, which is taken to be the full width at half maximum of the spatial optical response. The new design achieves approximately 1.4 mm localization at a focal length of 148.7 mm, improving on previously published designs by an order of magnitude and approaching the localization achieved by the conventional method. The confocal method, however, does so without requiring a pair of separated, perpendicular optical paths. The confocal technique therefore eases the two window access requirement of the conventional method, extending the application of LIF to experiments where conventional LIF measurements have been impossible or difficult, or where multiple viewports are scarce

Evidence for Electron Energization Accompanying Spontaneous Formation of Ion Acceleration Regions in Expanding Plasmas

We report experiments conducted in an expanding argon plasma generated in the inductive mode of a helicon source in the Hot hELIcon eXperiment–Large Experiment on Instabilities and Anisotropies facility. As the neutral gas pressure increases, the supersonic ion acceleration weakens. Increasing neutral pressure also alters the radial profile of electron temperature, density, and plasma potential upstream of the plasma expansion region. Langmuir probe measurements of the electron energy probability function (EEPF) show that heating of electrons at the plasma edge by RF fields diminishes with increasing gas pressure, yielding a plasma with a centrally peaked electron temperature, and flat potential profiles at higher neutral pressures. For neutral pressures at which ion acceleration regions develop in the expanding plasma plume, EEPFs reveal electrons with two temperature components

Early warning signals of simulated Amazon rainforest dieback

Copyright © The Author(s) 2013. This article is published with open access at Springerlink.comWe test proposed generic tipping point early warning signals in a complex climate model (HadCM3) which simulates future dieback of the Amazon rainforest. The equation governing tree cover in the model suggests that zero and non-zero stable states of tree cover co-exist, and a transcritical bifurcation is approached as productivity declines. Forest dieback is a non-linear change in the non-zero tree cover state, as productivity declines, which should exhibit critical slowing down. We use an ensemble of versions of HadCM3 to test for the corresponding early warning signals. However, on approaching simulated Amazon dieback, expected early warning signals of critical slowing down are not seen in tree cover, vegetation carbon or net primary productivity. The lack of a convincing trend in autocorrelation appears to be a result of the system being forced rapidly and non-linearly. There is a robust rise in variance with time, but this can be explained by increases in inter-annual temperature and precipitation variability that force the forest. This failure of generic early warning indicators led us to seek more system-specific, observable indicators of changing forest stability in the model. The sensitivity of net ecosystem productivity to temperature anomalies (a negative correlation) generally increases as dieback approaches, which is attributable to a non-linear sensitivity of ecosystem respiration to temperature. As a result, the sensitivity of atmospheric CO2 anomalies to temperature anomalies (a positive correlation) increases as dieback approaches. This stability indicator has the benefit of being readily observable in the real world.NERCJoint DECC/Defra Met Office Hadley Centre Climate ProgrammeUniversity of Exete

Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes

Genetic variation in the pleiotropic association between physical activity and body weight in mice

<p>Abstract</p> <p>Background</p> <p>A sedentary lifestyle is often assumed to lead to increases in body weight and potentially obesity and related diseases but in fact little is known about the genetic association between physical activity and body weight. We tested for such an association between body weight and the distance, duration, and speed voluntarily run by 310 mice from the F₂generation produced from an intercross of two inbred lines that differed dramatically in their physical activity levels.</p> <p>Methods</p> <p>We used a conventional interval mapping approach with SNP markers to search for QTLs that affected both body weight and activity traits. We also conducted a genome scan to search for relationship QTLs (<it>rel</it>QTLs), or chromosomal regions that affected an activity trait variably depending on the phenotypic value of body weight.</p> <p>Results</p> <p>We uncovered seven quantitative trait loci (QTLs) affecting body weight, but only one co-localized with another QTL previously found for activity traits. We discovered 19 <it>rel</it>QTLs that provided evidence for a genetic (pleiotropic) association of physical activity and body weight. The three genotypes at each of these loci typically exhibited a combination of negative, zero, and positive regressions of the activity traits on body weight, the net effect of which was to produce overall independence of body weight from physical activity. We also demonstrated that the <it>rel</it>QTLs produced these varying associations through differential epistatic interactions with a number of other epistatic QTLs throughout the genome.</p> <p>Conclusion</p> <p>It was concluded that individuals with specific combinations of genotypes at the <it>rel</it>QTLs and <it>epi</it>QTLs might account for some of the variation typically seen in plots of the association of physical activity with body weight.</p

Novel human genetic variants associated with extrapulmonary tuberculosis: a pilot genome wide association study

<p>Abstract</p> <p>Background</p> <p>Approximately 5-10% of persons infected with <it>M. tuberculosis </it>develop tuberculosis, but the factors associated with disease progression are incompletely understood. Both linkage and association studies have identified human genetic variants associated with susceptibility to pulmonary tuberculosis, but few genetic studies have evaluated extrapulmonary disease. Because extrapulmonary and pulmonary tuberculosis likely have different underlying pathophysiology, identification of genetic mutations associated with extrapulmonary disease is important.</p> <p>Findings</p> <p>We performed a pilot genome-wide association study among 24 persons with previous extrapulmonary tuberculosis and well-characterized immune defects; 24 pulmonary tuberculosis patients and 57 patients with <it>M. tuberculosis </it>infection served as controls. The Affymetrix GeneChip Human Mapping Xba Array was used for genotyping; after careful quality control, genotypes at 44,175 single nucleotide polymorphisms (SNPs) were available for analysis. Eigenstrat quantified population stratification within our sample; logistic regression, using results of the Eigenstrat analysis as a covariate, identified significant associations between groups. Permutation testing controlled the family-wise error rate for each comparison between groups. Four SNPs were significantly associated with extrapulmonary tuberculosis compared to controls with <it>M. tuberculosis </it>infection; one (rs4893980) in the gene PDE11A, one (rs10488286) in KCND2, and one (rs2026414) in PCDH15; one was in chromosome 7 but not associated with a known gene. Two additional variants were significantly associated with extrapulmonary tuberculosis compared with pulmonary tuberculosis; one (rs340708) in the gene FAM135B and one in chromosome 13 but not associated with a known gene. The function of all four genes affects cell signaling and activity, including in the brain.</p> <p>Conclusions</p> <p>In this pilot study, we identified 6 novel variants not previously known to be associated with extrapulmonary tuberculosis, including two SNPs more common in persons with extrapulmonary than pulmonary tuberculosis. This provides some support for the hypothesis that the pathogenesis and genetic predisposition to extrapulmonary tuberculosis differs from pulmonary tuberculosis. Further study of these novel SNPs, and more well-powered genome-wide studies of extrapulmonary tuberculosis, is warranted.</p

Evolutionary Genetics of an S-Like Polymorphism in Papaveraceae with Putative Function in Self-Incompatibility

Papaver rhoeas possesses a gametophytic self-incompatibility (SI) system not homologous to any other SI mechanism characterized at the molecular level. Four previously published full length stigmatic S-alleles from the genus Papaver exhibited remarkable sequence divergence, but these studies failed to amplify additional S-alleles despite crossing evidence for more than 60 S-alleles in Papaver rhoeas alone.Using RT-PCR we identified 87 unique putative stigmatic S-allele sequences from the Papaveraceae Argemone munita, Papaver mcconnellii, P. nudicuale, Platystemon californicus and Romneya coulteri. Hand pollinations among two full-sib families of both A. munita and P. californicus indicate a strong correlation between the putative S-genotype and observed incompatibility phenotype. However, we also found more than two S-like sequences in some individuals of A. munita and P. californicus, with two products co-segregating in both full-sib families of P. californicus. Pairwise sequence divergence estimates within and among taxa show Papaver stigmatic S-alleles to be the most variable with lower divergence among putative S-alleles from other Papaveraceae. Genealogical analysis indicates little shared ancestral polymorphism among S-like sequences from different genera. Lack of shared ancestral polymorphism could be due to long divergence times among genera studied, reduced levels of balancing selection if some or all S-like sequences do not function in incompatibility, population bottlenecks, or different levels of recombination among taxa. Preliminary estimates of positive selection find many sites under selective constraint with a few undergoing positive selection, suggesting that self-recognition may depend on amino acid substitutions at only a few sites.Because of the strong correlation between genotype and SI phenotype, sequences reported here represent either functional stylar S-alleles, tightly linked paralogs of the S-locus or a combination of both. The considerable complexity revealed in this study shows we have much to learn about the evolutionary dynamics of self-incompatibility systems

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16,