Interview: Chris Anderton, CDRS Web Developer

Chris Anderton, Web Developer at the Center for Digital Research and Scholarship, discusses his experiences adapting to an Agile project methodology and designing the user interfaces for Dangerous Citizens

Peptide immunotherapy for childhood allergy - addressing translational challenges

Allergic sensitisation usually begins early in life. The number of allergens a patient is sensitised to can increase over time and the development of additional allergic conditions is increasingly recognised. Targeting allergic disease in childhood is thus likely to be the most efficacious means of reducing the overall burden of allergic disease. Specific immunotherapy involves administering protein allergen to tolerise allergen reactive CD4+ T cells, thought key in driving allergic responses. Yet specific immunotherapy risks allergic reactions including anaphylaxis as a consequence of preformed allergen-specific IgE antibodies binding to the protein, subsequent cross-linking and mast cell degranulation. CD4+ T cells direct their responses to short "immunodominant" peptides within the allergen. Such peptides can be given therapeutically to induce T cell tolerance without facilitating IgE cross-linking. Peptide immunotherapy (PIT) offers attractive treatment potential for allergic disease. However, PIT has not yet been shown to be effective in children. This review discusses the immunological mechanisms implicated in PIT and briefly covers outcomes from adult PIT trials. This provides a context for discussion of the challenges for the application of PIT, both generally and more specifically in relation to children

Race, Class, and the Distribution of Radioactive Waste in New England

Objective. Inequity in the distribution of environmental burdens among social groups, for example, minority and disadvantaged segments of the population, is an important topic in policy research. This research has largely focused on hazardous waste facilities and Superfund sites. Yet federal mandates to the states raise similar concerns over the social distribution of low-level radioactive waste facilities (LLRWFs). This study seeks to provide the first evaluation of equity in the distribution of LLRWFs within a state. Methods. We use data from the 1990 Census to compare selected characteristics of tracts with low-level radioactive waste facilities to tracts without, tracts nearby LLRWFs to those more distant, and tracts with LLRWFs, which may be more, and less, undesirable to other tracts. Results. Findings suggest that communities with LLRWFs differ from other tracts in their residents\u27 racial composition, socioeconomic status, industrial employment, and housing characteristics. LLRWFs more likely to be viewed as undesirable are even more likely to be located in areas with fewer white and affluent populations. Conclusions. Despite difficulties in assessing the relative risks and benefits of LLRWFs, our results support concern for environmental justice issues in the future siting of LLRWFs and in mandated state planning for low-level radioactive waste long-term storage

Tolerance without clonal expansion: Self-antigen-expressing B cells program self-reactive T cells for future deletion

B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells

The R18 polyarginine peptide is more effective than the TAT-NR2B9c (NA-1) peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat

We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO).The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours afterMCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective.The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model.The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke

Notes

Notes by John M. Anderton, B. M. Apker, J. V. Wilcox, Leonard Boykin, Jr., John J. Broderick, Jr., Thomas F. Broden, Robert F. Burns, John E. Cosgrove, James K. Sugnet, and James D. Sullivan

Pastures from Space - Application of Satellite-Derived Pasture Predictions Improve the Profitability of Australian Sheep Producers

Pastures from Space, a collaborative program between CSIRO Livestock Industries and the Western Australian state Departments of Agriculture and Land Information, has developed the capacity to measure both the biomass and growth rate of annual pasture in the winter rainfall regions of southern Australia using satellite images (Edirisinghe et al., 2002). Producer groups were set up to pilot test the delivery of satellitederived pasture growth rate (PGR, kg dry matter/hectare.day) and biomass (feed on offer or FOO, kg dry matter/hectare) predictions for paddocks on individual farms in Western Australia. This paper reports on the value to Australian sheep producers of satellite-derived PGR information on pastures

Internal evaluation of a physically-based distributed model using data from a Mediterranean mountain catchment

An evaluation of the performance of a physically-based distributed model of a small Mediterranean mountain catchment is presented. This was carried out using hydrological response data, including measurements of runoff, soil moisture, phreatic surface level and actual evapotranspiration. <i>A-priori</i> model parameterisation was based as far as possible on property data measured in the catchment. Limited model calibration was required to identify an appropriate value for terms controlling water loss to a deeper regional aquifer. The model provided good results for an initial calibration period, when judged in terms of catchment discharge. However, model performance for runoff declined substantially when evaluated against a consecutive, rather drier, period of data. Evaluation against other catchment responses allowed identification of the problems responsible for the observed lack of model robustness in flow simulation. In particular, it was shown that an incorrect parameterisation of the soil water model was preventing adequate representation of drainage from soils during hydrograph recessions. This excess moisture was then being removed via an overestimation of evapotranspiration. It also appeared that the model underestimated canopy interception. The results presented here suggest that model evaluation against catchment scale variables summarising its water balance can be of great use in identifying problems with model parameterisation, even for distributed models. Evaluation using spatially distributed data yielded less useful information on model performance, owing to the relative sparseness of data points, and problems of mismatch of scale between the measurement and the model grid.</p> <p style='line-height: 20px;'><b>Keywords: </b>physically-based distributed model, SHETRAN, parameterisation, Mediterranean mountain catchment, internal evaluation, multi-respons

Poly-arginine peptides reduce infarct volume in a permanent middle cerebral artery rat stroke model

Background: We recently reported that poly-arginine peptides have neuroprotective properties both in vitro and in vivo. In cultured cortical neurons exposed to glutamic acid excitotoxicity, we demonstrated that neuroprotective potency increases with polymer length plateauing at R15 to R18 (R = arginine resides). In an in vivo study in rats, we also demonstrated that R9D (R9 peptide synthesised with D-isoform amino acids) administered intravenously at a dose of 1000 nmol/kg 30 min after permanent middle cerebral artery occlusion (MCAO) reduces infarct volume. Based on these positive in vitro and in vivo findings, we decided to examine the neuroprotective efficacy of the L-isoform poly-arginine peptides, R12, R15 and R18 when administered at a dose of 1000 nmol/kg 30 min after permanent MCAO in the rat. Results: At 24 h post-MCAO, there was reduced total infarct volume for R12 (12.8 % reduction) and R18 (20.5 % reduction), but this reduction only reached statistical significance for R18. Brain slice analysis revealed significantly reduced injury in coronal slices 4 and 5 for R18, and slice 5 for R12. The R15 peptide had no effect on infarct volume. Peptide treatment did not reveal any statistical significant improvement in functional outcomes. Conclusion: While these findings confirm the in vivo neuroprotective properties of poly-arginine peptides, additional dose studies are required particularly in less severe transient MCAO models so as to further assess the potential of these agents as a stroke therapy