Projections of annual rainfall and surface temperature from CMIP5 models over the BIMSTEC countries

Bay of Bengal Initiative for Multi-Sectoral Technical and Economic Cooperation (BIMSTEC) comprising Bangladesh, Bhutan, India, Myanmar, Nepal, Sri Lanka and Thailand brings together 21% of the world population. Thus the impact of climate change in this region is a major concern for all. To study the climate change, fifth phase of Climate Model Inter-comparison Project models have been used to project the climate for the 21st century under the Representative Concentration Pathways (RCPs) 4.5 and 8.5 over the BIMSTEC countries for the period 1901 to 2100 (initial 105 years are historical period and the later 95 years are projected period). Climate change in the projected period has been examined with respect to the historical period. In order to validate the models, the mean annual rainfall has been compared with observations from multiple sources and temperature has been compared with the data from Climatic Research Unit (CRU) during the historical period. Comparison reveals that ensemble mean of the models is able to represent the observed spatial distribution of rainfall and temperature over the BIMSTEC countries. Therefore, data from these models may be used to study the future changes in the 21st century. Four out of six models show that the rainfall over India, Thailand and Myanmar has decreasing trend and Bangladesh, Bhutan, Nepal and Sri Lanka show an increasing trend in both the RCP scenarios. In case of temperature, all the models show an increasing trend over all the BIMSTEC countries in both the scenarios, however, the rate of increase is relatively less over Sri Lanka than the other countries. The rate of increase/decrease in rainfall and temperature are relatively more in RCP8.5 than RCP4.5 over all these countries. Inter-model comparison show that there are uncertainties within the CMIP5 model projections. More similar studies are required to be done for better understanding the model uncertainties in climate projections over this region

Does microbicide use in consumer products promote antimicrobial resistance? A critical review and recommendations for a cohesive approach to risk assessment

The increasing use of microbicides in consumer products is raising concerns related to enhanced microbicide resistance in bacteria and potential cross resistance to antibiotics. The recently published documents on this topic from the European Commission have spawned much interest to better understand the true extent of the putative links for the benefit of the manufacturers, regulators, and consumers alike. This white paper is based on a 2-day workshop (SEAC-Unilever, Bedford, United Kingdom; June 2012) in the fields of microbicide usage and resistance. It identifies gaps in our knowledge and also makes specific recommendations for harmonization of key terms and refinement/standardization of methods for testing microbicide resistance to better assess the impact and possible links with cross resistance to antibiotics. It also calls for a better cohesion in research in this field. Such information is crucial to developing any risk assessment framework on microbicide use notably in consumer products. The article also identifies key research questions where there are inadequate data, which, if addressed, could promote improved knowledge and understanding to assess any related risks for consumer and environmental safety

Oral Delivery of Acid Alpha Glucosidase Epitopes Expressed in Plant Chloroplasts Suppresses Antibody Formation in Treatment of Pompe Mice

Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation

DESIGNING EFFICIENT LOCALIZED SURFACE PLASMON RESONANCE-BASED SENSING PLATFORMS: OPTIMIZATION OF SENSOR RESPONSE BY CON-TROLLING THE EDGE LENGTH OF GOLD NANOPRISMS

poster abstractOver the last few years, the unique localized surface plasmon resonance (LSPR) properties of plasmonic nanostructures have been used to design la-bel-free biosensors. In this research, we demonstrate that it is the difference in edge length of gold nanoprisms that significantly influences their bulk re-fractive index sensitivity and local sensing efficiency. Nanoprisms with edge lengths in the range of 28-51 nm were synthesized by the chemical-reduction method and sensing platforms were fabricated by chemisorptions of these nanoprisms onto silanized glass substrates. The plasmonic nanosensors prepared from 28 nm edge length nanoprisms exhibited the largest sensitivity to change in bulk refractive index with a value of 647 nm/RIU. The refractive index sensitivity decreased with increasing edge length, with nanoprisms of 51 nm edge lengths displaying a sensitivity of 384 nm/RIU. In contrast, we found that the biosensing efficiency of sensing platforms modified with biotin increased with increasing edge length, and the sensing platforms fabricated from 51 nm edge length nanoprisms displaying the highest local sensing efficiency. The lowest concentration of streptavidin that could be measured reliably was 1.0 pM and the limit of detection for the sensing platforms fabricated from 51 nm edge length nanoprisms was 0.5 pM, which is much lower than found with gold bipyramids, nanostars, and nanorods

B-splines, Pólya curves, and duality

AbstractLocal duality between B-splines and Pólya curves is examined, mostly from the viewpoint of computer-aided geometric design. Certain known results for the two curve types are shown to be related. A few new results for Pólya curves and a curve scheme related to B-splines also follow from these investigations

Proxy reconstruction of ultraviolet-B irradiance at the Earth’s surface, and its relationship with solar activity and ozone thickness

Solar ultraviolet-B (UV-B) irradiance that reaches the Earth’s surface acts as a biotic stressor and has the potential to modify ecological and environmental functioning. The challenges of reconstructing ultraviolent (UV) irradiance prior to the satellite era mean that there is uncertainty over long-term surface UV-B patterns, especially in relation to variations in solar activity over centennial and millennial timescales. Here, we reconstruct surface UV-B irradiance over the last 650 years using a novel UV-B proxy based on the chemical signature of pollen grains. We demonstrate a statistically significant positive relationship between the abundance of UV-B absorbing compounds in Pinus pollen and modelled solar UV-B irradiance. These results show that trends in surface UV-B follow the overall solar activity pattern over centennial timescales, and that variations in solar output are the dominant control on surface level UV-B flux, rather than solar modulated changes in ozone thickness. The Pinus biochemical response demonstrated here confirms the potential for solar activity driven surface UV-B variations to impact upon terrestrial biotas and environments over long timescales

Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis

Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from individuals with and without craniosynostosis.Anna K Coussens, Christopher R Wilkinson, Ian P Hughes, C Phillip Morris, Angela van Daal, Peter J Anderson and Barry C Powel

Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/