Delayed-Type hypersensitivity to latex: Computational prediction of MHC class II epitopes on latex allergens

Delayed type hypersensitivity to natural rubber latex is rare compared to IgE mediated immediate reactions. Binding of allergens to MHC Class II is a crucial step in the presentation of antigens to CD4+ T Cells responsible for delayed reactions. Computational prediction of MHC class II epitopes on thirteen known latex allergens using SMM-align method revealed strong binding with several alleles. This shows that latex allergens are capable of initiating delayed type hypersensitivity in susceptible individuals.
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Research in Cosmetic Dermatology: Reconciling medicine with business

Cosmetic dermatology is a marriage between medicine and business. Research in cosmetic dermatology shares the fundamental principles of clinical and pharmaceutical research. Research team can help the decision makers by giving a realistic picture of the uncertainties involved. Certain mathematical models and market research techniques can aid decision making.Research; cosmeceutical; decision making

Beyond the Maxwell Limit: Thermal Conduction in Nanofluids with Percolating Fluid Structures

In a well-dispersed nanofluid with strong cluster-fluid attraction, thermal conduction paths can arise through percolating amorphous-like interfacial structures. This results in a thermal conductivity enhancement beyond the Maxwell limit of 3*phi, with phi being the nanoparticle volume fraction. Our findings from non-equilibrium molecular dynamics simulations, which are amenable to experimental verification, can provide a theoretical basis for the development of future nanofluids.Comment: 5 Pages, 3 Figures, In Review: APL, Accepted for presentation at "Nanofluids: Fundamentals and Applications", September 16-20, 2007, Copper Mountain, Colorad

Technical terms in fishing gear materials and gear fabrication

Papers dealing with technical terms in fisheries science are few. This paper however, covers only one or two aspects of the subject, namely fishing gear materials and fishing gear fabrication. Similar papers on other aspects are also planned. Short explanations or descriptions are also given wherever considered necessary

Developmental and mental health disorders: Two sides of the same coin

AbstractChildren with developmental disorders (DD) are at substantially greater risk of developing mental health problems compared to typically developing children. However, the mental health co-morbidity is often missed or hidden in the context of DD leading to reduced quality of life and increased burden of care. Mental health problems in the context of DD also result in less optimal school and post-school outcomes with reduced opportunities for employment and community participation. There is also considerable overlap in the risk factors for both conditions, and these follow a cumulative risk model. Although awareness among clinicians and the public is improving, there is paucity of theoretical models, early identification frameworks as well as care pathways for interventions. This paper presents a framework for evaluating developmental vulnerability that highlights common risk factors for developmental and mental health disorders

Rural industrialisation in Kerala : re-examining the issue of rural growth linkages

The main purpose of our paper is to re-examine the role of linkages in a process of rural industrialisation (RI) deriving from the field experience in two purposively selected, newly emerging areas of industrial growth in an industrially backward state. While considerable evidence on survival of manufacturing activities in rural areas, particularly an agriculture-linked process of rural industrialisation, was not very encouraging, our perserverence arose out of (a) what we perceived as a rather narrow view of intra-spatial linkages in most of the studies taken up; and (b) the possibility of its greater potential in the sub region we attempted to study viz. the state of Kerala, marked by a relatively favourable rural infrastructure. We argue that: (a) an excessive concentration on agriculture induced linkages has resulted in an underestimation of the potential of rural linkages for rural manufacturing. The fast growing service sector in rural areas and its demand for simple intermediate goods provides considerable scope for production linkages; (b) at the same time the relative importance of agricultural linkages very often tends to be swamped out by ‘urban’ indicators of rural diversification. The former could play a dominant role in generating non-agricultural employment in relatively isolated rural areas primarily through consumption linkages; and (c) the local capital linkage or indigenous entrepreneurship has been relatively underemphasised. Stimulating local initiative can facilitate a rurally-linked process of RI. There is a real (psychic) advantage for local entrepreneurs operating in a local environment which redresses to some extent the relative place specific disadvantages of rural locations. Key words: rural industrialisation, rural non-farm employment, rural development, local linkages, rural growth linkages, entrepreneurship JEL Classification : M13, O18, R1

Economic diversification in Kerala : a spatial analysis

The issue of rural economic diversification as a critical component of rural transformation in less developed economies, has assumed considerable importance in the development dialogue since the seventies. Given the failure of the industrialisation led development strategies to "trickle down" to the rural poor, a need was felt for restructuring the development strategy of the fifties. The agricultural-rural sector was to be regarded as having greater flexibility in absorbing labour and generating extenstive growth, rather than as a sector passively supplying labour to an urban based industrial sector. While the labour absorption capacity of agriculture in the aggregate appeared to be limited, it was the creation of non-agricultural activities, in particular rural small-scale manufacturing enterprises, that was more crucial in the restructured strategy. An issue which came to be much debated in this context was: Is the process of rural diversification primarily agricultural-rural induced or did the impulses lie outside the rural economy? Our study also addresses this question in an attempt to examine structural transformation of employment, spatially, over the period 1971-91 in Kerala. This state is unique in many respects among the states of India, one of which is its settlement pattern, characterised by a rural-urban continuum. Applying the "continuous method" to study spatial change in the occupational structure across rural, small towns and large urban units (comprising of cities/big/medium towns and agglomerations), we find that economic diversification in general and manufacturing in particular, has been fairly rapid in rural areas. Within the latter, some rural settlements, numbering about 128 villages, were transformed into urban areas during 1971-91. An examination of certain socio-economic characteristics of these villages, which can be used as proxies for "agricultural-rural" and "urban" linkages reveals that, in fact, both types of linkages play a dominant role in economic diversification depending on the location of the village visa- vis large urban units. In other words higher agriculture linked indicators are associated with highly diversified "isolated" villages while urban linkages determine the growth of non-agricultural activities in extensions/ outgrowths of urban agglomerations. JEL Classification: J 21, O18 Key Words: Diversification, non-agricultural employment, linkage

Development of peptide inhibitors as molecular therapeutics against tandem-repeat proteins

Tandem-repeat (TR) domains occur in approximately one third of all proteins, yet these domains are less well understood compared with their globular counterparts. TR proteins act as molecular scaffolds that facilitate protein-protein interactions (PPIs) in diverse biological contexts. In disease pathologies such as cancers, misfolded, mutated or deregulated TR function is often the cause. However, targeting tandem-repeat proteins is challenging due to their flat and large interaction interfaces. In this thesis, I have explored the development of peptide-based inhibitors of PPIs involving two targets, Tankyrase (TNKS) the Anaphase Promoting Complex/Cyclosome (APC/C-Cdc20). TNKS belong to the poly-ADP-ribose polymerases (PARP) family of enzymes that PARylate their substrates, leading to ubiquitination and subsequent degradation. TNKS bind their protein substrates through an ankyrin-repeat domain comprising five so-called Ankyrin Repeat Clusters (ARCs). TNKS is of particular therapeutic interest in cancers due to its PARylation of Axin1, a subunit of the β-catenin destruction complex. We investigated the design of peptide inhibitors of TNKS ARC domains through a structure guided approach. We first attempted to expand the range of biophysical assays to assess ligand binding to TNKS ARCs. We then designed and tested a set of linear and chemically constrained peptides for their ability to bind to the ARCs. The APC/C is an E3 ubiquitin ligase that has broad substrate-specificity via its two WD40-domain co-activators, Cdc20 and Cdh1, which recognise three peptide motifs (degrons) on its substrates: the D-box, the KEN box and the ABBA motif. The regulation of mitotic exit is tightly controlled by modulating the levels of Cdc20 and Cdh1 through different stages of the cell cycle. Cdc20 overexpression is associated with many cancers. Currently, no specific inhibitors of the APC/C-Cdc20 exist in the clinic or in clinical trials. We designed a series of synthetic peptides based on the D-box to bind to Cdc20, and thereby modulate APC/C activity. Peptides were tested using surface plasmon resonance and differential scanning fluorimetry assays using recombinant Cdc20. Furthermore, D-box peptides were able to bind exogenous Cdc20 in mammalian cell lysates using a Cellular Thermal Shift Assay (CETSA). Lastly, I determined the co-crystal structures of three of the highest affinity D-box peptides bound to Cdc20, providing high-resolution insights into the binding interface, which should aid in the further development of Cdc20 inhibitors.AstraZeneca PhD studentshi