AntigenDB:an immunoinformatics database of pathogen antigens

The continuing threat of infectious disease and future pandemics, coupled to the continuous increase of drug-resistant pathogens, makes the discovery of new and better vaccines imperative. For effective vaccine development, antigen discovery and validation is a prerequisite. The compilation of information concerning pathogens, virulence factors and antigenic epitopes has resulted in many useful databases. However, most such immunological databases focus almost exclusively on antigens where epitopes are known and ignore those for which epitope information was unavailable. We have compiled more than 500 antigens into the AntigenDB database, making use of the literature and other immunological resources. These antigens come from 44 important pathogenic species. In AntigenDB, a database entry contains information regarding the sequence, structure, origin, etc. of an antigen with additional information such as B and T-cell epitopes, MHC binding, function, gene-expression and post translational modifications, where available. AntigenDB also provides links to major internal and external databases. We shall update AntigenDB on a rolling basis, regularly adding antigens from other organisms and extra data analysis tools. AntigenDB is available freely at http://www.imtech.res.in/raghava/antigendb and its mirror site http://www.bic.uams.edu/raghava/antigendb.

Constructing institutional change: emergence, contestation and convergence of business models in the field of Java application servers

How are innovative new business models established if organizations constantly compare themselves against existing criteria and expectations? The objective is to address this question from the perspective of innovators and their ability to redefine established expectations and evaluation criteria. The research questions ask whether there are discernible patterns of discursive action through which innovators theorize institutional change and what role such theorizations play for mobilizing support and realizing change projects. These questions are investigated through a case study on a critical area of enterprise computing software, Java application servers. In the present case, business practices and models were already well established among incumbents with critical market areas allocated to few dominant firms. Fringe players started experimenting with a new business approach of selling services around freely available opensource application servers. While most new players struggled, one new entrant succeeded in leading incumbents to adopt and compete on the new model. The case demonstrates that innovative and substantially new models and practices are established in organizational fields when innovators are able to refine expectations and evaluation criteria within an organisational field. The study addresses the theoretical paradox of embedded agency. Actors who are embedded in prevailing institutional logics and structures find it hard to perceive potentially disruptive opportunities that fall outside existing ways of doing things. Changing prevailing institutional logics and structures requires strategic and institutional work aimed at overcoming barriers to innovation. The study addresses this problem through the lens of (new) institutional theory. This discourse methodology traces the process through which innovators were able to establish a new social and business model in the field.

Why organizational and community diversity matter:the emergence of incivility and organizational outcomes

Integrating sociological and psychological perspectives, this research considers the value of organizational ethnic diversity as a function of community diversity. Employee and patient surveys, census data, and performance indexes relevant to 142 hospitals in the United Kingdom suggest that intraorganizational ethnic diversity is associated with reduced civility toward patients. However, the degree to which organizational demography was representative of community demography was positively related to civility experienced by patients and ultimately enhanced organizational performance. These findings underscore the understudied effects of community context and imply that intergroup biases manifested in incivility toward out-group members hinder organizational performance.

A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterisation of type 1 cell surface-associated antigens

We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 64?% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.

The emergence of knowledge exchange:an agent-based model of a software market

We investigate knowledge exchange among commercial organizations, the rationale behind it, and its effects on the market. Knowledge exchange is known to be beneficial for industry, but in order to explain it, authors have used high-level concepts like network effects, reputation, and trust. We attempt to formalize a plausible and elegant explanation of how and why companies adopt information exchange and why it benefits the market as a whole when this happens. This explanation is based on a multiagent model that simulates a market of software providers. Even though the model does not include any high-level concepts, information exchange naturally emerges during simulations as a successful profitable behavior. The conclusions reached by this agent-based analysis are twofold: 1) a straightforward set of assumptions is enough to give rise to exchange in a software market, and 2) knowledge exchange is shown to increase the efficiency of the market.

Urban labour, voice and legitimacy:economic development and the emergence of community unionism

Community unionism has emerged in the past decade as a growing strand of industrial relations research and is influencing trade union strategies for renewal. This article seeks to further develop the concept, while exploring the potential roles for unions in communities subject to projects of urban regeneration.

Emergence of equilibriumlike domains within nonequilibrium Ising spin systems

Many natural, technological and social systems are inherently not in equilibrium. We show, by detailed analysis of exemplar models, the emergence of equilibriumlike behavior in localized or nonlocalized domains within nonequilibrium Ising spin systems. Equilibrium domains are shown to emerge either abruptly or gradually depending on the system parameters and disappear, becoming indistinguishable from the remainder of the system for other parameter values. © 2013 American Physical Society.

Emergence in genetic programming:let's exploit it!

Banzhaf explores the concept of emergence and how and where it happens in genetic programming [1]. Here we consider the question: what shall we do with it? We argue that given our ultimate goal to produce genetic programming systems that solve new and difficult problems, we should take advantage of emergence to get closer to this goal. © 2013 Springer Science+Business Media New York.

Diffusion of technology in flour milling and the emergence of the modern British milling industry

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Synthesis and screening of potential antimicrobial compounds

Tuberculosis (TB), an infection caused by human pathogen Mycobacterium tuberculosis, continues to kill millions each year and is as prevalent as it was in the pre-antimicrobial era. With the emergence of continuously-evolving multi-drug resistant strains (MDR) and the implications of the HIV epidemic, it is crucial that new drugs with better efficacy and affordable cost are developed to treat TB. With this in mind, the first part of this thesis discusses the synthesis of libraries of derivatives of pyridine carboxamidrazones, along with cyclised (1,2,4-triazole and 1,2,4-oxadiazole) and fluorinated analogues. Microbiological screening against M. tuberculosis was carried out at the TAACF, NIAID and IDRI (USA). This confirmed the earlier findings that 2-pyridyl-substituted carboxamidrazones were more active than the 4-pyridyl-substituted carboxamidrazones. Another important observation was that upon cyclisation of these carboxamidrazones, a small number of the triazoles retained their activity while in most of the remaining compounds the activity was diminished. This might be attributed to the significant increase in logP value caused by cyclisation of these linear carboxamidrazones, resulting in high lipophilicity and decreased permeability. Another reason might be that the rigidity conferred upon the compound due to cyclisation, results in failure of the compound to fit into the active site of the putative target enzyme. In order to investigate the potential change to the compounds’ metabolism in the organism and/or host, the most active compounds were selected and a fluorine atom was introduced in the pyridine ring. The microbiological results shows a drastic improvement in the activity of the fluorinated carboxamidrazone amides as compared to their non fluorinated counterpart. This improvement in the activity could possibly be the result of the increased cell permeability caused by the fluorine. In a subsidiary strand, a selection of long-chain , -unsaturated carboxylic esters, -keto, -hydroxy carboxylic esters and -keto, -hydroxy carboxylic esters, structurally similar to mycolic acids, were synthesised. The microbiological data revealed that one of the open chain compound was active against the Mycobacterium tuberculosis H37Rv strain and some resistant isolates. The possible compound activity could be its potential to disrupt mycobacterial cell wall synthesis by interfering with the FAS-II pathway.