Ontology engineering for simulation component reuse

Commercial-off-the-shelf (COTS) simulation packages (CSPs) are widely used in industry, although they have yet to operate across organizational boundaries. Reuse across organizations is restricted by the same semantic issues that restrict the inter-organizational use of web services. The current representations of web components are predominantly syntactic in nature lacking the fundamental semantic underpinning required to support discovery on the emerging semantic web. Semantic models, in the form of ontology, utilized by web service discovery and deployment architectures provide one approach to support simulation model reuse. Semantic interoperation is achieved through the use of simulation component ontologies to identify required components at varying levels of granularity (including both abstract and specialized components). Selected simulation components are loaded into a CSP, modified according to the requirements of the new model and executed. The paper presents the development of an ontology, connector software and web service discovery architecture. The ontology is extracted from simulation scenarios involving airport, restaurant and kitchen service suppliers. The ontology engineering framework and discovery architecture provide a novel approach to inter-organizational simulation, adopting a less intrusive interface between participants. Although specific to CSPs the work has wider implications for the simulation community

Semantic web services for simulation component reuse and interoperability: An ontology approach

Commercial-off-the-shelf (COTS) Simulation Packages (CSPs) are widely used in industry primarily due to economic factors associated with developing proprietary software platforms. Regardless of their widespread use, CSPs have yet to operate across organizational boundaries. The limited reuse and interoperability of CSPs are affected by the same semantic issues that restrict the inter-organizational use of software components and web services. The current representations of Web components are predominantly syntactic in nature lacking the fundamental semantic underpinning required to support discovery on the emerging Semantic Web. The authors present new research that partially alleviates the problem of limited semantic reuse and interoperability of simulation components in CSPs. Semantic models, in the form of ontologies, utilized by the authors’ Web service discovery and deployment architecture provide one approach to support simulation model reuse. Semantic interoperation is achieved through a simulation component ontology that is used to identify required components at varying levels of granularity (i.e. including both abstract and specialized components). Selected simulation components are loaded into a CSP, modified according to the requirements of the new model and executed. The research presented here is based on the development of an ontology, connector software, and a Web service discovery architecture. The ontology is extracted from simulation scenarios involving airport, restaurant and kitchen service suppliers. The ontology engineering framework and discovery architecture provide a novel approach to inter-organizational simulation, by adopting a less intrusive interface between participants Although specific to CSPs this work has wider implications for the simulation community. The reason being that the community as a whole stands to benefit through from an increased awareness of the state-of-the-art in Software Engineering (for example, ontology-supported component discovery and reuse, and service-oriented computing), and it is expected that this will eventually lead to the development of a unique Software Engineering-inspired methodology to build simulations in future

Health surveillance for occupational asthma in the UK

Background Periodic health surveillance (HS) of workers can identify early cases of occupational asthma. Information about its uptake and its content in the UK is lacking. Aims To identify the overall levels of uptake and quality of HS for occupational asthma within three high risk industry sectors in the UK. Methods A telephone survey of employers, and their occupational health (OH) professionals, carried out in three sectors with exposures potentially capable of causing occupational asthma (bakeries, wood working and motor vehicle repair). Results A total of 457 organizations participated (31% response rate). About 77% employed <10 people, 17% between 10 and 50 and 6% >50. Risk assessments were common (67%) and 14% carried out some form of HS for occupational asthma, rising to 19% if only organizations reporting asthma hazards and risks were considered. HS was carried out both by in-house (31%) and external providers (69%). Organizational policies were often used to define HS approaches (80%), but infrequently shared with the OH provider. OH providers described considerable variation in practice. Record keeping was universal, but worker-held records were not reported. HS tools were generally developed in-house. Lung function was commonly measured, but only limited interpretation evident. Referral of workers to local specialist respiratory services was variable. Conclusions This study provided new insights into the real world of HS for occupational asthma. We consider that future work could and should define simpler, more practical and evidence-based approaches to HS to ensure maximal consistency and use of high-quality approaches

SCS: 60 years and counting! A time to reflect on the Society's scholarly contribution to M&S from the turn of the millennium.

The Society for Modeling and Simulation International (SCS) is celebrating its 60th anniversary this year. Since its inception, the Society has widely disseminated the advancements in the field of modeling and simulation (M&S) through its peer-reviewed journals. In this paper we profile research that has been published in the journal SIMULATION: Transactions of the Society for Modeling and Simulation International from the turn of the millennium to 2010; the objective is to acknowledge the contribution of the authors and their seminal research papers, their respective universities/departments and the geographical diversity of the authors' affiliations. Yet another objective is to contribute towards the understanding of the overall evolution of the discipline of M&S; this is achieved through the classification of M&S techniques and its frequency of use, analysis of the sectors that have seen the predomination application of M&S and the context of its application. It is expected that this paper will lead to further appreciation of the contribution of the Society in influencing the growth of M&S as a discipline and, indeed, in steering its future direction

Prospective Investigation of Pesticide Applicators' Health (PIPAH) study: a cohort study of professional pesticide users in Great Britain

PURPOSE: The purpose of the study is to monitor the exposure and health of workers in Great Britain who use pesticides as a part of their job, and to gain a better understanding of the relationship between long-term exposure to pesticides and health. PARTICIPANTS: Study participants are professional pesticide users who are certified in the safe use of pesticides or who were born before 1965 and apply pesticides under 'grandfather rights'. Overall response rate was 20%; participants are mostly male (98%) and the average age is 54 years, ranging from 17 to over 80 years. FINDINGS TO DATE: Participants have completed a baseline general questionnaire and three follow-up questionnaires on the use of pesticides. These data will enable investigations into the relationship between occupational pesticide exposure and health outcomes taking into account non-occupational confounding factors. FUTURE PLANS: There is no set end date for data collection. Recruitment into the cohort will continue, and for the foreseeable future there will be annual pesticide use questionnaires and five yearly follow-up general questionnaires.The intention is to validate the pesticide use questionnaire, and to develop a crop/job exposure matrix (C/JEM) which can be updated regularly. This C/JEM will be able to look at general categories of pesticide, such as insecticides, structurally related pesticides, such as organochlorines, or individual active ingredients. Data collected on use of personal protective equipment and method of application will provide information on how potential exposure to pesticide during application may have been modified. The study will be able to estimate changes in individual pesticide use over time, and to examine the associations between pesticide use and both baseline and long-term health outcomes.The cohort members will be linked to national databases for notification of hospital episode statistics, cancer incidence and mortality for follow-up of health outcomes

Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies

Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine

D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites

Multiple mantle upwellings in the transition zone beneath the northern East-African Rift system from relative P-wave travel-time tomography

Mantle plumes and consequent plate extension have been invoked as the likely cause of East African Rift volcanism. However, the nature of mantle upwelling is debated, with proposed configurations ranging from a single broad plume connected to the large low-shear-velocity province beneath Southern Africa, the so-called African Superplume, to multiple lower-mantle sources along the rift. We present a new P-wave travel-time tomography model below the northern East-African, Red Sea, and Gulf of Aden rifts and surrounding areas. Data are from stations that span an area from Madagascar to Saudi Arabia. The aperture of the integrated data set allows us to image structures of 100 km length-scale down to depths of 700– 800 km beneath the study region. Our images provide evidence of two clusters of low-velocity structures consisting of features with diameter of 100–200 km that extend through the transition zone, the first beneath Afar and a second just west of the Main Ethiopian Rift, a region with off-rift volcanism. Considering seismic sensitivity to temperature, we interpret these features as upwellings with excess temperatures of 100 6 50 K. The scale of the upwellings is smaller than expected for lower mantle plume sources. This, together with the change in pattern of the low-velocity anomalies across the base of the transition zone, suggests that ponding or flow of deep-plume material below the transition zone may be spawning these upper mantle upwellings

Molecular mechanism of ligand recognition by membrane transport protein, Mhp1

The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1