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

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

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors

Evaluating operational AVHRR sea surface temperature data at the coastline using surfers

Sea surface temperature (SST) is an essential climate variable that can be measured routinely from Earth Observation (EO) with high temporal and spatial coverage. To evaluate its suitability for an application, it is critical to know the accuracy and precision (performance) of the EO SST data. This requires comparisons with co-located and concomitant in situ data. Owing to a relatively large network of in situ platforms there is a good understanding of the performance of EO SST data in the open ocean. However, at the coastline this performance is not well known, impeded by a lack of in situ data. Here, we used in situ SST measurements collected by a group of surfers over a three year period in the coastal waters of the UK and Ireland, to improve our understanding of the performance of EO SST data at the coastline. At two beaches near the city of Plymouth, UK, the in situ SST measurements collected by the surfers were compared with in situ SST collected from two autonomous buoys located ∼7 km and ∼33 km from the coastline, and showed good agreement, with discrepancies consistent with the spatial separation of the sites. The in situ SST measurements collected by the surfers around the coastline, and those collected offshore by the two autonomous buoys, were used to evaluate the performance of operational Advanced Very High Resolution Radiometer (AVHRR) EO SST data. Results indicate: (i) a significant reduction in the performance of AVHRR at retrieving SST at the coastline, with root mean square errors in the range of 1.0 to 2.0 °C depending on the temporal difference between match-ups, significantly higher than those at the two offshore stations (0.4 to 0.6 °C); (ii) a systematic negative bias in the AVHRR retrievals of approximately 1 °C at the coastline, not observed at the two offshore stations; and (iii) an increase in the root mean square error at the coastline when the temporal difference between match-ups exceeded three hours. Harnessing new solutions to improve in situ sampling coverage at the coastline, such as tagging surfers with sensors, can improve our understanding of the performance of EO SST data in coastal regions, helping inform users interested in EO SST products for coastal applications. Yet, validating EO SST products using in situ SST data at the coastline is challenged by difficulties reconciling the two measurements, which are provided at different spatial scales in a dynamic and complex environment

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years

Background: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. Methods: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. Results: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0–6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. Conclusion: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors