Describing results of 4000 hours of multi environment model verification test Final report

Investigating categorization and formulation of stress and strength factors for semiconductor diodes to provide improved failure rate prediction from mathematical model

The Benefits and Beneficiaries of "Public" Investment in Herbicide Use Research and Development

The allocation of benefits from research and development of new herbicide uses is dependent on patent status. The agricultural chemical industry will preferentially invest in herbicide R&D that increases the use of on-patent herbicides from which a company can capture a price premium. The distribution of benefits from increased use of on-patent herbicide will alter over time, with grain growers benefiting at the expense of agrichemical companies once the patent expires. Public sector investment in herbicide R&D may also benefit the agrichemical industry. The size and allocation of the benefits from R&D into on-patent herbicides is analyzed using economic surplus techniques. Two case studies are examined. One involves research into the choice and application of herbicide for new wheat varieties. The second case study involves returns from R&D investment in research into an alternative for the commonly used off-patent herbicide trifluralin. The results from the case studies show that herbicide patent status may not have important implications for "public" R&D investment decisions.Research and Development/Tech Change/Emerging Technologies, Q16, Q18, Q28,

Clustering and collisions of heavy particles in random smooth flows

Finite-size impurities suspended in incompressible flows distribute inhomogeneously, leading to a drastic enhancement of collisions. A description of the dynamics in the full position-velocity phase space is essential to understand the underlying mechanisms, especially for polydisperse suspensions. These issues are here studied for particles much heavier than the fluid by means of a Lagrangian approach. It is shown that inertia enhances collision rates through two effects: correlation among particle positions induced by the carrier flow and uncorrelation between velocities due to their finite size. A phenomenological model yields an estimate of collision rates for particle pairs with different sizes. This approach is supported by numerical simulations in random flows.Comment: 12 pages, 9 Figures (revTeX 4) final published versio

Endocannabinoid modulation of secretory and inflammatory causes of gastric pathology

Non-steroidal anti-inflammatory drugs (NSAIDs) are common analgesic drugs that also cause well-known, negative gastrointestinal (GI) side effects. The specific physiological mechanism(s) of NSAID-induced GI damage are unknown, and are likely due to multiple causes. The most studied components include: increased gastric acid secretions, inflammation of the gastric epithelium, and increased gastric motility. Currently, proton pump inhibitor (PPI) antacids are used by chronic NSAID users, with the expectation that decreasing gastric acid output will reduce gastric epithelial irritation. However, PPIs are associated with side effects like infection, gastric polyps, and dementia. Therefore, new gastroprotective treatments that prevent NSAID-induced gastropathy are needed. The endocannabinoid system has several possible targets to reduce NSAID-induced ulcers, including the endocannabinoid 2-AG (2-arachidonoylglycerol), and the primary enzyme that metabolizes 2-AG, monoacylglycerol lipase (MAGL). Blocking the MAGL enzyme increases stomach levels of 2-AG and reduces NSAID-induced ulcers in male mice. The present project was designed to determine which ulcerogenic effects of the NSAID diclofenac are reversed by MAGL inhibition. We hypothesized that MAGL inhibition would reverse the following effects of diclofenac: (1) increased gastric acid secretion; (2) increased gastric inflammation; and (3) increased gastric motility. Diclofenac induced gastric hemorrhages to a similar extent in both male and female mice. Diclofenac dose-dependently increased neutrophil infiltration in both male and female mice, indicating that diclofenac induces a cell-mediated inflammatory response. Gastric hemorrhage severity correlated with myeloperoxidase levels, an objective measure of immune cell infiltration, indicating its use as a potential biomarker of gastric damage. Diclofenac significantly increased inflammatory cytokines in male mice, whereas administration of JZL184, a MAGL inhibitor, prior to diclofenac had no effect in male mice and increased gastric inflammatory cytokine levels in female mice. Neither JZL184 nor diclofenac produced any changes on gastric acid secretions when evaluated during the gastric hemorrhage procedure. However, in the pentagastrin-stimulated acid model, JZL184 decreased gastric acid secretions in both basal and stimulated conditions. As hypothesized, JZL184 decreased gastric motility, although diclofenac, contrary to expectations, slowed gastric motility, indicating that diclofenac-induced ulcers most likely do not occur through increased gastric motility, at least not as measured in the present study. The present data indicate that MAGL inhibition may proffer gastroprotection through modulating the secretory pathway of gastric hemorrhage. These data underscore the importance of sampling multiple time points and using both sexes in research, in addition to multiple mechanistic targets, and contribute to the basic understanding of NSAID-induced gastric inflammation

Synergistic inhibition of cyclooxygenases and monoacylglycerol lipase in neuropathic pain

Neuropathic pain is caused by altered nerve function that often presents as allodynia, which is the painful perception of typically non-noxious stimuli. Neuropathic pain is commonly treated with GABA analogues, steroids, or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit one or more cyclooxygenase (COX) enzymes and are effective, commonly used analgesics that have relatively fewer side effects than other treatments. However, chronic cyclooxygenase inhibition also causes gastrointestinal inflammation and increased risk of cardiac events. Like NSAIDs, cannabinoids have analgesic and anti-inflammatory properties and reduce neuropathic pain in preclinical models. The present study investigated the analgesic effects of inhibiting both monoacylglycerol lipase (MAGL) and cyclooxygenase enzymes. Mice subjected to the chronic constriction injury (CCI) model of neuropathic pain were administered either the MAGL inhibitor, JZL184 (1-40 mg/kg, i.p.) or the nonselective COX inhibitor diclofenac sodium (1-100 mg/kg, i.p.) and tested for mechanical and cold allodynia. Then, both drugs were coadministered at various doses in ratios of 1:3, 1:1, and 3:1 parts of either compound. Isobolographic analyses revealed that combining low doses of JZL184 and diclofenac synergistically attenuated mechanical allodynia and additively reduced cold allodynia. These data support dual COX/MAGL inhibition as a promising therapeutic approach for neuropathic pain

Hot Streak Characterization in Serpentine Exhaust Nozzles

Modern aircraft of the United States Air Force face increasingly demanding cost, weight, and survivability requirements. Serpentine exhaust nozzles within an embedded engine allow a weapon system to fulfill mission survivability requirements by providing denial of direct line-of-sight into the high-temperature components of the engine. Recently, aircraft have experienced material degradation and failure along the aft deck due to extreme thermal loading. Failure has occurred in specific regions along the aft deck where concentrations of hot gas have come in contact with the surface causing hot streaks. The prevention of these failures will be aided by the accurate prediction of hot streaks. Additionally, hot streak prediction will improve future designs by identifying areas of the nozzle and aft deck surfaces that require thermal management. To this end, the goal of this research is to observe and characterize the underlying flow physics of hot streak phenomena. The goal is accomplished by applying computational fluid dynamics to determine how hot streak phenomena is affected by changes in nozzle geometry. The present research first validates the computational methods using serpentine inlet experimental and computational studies. A design methodology is then established for creating six serpentine exhaust nozzles investigated in this research. A grid independent solution is obtained on a nozzle using several figures of merit and the grid-convergence index method. An investigation into the application of a second-order closure turbulence model is accomplished. Simulations are performed for all serpentine nozzles at two flow conditions. The research introduces a set of characterization and performance parameters based on the temperature distribution and now conditions at the nozzle throat and exit. Examination of the temperature distribution on the upper and lower nozzle surfaces reveals critical information concerning changes in hot streak phenomena due to changes in nozzle geometry

Praxis in healthcare OR: An empirical behavioural OR study

Operational researchers working in academia commonly struggle in attempts to influence practice and decision making in healthcare amid a growing recognition that behaviour is key to effective operational research (OR). To further our understanding of the behavioural factors that operational researchers working in healthcare consider influence their work’s impact, we interviewed 24 OR practitioners working in academia and with experience of working with the UK National Health Service (NHS). The semi-structured interviews were consented, recorded, transcribed, and analysed thematically using a framework approach. Five dominant themes emerged that highlighted: behavioural challenges concerning flexibility, pivoting and the abandonment of projects; the influence of the evolving ambitions, maturity and behaviours of a practitioner’s OR group; the hidden and changing motivations of host healthcare organisations; the reliance of practitioners on intuition and how their praxis is influenced by their agency within their group and its relationships with healthcare organisations; and how attributes of altruism, broader life experience and creative risk-taking influence an individuals’ praxis. In summary, we identified numerous behavioural factors considered important to success that operate within and across individual projects