Investigations into the triggered lightning response of the F106B thunderstorm research aircraft

An investigation has been conducted into the lightning characteristics of the NASA F106B thunderstorm research aircraft. The investigation includes analysis of measured data from the aircraft in the time and frequency domains. Linear and nonlinear computer modelling has also been performed. In addition, new computer tools have been developed, including a new enhanced nonlinear air breakdown model, and a subgrid model useful for analyzing fine details of the aircraft's geometry. Comparison of measured and calculated electromagnetic responses of the aircraft to a triggered lightning environment are presented

Evaluating the recruitment of American eel, Anguilla rostrata, to the Potomac - Spring 2000 : March 2000 - June 2000

Measures of juvenile recruitment success have long been recognized as a valuable fisheries management tool. In the Chesapeake Bay, these measures have provided reliable indicators for future year class strength for blue crabs (Lipcius and van Engel, 1990), striped bass (Goodyear, 1985), and several other recreationally important fishes (Geer and Austin, 1999). The American eel, Anguilla rostrata, is a valuable commercial species along the entire Atlantic coast from New Brunswick to Florida. Landings along the U.S. Atlantic coast have varied from 290 MT in 1962 to a high of 1600 MT in 1975 (NMFS, 1999). In recent years there seems to be declining harvest, with similar pattems seen in the Canadian maritime providences. The Mid-Atlantic states (New York, New Jersey, Delaware, Maryland, and Virginia) have comprised the largest portion of the East Coast catch (88% of the reported landings) since 1988 (NMFS 1999). The Chesapeake Bay jurisdictions ofVirginia, Maryland, and Potomac River Fisheries Commission (PRFC) alone represent 30, 15, and 18% respectively, of the annual United States (Gulf and Atlantic coast states) commercial harvest for the years 1987-1996 (ASMFC, 1999). Some fishery -independent indices have shown a decline in abundance in recent years (Richkus and Whalens 1999). Hypotheses for the decline include shifts in the Gulf Stream, pollution, over- fishing, parasites, and barriers to passage (Castonguay et al. 1994 ). Many fisheries management teclmiques have not been applied to American eels because little basic biological infom1ation is known. Variation in growth rates, length at age, and other biological parameters has complicated stock assessment methodologies and management efforts. Additionally, few studies have addressed the recruitment of glass eels to the estuaries from the spawning grounds in the Sargasso Sea

Enhancing Rural Manufacturers Competitiveness Through Design Automation For New Product Development

The competitiveness of third world manufacturing has placed pressure on U.S. manufacturers to create new products to survive.  Computer aided solid modeling and rapid prototyping technologies accelerate new product development, but rural manufacturers are often left behind.  This paper describes a cooperative venture between a state university and a federal agency to improve the new product development process of selected rural manufacturers by introducing them to leading-edge design automation technologies. Use of these tools allows better cross-functional communication among top management, marketing, designers, engineers, and manufacturing as they proceed through the new product creation process. Participating companies produced new product options, enhanced employment, and increased revenues

Latin American and US Latino Lutheranism Partnership Issue (LOGIA vol. 19, no. 1, Epiphany 2010)

As a vicar in Caracas, Venezuela, I ventured every so often to one of the largest Roman Catholic bookstores downtown to peruse various collections of dogmatic treatises. On one of my visits, I started a casual conversation with a Venezuelan priest who asked about my background. After learning that I was a Lutheran seminarian, the priest, somewhat perplexed, exclaimed something like, “Latino Lutheran? That is not possible. You cannot be Latino and Lutheran.

A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

Clues to Alzheimer disease (AD) pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP) and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs) and modulators (GSMs). GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF), suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative

Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.

Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid-β peptide (Aβ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred tγ-secretase modulatoro as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides. These modulators potently lower Aβ42 levels without inhibiting the γ-secretase-mediated proteolysis of Notch or causing accumulation of carboxyl-terminal fragments of APP. In this study, we report a large number of pharmacological studies and early assessment of toxicology characterizing a highly potent γ-secretase modulator (GSM), (S)-N-(1-(4-fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to significantly lower Aβ42 levels in the central nervous system of rats and mice at doses as low as 5-10 mg/kg, significantly reduce Aβ neuritic plaque load in an AD transgenic mouse model, and significantly reduce levels of insoluble Aβ42 and pThr181 tau in a three-dimensional human neural cell culture model. Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose toxicity studies in nonhuman primates have designated this GSM for 28-day Investigational New Drug-enabling good laboratory practice studies and positioned it as a candidate for human clinical trials

The shape of things to come? Expanding the inequality and grievance model for civil war forecasts with event data

© The Author(s) 2017. We examine if dynamic information from event data can help improve on a model attempting to forecast civil war using measures reflecting plausible motivation and grievances. Buhaug, Cederman, and Gleditsch predict the risk of civil war using a horizontal inequality model with measures reflecting motivation and relevant group characteristics at the country level. The predictions from their model outperform in an out-of-sample forecast conventional countrylevel models of civil war, emphasizing vertical inequality and country characteristics. However, most grievance measures change little over time. We surmise that a model reflecting potential motivation for conflict can be improved with more dynamic information on mobilization and the behavior of actors. Our conjecture receives some support in the empirical analysis, where we consider both conflict onset and termination over territorial and governmental incompatibilities in the Uppsala/PRIO Armed Conflict Data, and find some evidence that event data can help improve forecasts. Moreover, models with the original grievance measures do better than purely event based models, supporting our claim that both structure and event based components can add value to conflict prediction models. However, the contribution of events to improving predictive power is modest and not entirely consistent, and some types of conflict events seem easier to forecast than others

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.