Flight evaluation of a simple total energy-rate system with potential wind-shear application

Wind shears can create havoc during aircraft terminal area operations and have been cited as the primary cause of several major aircraft accidents. A simple sensor, potentially having application to the wind-shear problem, was developed to rapidly measure aircraft total energy relative to the air mass. Combining this sensor with either a variometer or a rate-of-climb indicator provides a total energy-rate system which was successfully applied in soaring flight. The measured rate of change of aircraft energy can potentially be used on display/control systems of powered aircraft to reduce glide-slope deviations caused by wind shear. The experimental flight configuration and evaluations of the energy-rate system are described. Two mathematical models are developed: the first describes operation of the energy probe in a linear design region and the second model is for the nonlinear region. The calculated total rate is compared with measured signals for many different flight tests. Time history plots show the tow curves to be almost the same for the linear operating region and very close for the nonlinear region

Evaluation of a total energy-rate sensor on a transport airplane

A sensor that measures the rate of change of total energy of an airplane with respect to the airstream has been evaluated. The sensor consists of two cylindrical probes located on the fuselage of a transport airplane, an in line acoustic filter, and a pressure sensing altitude rate transducer. Sections of this report include the sensor description and experimental configuration, frequency response tests, analytical model development, and flight test results for several airplane maneuvers. The results section includes time history comparisons between data generated by the total energy rate sensor and calculated data derived from independent sources

The public health utility of genome-wide association study results for smoking behavior

New approaches to improve smoking cessation rates are needed. In recent years, substantial progress has been made in understanding the genetics of smoking behavior, and this knowledge may eventually be used to personalize treatment for smokers. Although there are highly significant and reproducible genetic associations, none are yet ready for clinical applications. We suggest that translational research from several disciplines, including behavioral science, ethics and economics, should be performed in parallel with ongoing genome-wide association studies for smoking behavior and pharmacogenetic trials. The coordinated effort of multidisciplinary research teams will help reveal the circumstances under which we can translate genetic insights into clinical practice in the hope of reducing the burden of smoking in society

A novel vaccine platform using glucan particles for induction of protective responses against Francisella tularensis and other pathogens

Vaccines are considered the bedrock of preventive medicine. However, for many pathogens, it has been challenging to develop vaccines that stimulate protective, long-lasting immunity. We have developed a novel approach using beta-1,3-D-glucans (BGs), natural polysaccharides abundantly present in fungal cell walls, as a biomaterial platform for vaccine delivery. BGs simultaneously provide for receptor-targeted antigen delivery to specialized antigen-presenting cells together with adjuvant properties to stimulate antigen-specific and trained non-specific immune responses. This review focuses on various approaches of using BG particles (GPs) to develop bacterial and fungal vaccine candidates. A special case history for the development of an effective GP tularaemia vaccine candidate is highlighted

Metamodel-based model conformance and multiview consistency checking

Model-driven development, using languages such as UML and BON, often makes use of multiple diagrams (e.g., class and sequence diagrams) when modeling systems. These diagrams, presenting different views of a system of interest, may be inconsistent. A metamodel provides a unifying framework in which to ensure and check consistency, while at the same time providing the means to distinguish between valid and invalid models, that is, conformance. Two formal specifications of the metamodel for an object-oriented modeling language are presented, and it is shown how to use these specifications for model conformance and multiview consistency checking. Comparisons are made in terms of completeness and the level of automation each provide for checking multiview consistency and model conformance. The lessons learned from applying formal techniques to the problems of metamodeling, model conformance, and multiview consistency checking are summarized

An Inactivated Bacterium (Paraprobiotic) Expressing \u3ci\u3eBacillus thuringiensis\u3c/i\u3e Cry5B as a Therapeutic for \u3ci\u3eAscaris\u3c/i\u3e and \u3ci\u3eParascaris\u3c/i\u3e spp. Infections in Large Animals

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world

Bacillus thuringiensis Cry5B protein as a new pan-hookworm cure

Hookworms are intestinal nematode parasites that infect nearly half a billion people and are globally one of the most important contributors to iron-deficiency anemia. These parasites have significant impacts in developing children, pregnant women and working adults. Of all the soil-transmitted helminths or nematodes (STNs), hookworms are by far the most important, with disease burdens conservatively estimated at four million DALYs (Disability-Adjusted Life Years) and with productivity losses of up to US$139 billion annually. To date, mainly one drug, albendazole is used for hookworm therapy in mass drug administration, which has on average approximately 80% cure rate that is lower ( \u3c 40%) in some places. Given the massive numbers of people needing treatment, the threat of parasite resistance, and the inadequacy of current treatments, new and better cures against hookworms are urgently needed. Cry5B, a pore-forming protein produced by the soil bacterium Bacillus thuringiensis (Bt) has demonstrated good efficacy against Ancylostoma ceylanicum hookworm infections in hamsters. Here we broaden studies of Cry5B to include tests against infections of Ancylostoma caninum hookworms in dogs and against infections of the dominant human hookworm, Necator americanus, in hamsters. We show that Cry5B is highly effective against all hookworm parasites tested in all models. Neutralization of stomach acid improves Cry5B efficacy, which will aid in practical application of Cry5B significantly. Importantly, we also demonstrate that the anti-nematode therapeutic efficacy of Cry5B is independent of the host immune system and is not itself negated by repeated dosing. This study indicates that Bt Cry5B is a pan-hookworm anthelmintic with excellent properties for use in humans and other animals