Total energy-rate feedback for automatic glide-slope tracking during wind-shear penetration

Low-altitude wind shear is recognized as an infrequent but significant hazard to all aircraft during the take-off and landing phases of flight. A total energy-rate sensor was developed for measuring the specific total energy rate of an airplane with respect to the air mass. Control-system designs, both with and without energy-rate feedback, for the approach to landing of a transport airplane through a severe-wind-shear and gust environment are presented in order to evaluate this application of the sensor. A system model incorporates wind-shear-dynamics equations with the airplane equations of motion to permit analysis of the control systems under various wind-shear conditions. The control systems are designed using optimal-output feedback and are analyzed using frequency-domain control-theory techniques. Control-system performance is evaluated using a complete nonlinear simulation of the airplane combined with a severe-wind-shear and gust data package. This evaluation is concerned with control system stability and regulation capability only

Candidate control design metrics for an agile fighter

Success in the fighter combat environment of the future will certainly demand increasing capability from aircraft technology. These advanced capabilities in the form of superagility and supermaneuverability will require special design techniques which translate advanced air combat maneuvering requirements into design criteria. Control design metrics can provide some of these techniques for the control designer. Thus study presents an overview of control design metrics and investigates metrics for advanced fighter agility. The objectives of various metric users, such as airframe designers and pilots, are differentiated from the objectives of the control designer. Using an advanced fighter model, metric values are documented over a portion of the flight envelope through piloted simulation. These metric values provide a baseline against which future control system improvements can be compared and against which a control design methodology can be developed. Agility is measured for axial, pitch, and roll axes. Axial metrics highlight acceleration and deceleration capabilities under different flight loads and include specific excess power measurements to characterize energy meneuverability. Pitch metrics cover both body-axis and wind-axis pitch rates and accelerations. Included in pitch metrics are nose pointing metrics which highlight displacement capability between the nose and the velocity vector. Roll metrics (or torsion metrics) focus on rotational capability about the wind axis

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

Barriers to mental health service use among distressed family caregivers of lung cancer patients

Although family caregivers of patients with lung and other cancers show high rates of psychological distress, they underuse mental health services. This qualitative study aimed to identify barriers to mental health service use among 21 distressed family caregivers of lung cancer patients. Caregivers had not received mental health services during the patient's initial months of care at a comprehensive cancer centre in New York City. Thematic analysis of interview data was framed by Andersen's model of health service use and Corrigan's stigma theory. Results of our analysis expand Andersen's model by providing a description of need variables (e.g. psychiatric symptoms), enabling factors (e.g. finances), and psychosocial factors associated with caregivers' non-use of mental health services. Regarding psychosocial factors, caregivers expressed negative perceptions of mental health professionals and a desire for independent management of emotional concerns. Additionally, caregivers perceived a conflict between mental health service use and the caregiving role (e.g. prioritising the patient's needs). Although caregivers denied stigma associated with service use, their anticipated negative self-perceptions if they were to use services suggest that stigma may have influenced their decision to not seek services. Findings suggest that interventions to improve caregivers' uptake of mental health services should address perceived barriers

Restructurable Controls

Restructurable control system theory, robust reconfiguration for high reliability and survivability for advanced aircraft, restructurable controls problem definition and research, experimentation, system identification methods applied to aircraft, a self-repairing digital flight control system, and state-of-the-art theory application are addressed

Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib.

BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264

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

Glucan Particles for Macrophage Targeted Delivery of Nanoparticles

Glucan particles (GPs) are hollow, porous 2–4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules) encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL) synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP) or electrostatically bound to the surface of chemically derivatized GPs (NP-GP). GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs) containing the chemotherapeutic doxorubicin (Dox) were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest

Wild-type huntingtin regulates human macrophage function

The huntingtin (HTT) protein in its mutant form is the cause of the inherited neurodegenerative disorder, Huntington\u27s disease. Beyond its effects in the central nervous system, disease-associated mutant HTT causes aberrant phenotypes in myeloid-lineage innate immune system cells, namely monocytes and macrophages. Whether the wild-type form of the protein, however, has a role in normal human macrophage function has not been determined. Here, the effects of lowering the expression of wild-type (wt)HTT on the function of primary monocyte-derived macrophages from healthy, non-disease human subjects were examined. This demonstrated a previously undescribed role for wtHTT in maintaining normal macrophage health and function. Lowered wtHTT expression was associated, for instance, with a diminished release of induced cytokines, elevated phagocytosis and increased vulnerability to cellular stress. These may well occur by mechanisms different to that associated with the mutant form of the protein, given an absence of any effect on the intracellular signalling pathway predominantly associated with macrophage dysfunction in Huntington\u27s disease

The Role of Entrepreneur-Venture Fit in Online Home-based Entrepreneurship: A Systematic Literature Review

Home-based businesses and their founders represent an important, but under-researched facet of entrepreneurship. Far from being small, hobby-businesses with little economic impact, home-based business make significant contribution to national economies in terms of both turnover and employment. Online home-based businesses have been recognised as an important and distinct sector of the home-based business domain, offering unique opportunity for innovation and business diversity. The paper presents a systematic literature review of extant research on online home-based entrepreneurs and their businesses. The findings of the review are structured and discussed using the theoretical lens of entrepreneur-venture fit. Use of this lens allows the study to bring coherence to previously fragmented extant studies, providing a basis for future research in this domain. The study also develops a novel model of entrepreneur-venture fit in the specific case of online home-based businesses. This allows us to suggest five positive interactions between entrepreneurial and venture characteristics. It also allows us to suggest a number of previously unidentified negative interactions, which may result in entrepreneurs becoming ‘locked-in’ and suffering multiple sources of stress