General Rotorcraft Aeromechanical Stability Program (GRASP) version 1.03: User's manual

The Rotorcraft Dynamics Division, Aeroflightdynamics Directorate, U.S. Army Aviation Research and Technology Activity has developed the General Rotorcraft Aeromechanical Stability Program (GRASP) to perform calculations that will assess the stability of rotorcraft in hovering flight and ground contact conditions. The program is designed to be state-of-the-art, hybrid, finite-element/multibody code that can be applied to all existing and future helicopter configurations. While GRASP was specifically designed to solve rotorcraft stability problems, its innovative structure and formulation allow for application to a wide range of structures. This manual describes the preparation of the input file required by Version 1.03 of GRASP, the procedures used to invoke GRASP on the NASA Ames Research Center CRAY X-MP 48 computer, and the interpretation of the output produced by GRASP. The parameters used by the input file are defined, and summaries of the input file and the job control language are included

Workshop on Exercise Prescription for Long-Duration Space Flight

The National Aeronautics and Space Administration has a dedicated history of ensuring human safety and productivity in flight. Working and living in space long term represents the challenge of the future. Our concern is in determining the effects on the human body of living in space. Space flight provides a powerful stimulus for adaptation, such as cardiovascular and musculoskeletal deconditioning. Extended-duration space flight will influence a great many systems in the human body. We must understand the process by which this adaptation occurs. The NASA is agressively involved in developing programs which will act as a foundation for this new field of space medicine. The hallmark of these programs deals with prevention of deconditioning, currently referred to as countermeasures to zero g. Exercise appears to be most effective in preventing the cardiovascular and musculoskeletal degradation of microgravity

Summary and recommendations for initial exercise prescription

The recommendations summarized herein constitute a basis on which an initial exercise prescription can be formulated. It is noteworthy that any exercise program designed currently would be an approximation. Examination of the existing space-flight data reveals a scarcity of in-flight data on which to rigorously design an exercise program. The relevant experience within the U.S. space program (with regard to long-duration space flight) is limited to the Skylab Program. Lessons learned from Skylab are relevant to the design of a Space Station exercise program, especially with regard to the total length of exercise time required, cardiovascular (CV) deconditioning/reconditioning, and bone loss. Certain observations of the U.S.S.R. exercise activities can also contribute to the formulation of an exercise prescription of Space Station. Reportedly, the U.S.S.R. uses both a bicycle ergometer and a treadmill device on long-duration missions with some degree of success. Using the third crew of Salyut 6, which was a 175-day stay, as a representative mission, the typical time dedicated to exercise varies from 2 to 3 hours per day. In addition, the cosmonauts wear an elasticized suit, called a penquin suit, for time periods ranging from 12 to 16 hours per day. This device provides a load across the axial skeleton against which the wearer must exert himself. Despite these extensive countermeasures, the effects of adaptation are not totally prevented

General Rotorcraft Aeromechanical Stability Program (GRASP): Theory manual

The general rotorcraft aeromechanical stability program (GRASP) was developed to calculate aeroelastic stability for rotorcraft in hovering flight, vertical flight, and ground contact conditions. GRASP is described in terms of its capabilities and its philosophy of modeling. The equations of motion that govern the physical system are described, as well as the analytical approximations used to derive them. The equations include the kinematical equation, the element equations, and the constraint equations. In addition, the solution procedures used by GRASP are described. GRASP is capable of treating the nonlinear static and linearized dynamic behavior of structures represented by arbitrary collections of rigid-body and beam elements. These elements may be connected in an arbitrary fashion, and are permitted to have large relative motions. The main limitation of this analysis is that periodic coefficient effects are not treated, restricting rotorcraft flight conditions to hover, axial flight, and ground contact. Instead of following the methods employed in other rotorcraft programs. GRASP is designed to be a hybrid of the finite-element method and the multibody methods used in spacecraft analysis. GRASP differs from traditional finite-element programs by allowing multiple levels of substructure in which the substructures can move and/or rotate relative to others with no small-angle approximations. This capability facilitates the modeling of rotorcraft structures, including the rotating/nonrotating interface and the details of the blade/root kinematics for various types. GRASP differs from traditional multibody programs by considering aeroelastic effects, including inflow dynamics (simple unsteady aerodynamics) and nonlinear aerodynamic coefficients

Hoteliers and Hotels: Case Studies in the Growth and Development of U.K. Hotel Companies 1945-1989

The aim of this thesis is to establish the characteristic features of hoteliers and hotels in the main sectors of the U.K. hotel industry, and to demonstrate, through case studies, patterns of growth, development and performance in hotel companies in the period 1945 - 1989. The year 1945, which marked the end of the Second World War, is a natural start point for such a work whilst by 1989 the U.K. hotel industry had established a standard of hospitality combined with general management skills at least equal to and in many cases superior to that offered on the Continent of Europe and throughout the New World. Subsequent to outlining the economic context of the industry in the introductory chapter, the thesis demonstrates the growth and development of the industry by charting the progress of twelve separate hotel companies. These are divided into three groups - hotels in the independent sector, hotel companies which operate throughout the U.K. and whose basis for growth has been the underlying asset value of their property portfolio linked to their ability to operate in a specialised retail environment and hotel companies which have grown principally as a result of international expansion and diversification. The final chapter is directed towards an evaluation of the case studies and to factors which have been central to the growth and development of each company

Large scale motions of Neptune's bow shock: Evidence for control of the shock position by the rotation phase of Neptune's magnetic field

The Voyager 2 spacecraft observed high levels of Langmuir waves before the inbound crossing of Neptune's bow shock, thereby signifying magnetic connection of the bow shock. The Langmuir waves occurred in multiple bursts throughout two distinct periods separated by an 85 minute absence of wave activity. The times of onsets, peaks, and disappearances of the waves were used together with the magnetic field directions and spacecraft position, to perform a 'remote-sensing' analysis of the shape and location of Neptune's bow shock prior to the inbound bow shock crossing. The bow shock is assumed to have a parabolidal shape with a nose location and flaring parameter determined independently for each wave event. The remote-sensing analysis give a shock position consistent with the time of the inbound shock crossing. The flaring parameter of the shock remains approximately constant throughout each period of wave activity but differs by a factor of 10 between the two periods. The absence of waves between two periods of wave activity coincides with a large rotation of the magnetic field and a large increase in the solar wind ram pressure' both these effects lead to magnetic disconnection of the spacecraft from shock. The planetwards motion of the shock's nose from 38.5 R(sub N) to 34.5 R(sub N) during the second time period occurred while the solar wind ram pressure remained constant to within 15 percent. This second period of planetwards motion of the shock is therefore strong evidence for Neptune's bow shock moving in response to the rotation of Neptune's oblique, tilted magnetic dipole. Normalizing the ram pressure, the remotely-sensed shock moves sunwards during the first wave period and planetwards in the second wave period. The maximum standoff distance occurs while the dipole axis is close to being perpendicular to the Sun-Neptune direction. The remote-sensing analysis provides strong evidence that the location of Neptune's bow shock is controlled by Neptune's rotation phase

Use of Most Bothersome Symptom as a Coprimary Endpoint in Migraine Clinical Trials: A Post-Hoc Analysis of the Pivotal ZOTRIP Randomized, Controlled Trial.

ObjectiveTo better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions.BackgroundAdhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo.MethodsWe undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia.ResultsOf the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n = 79), phonophobia (n = 43), and nausea (n = 37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P = .02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P = .05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P = .01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P < .01) for photophobia, 55% vs 43% (P = .45) for phonophobia, and 89% vs 58% for nausea (P = .04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea.ConclusionIn this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co-primary endpoints

Replication confers β cell immaturity.

Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques