Validation of the Lockheed Martin Morphing Concept with Wind Tunnel Testing

The Morphing Aircraft Structures (MAS) program is a Defense Advanced Research Projects Agency (DARPA) led effort to develop morphing flight vehicles capable of radical shape change in flight. Two performance parameters of interest are loiter time and dash speed as these define the persistence and responsiveness of an aircraft. The geometrical characteristics that optimize loiter time and dash speed require different geometrical planforms. Therefore, radical shape change, usually involving wing area and sweep, allows vehicle optimization across many flight regimes. The second phase of the MAS program consisted of wind tunnel tests conducted at the NASA Langley Transonic Dynamics Tunnel to demonstrate two morphing concepts and their enabling technologies with large-scale semi-span models. This paper will focus upon one of those wind tunnel tests that utilized a model developed by Lockheed Martin Aeronautics Company (LM). Wind tunnel success criteria were developed by NASA to support the DARPA program objectives. The primary focus of this paper will be the demonstration of the DARPA objectives by systematic evaluation of the wind tunnel model performance relative to the defined success criteria. This paper will also provide a description of the LM model and instrumentation, and document pertinent lessons learned. Finally, as part of the success criteria, aeroelastic characteristics of the LM derived MAS vehicle are also addressed. Evaluation of aeroelastic characteristics is the most detailed criterion investigated in this paper. While no aeroelastic instabilities were encountered as a direct result of the morphing design or components, several interesting and unexpected aeroelastic phenomenon arose during testing

A novel in vitro cell model of the proteinase/antiproteinase balance observed in alpha-1 antitrypsin deficiency

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting from mutations in the alpha-1 antitrypsin (AAT) protein, a major systemic antiproteinase, resulting in reduced/no release of AAT, disrupting the proteinase/antiproteinase balance. A sustained imbalance can cause structural changes to the lung parenchyma, leading to emphysema. Predicting and assessing human responses to potential therapeutic candidates from preclinical animal studies have been challenging. Our aims were to develop a more physiologically relevant in vitro model of the proteinase/antiproteinase balance and assess whether the data generated could better predict the efficacy of pharmacological candidates to inform decisions on clinical trials, together with expected biomarker responses.Methods: We developed an in vitro model assessing the proteinase/antiproteinase balance by the changes in the fibrinogen cleavage products of neutrophil elastase (NE) and proteinase 3 (PR3). This allowed the assessment of physiological and pharmaceutical neutrophil serine proteinase (NSP) inhibitors to determine the putative threshold at which the maximal effect is achieved.Results: AAT significantly reduced NE and PR3 activity footprints, with the maximal reduction achieved at concentrations above 10 μM. The inhibitor MPH966 alone also significantly reduced NE footprint generation in a concentration-dependent manner, leveling out above 100 nM but had no effect on the PR3 footprint. At levels of AAT consistent with AATD, MPH966 had an additive effect, reducing the NE activity footprint more than either inhibitor alone.Conclusion: Our results support an inhibitor threshold above which the activity footprint generation appears resistant to increasing dosage. Our model can support the testing of inhibitors, confirming activity biomarkers as indicators of likely pharmaceutical efficacy, the assessment of NSP activity in the pathophysiology of emphysema, and the likely function of biological or pharmacological inhibitors in disease management

A novel in vitro cell model of the proteinase/antiproteinase balance observed in alpha-1 antitrypsin deficiency

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting from mutations in the alpha-1 antitrypsin (AAT) protein, a major systemic antiproteinase, resulting in reduced/no release of AAT, disrupting the proteinase/antiproteinase balance. A sustained imbalance can cause structural changes to the lung parenchyma, leading to emphysema. Predicting and assessing human responses to potential therapeutic candidates from preclinical animal studies have been challenging. Our aims were to develop a more physiologically relevant in vitro model of the proteinase/antiproteinase balance and assess whether the data generated could better predict the efficacy of pharmacological candidates to inform decisions on clinical trials, together with expected biomarker responses.Methods: We developed an in vitro model assessing the proteinase/antiproteinase balance by the changes in the fibrinogen cleavage products of neutrophil elastase (NE) and proteinase 3 (PR3). This allowed the assessment of physiological and pharmaceutical neutrophil serine proteinase (NSP) inhibitors to determine the putative threshold at which the maximal effect is achieved.Results: AAT significantly reduced NE and PR3 activity footprints, with the maximal reduction achieved at concentrations above 10 μM. The inhibitor MPH966 alone also significantly reduced NE footprint generation in a concentration-dependent manner, leveling out above 100 nM but had no effect on the PR3 footprint. At levels of AAT consistent with AATD, MPH966 had an additive effect, reducing the NE activity footprint more than either inhibitor alone.Conclusion: Our results support an inhibitor threshold above which the activity footprint generation appears resistant to increasing dosage. Our model can support the testing of inhibitors, confirming activity biomarkers as indicators of likely pharmaceutical efficacy, the assessment of NSP activity in the pathophysiology of emphysema, and the likely function of biological or pharmacological inhibitors in disease management

Stabilization of Extra Dimensions at Tree Level

By considering the effects of string winding and momentum modes on a time dependent background, we find a method by which six compact dimensions become stabilized naturally at the self-dual radius while three dimensions grow large.Comment: 15 pages, 2 figures, minor typos correcte

Genetic influence on East African running success

East African athletes now dominate international distance running events from the 800 m to the marathon. Explanations for their phenomenal success have included optimal environmental conditions for developing distance running performance, psychological advantage and advantageous physiological characteristics. It is well established that genetics plays a role in determining inter-individual differences in exercise performance and adaptation to training stimuli. It is not known, however, to what extent inter-population differences (i.e. between ‘races’ and/or ethnic groups) in exercise performance can be attributed to genetics. There have been considerations that ‘black’ athletes are genetically adapted towards performance, given the concurrent success of athletes of West African ancestry in sprint events. However, the current notion of ‘race’ is not universally accepted, and genetic differences within and between populations are not clearly delineated by geographical or ethnic categorizations. Recent findings from mitochondrial DNA show that the populations from which Ethiopian athletes are drawn have not been isolated populations and are not genetically distinct from other Ethiopians. Y-chromosome analysis of the same population shows concurrent results, although some differences are present between athletes and the general Ethiopian population, suggesting an influence of the Y chromosome on athlete status in Ethiopia. It is concluded that there may be a role for genetics in the success of East African athletes; however, any genetic component to their success is unlikely to be limited to East Africans and is more likely to be found in other populations. At present it is unjustified to implicate a role for genetics in the success of East African runners when no genes have been identified as being important to their performance

The Role and Responsibility of the Public

It\u27s the title of the conference—the court of public opinion—and the topic of this panel. Professor Christopher Schroeder of Duke Law School is joined by media and public policy professor Kim Gross, senior attorney for the Institute for Justice Scott Bullock, and litigation director of the ACLU Steve Shapiro to contemplate both the influence of the media on public opinion and ways to use the media as an advocacy tool. Gross discusses her research into the influence of media coverage on the public, followed by Bullock and Shapiro who explain the ways in which public interest law may choose to incorporate a media strategy into a larger legal battle. Questions/themes/discussion topics Media framing How media coverage can influence public opinion Factors that influence the media\u27s power How the Duke lacrosse case differs from typical crime coverage Legal strategies of public interest organizations Winning in the court of law, but losing in the court of public opinion Losing in the court of law, but winning in the court of public opinio

Measuring AGN Feedback with the Sunyaev-Zel'dovich Effect

One of the most important and poorly-understood issues in structure formation is the role of outflows driven by active galactic nuclei (AGN). Using large-scale cosmological simulations, we compute the impact of such outflows on the small-scale distribution of the cosmic microwave background (CMB). Like gravitationally-heated structures, AGN outflows induce CMB distortions both through thermal motions and peculiar velocities, by processes known as the thermal and kinetic Sunyaev-Zel'dovich (SZ) effects, respectively. For AGN outflows the thermal SZ effect is dominant, doubling the angular power spectrum on arcminute scales. But the most distinct imprint of AGN feedback is a substantial increase in the thermal SZ distortions around elliptical galaxies, post-starburst ellipticals, and quasars, which is linearly proportional to the outflow energy. While point source subtraction is difficult for quasars, we show that by appropriately stacking microwave measurements around early-type galaxies, the new generation of small-scale microwave telescopes will be able to directly measure AGN feedback at the level important for current theoretical models.Comment: 12 pages, 12 figures, submitted to ApJ (comments welcome

Effects of siRNA-mediated knockdown of GSK3β on retinal ganglion cell survival and neurite/axon growth

There are contradictory reports on the role of the serine/threonine kinase isoform glycogen synthase kinase-3β (GSK3β) after injury to the central nervous system (CNS). Some report that GSK3 activity promotes axonal growth or myelin disinhibition, whilst others report that GSK3 activity prevents axon regeneration. In this study, we sought to clarify if suppression of GSK3β alone and in combination with the cellular-stress-induced factor RTP801 (also known as REDD1: regulated in development and DNA damage response protein), using translationally relevant siRNAs, promotes retinal ganglion cell (RGC) survival and neurite outgrowth/axon regeneration. Adult mixed retinal cell cultures, prepared from rats at five days after optic nerve crush (ONC) to activate retinal glia, were treated with siRNA to GSK3β (siGSK3β) alone or in combination with siRTP801 and RGC survival and neurite outgrowth were quantified in the presence and absence of Rapamycin or inhibitory Nogo-A peptides. In in vivo experiments, either siGSK3β alone or in combination with siRTP801 were intravitreally injected every eight days after ONC and RGC survival and axon regeneration was assessed at 24 days. Optimal doses of siGSK3β alone promoted significant RGC survival, increasing the number of RGC with neurites without affecting neurite length, an effect that was sensitive to Rapamycin. In addition, knockdown of GSK3β overcame Nogo-A-mediated neurite growth inhibition. Knockdown of GSK3β after ONC in vivo enhanced RGC survival but not axon number or length, without potentiating glial activation. Knockdown of RTP801 increased both RGC survival and axon regeneration, whilst the combined knockdown of GSK3β and RTP801 significantly increased RGC survival, neurite outgrowth, and axon regeneration over and above that observed for siGSK3β or siRTP801 alone. These results suggest that GSK3β suppression promotes RGC survival and axon initiation whilst, when in combination with RTP801, it also enhanced disinhibited axon elongation