NASA's Space Launch System Progress Report

Exploration beyond Earth will be an enduring legacy for future generations, confirming America's commitment to explore, learn, and progress. NASA's Space Launch System (SLS) Program, managed at the Marshall Space Flight Center, is responsible for designing and developing the first exploration-class rocket since the Apollo Program's Saturn V that sent Americans to the Moon. The SLS offers a flexible design that may be configured for the MultiPurpose Crew Vehicle and associated equipment, or may be outfitted with a payload fairing that will accommodate flagship science instruments and a variety of high-priority experiments. Both options support a national capability that will pay dividends for future generations. Building on legacy systems, facilities, and expertise, the SLS will have an initial lift capability of 70 metric tons (mT) and will be evolvable to 130 mT. While commercial launch vehicle providers service the International Space Station market, this capability will surpass all vehicles, past and present, providing the means to do entirely new missions, such as human exploration of asteroids and Mars. With its superior lift capability, the SLS can expand the interplanetary highway to many possible destinations, conducting revolutionary missions that will change the way we view ourselves, our planet and its place in the cosmos. To perform missions such as these, the SLS will be the largest launch vehicle ever built. It is being designed for safety and affordability - to sustain our journey into the space age. Current plans include launching the first flight, without crew, later this decade, with crewed flights beginning early next decade. Development work now in progress is based on heritage space systems and working knowledge, allowing for a relatively quick start and for maturing the SLS rocket as future technologies become available. Together, NASA and the U.S. aerospace industry are partnering to develop this one-of-a-kind asset. Many of NASA's space centers across the country will provide their unique expertise to the Space Launch System endeavor. Unique infrastructure to be used includes the Michoud Assembly Facility for tank manufacturing, Stennis Space Center for engine testing, and Kennedy Space Center for processing and launch. As this panel will discuss, the SLS team is dedicated to doing things differently-from applying lean oversight/insight models to smartly using legacy hardware and existing facilities. Building on the foundation laid by over 50 years of human and scientific space flight--and on the lessons learned from the Apollo, Space Shuttle, and Constellation Programs-the SLS team has delivered both technical trade studies and business case analyses to ensure that the SLS architecture will be safe, affordable, reliable, and sustainable

Mechanisms for Vascular Cell Adhesion Molecule-1 Activation of ERK1/2 during Leukocyte Transendothelial Migration

Background: During inflammation, adhesion molecules regulate recruitment of leukocytes to inflamed tissues. It is reported that vascular cell adhesion molecule-1 (VCAM-1) activates extracellular regulated kinases 1 and 2 (ERK1/2), but the mechanism for this activation is not known. Pharmacological inhibitors of ERK1/2 partially inhibit leukocyte transendothelial migration in a multi-receptor system but it is not known whether VCAM-1 activation of ERK1/2 is required for leukocyte transendothelial migration (TEM) on VCAM-1. Methodology/Principal Findings: In this study, we identified a mechanism for VCAM-1 activation of ERK1/2 in human and mouse endothelial cells. VCAM-1 signaling, which occurs through endothelial cell NADPH oxidase, protein kinase Ca (PKCa), and protein tyrosine phosphatase 1B (PTP1B), activates endothelial cell ERK1/2. Inhibition of these signals blocked VCAM-1 activation of ERK1/2, indicating that ERK1/2 is activated downstream of PTP1B during VCAM-1 signaling. Furthermore, VCAM-1-specific leukocyte migration under physiological laminar flow of 2 dynes/cm 2 was blocked by pretreatment of endothelial cells with dominant-negative ERK2 K52R or the MEK/ERK inhibitors, PD98059 and U0126, indicating for the first time that ERK regulates VCAM-1-dependent leukocyte transendothelial migration. Conclusions/Significance: VCAM-1 activation of endothelial cell NADPH oxidase/PKCa/PTP1B induces transient ERK1/2 activation that is necessary for VCAM-1-dependent leukocyte TEM

NASA's Space Launch System Progress Report

Exploration beyond Earth orbit will be an enduring legacy for future generations, as it provides a platform for science and exploration that will define new knowledge and redefine known boundaries. NASA s Space Launch System (SLS) Program, managed at the Marshall Space Flight Center, is responsible for designing and developing the first exploration-class rocket since the Apollo Program s Saturn V that sent Americans to the Moon in the 1960s and 1970s. The SLS offers a flexible design that may be configured for the Orion Multi-Purpose Crew Vehicle with associated life-support equipment and provisions for long journeys or may be outfitted with a payload fairing that will accommodate flagship science instruments and a variety of high-priority experiments. Building on legacy systems, facilities, and expertise, the SLS will have an initial lift capability of 70 tonnes (t) in 2017 and will be evolvable to 130 t after 2021. While commercial launch vehicle providers service the International Space Station market, this capability will surpass all vehicles, past and present, providing the means to do entirely new missions, such as human exploration of Mars. Building on the foundation laid by over 50 years of human and scientific space flight and on the lessons learned from the Apollo, Space Shuttle, and Constellation Programs the SLS team is delivering both technical trade studies and business case analyses to ensure that the SLS architecture will be safe, affordable, reliable, and sustainable. This panel will address the planning and progress being made by NASA s SLS Program

Mechanism for Initiation of Food Allergy: Dependence on skin barrier mutations and environmental allergen co-stimulation

Background Mechanisms for the development of food allergy in neonates are unknown but are clearly linked in patient populations to a genetic predisposition towards skin barrier defects. Whether skin barrier defects functionally contribute to development of food allergy is unknown. Objective The purpose of the study was to determine whether skin barrier mutations, that are primarily heterozygous in patient populations, contribute to the development of food allergy. Methods Mice heterozygous for the Flgft and Tmem79ma mutations were skin sensitized with environmental allergens and food allergens. After sensitization, mice received oral challenge with food allergen and then inflammation, inflammatory mediators, and anaphylaxis were measured. Results We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations following brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have elevated responses to suboptimal sensitization with food allergens. Importantly, the responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. Blockade of ST2 during skin sensitization inhibited development of anaphylaxis, antigen-specific IgE and inflammatory mediators. The neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen but, interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. Conclusion These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early life exposures and genetics in clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen

Measurement of a Model of Implementation for Health Care: Toward a Testable Theory

Greenhalgh et al. used a considerable evidence-base to develop a comprehensive model of implementation of innovations in healthcare organizations [1]. However, these authors did not fully operationalize their model, making it difficult to test formally. The present paper represents a first step in operationalizing Greenhalgh et al.\u27s model by providing background, rationale, working definitions, and measurement of key constructs.A systematic review of the literature was conducted for key words representing 53 separate sub-constructs from six of the model\u27s broad constructs. Using an iterative process, we reviewed existing measures and utilized or adapted items. Where no one measure was deemed appropriate, we developed other items to measure the constructs through consensus

Three-dimensional adaptive evolution of gravitational waves in numerical relativity

Adaptive techniques are crucial for successful numerical modeling of gravitational waves from astrophysical sources such as coalescing compact binaries, since the radiation typically has wavelengths much larger than the scale of the sources. We have carried out an important step toward this goal, the evolution of weak gravitational waves using adaptive mesh refinement in the Einstein equations. The 2-level adaptive simulation is compared with unigrid runs at coarse and fine resolution, and is shown to track closely the features of the fine grid run.Comment: REVTeX, 7 pages, including three figures; submitted to Physical Review

Combat-Related PTSD Nightmares and Imagery Rehearsal: Nightmare Characteristics and Relation to Treatment Outcome

The characteristics of nightmares of 48 male U.S. Vietnam war veterans with combat-related posttraumatic stress disorder (PTSD), as well as revised dream scripts developed in the course of Imagery Rehearsal therapy, were examined in relation to pretreatment symptomatology and treatment outcome. Features, content, and themes of nightmares and rescripted dreams were coded by 2 independent raters. Nightmares were replete with scenes of death and violence and were predominantly replays of actual combat events in which the veteran was under attack and feared for his life. Although addressing or resolving the nightmare theme with rescripting was associated with a reduction in sleep disturbance, references to violence in the rescripted dream were related to poorer treatment outcome in nightmare frequency; B = 5.69 (SE = 1.14). The experience of olfactory sensations in nightmares, a possible index of nightmare intensity, was also related to poorer treatment response; B = 2.95 (SE = 1.06). Imagery rehearsal for individuals with severe, chronic PTSD and fairly replicative nightmares may be most effective when the rescripted dream incorporates a resolution of the nightmare theme and excludes violent details

Mechanisms for Alternaria alternata Function in the Skin During Induction of Peanut Allergy in Neonatal Mice With Skin Barrier Mutations

Neonatal mice with heterozygous mutations in genes encoding the skin barrier proteins filaggrin and mattrin (flaky tail mice [FT+/−]) exhibit oral peanut-induced anaphylaxis after skin sensitization. As we have previously reported, sensitization in this model is achieved via skin co- exposure to the environmental allergen Alternaria alternata (Alt), peanut extract (PNE), and detergent. However, the function of Alt in initiation of peanut allergy in this model is little understood. The purpose of this study was to investigate candidate cytokines induced by Alt in the skin and determine the role of these cytokines in the development of food allergy, namely oncostatin M (Osm), amphiregulin (Areg), and IL-33. RT-qPCR analyses demonstrated that skin of FT+/− neonates expressed Il33 and Osm following Alt or Alt/PNE but not PNE exposure. By contrast, expression of Areg was induced by either Alt, PNE, or Alt/PNE sensitization in FT+/− neonates. In scRNAseq analyses, Osm, Areg, and Il33 were expressed by several cell types, including a keratinocyte cluster that was expanded in the skin of Alt/PNE-exposed FT+/− pups as compared to Alt/PNE-exposed WT pups. Areg and OSM were required for oral PNE-induced anaphylaxis since anaphylaxis was inhibited by administration of neutralizing anti-Areg or anti-OSM antibodies prior to each skin sensitization with Alt/PNE. It was then determined if intradermal injection of recombinant IL33 (rIL33), rAreg, or rOSM in the skin could substitute for Alt during skin sensitization to PNE. PNE skin sensitization with intradermal rIL33 was sufficient for oral PNE-induced anaphylaxis, whereas skin sensitization with intradermal rAreg or rOSM during skin exposure to PNE was not sufficient for anaphylaxis to oral PNE challenge. Based on these studies a pathway for IL33, Areg and OSM in Alt/PNE sensitized FT+/− skin was defined for IgE induction and anaphylaxis. Alt stimulated two pathways, an IL33 pathway and a pathway involving OSM and Areg. These two pathways acted in concert with PNE to induce food allergy in pups with skin barrier mutations

Event Horizons in Numerical Relativity II: Analyzing the Horizon

We present techniques and methods for analyzing the dynamics of event horizons in numerically constructed spacetimes. There are three classes of analytical tools we have investigated. The first class consists of proper geometrical measures of the horizon which allow us comparison with perturbation theory and powerful global theorems. The second class involves the location and study of horizon generators. The third class includes the induced horizon 2-metric in the generator comoving coordinates and a set of membrane-paradigm like quantities. Applications to several distorted, rotating, and colliding black hole spacetimes are provided as examples of these techniques.Comment: 23 double column pages including 28 figures. Higher quality figures (big size!) available upon request (jmasso OR [email protected]

Three dimensional numerical relativity: the evolution of black holes

We report on a new 3D numerical code designed to solve the Einstein equations for general vacuum spacetimes. This code is based on the standard 3+1 approach using cartesian coordinates. We discuss the numerical techniques used in developing this code, and its performance on massively parallel and vector supercomputers. As a test case, we present evolutions for the first 3D black hole spacetimes. We identify a number of difficulties in evolving 3D black holes and suggest approaches to overcome them. We show how special treatment of the conformal factor can lead to more accurate evolution, and discuss techniques we developed to handle black hole spacetimes in the absence of symmetries. Many different slicing conditions are tested, including geodesic, maximal, and various algebraic conditions on the lapse. With current resolutions, limited by computer memory sizes, we show that with certain lapse conditions we can evolve the black hole to about $t=50M$, where $M$ is the black hole mass. Comparisons are made with results obtained by evolving spherical initial black hole data sets with a 1D spherically symmetric code. We also demonstrate that an ``apparent horizon locking shift'' can be used to prevent the development of large gradients in the metric functions that result from singularity avoiding time slicings. We compute the mass of the apparent horizon in these spacetimes, and find that in many cases it can be conserved to within about 5\% throughout the evolution with our techniques and current resolution.Comment: 35 pages, LaTeX with RevTeX 3.0 macros. 27 postscript figures taking 7 MB of space, uuencoded and gz-compressed into a 2MB uufile. Also available at http://jean-luc.ncsa.uiuc.edu/Papers/ and mpeg simulations at http://jean-luc.ncsa.uiuc.edu/Movies/ Submitted to Physical Review