Delta Advanced Reusable Transport (DART): An alternative manned spacecraft

Although the current U.S. Space Transportation System (STS) has proven successful in many applications, the truth remains that the space shuttle is not as reliable or economical as was once hoped. In fact, the Augustine Commission on the future of the U.S. Space Program has recommended that the space shuttle only be used on missions directly requiring human capabilities on-orbit and that the shuttle program should eventually be phased out. This poses a great dilemma since the shuttle provides the only current or planned U.S. means for human access to space at the same time that NASA is building toward a permanent manned presence. As a possible solution to this dilemma, it is proposed that the U.S. begin development of an Alternative Manned Spacecraft (AMS). This spacecraft would not only provide follow-on capability for maintaining human space flight, but would also provide redundancy and enhanced capability in the near future. Design requirements for the AMS studied include: (1) capability of launching on one of the current or planned U.S. expendable launch vehicles (baseline McDonnell Douglas Delta II model 7920 expendable booster); (2) application to a wide variety of missions including autonomous operations, space station support, and access to orbits and inclinations beyond those of the space shuttle; (3) low enough costing to fly regularly in augmentation of space shuttle capabilities; (4) production surge capabilities to replace the shuttle if events require it; (5) intact abort capability in all flight regimes since the planned launch vehicles are not man-rated; (6) technology cut-off date of 1990; and (7) initial operational capability in 1995. In addition, the design of the AMS would take advantage of scientific advances made in the 20 years since the space shuttle was first conceived. These advances are in such technologies as composite materials, propulsion systems, avionics, and hypersonics

Disaccharide topology induces slow down in local water dynamics

Molecular level insight into water structure and structural dynamics near proteins, lipids and nucleic acids is critical to the quantitative understanding of many biophysical processes. Un- fortunately, understanding hydration and hydration dynamics around such large molecules is challenging because of the necessity of deconvoluting the effects of topography and chemical heterogeneity. Here we study, via classical all atom simulation, water structure and structural dynamics around two biologically relevant solutes large enough to have significant chemical and topological heterogeneity but small enough to be computationally tractable: the disaccharides Kojibiose and Trehalose. We find both molecules to be strongly amphiphilic (as quantified from normalized local density fluctuations) and to induce nonuniform local slowdown in water translational and rotational motion. Detailed analysis of the rotational slowdown shows that while the rotational mechanism is similar to that previously identified in other aqueous systems by Laage, Hynes and coworkers, two novel characteristics are observed: broadening of the transition state during hydrogen bond exchange (water rotation) and a subpopulation of water for which rotation is slowed because of hindered access of the new accepting water molecule to the transition state. Both of these characteristics are expected to be generic features of water rotation around larger biomolecules and, taken together, emphasize the difficulty in transferring insight into water rotation around small molecules to much larger amphiphilic solutes.This work is part of the research program of the “Stichting voor Fundamenteel Onderzoek der Materie (FOM)” which is financially supported by the “Nederlandse organisatie voor Wetenschap- pelijk Onderzoek (NWO)”. Further financial support was provided by a Marie Curie Incoming International Fellowship (RKC). We gratefully acknowledge SARA, the Dutch center for high- performance computing, for computational time and Huib Bakker and Daan Frenkel for useful critical reviews on an earlier version of this work. We thank two anonymous reviewers for their excellent work, especially for bringing to our attention calculations done on the transition state geometry of dimers and the overstructuring of the O-O radial distribution function of SPC/E water

SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens

Depression is a recurring and life-threatening illness that affects up to 120 million people worldwide. In the present study, we show that chronic social defeat stress, an ethologically validated model of depression in mice, increases SIRT1 levels in the nucleus accumbens (NAc), a key brain reward region. Increases in SIRT1, a well characterized class III histone deacetylase, after chronic social defeat suggest a role for this enzyme in mediating depression-like behaviors. When resveratrol, a pharmacological activator of SIRT1, was directly infused bilaterally into the NAc, we observed an increase in depression- and anxiety-like behaviors. Conversely, intra-NAc infusions of EX-527, a SIRT1 antagonist, reduced these behaviors; EX-527 also reduced acute stress responses in stress-naive mice. Next, we increased SIRT1 levels directly in NAc by use of viral-mediated gene transfer and observed an increase in depressive- and anxiety-like behaviors when mice were assessed in the open-field, elevated-plus-maze, and forced swim tests. Using a Cre-inducible viral vector system to overexpress SIRT1 selectively in dopamine D1 or D2 subpopulations of medium spiny neurons (MSNs) in the NAc, we found that SIRT1 promotes depressive-like behaviors only when overexpressed in D1 MSNs, with no effect seen in D2 MSNs. Conversely, selective ablation of SIRT1 in the NAc using viral-Cre in floxed Sirt1 mice resulted in decreased depression- and anxiety-like behaviors. Together, these results demonstrate that SIRT1 plays an essential role in the NAc in regulating mood-related behavioral abnormalities and identifies a novel signaling pathway for the development of innovative antidepressants to treat major depressive disorders.Brain and Behavior Research FoundationNational Institute of Mental Health (U.S.

Concepts and problems in protein dynamics

The function of proteins depends crucially on conformational motions. The characteristic times of these motions extend from sub-picosecond to seconds. No single experimental tool can cover the entire time range and provide all necessary parameters for a complete understanding. Moreover, without a solid understanding of the data evaluation it is easy to misinterpret the complex phenomena. Because protein motions are truly complex, the evaluation of the data even from such well-known techniques as neutron scattering (Magazu and Migliardo, 2011 [1]) and the Mossbauer effect (Chen and Yang, 2007 [2]) can lead to erroneous concepts and conclusions. We believe that notions such as the Lamb-Mossbauer relation, the protein dynamic transition, the protein glass transition, and the dynamic crossover are misleading or misapplied. To justify this statement we first briefly describe our view of dynamic proteins and then explain why we believe that these notions should be revised or abandoned. (C) 2013 Elsevier B.V. All rights reserved