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

Exploiting the Automatic Dependent Surveillance-Broadcast System via False Target Injection

A new aircraft surveillance system, Automatic Dependent Surveillance-Broadcast (ADS-B), is being introduced by the Federal Aviation Administration (FAA) with mandated implementation in the United States by the year 2020. The rapid deployment of the system with current test-beds spread across the U.S. leaves very little chance for anyone to test the abilities of the system and more importantly the flaws of the system. The research conducted within this thesis explores some of the weaknesses of the system to include the relative ease with which false aircraft targets can be injected. As part of a proof of concept, false ADS-B messages were successfully generated using a system comprised of GNU Radio, a Universal Software Radio Peripheral (USRP), and software developed by the author. The ability to generate, transmit, and insert spoofed ADS-B messages on the display of a commercial ADS-B receiver, identified and exploited a weakness of the ADS-B system. Four demonstrations, conducted within an experimental environment, displayed the potential uses of the system created through this research and its associated impacts

SIRT1-FOXO3a Regulate Cocaine Actions in the Nucleus Accumbens

Previous studies have shown that chronic cocaine administration induces SIRT1, a Class III histone deacetylase, in the nucleus accumbens (NAc), a key brain reward region, and that such induction influences the gene regulation and place conditioning effects of cocaine. To determine the mechanisms by which SIRT1 mediates cocaine-induced plasticity in NAc, we used chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 1 d after 7 daily cocaine (20 mg/kg) or saline injections, to map SIRT1 binding genome-wide in mouse NAc. Our unbiased results revealed two modes of SIRT1 action. First, despite its induction in NAc, chronic cocaine causes depletion of SIRT1 from most affected gene promoters in concert with enrichment of H4K16ac (itself a deacetylation target of SIRT1), which is associated with increased expression of these genes. Second, we deduced the forkhead transcription factor (FOXO) family to be a downstream mechanism through which SIRT1 regulates cocaine action. We proceeded to demonstrate that SIRT1 induction causes the deacetylation and activation of FOXO3a in NAc, which leads to the induction of several known FOXO3a gene targets in other systems. Finally, we directly establish a role for FOXO3a in promoting cocaine-elicited behavioral responses by use of viral-mediated gene transfer: we show that overexpressing FOXO3a in NAc enhances cocaine place conditioning. The discovery of these two actions of SIRT1 in NAc in the context of behavioral adaptations to cocaine represents an important step forward in advancing our understanding of the molecular adaptations underlying cocaine action.National Institute on Drug AbuseNational Alliance for Research on Schizophrenia and Depression (U.S.)UNCF-Merc

SIRT1-FOXO3a Regulate Cocain Actions in the Nucleus Accumbens

Previous studies have shown that chronic cocain administration induces SIRT1, a Class III histone deacetylase, in the nucleus accumbens (NAc), a key brain reward region, and that such induction influences the gene regulation and place conditioning effects of cocaine. To determine the mechanisms by which SIRT1 mediates cocaine-induced plasticity in NAc, we used chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 1 d after 7 daily cocain (20 mg/kg) or saline injections, to map SIRT1 binding genome-wide in mouse NAc. Our unbiased results revealed two modes of SIRT1 action. First, despite its induction in NAc, chronic cocain causes depletion of SIRT1 from most affected gene promoters in concert with enrichment of H4K16ac (itself a deacetylation target of SIRT1), which is associated with increased expression of these genes. Second, we deduced the forkhead transcription factor (FOXO) familty to be a downstream mechanis through which SIRT1 regulates cocaine action. We proceeded to demonstrate that SIRT1 induction causes the deacetylation and activation of FOXO3a in NAc, which leads to the induction of several known FOXO3a gene targets in other systems. Finally, we directly establish a role for FOXO3a in promoting cocaine-elicited behavioral responses by use of viral-mediated gene transfer: we show that overexpressing FOXO3a in NAc enhances cocaine place conditioning. The discovery of these two actions of SIRT1 in NAc in the context of behavioral adaptations to cocaine represents an important step forward in advancing our understanding of the molecular adaptations underlying cocaine action

Effects of heavy ion particle irradiation on spore germination of bacillus spp. From extremely hot and cold environments

Extremophiles are optimal models in experimentally addressing questions about the effects of cosmic radiation on biological systems. The resistance to high charge energy (HZE) particles, and helium (He) ions and iron (Fe) ions (LET at 2.2 and 200 keV/µm, respectively, until 1000 Gy), of spores from two thermophiles, Bacillus horneckiae SBP3 and Bacillus licheniformis T14, and two psychrotolerants, Bacillus sp. A34 and A43, was investigated. Spores survived He irradiation better, whereas they were more sensitive to Fe irradiation (until 500 Gy), with spores from thermophiles being more resistant to irradiations than psychrotolerants. The survived spores showed different germination kinetics, depending on the type/dose of irradiation and the germinant used. After exposure to He 1000 Gy, D-glucose increased the lag time of thermophilic spores and induced germination of psychrotolerants, whereas L-alanine and L-valine increased the germination efficiency, except alanine for A43. FTIR spectra showed important modifications to the structural components of spores after Fe irradiation at 250 Gy, which could explain the block in spore germination, whereas minor changes were observed after He radiation that could be related to the increased permeability of the inner membranes and alterations of receptor complex structures. Our results give new insights on HZE resistance of extremophiles that are useful in different contexts, including astrobiology

Diagnostic delay and complications for older adults with multiple myeloma

Increased attention to timely diagnosis motivated us to study 5483 patients diagnosed with multiple myeloma using Medicare claims linked to tumor registries in the Surveillance, Epidemiology and End Results programme. We calculated the time between initial visits for anemia or back pain and for myeloma diagnosis, and used logistic regression to predict the likelihood of diagnostic delay, and also the likelihood of renal or skeletal complications. The median time between sign or symptom and myeloma diagnosis was 99 days. Patients with anemia, back pain and comorbidities were more likely to experience diagnostic delay (OR 1.6, 95% CI 1.3-2.0). Diagnosis while hospitalised (OR 2.5, 95% CI 2.2-2.9) and chemotherapy treatment within 6 months of diagnosis (OR 1.4, 95% CI 1.2-1.6) significantly predicted complications; diagnostic delay did not (OR 0.9, 95% CI 0.8-1.1). Our data suggest that complications are more strongly associated with health status and myeloma severity than with diagnostic delays.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94124/1/Diagnostic delay and complications for older adults with multiple myeloma.pd

Delays in referral and diagnosis for chronic hematological malignancies: A literature review

To better understand the extent of diagnostic and referral delays from primary care providers (PCPs) for chronic hematologic malignancies, causes of these delays, and their possible effects on cancer outcomes, an extensive review of the literature was performed. Over 50 studies were reviewed, including many that concern delays in referral and diagnosis for solid tumors, as there was only sparse literature on delays specific to the liquid tumors. Delays for some chronic hematologic malignancies have been documented, mainly in centralized health care systems. Possible reasons for delays include PCPs' lack of exposure to hematologic malignancies, limited knowledge of associated signs and symptoms, and a reliance on patient symptoms to prompt referral (as opposed to signs and screening). Patient characteristics such as age, gender and race-ethnicity are also likely to play a role, although it is unclear if these exert their effect primarily via patient or provider mechanisms. Unfortunately, the outcomes associated with such delays are largely unreported, possibly because delay is complex to define and difficult to measure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94128/1/Delays in referral and diagnosis for chronic hematological malignancies A literature review.pd

Model for solvent viscosity effect on enzymatic reactions

Why reaction rate constants for enzymatic reactions are typically inversely proportional to fractional power exponents of solvent viscosity remains to be already a thirty years old puzzle. Available interpretations of the phenomenon invoke to either a modification of 1. the conventional Kramers' theory or that of 2. the Stokes law. We show that there is an alternative interpretation of the phenomenon at which neither of these modifications is in fact indispensable. We reconcile 1. and 2. with the experimentally observable dependence. We assume that an enzyme solution in solvent with or without cosolvent molecules is an ensemble of samples with different values of the viscosity for the movement of the system along the reaction coordinate. We assume that this viscosity consists of the contribution with the weight $q$ from cosolvent molecules and that with the weight $1-q$ from protein matrix and solvent molecules. We introduce heterogeneity in our system with the help of a distribution over the weight $q$. We verify the obtained solution of the integral equation for the unknown function of the distribution by direct substitution. All parameters of the model are related to experimentally observable values. General formalism is exemplified by the analysis of literature experimental data for oxygen escape from hemerythin.Comment: 16 LaTex pages, 5 eps figure

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