Paper Session II-A - Lockheed Martin\u27s Next Generation Launch Systems

The space launch industry is experiencing a tremendous transition from a government dominated customer base to a commercial customer base. According to the Teal Group World Space Briefing, nearly 75 percent of satellites launched from 1997 to 2006 will be civil and commercial satellites (figure 1). Of these, the vast majority are commercial ventures in mobile communications, broadband multi-media services, or direct broadcast television satellites. Nearly three quarters of all proposed payloads are destined for Low Earth Orbit (LEO). Virtually all LEO satellites will belong to multi-satellite systems involving mobile communications or multimedia services. Lockheed Martin is a world leader in the expendable launch vehicle industry. Our heritage which began with the Titan and Atlas launch systems in the late 1950’s, has spanned four decades and over 1,000 launches. In the late 1980’s, the former General Dynamics Space Systems (GD), recognized the need to develop a launch vehicle that could compete in the international commercial market. In 1987, GDinitiated the first commercial launch vehicle, the Atlas II. TheAtlas vehicle has successfully evolved from II to IIA to IIAS and into today’s newest most powerful system yet - the Atlas IIAR which will be operational in late 1998. The driving force behind each system upgrade has been to improve performance while reducing cost and increasing reliability. Lockheed Martin combined the commercial industry expertise of the Atlas program with the heritage hardware of both the Atlas and Titan programs to develop their next generation launch vehicle the Common Core BoosterTM family. The Common Core BoosterTM family of launch vehicles will accommodate a wide range of customers, by providing a highly reliable, responsive system with streamlined launch operations. The Common Core BoosterTM vehicle allows Lockheed Martin tol effectively compete in international commercial markets, while satisfying the United States government requirements for low cost, reliable access to space. The purpose of this paper is to describe Lockheed Martin’s approach to incorporating the benefits and lessons learned from the Atlas and Titan launch systems into a launch vehicle family that will serve the payload community well into the 21st Century

Resolving Animal Distress and Pain: Principles and Examples of Good Practice in Various Fields of Research

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation. This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress dichotomy by adopting a holistic treatment of adverse effects, i.e., not parsing distress and pain, by providing guidance on how to assess deviations from normality through tools such as score sheets. Our aim is to provide practical information to IACUCs, scientists, technicians and animal care personnel. We organize the chapter according to specific research areas and case studies. However, the principles and approaches are readily generalized to other research areas. CONTENTS Effect of surgical technical skill on pain and distress in animals - Alicia Karas, DVM Carbon dioxide euthanasia: example of aversion techniques - Matthew C. Leach, PhD The Refinement of Infectious Disease Research - Karl A. Andrutis DVM, MS, DACLAM Polyclonal antibody production - Kathleen Conlee, BS, MPA Animal models of human psychopathology: anxiety - John P. Gluck PhD Refinement In Toxicology Testing: A Workshop to Promote Current Advances and Disseminate Best Practices - Andrew N. Rowan, Martin L. Stephens, and Kathleen M. Conle

Role of electric charge in shaping equilibrium configurations of fluid tori encircling black holes

Astrophysical fluids may acquire non-zero electrical charge because of strong irradiation or charge separation in a magnetic field. In this case, electromagnetic and gravitational forces may act together and produce new equilibrium configurations, which are different from the uncharged ones. Following our previous studies of charged test particles and uncharged perfect fluid tori encircling compact objects, we introduce here a simple test model of a charged perfect fluid torus in strong gravitational and electromagnetic fields. In contrast to ideal magnetohydrodynamic models, we consider here the opposite limit of negligible conductivity, where the charges are tied completely to the moving matter. This is an extreme limiting case which can provide a useful reference against which to compare subsequent more complicated astrophysically-motivated calculations. To clearly demonstrate the features of our model, we construct three-dimensional axisymmetric charged toroidal configurations around Reissner-Nordstr\"om black holes and compare them with equivalent configurations of electrically neutral tori.Comment: 14 pages, 7 figure

Designer diatom episomes delivered by bacterial conjugation.

Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify a yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research

An engineered nanosugar enables rapid and sustained glucose-responsive insulin delivery in diabetic mice

Glucose-responsive insulin-delivery platforms that are sensitive to dynamic glucose concentration fluctuations and provide both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. Here, biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release are engineered. The nanoparticles are "nanosugars" bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (approximate to 95% loading capacity) to form nanocomplexes. A single subcutaneous injection of nanocomplexes shows a rapid and efficient response to a glucose challenge in two distinct diabetic mouse models, resulting in optimal blood glucose levels (below 200 mg dL(-1)) for up to 13 h. The morphology of the nanocomplexes is found to be key to controlling rapid and extended glucose-regulated insulin delivery in vivo. These studies reveal that the injected nanocomplexes enabled efficient insulin release in the mouse, with optimal bioavailability, pharmacokinetics, and safety profiles. These results highlight a promising strategy for the development of a glucose-responsive insulin delivery system based on a natural and biodegradable nanosugar

Plasma Biomarkers of Brain Atrophy in Alzheimer's Disease

Peripheral biomarkers of Alzheimer's disease (AD) reflecting early neuropathological change are critical to the development of treatments for this condition. The most widely used indicator of AD pathology in life at present is neuroimaging evidence of brain atrophy. We therefore performed a proteomic analysis of plasma to derive biomarkers associated with brain atrophy in AD. Using gel based proteomics we previously identified seven plasma proteins that were significantly associated with hippocampal volume in a combined cohort of subjects with AD (N = 27) and MCI (N = 17). In the current report, we validated this finding in a large independent cohort of AD (N = 79), MCI (N = 88) and control (N = 95) subjects using alternative complementary methods—quantitative immunoassays for protein concentrations and estimation of pathology by whole brain volume. We confirmed that plasma concentrations of five proteins, together with age and sex, explained more than 35% of variance in whole brain volume in AD patients. These proteins are complement components C3 and C3a, complement factor-I, γ-fibrinogen and alpha-1-microglobulin. Our findings suggest that these plasma proteins are strong predictors of in vivo AD pathology. Moreover, these proteins are involved in complement activation and coagulation, providing further evidence for an intrinsic role of these pathways in AD pathogenesis

17β-Estradiol Prevents Early-Stage Atherosclerosis in Estrogen Receptor-Alpha Deficient Female Mice

Estrogen is atheroprotective and a high-affinity ligand for both known estrogen receptors, ERα and ERβ. However, the role of the ERα in early-stage atherosclerosis has not been directly investigated and is incompletely understood. ERα-deficient (ERα−/−) and wild-type (ERα+/+) female mice consuming an atherogenic diet were studied concurrent with estrogen replacement to distinguish the actions of 17β-estradiol (E2) from those of ERα on the development of early atherosclerotic lesions. Mice were ovariectomized and implanted with subcutaneous slow-release pellets designed to deliver 6 or 8 μg/day of exogenous 17β-estradiol (E2) for a period of up to 4 months. Ovariectomized mice (OVX) with placebo pellets (E2-deficient controls) were compared to mice with endogenous E2 (intact ovaries) and exogenous E2. Aortas were analyzed for lesion area, number, and distribution. Lipid and hormone levels were also determined. Compared to OVX, early lesion development was significantly (p < 0.001) attenuated by E2 with 55–64% reduction in lesion area by endogenous E2 and >90% reduction by exogenous E2. Compared to OVX, a decline in lesion number (2- to 4-fold) and lesser predilection (~4-fold) of lesion formation in the proximal aorta also occurred with E2. Lesion size, development, number, and distribution inversely correlated with circulating plasma E2 levels. However, atheroprotection was independent of ERα status, and E2 athero-protection in both genotypes was not explained by changes in plasma lipid levels (total cholesterol, triglyceride, and high-density lipoprotein cholesterol). The ERα is not essential for endogenous/exogenous E2-mediated protection against early-stage atherosclerosis. These observations have potentially significant implications for understanding the molecular and cellular mechanisms and timing of estrogen action in different estrogen receptor (ER) deletion murine models of atherosclerosis, as well as implications to human studies of ER polymorphisms and lipid metabolism. Our findings may contribute to future improved clinical decision-making concerning the use of hormone therapy

A Gene Regulatory Network for Root Epidermis Cell Differentiation in Arabidopsis

The root epidermis of Arabidopsis provides an exceptional model for studying the molecular basis of cell fate and differentiation. To obtain a systems-level view of root epidermal cell differentiation, we used a genome-wide transcriptome approach to define and organize a large set of genes into a transcriptional regulatory network. Using cell fate mutants that produce only one of the two epidermal cell types, together with fluorescence-activated cell-sorting to preferentially analyze the root epidermis transcriptome, we identified 1,582 genes differentially expressed in the root-hair or non-hair cell types, including a set of 208 “core” root epidermal genes. The organization of the core genes into a network was accomplished by using 17 distinct root epidermis mutants and 2 hormone treatments to perturb the system and assess the effects on each gene's transcript accumulation. In addition, temporal gene expression information from a developmental time series dataset and predicted gene associations derived from a Bayesian modeling approach were used to aid the positioning of genes within the network. Further, a detailed functional analysis of likely bHLH regulatory genes within the network, including MYC1, bHLH54, bHLH66, and bHLH82, showed that three distinct subfamilies of bHLH proteins participate in root epidermis development in a stage-specific manner. The integration of genetic, genomic, and computational analyses provides a new view of the composition, architecture, and logic of the root epidermal transcriptional network, and it demonstrates the utility of a comprehensive systems approach for dissecting a complex regulatory network