Space robotics: Recent accomplishments and opportunities for future research

The Langley Guidance, Navigation, and Control Technical Committee (GNCTC) was one of six technical committees created in 1991 by the Chief Scientist, Dr. Michael F. Card. During the kickoff meeting Dr. Card charged the chairmen to: (1) establish a cross-Center committee; (2) support at least one workshop in a selected discipline; and (3) prepare a technical paper on recent accomplishments in the discipline and on opportunities for future research. The Guidance, Navigation, and Control Committee was formed and selected for focus on the discipline of Space robotics. This report is a summary of the committee's assessment of recent accomplishments and opportunities for future research. The report is organized as follows. First is an overview of the data sources used by the committee. Next is a description of technical needs identified by the committee followed by recent accomplishments. Opportunities for future research ends the main body of the report. It includes the primary recommendation of the committee that NASA establish a national space facility for the development of space automation and robotics, one element of which is a telerobotic research platform in space. References 1 and 2 are the proceedings of two workshops sponsored by the committee during its June 1991, through May 1992 term. The focus of the committee for the June 1992 - May 1993 term will be to further define to the recommended platform in space and to add an additional discipline which includes aircraft related GN&C issues. To the latter end members performing aircraft related research will be added to the committee. (A preliminary assessment of future opportunities in aircraft-related GN&C research has been included as appendix A.

Blending Geospatial Technology and Traditional Ecological Knowledge to Enhance Restoration Decision-Support Processes in Coastal Louisiana

More informed coastal restoration decisions have become increasingly important given limited resources available for restoration projects and the increasing magnitude of marsh degradation and loss across the Gulf Coast. This research investigated the feasibility and benefits of integrating geospatial technology with the traditional ecological knowledge (TEK) of an indigenous Louisiana coastal population to assess the impacts of current and historical ecosystem change on community viability. The primary goal was to provide coastal resource managers with a decision-support tool that allows for a more comprehensive method of assessing localized ecological change in the Gulf Coast region, which can also benefit human community sustainability. Using remote sensing (RS) and geographic information systems (GIS) mapping products, integrated with a coastal community’s TEK to achieve this goal, the research team determined a method for producing vulnerability/sustainability mapping products for an ecosystem-dependent livelihood base of a coastal population based on information derived from RS imagery prioritized with TEK. This study also demonstrates how such an approach can engage affected community residents who are interested in determining and addressing the causes and mitigating the decline of marsh habitat. Historical image data sets of the study area were acquired to understand evolution of land change to current conditions and project future vulnerability. Image-processing procedures were developed and applied to produce maps that detail land change in the study area at time intervals from 1968 to 2009. This information was combined in a GIS with acquired TEK and scientific data sets relating to marsh vegetation health and vulnerability characteristics to produce mapping products that provide new information for use in the coastal restoration decision-making process. This information includes: (1) marsh areas that are most vulnerable; and (2) the areas that are most significant to community sustainability

Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen-the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen-the pentameric complex. We further demonstrated that following vaccination of a replication-defective virus with the restored pentameric complex, rhesus macaques can develop broadly neutralizing antibodies targeting multiple immunogenic sites of the pentameric complex. Such analyses of site-specific antibody responses are imperative to our assessment of the quality of vaccine-induced immunity in clinical studies

Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia

Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

This is the published version. Copyright 2003 American Society for Microbiology.The cellular immunogenicity of formulated plasmid DNA and replication-defective human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized human immunodeficiency virus type 1 gag gene was examined in baboons. The Ad5 vaccine was capable of inducing consistently strong, long-lived CD8+-biased T-cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune responses were weaker than those elicited by the Ad5 vaccine and highly variable; formulation with chemical adjuvants led to moderate increases in the levels of Gag-specific T cells. Increasing the DNA-primed responses with booster doses of either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in the relative levels of cytotoxic and helper responses. The implications of these results are discussed

1,3-Butadiene: Biomarkers and application to risk assessment

1,3-Butadiene (BD) is a known rodent and human carcinogen that is metabolized mainly by P450 2E1 to three epoxides, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB) and 1,2-epoxy-3,4-butanediol (EB-diol). The individual epoxides vary up to 200-fold in their mutagenic potency, with DEB being the most mutagenic metabolite. It is important to understand the internal formation of the individual epoxides to assign the relative risk for each metabolite and to understand the molecular mechanisms responsible for major species differences in carcinogenicity. We have conducted extensive exposure-biomarker studies on mice, rats and humans. Using low exposures that range from current occupational levels to human exposures from tobacco smoke has provided evidence that mice are very different from humans, with mice forming ~200 times more DEB than humans at exposures of 0.1–1.5 ppm BD. While no gender differences have been noted in mice and rats for globin adducts or N-7 guanine adducts, female rats and mice had 2–3-fold higher Hprt mutations and DNA-DNA cross-links, suggesting a gender difference in DNA repair. Numerous molecular epidemiology studies have evaluated globin adducts and Hprt mutations, SCEs and chromosomal abnormalities. None of the blinded studies have shown evidence of human genotoxicity at current occupational exposures and studies of globin adducts have shown similar or lower formation of adducts in females than males. If one calculates the EB dose-equivalents for the three species, mice clearly differ from rats and humans, being ~44 and 174 times greater than rats and humans, respectively. These data provide a scientific basis for improved risk assessment of BD

Single-camera three-dimensional tracking of natural particulate and zooplankton

We develop and characterize an image processing algorithm to adapt single-camera defocusing digital particle image velocimetry (DDPIV) for three-dimensional (3D) particle tracking velocimetry (PTV) of natural particulates, such as those present in the ocean. The conventional DDPIV technique is extended to facilitate tracking of non-uniform, non-spherical particles within a volume depth an order of magnitude larger than current single-camera applications (i.e. 10 cm  ×  10 cm  ×  24 cm depth) by a dynamic template matching method. This 2D cross-correlation method does not rely on precise determination of the centroid of the tracked objects. To accommodate the broad range of particle number densities found in natural marine environments, the performance of the measurement technique at higher particle densities has been improved by utilizing the time-history of tracked objects to inform 3D reconstruction. The developed processing algorithms were analyzed using synthetically generated images of flow induced by Hill's spherical vortex, and the capabilities of the measurement technique were demonstrated empirically through volumetric reconstructions of the 3D trajectories of particles and highly non-spherical, 5 mm zooplankton

Single-camera three-dimensional tracking of natural particulate and zooplankton

We develop and characterize an image processing algorithm to adapt single-camera defocusing digital particle image velocimetry (DDPIV) for three-dimensional (3D) particle tracking velocimetry (PTV) of natural particulates, such as those present in the ocean. The conventional DDPIV technique is extended to facilitate tracking of non-uniform, non-spherical particles within a volume depth an order of magnitude larger than current single-camera applications (i.e. 10 cm  ×  10 cm  ×  24 cm depth) by a dynamic template matching method. This 2D cross-correlation method does not rely on precise determination of the centroid of the tracked objects. To accommodate the broad range of particle number densities found in natural marine environments, the performance of the measurement technique at higher particle densities has been improved by utilizing the time-history of tracked objects to inform 3D reconstruction. The developed processing algorithms were analyzed using synthetically generated images of flow induced by Hill's spherical vortex, and the capabilities of the measurement technique were demonstrated empirically through volumetric reconstructions of the 3D trajectories of particles and highly non-spherical, 5 mm zooplankton

Development of growth equations from longitudinal studies of body weight and height in the full term and preterm neonate: From birth to four years postnatal age

Physiologically based pharmacokinetic (PBPK) models are developed from compound-independent information to describe important anatomical and physiological characteristics of an individual or population of interest. Modeling pediatric populations is challenging because of the rapid changes that occur during growth, particularly in the first few weeks and months after birth. Neonates who are born premature pose several unique challenges in PBPK model development. To provide appropriate descriptions for body weight (BW) and height (Ht) for age and appropriate incremental gains in PBPK models of the developing preterm and full term neonate, anthropometric measurements collected longitudinally from 1,063 preterm and 158 full term neonates were combined with 2,872 cross-sectional measurements obtained from the NHANES 2007–2010 survey. Age-specific polynomial growth equations for BW and Ht were created for male and female neonates with corresponding gestational birth ages of 25, 28, 31, 34, and 40 weeks. Model-predicted weights at birth were within 20% of published fetal/neonatal reference standards. In comparison to full term neonates, postnatal gains in BW and Ht were slower in preterm subgroups, particularly in those born at earlier gestational ages. Catch up growth for BW in neonates born at 25, 28, 31, and 34 weeks gestational age was complete by 13, 8, 6, and 2 months of life (males) and by 10, 6, 5, and 2 months of life (females), respectively. The polynomial growth equations reported in this paper represent extrauterine growth in full term and preterm neonates and differ from the intrauterine growth standards that were developed for the healthy unborn fetus