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  • 1
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    Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-04-28
    Description: New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research -- Saxena, Richa -- Voight, Benjamin F -- Lyssenko, Valeriya -- Burtt, Noel P -- de Bakker, Paul I W -- Chen, Hong -- Roix, Jeffrey J -- Kathiresan, Sekar -- Hirschhorn, Joel N -- Daly, Mark J -- Hughes, Thomas E -- Groop, Leif -- Altshuler, David -- Almgren, Peter -- Florez, Jose C -- Meyer, Joanne -- Ardlie, Kristin -- Bengtsson Bostrom, Kristina -- Isomaa, Bo -- Lettre, Guillaume -- Lindblad, Ulf -- Lyon, Helen N -- Melander, Olle -- Newton-Cheh, Christopher -- Nilsson, Peter -- Orho-Melander, Marju -- Rastam, Lennart -- Speliotes, Elizabeth K -- Taskinen, Marja-Riitta -- Tuomi, Tiinamaija -- Guiducci, Candace -- Berglund, Anna -- Carlson, Joyce -- Gianniny, Lauren -- Hackett, Rachel -- Hall, Liselotte -- Holmkvist, Johan -- Laurila, Esa -- Sjogren, Marketa -- Sterner, Maria -- Surti, Aarti -- Svensson, Margareta -- Svensson, Malin -- Tewhey, Ryan -- Blumenstiel, Brendan -- Parkin, Melissa -- Defelice, Matthew -- Barry, Rachel -- Brodeur, Wendy -- Camarata, Jody -- Chia, Nancy -- Fava, Mary -- Gibbons, John -- Handsaker, Bob -- Healy, Claire -- Nguyen, Kieu -- Gates, Casey -- Sougnez, Carrie -- Gage, Diane -- Nizzari, Marcia -- Gabriel, Stacey B -- Chirn, Gung-Wei -- Ma, Qicheng -- Parikh, Hemang -- Richardson, Delwood -- Ricke, Darrell -- Purcell, Shaun -- F32 DK079466/DK/NIDDK NIH HHS/ -- F32 DK079466-01/DK/NIDDK NIH HHS/ -- K23 DK067288/DK/NIDDK NIH HHS/ -- K23 DK080145/DK/NIDDK NIH HHS/ -- K23 DK080145-01/DK/NIDDK NIH HHS/ -- K23 DK65978-04/DK/NIDDK NIH HHS/ -- K23-HL083102/HL/NHLBI NIH HHS/ -- U01 HG004171/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 1;316(5829):1331-6. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463246" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics ; Aged ; Alleles ; Blood Glucose/analysis ; Case-Control Studies ; Chromosome Mapping ; Chromosomes, Human, Pair 9/genetics ; Diabetes Mellitus, Type 2/*genetics ; Female ; Genetic Markers ; *Genetic Predisposition to Disease ; *Genome, Human ; Genotype ; Haplotypes ; Humans ; Insulin Resistance/genetics ; Insulin-Like Growth Factor Binding Proteins/genetics ; Introns ; Male ; Meta-Analysis as Topic ; Middle Aged ; *Polymorphism, Single Nucleotide ; Quantitative Trait, Heritable ; Triglycerides/*blood
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Ancestral monogamy shows kin selection is key to the evolution of eusociality (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-05-31
    Description: Close relatedness has long been considered crucial to the evolution of eusociality. However, it has recently been suggested that close relatedness may be a consequence, rather than a cause, of eusociality. We tested this idea with a comparative analysis of female mating frequencies in 267 species of eusocial bees, wasps, and ants. We found that mating with a single male, which maximizes relatedness, is ancestral for all eight independent eusocial lineages that we investigated. Mating with multiple males is always derived. Furthermore, we found that high polyandry (〉2 effective mates) occurs only in lineages whose workers have lost reproductive totipotency. These results provide the first evidence that monogamy was critical in the evolution of eusociality, strongly supporting the prediction of inclusive fitness theory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughes, William O H -- Oldroyd, Benjamin P -- Beekman, Madeleine -- Ratnieks, Francis L W -- New York, N.Y. -- Science. 2008 May 30;320(5880):1213-6. doi: 10.1126/science.1156108.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Integrative and Comparative Biology, University of Leeds, Leeds, LS2 9JT, UK. w.o.h.hughes@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18511689" target="_blank"〉PubMed〈/a〉
    Keywords: Altruism ; Animals ; Ants ; Bees ; *Biological Evolution ; Female ; Male ; Phylogeny ; *Sexual Behavior, Animal ; *Social Behavior ; Sociobiology ; Wasps
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Cancer regression in patients after transfer of genetically engineered lymphocytes (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-02
    Description: Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267026/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morgan, Richard A -- Dudley, Mark E -- Wunderlich, John R -- Hughes, Marybeth S -- Yang, James C -- Sherry, Richard M -- Royal, Richard E -- Topalian, Suzanne L -- Kammula, Udai S -- Restifo, Nicholas P -- Zheng, Zhili -- Nahvi, Azam -- de Vries, Christiaan R -- Rogers-Freezer, Linda J -- Mavroukakis, Sharon A -- Rosenberg, Steven A -- Z01 BC010763-01/Intramural NIH HHS/ -- Z01 SC003811-32/Intramural NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 6;314(5796):126-9. Epub 2006 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946036" target="_blank"〉PubMed〈/a〉
    Keywords: *Adoptive Transfer ; Adult ; Antigens, Neoplasm/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/therapeutic use ; Cells, Cultured ; Electroporation ; Female ; Genetic Engineering ; *Genetic Therapy ; HLA-A Antigens/immunology ; HLA-A2 Antigen ; Humans ; Interleukin-2/immunology/therapeutic use ; MART-1 Antigen ; Male ; Melanoma/immunology/secondary/*therapy ; Middle Aged ; Neoplasm Proteins/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/*genetics/*immunology ; Transduction, Genetic ; Transgenes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    A Simple, Powerful Method for Optimal Guidance of Spacecraft Formations (2005)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: One of the most interesting and challenging aspects of formation guidance law design is the coupling of the orbit design and the science return. The analyst s role is more complicated than simply to design the formation geometry and evolution. He or she is also involved in designing a significant portion of the science instrument itself. The effectiveness of the formation as a science instrument is intimately coupled with the relative geoniet,ry and evolution of the collection of spacecraft. Therefore, the science return can be maximized by optimizing the orbit design according to a performance metric relevant to the science mission goals. In this work, we present a simple method for optimal formation guidance that is applicable to missions whose performance metric, requirements, and constraints can be cast as functions that are explicitly dependent upon the orbit states and spacecraft relative positions and velocities. We present a general form for the cost and constraint functions, and derive their semi-analytic gradients with respect to the formation initial conditions. The gradients are broken down into two types. The first type are gradients of the mission specific performance metric with respect to formation geometry. The second type are derivatives of the formation geometry with respect to the orbit initial conditions. The fact that these two types of derivatives appear separately allows us to derive and implement a general framework that requires minimal modification to be applied to different missions or mission phases. To illustrate the applicability of the approach, we conclude with applications to twc missims: the Magnetospheric Mu!tiscale mission (MMS), a,nd the TJaser Interferometer Space Antenna (LISA).
    Keywords: Spacecraft Design, Testing and Performance
    Type: 595 Flight Mechanics Symposium; Oct 18, 2005 - Oct 20, 2005; Greenbelt, MD; United States
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  • 5
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    Structural Analysis and Testing of the Inflatable Re-entry Vehicle Experiment (IRVE) (2006)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The Inflatable Re-entry Vehicle Experiment (IRVE) is a 3.0 meter, 60 degree half-angle sphere cone, inflatable aeroshell experiment designed to demonstrate various aspects of inflatable technology during Earth re-entry. IRVE will be launched on a Terrier-Improved Orion sounding rocket from NASA s Wallops Flight Facility in the fall of 2006 to an altitude of approximately 164 kilometers and re-enter the Earth s atmosphere. The experiment will demonstrate exo-atmospheric inflation, inflatable structure leak performance throughout the flight regime, structural integrity under aerodynamic pressure and associated deceleration loads, thermal protection system performance, and aerodynamic stability. Structural integrity and dynamic response of the inflatable will be monitored with photogrammetric measurements of the leeward side of the aeroshell during flight. Aerodynamic stability and drag performance will be verified with on-board inertial measurements and radar tracking from multiple ground radar stations. In addition to demonstrating inflatable technology, IRVE will help validate structural, aerothermal, and trajectory modeling and analysis techniques for the inflatable aeroshell system. This paper discusses the structural analysis and testing of the IRVE inflatable structure. Equations are presented for calculating fabric loads in sphere cone aeroshells, and finite element results are presented which validate the equations. Fabric material properties and testing are discussed along with aeroshell fabrication techniques. Stiffness and dynamics tests conducted on a small-scale development unit and a full-scale prototype unit are presented along with correlated finite element models to predict the in-flight fundamental mod
    Keywords: Spacecraft Design, Testing and Performance
    Type: AIAA Paper 2006-1699 , 47th AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics, and Materials Conference; May 01, 2006 - May 04, 2006; Newport, RI; United States
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  • 6
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    Inflatable Re-Entry Vehicle Experiment (IRVE) Design Overview (2005)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Inflatable aeroshells offer several advantages over traditional rigid aeroshells for atmospheric entry. Inflatables offer increased payload volume fraction of the launch vehicle shroud and the possibility to deliver more payload mass to the surface for equivalent trajectory constraints. An inflatable s diameter is not constrained by the launch vehicle shroud. The resultant larger drag area can provide deceleration equivalent to a rigid system at higher atmospheric altitudes, thus offering access to higher landing sites. When stowed for launch and cruise, inflatable aeroshells allow access to the payload after the vehicle is integrated for launch and offer direct access to vehicle structure for structural attachment with the launch vehicle. They also offer an opportunity to eliminate system duplication between the cruise stage and entry vehicle. There are however several potential technical challenges for inflatable aeroshells. First and foremost is the fact that they are flexible structures. That flexibility could lead to unpredictable drag performance or an aerostructural dynamic instability. In addition, durability of large inflatable structures may limit their application. They are susceptible to puncture, a potentially catastrophic insult, from many possible sources. Finally, aerothermal heating during planetary entry poses a significant challenge to a thin membrane. NASA Langley Research Center and NASA's Wallops Flight Facility are jointly developing inflatable aeroshell technology for use on future NASA missions. The technology will be demonstrated in the Inflatable Re-entry Vehicle Experiment (IRVE). This paper will detail the development of the initial IRVE inflatable system to be launched on a Terrier/Orion sounding rocket in the fourth quarter of CY2005. The experiment will demonstrate achievable packaging efficiency of the inflatable aeroshell for launch, inflation, leak performance of the inflatable system throughout the flight regime, structural integrity when exposed to a relevant dynamic pressure and aerodynamic stability of the inflatable system. Structural integrity and structural response of the inflatable will be verified with photogrammetric measurements of the back side of the aeroshell in flight. Aerodynamic stability as well as drag performance will be verified with on board inertial measurements and radar tracking from multiple ground radar stations. The experiment will yield valuable information about zero-g vacuum deployment dynamics of the flexible inflatable structure with both inertial and photographic measurements. In addition to demonstrating inflatable technology, IRVE will validate structural, aerothermal, and trajectory modeling techniques for the inflatable. Structural response determined from photogrammetrics will validate structural models, skin temperature measurements and additional in-depth temperature measurements will validate material thermal performance models, and on board inertial measurements along with radar tracking from multiple ground radar stations will validate trajectory simulation models.
    Keywords: Spacecraft Design, Testing and Performance
    Type: AIAA Paper 2005-1636 , 18th AIAA Aerodynamic Decelerator Systems Technology Conference and Seminar; May 23, 2005 - May 26, 2005; Munich; Germany
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  • 7
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    Initial Assessment of the Ares I-X Launch Vehicle Upper Stage to Vibroacoustic Flight Environments (2008)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The Ares I launch vehicle will be NASA s first new launch vehicle since 1981. Currently in design, it will replace the Space Shuttle in taking astronauts to the International Space Station, and will eventually play a major role in humankind s return to the Moon and eventually to Mars. Prior to any manned flight of this vehicle, unmanned test readiness flights will be flown. The first of these readiness flights, named Ares I-X, is scheduled to be launched in April 2009. The NASA Glenn Research Center is responsible for the design, manufacture, test and analysis of the Ares I-X upper stage simulator (USS) element. As part of the design effort, the structural dynamic response of the Ares I-X launch vehicle to its vibroacoustic flight environments must be analyzed. The launch vehicle will be exposed to extremely high acoustic pressures during its lift-off and aerodynamic stages of flight. This in turn will cause high levels of random vibration on the vehicle's outer surface that will be transmitted to its interior. Critical flight equipment, such as its avionics and flight guidance components are susceptible to damage from this excitation. This study addresses the modelling, analysis and predictions from examining the structural dynamic response of the Ares I-X upper stage to its vibroacoustic excitations. A statistical energy analysis (SEA) model was used to predict the high frequency response of the vehicle at locations of interest. Key to this study was the definition of the excitation fields corresponding to lift off acoustics and the unsteady aerodynamic pressure fluctuations during flight. The predicted results will be used by the Ares I-X Project to verify the flight qualification status of the Ares I-X upper stage components.
    Keywords: Spacecraft Design, Testing and Performance
    Type: NASA/TM-2008-215167 , E-16408 , 14th International Congress on Sound and Vibration (ICSV14); Jul 09, 2007 - Jul 12, 2007; Cairns; Australia
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  • 8
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    Hardware Outgassing Certification (2007)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: This course will provide students with the understanding necessary to calculate certification requirements for and interpret the data from hardware undergoing vacuum bakeout. The fundamental physics that driv e hardware outgassing and contaminant deposition will be explained, a nd data reduction techniques will be applied to examples.
    Keywords: Spacecraft Design, Testing and Performance
    Type: 24th Space Simulation Conference; Nov 06, 2006 - Nov 09, 2006; Annapolis, MD; United States
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  • 9
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    Aerodynamic and Aeroelastic Characteristics of a Tension Cone Inflatable Aerodynamic Decelerator (2009)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The supersonic aerodynamic and aeroelastic characteristics of a tension cone inflatable aerodynamic decelerator were investigated by wind tunnel testing. Two sets of tests were conducted: one using rigid models and another using textile models. Tests using rigid models were conducted over a Mach number range from 1.65 to 4.5 at angles of attack from -12 to 20 degrees. The axial, normal, and pitching moment coefficients were found to be insensitive to Mach number over the tested range. The axial force coefficient was nearly constant (C(sub A) = 1.45 +/- 0.05) with respect to angle of attack. Both the normal and pitching moment coefficients were nearly linear with respect to angle of attack. The pitching moment coefficient showed the model to be statically stable about the reference point. Schlieren images and video showed a detached bow shock with no evidence of large regions of separated flow and/or embedded shocks at all Mach numbers investigated. Qualitatively similar static aerodynamic coefficient and flow visualization results were obtained using textile models at a Mach number of 2.5. Using inflatable textile models the torus pressure required to maintain the model in the fully-inflated configuration was determined. This pressure was found to be sensitive to details in the structural configuration of the inflatable models. Additional tests included surface pressure measurements on rigid models and deployment and inflation tests with inflatable models.
    Keywords: Spacecraft Design, Testing and Performance
    Type: AIAA Paper 2009-2967 , LF99-8534 , 20th AIAA Aerodynamic Decelerator Systems Technology Conference; May 04, 2009 - May 07, 2009; Seattle, WA; United States
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  • 10
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    Deployable Aeroshell Flexible Thermal Protection System Testing (2009)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Deployable aeroshells offer the promise of achieving larger aeroshell surface areas for entry vehicles than otherwise attainable without deployment. With the larger surface area comes the ability to decelerate high-mass entry vehicles at relatively low ballistic coefficients. However, for an aeroshell to perform even at the low ballistic coefficients attainable with deployable aeroshells, a flexible thermal protection system (TPS) is required that is capable of surviving reasonably high heat flux and durable enough to survive the rigors of construction handling, high density packing, deployment, aerodynamic loading and aerothermal heating. The Program for the Advancement of Inflatable Decelerators for Atmospheric Entry (PAIDAE) is tasked with developing the technologies required to increase the technology readiness level (TRL) of inflatable deployable aeroshells, and one of several of the technologies PAIDAE is developing for use on inflatable aeroshells is flexible TPS. Several flexible TPS layups were designed, based on commercially available materials, and tested in NASA Langley Research Center's 8 Foot High Temperature Tunnel (8ft HTT). The TPS layups were designed for, and tested at three different conditions that are representative of conditions seen in entry simulation analyses of inflatable aeroshell concepts. Two conditions were produced in a single run with a sting-mounted dual wedge test fixture. The dual wedge test fixture had one row of sample mounting locations (forward) at about half the running length of the top surface of the wedge. At about two thirds of the running length of the wedge, a second test surface drafted up at five degrees relative to the first test surface established the remaining running length of the wedge test fixture. A second row of sample mounting locations (aft) was positioned in the middle of the running length of the second test surface. Once the desired flow conditions were established in the test section the dual wedge test fixture, oriented at 5 degrees angle of attack down, was injected into the flow. In this configuration the aft sample mounting location was subjected to roughly twice the heat flux and surface pressure of the forward mounting location. The tunnel was run at two different conditions for the test series: 1) 'Low Pressure', and 2) 'High Pressure'. At 'Low Pressure' conditions the TPS layups were tested at 6W/cm2 and 11W/cm2 while at 'High Pressure' conditions the TPS layups were tested at 11W/cm2 and 20W/cm2. This paper details the test configuration of the TPS samples in the 8Ft HTT, the sample holder assembly, TPS sample layup construction, sample instrumentation, results from this testing, as well as lessons learned.
    Keywords: Spacecraft Design, Testing and Performance
    Type: LF99-8607 , 20th AIAA Aerodynamic Decelerator Systems Technology Conference; May 04, 2009 - May 07, 2009; Seattle, WA; United States
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