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  • Fluid Mechanics and Thermodynamics  (5)
  • Gene Expression Profiling  (2)
  • Chemistry
  • Geophysics
  • 2010-2014  (7)
  • 1
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    The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-03-31
    Description: The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320027/" 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/PMC3320027/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barretina, Jordi -- Caponigro, Giordano -- Stransky, Nicolas -- Venkatesan, Kavitha -- Margolin, Adam A -- Kim, Sungjoon -- Wilson, Christopher J -- Lehar, Joseph -- Kryukov, Gregory V -- Sonkin, Dmitriy -- Reddy, Anupama -- Liu, Manway -- Murray, Lauren -- Berger, Michael F -- Monahan, John E -- Morais, Paula -- Meltzer, Jodi -- Korejwa, Adam -- Jane-Valbuena, Judit -- Mapa, Felipa A -- Thibault, Joseph -- Bric-Furlong, Eva -- Raman, Pichai -- Shipway, Aaron -- Engels, Ingo H -- Cheng, Jill -- Yu, Guoying K -- Yu, Jianjun -- Aspesi, Peter Jr -- de Silva, Melanie -- Jagtap, Kalpana -- Jones, Michael D -- Wang, Li -- Hatton, Charles -- Palescandolo, Emanuele -- Gupta, Supriya -- Mahan, Scott -- Sougnez, Carrie -- Onofrio, Robert C -- Liefeld, Ted -- MacConaill, Laura -- Winckler, Wendy -- Reich, Michael -- Li, Nanxin -- Mesirov, Jill P -- Gabriel, Stacey B -- Getz, Gad -- Ardlie, Kristin -- Chan, Vivien -- Myer, Vic E -- Weber, Barbara L -- Porter, Jeff -- Warmuth, Markus -- Finan, Peter -- Harris, Jennifer L -- Meyerson, Matthew -- Golub, Todd R -- Morrissey, Michael P -- Sellers, William R -- Schlegel, Robert -- Garraway, Levi A -- DP2 OD002750/OD/NIH HHS/ -- DP2 OD002750-01/OD/NIH HHS/ -- R33 CA126674/CA/NCI NIH HHS/ -- R33 CA126674-04/CA/NCI NIH HHS/ -- R33 CA155554/CA/NCI NIH HHS/ -- R33 CA155554-02/CA/NCI NIH HHS/ -- England -- Nature. 2012 Mar 28;483(7391):603-7. doi: 10.1038/nature11003.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460905" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Lineage ; Chromosomes, Human/genetics ; Clinical Trials as Topic/methods ; *Databases, Factual ; Drug Screening Assays, Antitumor/*methods ; *Encyclopedias as Topic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, ras/genetics ; Genome, Human/genetics ; Genomics ; Humans ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; *Models, Biological ; Neoplasms/*drug therapy/genetics/metabolism/*pathology ; Pharmacogenetics ; Plasma Cells/cytology/drug effects/metabolism ; Precision Medicine/methods ; Receptor, IGF Type 1/antagonists & inhibitors/metabolism ; Receptors, Aryl Hydrocarbon/genetics/metabolism ; Sequence Analysis, DNA ; Topoisomerase Inhibitors/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-01-24
    Description: Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278668/" 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/PMC3278668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boyden, Lynn M -- Choi, Murim -- Choate, Keith A -- Nelson-Williams, Carol J -- Farhi, Anita -- Toka, Hakan R -- Tikhonova, Irina R -- Bjornson, Robert -- Mane, Shrikant M -- Colussi, Giacomo -- Lebel, Marcel -- Gordon, Richard D -- Semmekrot, Ben A -- Poujol, Alain -- Valimaki, Matti J -- De Ferrari, Maria E -- Sanjad, Sami A -- Gutkin, Michael -- Karet, Fiona E -- Tucci, Joseph R -- Stockigt, Jim R -- Keppler-Noreuil, Kim M -- Porter, Craig C -- Anand, Sudhir K -- Whiteford, Margo L -- Davis, Ira D -- Dewar, Stephanie B -- Bettinelli, Alberto -- Fadrowski, Jeffrey J -- Belsha, Craig W -- Hunley, Tracy E -- Nelson, Raoul D -- Trachtman, Howard -- Cole, Trevor R P -- Pinsk, Maury -- Bockenhauer, Detlef -- Shenoy, Mohan -- Vaidyanathan, Priya -- Foreman, John W -- Rasoulpour, Majid -- Thameem, Farook -- Al-Shahrouri, Hania Z -- Radhakrishnan, Jai -- Gharavi, Ali G -- Goilav, Beatrice -- Lifton, Richard P -- KL2 RR024138/RR/NCRR NIH HHS/ -- KL2 RR024138-07/RR/NCRR NIH HHS/ -- P30 DK079310/DK/NIDDK NIH HHS/ -- P30 DK079310-04S1/DK/NIDDK NIH HHS/ -- P30-DK079310/DK/NIDDK NIH HHS/ -- UL1-RR024139/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 22;482(7383):98-102. doi: 10.1038/nature10814.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22266938" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Blood Pressure/genetics ; Carrier Proteins/chemistry/*genetics ; Cohort Studies ; Cullin Proteins/chemistry/*genetics ; Electrolytes ; Exons/genetics ; Female ; Gene Expression Profiling ; Genes, Dominant/genetics ; Genes, Recessive/genetics ; Genotype ; Homeostasis/genetics ; Humans ; Hydrogen-Ion Concentration ; Hypertension/complications/*genetics/physiopathology ; Male ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Phenotype ; Potassium/metabolism ; Pseudohypoaldosteronism/complications/*genetics/physiopathology ; Sodium Chloride/metabolism ; Water-Electrolyte Imbalance/complications/*genetics/physiopathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Flow Property Measurement Using Laser-Induced Fluorescence in the NASA Ames Interaction Heating Facility (2011)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The spectroscopic diagnostic technique of two photon absorption laser-induced fluorescence (TALIF) of atomic species has been applied to single-point measurements of velocity and static temperature in the NASA Ames Interaction Heating Facility (IHF) arc jet. Excitation spectra of atomic oxygen and nitrogen were recorded while scanning a tunable dye laser over the absorption feature. Thirty excitation spectra were acquired during 8 arc jet runs at two facility operating conditions; the number of scans per run varied between 2 and 6. Curve fits to the spectra were analyzed to recover their Doppler shifts and widths, from which the flow velocities and static temperatures, respectively, were determined. An increase in the number of independent flow property pairs from each as-measured scan was obtained by extracting multiple lower-resolution scans. The larger population sample size enabled the mean property values and their uncertainties for each run to be characterized with greater confidence. The average plus or minus 2 sigma uncertainties in the mean velocities and temperatures for all 8 runs were plus or minus 1.4% and plus or minus 11%, respectively.
    Keywords: Fluid Mechanics and Thermodynamics
    Type: ARC-E-DAA-TN2704 , 49th Aerospace Sciences Meeting and Exhibit; Jan 04, 2011 - Jan 07, 2011; Orlando, FL; United States
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  • 4
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    Microbiological Validation of the IVGEN System (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: The principal purpose of this report is to describe a validation process that can be performed in part on the ground prior to launch, and in space for the IVGEN system. The general approach taken is derived from standard pharmaceutical industry validation schemes modified to fit the special requirements of in-space usage.
    Keywords: Fluid Mechanics and Thermodynamics
    Type: GRC-E-DAA-TN7775 , NASA/CR-2013-216500 , E-18638
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  • 5
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    Operation of an ADR Using Helium Exchange Gas as a Substitute for a Failed Heat Switch (2014)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The Soft X-ray Spectrometer (SXS) is one of four instruments on the Japanese Astro-H mission, which is currently planned for launch in late 2015. The SXS will perform imaging spectroscopy in the soft X-ray band (0.3-12 keV) using a 6 6 pixel array of microcalorimeters cooled to 50 mK. The detectors are cooled by a 3-stage adiabatic demagnetization refrigerator (ADR) that rejects heat to either a superfluid helium tank (at 1.2 K) or to a 4.5 K Joule-Thomson (JT) cryocooler. Four gas-gap heat switches are used in the assembly to manage heat flow between the ADR stages and the heat sinks. The engineering model (EM) ADR was assembled and performance tested at NASA/GSFC in November 2011, and subsequently installed in the EM dewar at Sumitomo Heavy Industries, Japan. During the first cooldown in July 2012, a failure of the heat switch that linked the two colder stages of the ADR to the helium tank was observed. Operation of the ADR requires some mechanism for thermally linking the salt pills to the heat sink, and then thermally isolating them. With the failed heat switch unable to perform this function, an alternate plan was devised which used carefully controlled amounts of exchange gas in the dewar's guard vacuum to facilitate heat exchange. The process was successfully demonstrated in November 2012, allowing the ADR to cool the detectors to 50 mK for hold times in excess of 10 h. This paper describes the exchange-gas-assisted recycling process, and the strategies used to avoid helium contamination of the detectors at low temperature.
    Keywords: Fluid Mechanics and Thermodynamics
    Type: GSFC-E-DAA-TN23729 , Cryogenics; 64; 207-212
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  • 6
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    Pumping and Depressurizing of Insulation Materials (2010)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: The Fluids Testing and Technology Branch is a group that researches and tests efficient ways to use various Cryogenic Fluids, such as Liquid Nitrogen or Liquid Helium, in ground and space systems. Their main goal is to develop new technologies involving Cryogenic temperatures as well as making sure the existing technologies are understood. During my time here a lot of insulation testing has been done which is where insulation systems are tested for cryogenic systems that are in space for long durations.
    Keywords: Fluid Mechanics and Thermodynamics
    Type: KSC-2010-216
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  • 7
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    The Transition-Edge-Sensor Array for the Micro-X Sounding Rocket (2012)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: The Micro-X sounding rocket program will fly a 128-element array of transition-edge-sensor microcalorimeters to enable high-resolution X-ray imaging spectroscopy of the Puppis-A supernova remnant. To match the angular resolution of the optics while maximizing the field-of-view and retaining a high energy resolution (〈 4 eV at 1 keV), we have designed the pixels using 600 x 600 sq. micron Au/Bi absorbers, which overhang 140 x 140 sq. micron Mo/Au sensors. The data-rate capabilities of the rocket telemetry system require the pulse decay to be approximately 2 ms to allow a significant portion of the data to be telemetered during flight. Here we report experimental results from the flight array, including measurements of energy resolution, uniformity, and absorber thermalization. In addition, we present studies of test devices that have a variety of absorber contact geometries, as well as a variety of membrane-perforation schemes designed to slow the pulse decay time to match the telemetry requirements. Finally, we describe the reduction in pixel-to-pixel crosstalk afforded by an angle-evaporated Cu backside heatsinking layer, which provides Cu coverage on the four sidewalls of the silicon wells beneath each pixel.
    Keywords: Fluid Mechanics and Thermodynamics
    Type: GSFC.ABS.6327.2012 , Applied Superconductivity Conference; Oct 07, 2012 - Oct 11, 2012; Portland, OR; United States
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