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  • Electronics and Electrical Engineering  (6)
  • Gene Expression Profiling  (2)
  • 2010-2014  (8)
  • 1980-1984
  • 2012  (8)
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  • 2010-2014  (8)
  • 1980-1984
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  • 2012  (8)
  • 1
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    The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-03-31
    Beschreibung: 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〉
    Schlagwort(e): 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
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von 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
    Publikationsdatum: 2012-01-24
    Beschreibung: 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〉
    Schlagwort(e): 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
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
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  • 3
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    Performance of Large Format Transition Edge Sensor Microcalorimeter Arrays (2012)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: We have produced a variety of superconducting transition edge sensor array designs for microcalorimetric detection of x-rays. Arrays are characterized with a time division SQUID multiplexer such that greater than 10 devices from an array can be measured in the same cooldown. Designs include kilo pixel scale arrays of relatively small sensors (-75 micron pitch) atop a thick metal heatsinking layer as well as arrays of membrane-isolated devices on 250 micron and up to 600 micron pitch. We discuss fabrication and performance of microstripline wiring at the small scales achieved to date. We also address fabrication issues with reduction of absorber contact area in small devices.
    Schlagwort(e): Electronics and Electrical Engineering
    Materialart: GSFC.CP.7547.2013 , Applied Superconductivity Conference; Oct 08, 2012 - Oct 12, 2012; Portland, OR; United States
    Format: application/pdf
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  • 4
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    Single Pixel Characterization of X-Ray TES Microcalorimeter Under AC Bias at MHz Frequencies (2012)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: In this paper we present the progress made at SRON in the read-out of GSFC x-ray transition-edge sensor (TES) micro-calorimeters in the frequency domain. The experiments reported so far, whose aim was to demonstrate an energy resolution of 2eV at 6 keV with a TES acting as a modulator, were carried out at frequencies below 700 kHz using a standard flux locked loop (FLL) SQUID read-out scheme. The TES read-out suffered from the use of sub-optimal circuit components, large parasitic inductances, low quality factor resonators and poor magnetic field shielding. We have developed a novel experimental set-up, which allows us to test several read-out schemes in a single cryogenic run. In this set-up, the TES pixels are coupled via superconducting transformers to 18 high-Q lithographic LC filters with resonant frequencies ranging between 2 and 5 MHz. The signal is amplified by a two-stage SQUID current sensor and baseband feedback is used to overcome the limited SQUID dynamic range. We study the single pixel performance as a function of TES bias frequency, voltage and perpendicular magnetic field.
    Schlagwort(e): Electronics and Electrical Engineering
    Materialart: GSFC.ABS.01036.2012 , Applied Superconductivity Conference; Oct 07, 2012 - Oct 11, 2012; Portland, OR; United States
    Format: application/pdf
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  • 5
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    Study of the Dependency on Magnetic Field and Bias Voltage of an AC-Biased TES Microcalorimeter (2012)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: At SRON we are studying the performance of a Goddard Space Flight Center single pixel TES microcalorimeter operated in an AC bias configuration. For x-ray photons at 6 keV the pixel shows an x-ray energy resolution Delta E(sub FWHM) = 3.7 eV, which is about a factor 2 worse than the energy resolution observed in an identical DC-biased pixel. In order to better understand the reasons for this discrepancy we characterized the detector as a function of temperature, bias working point and applied perpendicular magnetic field. A strong periodic dependency of the detector noise on the TES AC bias voltage is measured. We discuss the results in the framework of the recently observed weak-link behaviour of a TES microcalorimeter.
    Schlagwort(e): Electronics and Electrical Engineering
    Materialart: GSFC.JA.7035.2012 , Journal of Low Temperature Physics; 167; 4-Mar; 185-189
    Format: application/pdf
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  • 6
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    Fabrication and Performance of Large Format Transition Edge Sensor Microcalorimeter Arrays (2012)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-19
    Beschreibung: We have produced a variety of superconducting transition edge sensor array designs for microcalorimetric detection of x-rays. Designs include kilopixel scale arrays of relatively small sensors (~75 micron pitch) atop a thick metal heatsinking layer as well as arrays of membrane-isolated devices on 250 micron pitch and smaller arrays of devices up to 600 micron pitch. We discuss the fabrication techniques used for each type of array focusing on unique aspects where processes vary to achieve the particular designs and required device parameters. For example, we evaluate various material combinations in the production of the thick metal heatsinking, including superconducting and normal metal adhesion layers. We also evaluate the impact of added heatsinking on the membrane isolated devices as it relates to basic device parameters. Arrays can be characterized with a time division SQUID multiplexer such that greater than 10 devices from an array can be measured in the same cooldown. Device parameters can be measured simultaneously so that environmental events such as thermal drifts or changes in magnetic fields can be controlled. For some designs, we will evaluate the uniformity of parameters impacting the intrinsic performance of the microcalorimeters under bias in these arrays and assess the level of thermal crosstalk.
    Schlagwort(e): Electronics and Electrical Engineering
    Materialart: GSFC.ABS.01103.2012 , Applied Superconductivity Conference; Oct 08, 2012 - Oct 12, 2012; Portland, OR; United States
    Format: application/pdf
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  • 7
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    Large Format Transition Edge Sensor Microcalorimeter Arrays (2012)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: We have produced a variety of superconducting transition edge sensor array designs for microcalorimetric detection of x-rays. Designs include kilopixel scale arrays of relatively small sensors (approximately 75 micron pitch) atop a thick metal heat sinking layer as well as arrays of membrane-isolated devices on 250 micron and up to 600 micron pitch. We discuss fabrication and performance of microstripline wiring at the small scales achieved to date. We also address fabrication issues with reduction of absorber contact area in small devices.
    Schlagwort(e): Electronics and Electrical Engineering
    Materialart: GSFC.OVPR.7473.2012 , Applied Superconductivity Conference; Oct 08, 2012 - Oct 12, 2012; Portland, OR; United States
    Format: application/pdf
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  • 8
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    Fabrication of Microstripline Wiring for Large Format Transition Edge Sensor Arrays (2012)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: We have developed a process to integrate microstripline wiring with transition edge sensors (TES). The process includes additional layers for metal-etch stop and dielectric adhesion to enable recovery of parameters achieved in non-microstrip pixel designs. We report on device parameters in close-packed TES arrays achieved with the microstrip process including R(sub n), G, and T(sub c) uniformity. Further, we investigate limits of this method of producing high-density, microstrip wiring including critical current to determine the ultimate scalability of TES arrays with two layers of wiring.
    Schlagwort(e): Electronics and Electrical Engineering
    Materialart: GSFC.JA.7324.2012 , GSFC-E-DAA-TN9557 , Journal of Low Temperature Physics; 167; 4-Mar; 547-553
    Format: application/pdf
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