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  • 1
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    Efficient tumour formation by single human melanoma cells (2008)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2008-12-05
    Beschreibung: A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1-0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg(-/-)) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single-cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597380/" 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/PMC2597380/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quintana, Elsa -- Shackleton, Mark -- Sabel, Michael S -- Fullen, Douglas R -- Johnson, Timothy M -- Morrison, Sean J -- 5P60-DK20572/DK/NIDDK NIH HHS/ -- CA46592/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Dec 4;456(7222):593-8. doi: 10.1038/nature07567.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052619" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *Cell Count ; Humans ; Interleukin Receptor Common gamma Subunit/deficiency/genetics ; Melanoma/*pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; *Neoplasm Transplantation ; Neoplastic Stem Cells/pathology ; *Transplantation, Heterologous
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    NLRX1 is a regulator of mitochondrial antiviral immunity (2008)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2008-01-18
    Beschreibung: The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus-induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen-associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, Chris B -- Bergstralh, Daniel T -- Duncan, Joseph A -- Lei, Yu -- Morrison, Thomas E -- Zimmermann, Albert G -- Accavitti-Loper, Mary A -- Madden, Victoria J -- Sun, Lijun -- Ye, Zhengmao -- Lich, John D -- Heise, Mark T -- Chen, Zhijian -- Ting, Jenny P-Y -- England -- Nature. 2008 Jan 31;451(7178):573-7. doi: 10.1038/nature06501. Epub 2008 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology-Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18200010" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adaptor Proteins, Signal Transducing/antagonists & inhibitors/metabolism ; Animals ; Cell Line ; Cloning, Molecular ; Computational Biology ; Humans ; Interferon-beta/biosynthesis/genetics/metabolism ; Mice ; Mitochondria/*immunology/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; NF-kappa B/metabolism ; Protein Binding ; Protein Transport ; RNA, Small Interfering/genetics/metabolism ; Signal Transduction ; Virus Replication ; Viruses/*immunology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    Human-specific gain of function in a developmental enhancer (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2008-09-06
    Beschreibung: Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658639/" 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/PMC2658639/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prabhakar, Shyam -- Visel, Axel -- Akiyama, Jennifer A -- Shoukry, Malak -- Lewis, Keith D -- Holt, Amy -- Plajzer-Frick, Ingrid -- Morrison, Harris -- Fitzpatrick, David R -- Afzal, Veena -- Pennacchio, Len A -- Rubin, Edward M -- Noonan, James P -- 1-F32-GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367-02/GM/NIGMS NIH HHS/ -- HG003988/HG/NHGRI NIH HHS/ -- HL066681/HL/NHLBI NIH HHS/ -- MC_U127561093/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1346-50. doi: 10.1126/science.1159974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772437" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Base Sequence ; Binding Sites ; Body Patterning/*genetics ; Conserved Sequence ; Embryonic Development ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Extremities/*embryology ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Humans ; Limb Buds/embryology/metabolism ; Macaca mulatta/genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; PAX9 Transcription Factor/metabolism ; Pan troglodytes/genetics ; Selection, Genetic ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    H2S induces a suspended animation-like state in mice (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2005-04-23
    Beschreibung: Mammals normally maintain their core body temperature (CBT) despite changes in environmental temperature. Exceptions to this norm include suspended animation-like states such as hibernation, torpor, and estivation. These states are all characterized by marked decreases in metabolic rate, followed by a loss of homeothermic control in which the animal's CBT approaches that of the environment. We report that hydrogen sulfide can induce a suspended animation-like state in a nonhibernating species, the house mouse (Mus musculus). This state is readily reversible and does not appear to harm the animal. This suggests the possibility of inducing suspended animation-like states for medical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blackstone, Eric -- Morrison, Mike -- Roth, Mark B -- GM48435/GM/NIGMS NIH HHS/ -- T32 AG00057/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2005 Apr 22;308(5721):518.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15845845" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Basal Metabolism/*drug effects ; Behavior, Animal/drug effects ; Body Temperature/*drug effects ; Carbon Dioxide/metabolism ; Dose-Response Relationship, Drug ; Estivation ; Female ; Hibernation ; Hydrogen Sulfide/*pharmacology/toxicity ; Mice ; Mice, Inbred C57BL ; Oxygen Consumption/drug effects ; Temperature
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Statistical Analysis of the AIAA Drag Prediction Workshop CFD Solutions (2007)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: The first AIAA Drag Prediction Workshop (DPW), held in June 2001, evaluated the results from an extensive N-version test of a collection of Reynolds-Averaged Navier-Stokes CFD codes. The code-to-code scatter was more than an order of magnitude larger than desired for design and experimental validation of cruise conditions for a subsonic transport configuration. The second AIAA Drag Prediction Workshop, held in June 2003, emphasized the determination of installed pylon-nacelle drag increments and grid refinement studies. The code-to-code scatter was significantly reduced compared to the first DPW, but still larger than desired. However, grid refinement studies showed no significant improvement in code-to-code scatter with increasing grid refinement. The third AIAA Drag Prediction Workshop, held in June 2006, focused on the determination of installed side-of-body fairing drag increments and grid refinement studies for clean attached flow on wing alone configurations and for separated flow on the DLR-F6 subsonic transport model. This report compares the transonic cruise prediction results of the second and third workshops using statistical analysis.
    Schlagwort(e): Fluid Mechanics and Thermodynamics
    Materialart: NATO-RTO AVT-147 Symposium on Computational Uncertainty in Military Vehicle Design; Dec 03, 2007 - Dec 06, 2007; Athens; Greece
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
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    Drag Prediction for the DLR-F6 Wing/Body and DPW Wing using CFL3D and OVERFLOW Overset Mesh (2007)
    In:  CASI
    Details
    Publikationsdatum: 2019-07-13
    Beschreibung: A series of overset grids was generated in response to the 3rd AIAA CFD Drag Prediction Workshop (DPW-III) which preceded the 25th Applied Aerodynamics Conference in June 2006. DPW-III focused on accurate drag prediction for wing/body and wing-alone configurations. The grid series built for each configuration consists of a coarse, medium, fine, and extra-fine mesh. The medium mesh is first constructed using the current state of best practices for overset grid generation. The medium mesh is then coarsened and enhanced by applying a factor of 1.5 to each (I,J,K) dimension. The resulting set of parametrically equivalent grids increase in size by a factor of roughly 3.5 from one level to the next denser level. CFD simulations were performed on the overset grids using two different RANS flow solvers: CFL3D and OVERFLOW. The results were post-processed using Richardson extrapolation to approximate grid converged values of lift, drag, pitching moment, and angle-of-attack at the design condition. This technique appears to work well if the solution does not contain large regions of separated flow (similar to that seen n the DLR-F6 results) and appropriate grid densities are selected. The extra-fine grid data helped to establish asymptotic grid convergence for both the OVERFLOW FX2B wing/body results and the OVERFLOW DPW-W1/W2 wing-alone results. More CFL3D data is needed to establish grid convergence trends. The medium grid was utilized beyond the grid convergence study by running each configuration at several angles-of-attack so drag polars and lift/pitching moment curves could be evaluated. The alpha sweep results are used to compare data across configurations as well as across flow solvers. With the exception of the wing/body drag polar, the two codes compare well qualitatively showing consistent incremental trends and similar wing pressure comparisons.
    Schlagwort(e): Fluid Mechanics and Thermodynamics
    Materialart: AIAA Paper 2007-257 , 45th AIAA Aerospace Sciences Meeting and Exhibit; Jan 08, 2007 - Jan 11, 2007; Reno, NV; United States
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    ISS Internal Active Thermal Control System (IATCS) Coolant Remediation Project (2005)
    In:  CASI
    Details
    Publikationsdatum: 2019-08-15
    Beschreibung: The IATCS coolant has experienced a number of anomalies in the time since the US Lab was first activated on Flight 5A in February 2001. These have included: 1) a decrease in coolant pH, 2) increases in inorganic carbon, 3) a reduction in phosphate buffer concentration, 4) an increase in dissolved nickel and precipitation of nickel salts, and 5) increases in microbial concentration. These anomalies represent some risk to the system, have been implicated in some hardware failures and are suspect in others. The ISS program has conducted extensive investigations of the causes and effects of these anomalies and has developed a comprehensive program to remediate the coolant chemistry of the on-orbit system as well as provide a robust and compatible coolant solution for the hardware yet to be delivered. The remediation steps include changes in the coolant chemistry specification, development of a suite of new antimicrobial additives, and development of devices for the removal of nickel and phosphate ions from the coolant. This paper presents an overview of the anomalies, their known and suspected system effects, their causes, and the actions being taken to remediate the coolant.
    Schlagwort(e): Fluid Mechanics and Thermodynamics
    Materialart: SAE-051CES-279 , 2005 International Conference on Environmental Systems (ICES) 35th Annual Meeting; Jul 11, 2005 - Jul 14, 2005; Rome; Italy
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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