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  • 1
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    Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-11
    Description: The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems. The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885001/" 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/PMC2885001/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carvajal-Vergara, Xonia -- Sevilla, Ana -- D'Souza, Sunita L -- Ang, Yen-Sin -- Schaniel, Christoph -- Lee, Dung-Fang -- Yang, Lei -- Kaplan, Aaron D -- Adler, Eric D -- Rozov, Roye -- Ge, Yongchao -- Cohen, Ninette -- Edelmann, Lisa J -- Chang, Betty -- Waghray, Avinash -- Su, Jie -- Pardo, Sherly -- Lichtenbelt, Klaske D -- Tartaglia, Marco -- Gelb, Bruce D -- Lemischka, Ihor R -- 5R01GM078465/GM/NIGMS NIH HHS/ -- R01 GM078465/GM/NIGMS NIH HHS/ -- R01 GM078465-03/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jun 10;465(7299):808-12. doi: 10.1038/nature09005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Gene and Cell Medicine, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA. xcarvajal@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535210" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cells, Cultured ; Embryonic Stem Cells/metabolism ; Enzyme Activation ; Female ; Fibroblasts/metabolism/pathology ; Gene Expression Profiling ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/enzymology/metabolism/*pathology ; LEOPARD Syndrome/drug therapy/metabolism/*pathology ; Male ; Mitogen-Activated Protein Kinases/metabolism ; *Models, Biological ; Myocytes, Cardiac/metabolism/pathology ; NFATC Transcription Factors/genetics/metabolism ; Octamer Transcription Factor-3/genetics ; Phosphoproteins/analysis ; Polymerase Chain Reaction ; *Precision Medicine ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/metabolism ; SOXB1 Transcription Factors/genetics
    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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    The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-03-12
    Description: The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFalpha-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFalpha-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFalpha signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFalpha-mediated pathologies and conditions, including rheumatoid arthritis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104397/" 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/PMC3104397/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Wei -- Lu, Yi -- Tian, Qing-Yun -- Zhang, Yan -- Guo, Feng-Jin -- Liu, Guang-Yi -- Syed, Nabeel Muzaffar -- Lai, Yongjie -- Lin, Edward Alan -- Kong, Li -- Su, Jeffrey -- Yin, Fangfang -- Ding, Ai-Hao -- Zanin-Zhorov, Alexandra -- Dustin, Michael L -- Tao, Jian -- Craft, Joseph -- Yin, Zhinan -- Feng, Jian Q -- Abramson, Steven B -- Yu, Xiu-Ping -- Liu, Chuan-ju -- AI43542/AI/NIAID NIH HHS/ -- AR040072/AR/NIAMS NIH HHS/ -- AR050620/AR/NIAMS NIH HHS/ -- AR053210/AR/NIAMS NIH HHS/ -- GM061710/GM/NIGMS NIH HHS/ -- R01 AI030165/AI/NIAID NIH HHS/ -- R01 AI030165-20/AI/NIAID NIH HHS/ -- R01 GM061710/GM/NIGMS NIH HHS/ -- R01 GM061710-08/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):478-84. doi: 10.1126/science.1199214. Epub 2011 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Orthopaedic Surgery, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, NY 10003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21393509" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/metabolism/pharmacology/therapeutic use ; Arthritis, Experimental/*drug therapy/*immunology/pathology/physiopathology ; Cartilage, Articular/metabolism/pathology ; Female ; Humans ; Intercellular Signaling Peptides and ; Proteins/chemistry/genetics/*metabolism/therapeutic use ; Ligands ; Male ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Protein Interaction Domains and Motifs ; Receptors, Tumor Necrosis Factor, Type I/genetics/*metabolism ; Receptors, Tumor Necrosis Factor, Type II/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism/pharmacology/therapeutic use ; Recombinant Proteins/therapeutic use ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology/physiology ; Tumor Necrosis Factor-alpha/*metabolism ; Young Adult
    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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  • 3
    Electronic Resource
    Electronic Resource
    Effect of pore structure on char oxidation kinetics (1985)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 31 (1985), S. 973-981 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Prior studies have demonstrated that char gasification rates vary with conversion, showing a maximum at an intermediate level. In this work experimentally determined char-air reaction rates and corresponding pore structures are compared to assess the applicability of a previously proposed random pore model and to extract pertinent chemical and physical parameters. Results on six different chars are presented and analyzed to obtain structure parameters, intrinsic kinetics, and activation energies. Agreement between two independent evaluations of the structure parameters demonstrates the degree of applicability of the random pore model and supports the view that rate variations with conversion are controlled by pore structural changes, even though overall rates also include contributions of intrinsic reactivity.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690310614
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of chemisorbed oxygen on char reactivity (1985)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 31 (1985), S. 1725-1727 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690311017
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  • 5
    Electronic Resource
    Electronic Resource
    Porosity effects on catalytic char oxidation. Part I: A catalyst deposition model (1985)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 31 (1985), S. 957-964 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Six char samples generated from two coals were impregnated by solutions with different concentrations of Na2CO3 and /or K2CO3. The catalyst solution penetration was studied, the catalyst uptake was measured, and the effects of impregnation on the char pore structure were determined experimentally. The results indicate that the impregnated catalysts reside only on particle exteriors without significant penetration. The overall rate of reaction is therfore the combination of catalytic reaction on particle exteriors and noncatalytic reaction on the pore surfaces inside the particle. A kinetic model is presented that takes these findings into account.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690310612
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  • 6
    Electronic Resource
    Electronic Resource
    Porosity effects on catalytic char oxidation. Part II: Experimental results (1985)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 31 (1985), S. 965-972 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Oxidation rates of Na2CO3- and K2CO3-impregnated char samples were measured in an isothermal kinetic control regime. The results were analyzed by a previously developed model to extract the intrinsic catalytic reactivities, freed from superimposed noncatalytic and structural effects. Although the overall catalyzed rates are only several times greater than their uncatalyzed counterparts, the intrinsic catalytic rates were found to be four orders of magnitude greater. The results further indicate that the function of the catalyst is to increase the number of active sites without affecting the activation energy. The overall reaction kinetics are demonstrated to contain the combined contributions of both catalytic and noncatalytic reactions, and in this context the effects of multiple catalysts as well as of the pore structure development during reaction can be understood and interpreted.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690310613
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  • 7
    Electronic Resource
    Electronic Resource
    Ferroelectric and piezoelectric properties of nylon 11/poly(vinylidene fluoride) bilaminate films (1995)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 33 (1995), S. 85-91 
    Details
    ISSN: 0887-6266
    Keywords: ferroelectricity ; piezoelectricity ; bilaminate ; nylon 11 ; PVF2 ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The ferroelectric and piezoelectric properties of a new class of polymer ferroelectric and piezoelectric materials, nylon 11/polyvinylidene fluoride (PVF2) bilaminate films, prepared by a co-melt-pressing method, is presented. The bilaminate films exhibit typical ferroelectric D-E hysteresis behavior with a remanent polarization, Pr, of about 75 mC/m2, which is higher than the value of 52 mC/m2 observed for PVF2 or nylon 11 films measured under the same conditions. The coercive field, Ec, of the bilaminate films is ∼ 78 MV/m, which is higher than that of either PVF2 or nylon 11 films. Measurements of the temperature dependence of the piezoelectric strain coefficient, d31, and the piezoelectric stress coefficient, e31, were also carried out. The bilaminate films exhibit a piezoelectric strain coefficient, d31, of 41 pC/N at room temperature, which is significantly higher than the PVF2 films (25 pC/N) and the nylon 11 films (3.1 pC/N). When the temperature is increased to 110°C, d31 of the bilaminate films reaches a maximum value of 63 pC/N, more than five times that of PVF2 (11 pC/N) and more than four times that of nylon 11 (14 pC/N) at the same temperature. The piezoelectric stress coefficient, e31, of the bilaminate films shows a value of 109 mC/m2 at room temperature, almost twice that of the PVF2 films (59 mC/m2) and about 18 times that of the nylon 11 films (6.2 mC/m2). Measurement of the temperature dependence of the hydrostatic piezoelectric coefficient, dh, of the bilaminate films also shows an enhancement with respect to the individual components, PVF2 and nylon 11. ©1995 John Wiley & Sons, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/polb.1995.090330110
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  • 8
    Electronic Resource
    Electronic Resource
    The rate of methyl radical decomposition at high temperatures and pressuresDedicated to the memory of R.A. Back. (1994)
    New York, NY : Wiley-Blackwell
    International Journal of Chemical Kinetics 26 (1994), S. 159-169 
    Details
    ISSN: 0538-8066
    Keywords: Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rate constants are calculated for CH3 (+ Ar) ⇄ CH2 + H (+ Ar) at the limiting low-pressure, the limiting high-pressure, as well as the intermediate fall-off ranges. The results show that published experimental rate constants for methyl dissociation correspond to the fall-off region close to the low-pressure limit. At the low-pressure limit the activation energy is less than the bond dissociation energy, in agreement with experimental results. Forward and backward rate coefficients at the high-pressure limit are compared with other theoretical calculations. More theoretical and experimental work is necessary to understand the reverse reaction and its competing reactions, as well as the decomposition channel leading to CH + H2. © 1994 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/kin.550260116
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