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  • American Institute of Physics (AIP)  (10)
  • Nature Publishing Group (NPG)  (3)
  • Institute of Physics (IOP)  (2)
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  • 1
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    Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5 (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-24
    Description: Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues. This results in phosphorylation of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma), a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. This modification of PPARgamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin. The phosphorylation of PPARgamma by Cdk5 is blocked by anti-diabetic PPARgamma ligands, such as rosiglitazone and MRL24. This inhibition works both in vivo and in vitro, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPARgamma phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. All these findings strongly suggest that Cdk5-mediated phosphorylation of PPARgamma may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs through PPARgamma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987584/" 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/PMC2987584/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Jang Hyun -- Banks, Alexander S -- Estall, Jennifer L -- Kajimura, Shingo -- Bostrom, Pontus -- Laznik, Dina -- Ruas, Jorge L -- Chalmers, Michael J -- Kamenecka, Theodore M -- Bluher, Matthias -- Griffin, Patrick R -- Spiegelman, Bruce M -- DK087853/DK/NIDDK NIH HHS/ -- DK31405/DK/NIDDK NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R01 GM084041/GM/NIGMS NIH HHS/ -- R01 GM084041-03/GM/NIGMS NIH HHS/ -- R01-GM084041/GM/NIGMS NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- R37 DK031405-30/DK/NIDDK NIH HHS/ -- S10 RR027270/RR/NCRR NIH HHS/ -- U54 MH084512/MH/NIMH NIH HHS/ -- U54 MH084512-020010/MH/NIMH NIH HHS/ -- U54-MH084512/MH/NIMH NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Jul 22;466(7305):451-6. doi: 10.1038/nature09291.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651683" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/drug effects/metabolism/physiopathology ; Amino Acid Sequence ; Animals ; Cell Line ; Cyclin-Dependent Kinase 5/*antagonists & inhibitors/genetics/metabolism ; Diabetes Mellitus, Experimental/complications/*drug therapy/metabolism ; Dietary Fats/pharmacology ; Humans ; Insulin/metabolism ; Ligands ; Mice ; Models, Molecular ; Obesity/chemically induced/complications/*metabolism/physiopathology ; PPAR gamma/agonists/*metabolism ; Phosphorylation/drug effects ; Phosphoserine/metabolism ; Protein Conformation ; Thiazolidinediones/*pharmacology/therapeutic use
    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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    Antidiabetic actions of a non-agonist PPARgamma ligand blocking Cdk5-mediated phosphorylation (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-09-06
    Description: PPARgamma is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone. These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPARgamma-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPARgamma by Cdk5. Here we describe novel synthetic compounds that have a unique mode of binding to PPARgamma, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPARgamma drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPARgamma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179551/" 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/PMC3179551/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Jang Hyun -- Banks, Alexander S -- Kamenecka, Theodore M -- Busby, Scott A -- Chalmers, Michael J -- Kumar, Naresh -- Kuruvilla, Dana S -- Shin, Youseung -- He, Yuanjun -- Bruning, John B -- Marciano, David P -- Cameron, Michael D -- Laznik, Dina -- Jurczak, Michael J -- Schurer, Stephan C -- Vidovic, Dusica -- Shulman, Gerald I -- Spiegelman, Bruce M -- Griffin, Patrick R -- 1RC4DK090861/DK/NIDDK NIH HHS/ -- DK31405/DK/NIDDK NIH HHS/ -- R01 DK040936/DK/NIDDK NIH HHS/ -- R01 GM084041/GM/NIGMS NIH HHS/ -- R01 GM084041-03/GM/NIGMS NIH HHS/ -- R01-GM084041/GM/NIGMS NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- R37 DK031405-30/DK/NIDDK NIH HHS/ -- R37 DK031405-31/DK/NIDDK NIH HHS/ -- RC4 DK090861/DK/NIDDK NIH HHS/ -- RC4 DK090861-01/DK/NIDDK NIH HHS/ -- S10 RR027270/RR/NCRR NIH HHS/ -- U24 DK059635/DK/NIDDK NIH HHS/ -- U54 MH074404/MH/NIMH NIH HHS/ -- U54 MH074404-01/MH/NIMH NIH HHS/ -- U54-MH074404/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Sep 4;477(7365):477-81. doi: 10.1038/nature10383.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21892191" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/drug effects/metabolism ; Adipose Tissue, White/drug effects/metabolism ; Animals ; Biphenyl Compounds/chemistry/pharmacology ; Body Fluids/drug effects ; COS Cells ; Cercopithecus aethiops ; Cyclin-Dependent Kinase 5/*antagonists & inhibitors ; Dietary Fats/pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; HEK293 Cells ; Humans ; Hypoglycemic Agents/adverse effects/chemistry/*pharmacology ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Models, Molecular ; Obesity/chemically induced/metabolism ; Osteogenesis/drug effects ; PPAR gamma/agonists/chemistry/*metabolism ; Phosphorylation/drug effects ; Phosphoserine/metabolism ; Thiazolidinediones/adverse effects/pharmacology ; Transcription, Genetic/drug effects ; Tumor Necrosis Factor-alpha/pharmacology ; Weight Gain/drug effects
    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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    A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-01-13
    Description: Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-gamma co-activator-1 alpha (PGC1-alpha). Here we show in mouse that PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522098/" 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/PMC3522098/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bostrom, Pontus -- Wu, Jun -- Jedrychowski, Mark P -- Korde, Anisha -- Ye, Li -- Lo, James C -- Rasbach, Kyle A -- Bostrom, Elisabeth Almer -- Choi, Jang Hyun -- Long, Jonathan Z -- Kajimura, Shingo -- Zingaretti, Maria Cristina -- Vind, Birgitte F -- Tu, Hua -- Cinti, Saverio -- Hojlund, Kurt -- Gygi, Steven P -- Spiegelman, Bruce M -- DK31405/DK/NIDDK NIH HHS/ -- DK54477/DK/NIDDK NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R01 DK054477/DK/NIDDK NIH HHS/ -- R01 DK061562/DK/NIDDK NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- England -- Nature. 2012 Jan 11;481(7382):463-8. doi: 10.1038/nature10777.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237023" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/drug effects/metabolism ; Adipose Tissue, Brown/*cytology/drug effects/metabolism ; Adipose Tissue, White/*cytology/drug effects/metabolism ; Animals ; Cell Respiration/drug effects ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Energy Metabolism/drug effects/genetics/physiology ; Exercise/physiology ; Gene Expression Regulation/drug effects/genetics ; Hormones/metabolism/secretion ; Humans ; Insulin Resistance/physiology ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Ion Channels/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Mitochondrial Proteins/metabolism ; Models, Animal ; Muscle Cells/metabolism ; Obesity/blood/chemically induced/prevention & control ; Physical Conditioning, Animal/physiology ; Plasma/chemistry ; Subcutaneous Fat/cytology/drug effects/metabolism ; *Thermogenesis/drug effects/genetics ; Trans-Activators/deficiency/genetics/*metabolism/secretion ; Transcription Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Ambipolar behavior in MoS2 field effect transistors by using catalytic oxidation (2016)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2016-11-01
    Description: Modulation of electrical properties in MoS 2 flakes is an attractive issue from the point of view of device applications. In this work, we demonstrate that an ambipolar behavior in MoS 2 field effect transistors (FETs) can be easily obtained by heating MoS 2 flakes under air atmosphere in the presence of cobalt oxide catalyst (MoS 2  + O 2  → MoO x  + SO x ). The catalytic oxidation of MoS 2 flakes between source-drain electrodes resulted in lots of MoO x nanoparticles (NPs) on MoS 2 flakes with thickness reduction from 64 nm to 17 nm. Consequently, N-type behavior of MoS 2 FETs was converted into ambipolar transport characteristics by MoO x NPs which inject hole carriers to MoS 2 flakes.
    Print ISSN: 0003-6951
    Electronic ISSN: 1077-3118
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 5
    Electronic Resource
    Electronic Resource
    Vibrational dynamics of the bifluoride ion. I. Construction of a model potential surface (1990)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 92 (1990), S. 466-472 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Construction of an extended model potential surface for the bifluoride ion [FHF−] is described, based on ab initio calculations for the free ion at the CID (configuration interaction, double replacement) level with a Huzinaga–Dunning double-zeta basis set. 710 data points were generated, for displacements in the three noncyclic vibrational coordinates exploring the potential surface to a height at least 30 000 cm−1 above its minimum, and giving a realistic account of the dissociation into HF+F−. Analogous calculations were made for HF and F− using the same basis. The predicted hydrogen bond energy (De) is 48.13 kcal/mol, with equilibrium F–F separation Re =4.2905 a.u., in good agreement with other recent calculations. A model potential has been constructed, based on a superposition of Morse potentials associated with each H–F distance plus a fairly structureless correction function expressible as a 36-term least-squares polynomial in the prolate spheroidal coordinates used to describe vibrational displacements. The resulting model surface fits all 710 ab initio data points with an r.m.s. deviation of 65.6 cm−1, and points less than 15 000 cm−1 above the minimum with a deviation of 26.3 cm−1. This surface provides the basis for a series of vibrational dynamics studies on the FHF− system being done in this laboratory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.458449
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  • 6
    Electronic Resource
    Electronic Resource
    A calibration method of a radio frequency magnetic probe (1999)
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 70 (1999), S. 3774-3775 
    Details
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: We demonstrate a simple calibration method of a rf magnetic probe by utilizing a two port network analysis method. The sensitivity (V/G) of the probe is determined by measuring the scattering parameters of S11 and S21. The magnetic field generated by the Helmholtz coil is calculated from S11 and the probe sensitivity is obtained from S21. The measured probe sensitivity is 0.1–0.6 V/G in the frequency range of 1–15 MHz. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1149951
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  • 7
    Electronic Resource
    Electronic Resource
    Classical and quantum proton vibration in a nonharmonic strongly coupled system (1993)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 99 (1993), S. 4611-4627 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Classical and quantum descriptions of proton vibration are compared for a coupled nonharmonic model based on an ab initio potential for the bifluoride ion, [FHF]−. Accurate quantum calculations and exact classical dynamics are compared with quantum and classical versions of the self-consistent-field (SCF) approximation. Semiclassical and quantum SCF eigenvalues agree within JWKB-type errors. The SCF scheme closely approximates exact quantum states for the lowest 4–5 vibrational levels of each symmetry, except at avoided crossings where strong CI mixing of SCF levels occurs. True classical motion, however, is mainly irregular except at very low energies, and even where it remains regular it may be strongly reorganized by a 1:1 periodic resonance associated with major potential surface features. Strongly mixed CI states at systematic avoided crossings of SCF levels at higher energies do have classical analogs in the reorganized classical motions seen at low energies; stabilized CI components correspond to a stable periodic 1:1 orbit, destabilized components to an unstable periodic 1:1 elliptical orbit. Canonical perturbation theory is used to study further the sense in which the exactly separable classical SCF Hamiltonian is "close'' to the true Hamiltonian. Where true motion is modal or SCF-like, first-order perturbed trajectories and second-order perturbed energies describe it very accurately. However since the dynamics can be strongly disturbed even at very low energies, correlation effects are obviously not "small'' in the sense usually meant in classical dynamics, i.e., that regular trajectories mostly remain regular in the nonseparable perturbed system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.466060
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  • 8
    Electronic Resource
    Electronic Resource
    Simplified large current crowbar switch using thyristors (1993)
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 64 (1993), S. 3006-3008 
    Details
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: We demonstrate a large current power crowbar switch using thyristors without complex snubber circuits. Current sharing was obtained by selecting circuit elements for uniform impedance of parallel switches and varistors were used for voltage sharing between series elements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1144347
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  • 9
    Electronic Resource
    Electronic Resource
    Measurements of the electron temperature by the Thomson scattering system on the Hanbit magnetic mirror device : Papers from the thirteenth topical conference on high temperature plasma diagnostics (2001)
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 72 (2001), S. 1118-1121 
    Details
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: A Thomson scattering system on the Hanbit magnetic mirror device has been installed to measure the electron temperature and density of the plasma in the central cell. The configuration is based on a standard 90° scattering scheme. The optical system consists of a Q-switched Nd:YAG laser, input optics, collection optics, spectrograph optics, detectors, and a data acquisition system. Although the laser beam path is about 50 m long and the background emissions are not low, the electron temperature measurements have been made at a single point on a shot-by-shot basis, in which the stray light was considerably suppressed by using a beam dump, a viewing dump, and baffles. The measured electron temperature is about 50–70 eV in experiments for plasma production and heating by ICRF of 200-kW-rf power using a slot antenna. A description of the installed system and the experimental results are presented. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1321749
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  • 10
    Electronic Resource
    Electronic Resource
    Performance of Co/Al2O3/NiFe magnetic tunnel junctions prepared by a two-step rf plasma oxidation method (2001)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 79 (2001), S. 1160-1162 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A two-step rf plasma oxidation technique of an insulating layer has been performed to enhance electrical and structural properties of magnetic tunnel junction (MTJ) devices. Comparison was made by analyzing properties of the MTJ oxidized by conventional rf and two-step rf plasma oxidation methods. Experimentally observed results give improved surface imaging and sufficient oxygen contents of the insulating layer under the two-step oxidation method. In addition, electrical breakdown voltage and magnetoresistance of the MTJ were increased from 0.7 to 1.8 V and from 4.5% to 6.8%, respectively, correlated with improved structural information. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1391407
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