ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-11-15
    Description: Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic beta-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lloyd, David J -- St Jean, David J Jr -- Kurzeja, Robert J M -- Wahl, Robert C -- Michelsen, Klaus -- Cupples, Rod -- Chen, Michelle -- Wu, John -- Sivits, Glenn -- Helmering, Joan -- Komorowski, Renee -- Ashton, Kate S -- Pennington, Lewis D -- Fotsch, Christopher -- Vazir, Mukta -- Chen, Kui -- Chmait, Samer -- Zhang, Jiandong -- Liu, Longbin -- Norman, Mark H -- Andrews, Kristin L -- Bartberger, Michael D -- Van, Gwyneth -- Galbreath, Elizabeth J -- Vonderfecht, Steven L -- Wang, Minghan -- Jordan, Steven R -- Veniant, Murielle M -- Hale, Clarence -- England -- Nature. 2013 Dec 19;504(7480):437-40. doi: 10.1038/nature12724. Epub 2013 Nov 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Metabolic Disorders, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. ; Department of Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. ; Department of Comparative Biology & Safety Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24226772" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Blood Glucose/metabolism ; Carrier Proteins/*antagonists & inhibitors/metabolism ; Cell Nucleus/enzymology ; Crystallography, X-Ray ; Diabetes Mellitus, Type 2/blood/*drug therapy/enzymology ; Disease Models, Animal ; Hepatocytes ; Humans ; Hyperglycemia/blood/drug therapy/enzymology ; Hypoglycemic Agents/chemistry/*pharmacology/*therapeutic use ; Liver/cytology/enzymology/metabolism ; Male ; Models, Molecular ; Organ Specificity ; Phosphorylation/drug effects ; Piperazines/chemistry/metabolism/pharmacology/therapeutic use ; Protein Binding/drug effects ; Protein Transport/drug effects ; Rats ; Rats, Wistar ; Sulfonamides/chemistry/metabolism/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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    Electronic Resource
    Electronic Resource
    A climatological study of the nocturnal planetary boundary layer (1991)
    Springer
    Boundary layer meteorology 54 (1991), S. 105-128 
    Details
    ISSN: 1573-1472
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Seventy-five nights of fast-response wind and temperature data taken from a 300 m tower near Augusta, GA, were analyzed to determine the time-height structure of the nocturnal planetary boundary layer. The nights were selected from all four seasons over a wide range of synoptic conditions. Statistical summaries of Pasquill-Gifford stability, boundary-layer depth, nocturnal jet height, directional shear, gravity wave occurrence, and azimuthal meandering were obtained. The diversity of nocturnal conditions for the 75 cases resulted in histograms with broad peaks and slowly-varying distributions. To reduce the overall variance, we grouped the nights into two classes: steady nights and unsteady nights. Nights classified as “steady” maintained relatively uniform wind conditions. The data base was large enough to permit a further breakdown of the steady nights into three subclasses based on the height and strength of the wind maximum. “Unsteady” nights were more disturbed, showing time-dependent features in the wind field and were also divided into three subclasses, depending on the predominant features observed: microfrontal passage, trend, or variable conditions. Although the subclasses were based mainly on wind structure, they correlated well with other NPBL properties, such as mixed-layer depth and inversion strength. Thus, the classification procedure tended to group together nights with similar dispersion characteristics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00119415
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    facet.materialart.
    Unknown
    Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2) (2006)
    National Academy of Sciences
    Details
    Publication Date: 2006-06-16
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    A climatological study of the nocturnal planetary boundary layer (1991)
    Springer
    Details
    Publication Date: 1991-01-01
    Print ISSN: 0006-8314
    Electronic ISSN: 1573-1472
    Topics: Geosciences , Physics
    Published by Springer
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Numerical Experiments with a General Circulation Model Concerning the Distribution of Ozone in the Stratosphere (1984)
    American Meteorological Society
    Details
    Publication Date: 1984-07-01
    Print ISSN: 0022-4928
    Electronic ISSN: 1520-0469
    Topics: Geography , Geosciences , Physics
    Published by American Meteorological Society
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Far-Field Transient Backscattering by Water Drops (1971)
    American Meteorological Society
    Details
    Publication Date: 1971-07-01
    Print ISSN: 0022-4928
    Electronic ISSN: 1520-0469
    Topics: Geography , Geosciences , Physics
    Published by American Meteorological Society
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    On the impact of atmospheric waves on fluxes and turbulence statistics during nighttime conditions: a case study (2013)
    Copernicus
    Details
    Publication Date: 2013-03-14
    Description: The interpretation of flux measurements in the nocturnal stable boundary layer is typically fraught with difficulties. This paper reports on how the presence of waves in a time series leads to an overestimation of turbulence statistics and errors in turbulent flux calculations. Using time series of the pressure signal from a microbarograph, the presence of waves at a flux measurement site near Aiken, SC is identified and removed. Our findings suggest that filtering of eddy-covariance data in the presence of wave events prevents both an overestimation of turbulence statistics and errors in turbulent flux calculations. The results showed that large amplitude wave-like events occurred on 31% of the nights considered in the present study. Remarkably, in low-turbulence environments, the presence of a gravity wave can enhance turbulence statistics more than 50%. The presence of the wave modulates the calculated turbulent fluxes of CO2, resulting in erroneous flux calculations of the order of 10% depending on the averaging time and pressure perturbation threshold criteria. In addition, u∗ was affected by the presence of the wave, and in at least one case, a 10% increase caused u∗ to exceed the arbitrary 0.25 ms–1 threshold used in many studies. These preliminary results suggest that biases due to nocturnal atmospheric phenomena can easily creep unnoticed into flux data. The impact of different averaging periods was found to depend on the choice of the variables. This is a product of the width of the averaging window in relation to the wave cycle and dealt with the phase relationship of the variables being analyzed; hence, these errors are primarily introduced through our processing methods. These results provide a novel insight into errors introduced in turbulent fluxes. By contributing more accurate inputs of both turbulent kinetic energy and u∗, these results could be invaluable in improving modeling efforts applied to nocturnal exchange.
    Print ISSN: 1810-6277
    Electronic ISSN: 1810-6285
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    On the impact of wave-like disturbances on turbulent fluxes and turbulence statistics in nighttime conditions: a case study (2013)
    Copernicus
    Details
    Publication Date: 2013-12-23
    Description: The interpretation of flux measurements in nocturnal conditions is typically fraught with challenges. This paper reports on how the presence of wave-like disturbances in a time series, can lead to an overestimation of turbulence statistics, errors when calculating the stability parameter, erroneous estimation of the friction velocity u* used to screen flux data, and errors in turbulent flux calculations. Using time series of the pressure signal from a microbarograph, wave-like disturbances at an AmeriFlux site are identified. The wave-like disturbances are removed during the calculation of turbulence statistics and turbulent fluxes. Our findings suggest that filtering eddy-covariance data in the presence of wave-like events prevents both an~overestimation of turbulence statistics and errors in turbulent flux calculations. Results show that large-amplitude wave-like events, events surpassing three standard deviations, occurred on 18% of the nights considered in the present study. Remarkably, on flux towers located in a very stably stratified boundary-layer regime, the presence of a gravity wave can enhance turbulence statistics more than 50%. In addition, the presence of the disturbance modulates the calculated turbulent fluxes of CO2 resulting in erroneous turbulent flux calculations of the order of 10% depending on averaging time and pressure perturbation threshold criteria. Furthermore, the friction velocity u* was affected by the presence of the wave, and in at least one case, a 10% increase caused u* to exceed the arbitrary 0.25 m s−1 threshold used in many studies. This results in an unintended bias in the data selected for analysis in the flux calculations. The impact of different averaging periods was also examined and found to be variable specific. These early case study results provide an insight into errors introduced when calculating "purely" turbulent fluxes. These results could contribute to improving modeling efforts by providing more accurate inputs of both turbulent kinetic energy, and isolating the turbulent component of u* for flux selection in the stable nocturnal boundary layer.
    Print ISSN: 1726-4170
    Electronic ISSN: 1726-4189
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Description of data on the Nimbus 7 LIMS map archive tape: Ozone and nitric acid (1986)
    In:  CASI
    Details
    Publication Date: 2019-06-28
    Description: The Nimbus 7 Limb Infrared Monitor of the Stratosphere (LIMS) data set has been processed into a Fourier coefficient representation with a Kalman filter algorithm applied to profile data at individual latitudes and pressure levels. The algorithm produces synoptic data at noon Greenwich Mean Time (GMT) from the asynoptic orbital profiles. This form of the data set is easy to use and is appropriate for time series analysis and further data manipulation and display. Ozone and nitric acid results are grouped together in this report because the LIMS vertical field of views (FOV's) and analysis characteristics for these species are similar. A comparison of the orbital input data with mixing ratios derived from Kalman filter coefficients indicates errors in mixing ratio of generally less than 5 percent, with 15 percent being a maximum error. The high quality of the mapped data was indicated by coherence of both the phases and the amplitudes of waves with latitude and pressure. Examples of the mapped fields are presented, and details are given concerning the importance of diurnal variations, the removal of polar stratospheric cloud signatures, and the interpretation of bias effects in the data near the tops of profiles.
    Keywords: GEOPHYSICS
    Type: NASA-TP-2625 , L-16136 , NAS 1.60:2625
    Format: application/pdf
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    NASA TECHNICAL REPORTS
  • 10
    facet.materialart.
    Unknown
    The transport of trace chemicals by steady planetary waves in the stratosphere (1981)
    In:  Other Sources
    Details
    Publication Date: 2019-01-25
    Keywords: GEOPHYSICS
    Type: Illinois Univ. Middle Atmosphere Program. Handbook for MAP. Volume 2: (NASA-CR-175509); p 395-399
    Format: text
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    NASA TECHNICAL REPORTS
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...