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  • Meteorology and Climatology  (9)
  • Life Sciences (General)  (4)
  • Mice
  • GEOPHYSICS
  • 2000-2004  (14)
  • 1
    Publikationsdatum: 2003-11-01
    Beschreibung: Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Changelian, Paul S -- Flanagan, Mark E -- Ball, Douglas J -- Kent, Craig R -- Magnuson, Kelly S -- Martin, William H -- Rizzuti, Bonnie J -- Sawyer, Perry S -- Perry, Bret D -- Brissette, William H -- McCurdy, Sandra P -- Kudlacz, Elizabeth M -- Conklyn, Maryrose J -- Elliott, Eileen A -- Koslov, Erika R -- Fisher, Michael B -- Strelevitz, Timothy J -- Yoon, Kwansik -- Whipple, David A -- Sun, Jianmin -- Munchhof, Michael J -- Doty, John L -- Casavant, Jeffrey M -- Blumenkopf, Todd A -- Hines, Michael -- Brown, Matthew F -- Lillie, Brett M -- Subramanyam, Chakrapani -- Shang-Poa, Chang -- Milici, Anthony J -- Beckius, Gretchen E -- Moyer, James D -- Su, Chunyan -- Woodworth, Thasia G -- Gaweco, Anderson S -- Beals, Chan R -- Littman, Bruce H -- Fisher, Douglas A -- Smith, James F -- Zagouras, Panayiotis -- Magna, Holly A -- Saltarelli, Mary J -- Johnson, Kimberly S -- Nelms, Linda F -- Des Etages, Shelley G -- Hayes, Lisa S -- Kawabata, Thomas T -- Finco-Kent, Deborah -- Baker, Deanna L -- Larson, Michael -- Si, Ming-Sing -- Paniagua, Ricardo -- Higgins, John -- Holm, Bari -- Reitz, Bruce -- Zhou, Yong-Jie -- Morris, Randall E -- O'Shea, John J -- Borie, Dominic C -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):875-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA. paul_s_changelian@groton.pfizer.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593182" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Enzyme Inhibitors/administration & dosage/pharmacology/therapeutic use/toxicity ; Gene Expression Regulation/drug effects ; Graft Rejection/*prevention & control ; Graft Survival/drug effects ; *Heart Transplantation ; Humans ; Immunosuppressive Agents/administration & dosage/*pharmacology/therapeutic ; use/toxicity ; Interleukin-2/immunology ; Janus Kinase 3 ; *Kidney Transplantation ; Lymphocyte Activation/drug effects ; Lymphocyte Count ; Lymphocyte Culture Test, Mixed ; Lymphocyte Subsets/drug effects ; Macaca fascicularis ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Myocardium/metabolism ; Piperidines ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Pyrimidines/administration & dosage/*pharmacology/therapeutic use/toxicity ; Pyrroles/administration & dosage/*pharmacology/therapeutic use/toxicity ; Transplantation, Heterotopic ; Transplantation, Homologous ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2011-08-24
    Beschreibung: BACKGROUND: We tested the hypothesis that a common oscillatory pattern might characterize the rhythmic discharge of muscle sympathetic nerve activity (MSNA) and the spontaneous variability of heart rate and systolic arterial pressure (SAP) during a physiological increase of sympathetic activity induced by the head-up tilt maneuver. METHODS AND RESULTS: Ten healthy subjects underwent continuous recordings of ECG, intra-arterial pressure, respiratory activity, central venous pressure, and MSNA, both in the recumbent position and during 75 degrees head-up tilt. Venous samplings for catecholamine assessment were obtained at rest and during the fifth minute of tilt. Spectrum and cross-spectrum analyses of R-R interval, SAP, and MSNA variabilities and of respiratory activity provided the low (LF, 0.1 Hz) and high frequency (HF, 0.27 Hz) rhythmic components of each signal and assessed their linear relationships. Compared with the recumbent position, tilt reduced central venous pressure, but blood pressure was unchanged. Heart rate, MSNA, and plasma epinephrine and norepinephrine levels increased, suggesting a marked enhancement of overall sympathetic activity. During tilt, LF(MSNA) increased compared with the level in the supine position; this mirrored similar changes observed in the LF components of R-R interval and SAP variabilities. The increase of LF(MSNA) was proportional to the amount of the sympathetic discharge. The coupling between LF components of MSNA and R-R interval and SAP variabilities was enhanced during tilt compared with rest. CONCLUSIONS: During the sympathetic activation induced by tilt, a similar oscillatory pattern based on an increased LF rhythmicity characterized the spontaneous variability of neural sympathetic discharge, R-R interval, and arterial pressure.
    Schlagwort(e): Life Sciences (General)
    Materialart: Circulation (ISSN 0009-7322); Volume 101; 8; 886-92
    Format: text
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2013-08-29
    Beschreibung: Idealized numerical simulations are performed with a coupled atmosphere/land-surface model to identify the roles of initial soil moisture, coastline curvature, and land breeze circulations on sea breeze initiated precipitation. Data collected on 27 July 1991 during the Convection and Precipitation Electrification Experiment (CAPE) in central Florida are used. The 3D Goddard Cumulus Ensemble (GCE) cloud resolving model is coupled with the Goddard Parameterization for Land-Atmosphere-Cloud Exchange (PLACE) land surface model, thus providing a tool to simulate more realistically land-surface/atmosphere interaction and convective initiation. Eight simulations are conducted with either straight or curved coast-lines, initially homogeneous soil moisture or initially variable soil moisture, and initially homogeneous horizontal winds or initially variable horizontal winds (land breezes). All model simulations capture the diurnal evolution and general distribution of sea-breeze initiated precipitation over central Florida. The distribution of initial soil moisture influences the timing, intensity and location of subsequent precipitation. Soil moisture acts as a moisture source for the atmosphere, increases the connectively available potential energy, and thus preferentially focuses heavy precipitation over existing wet soil. Strong soil moisture-induced mesoscale circulations are not evident in these simulations. Coastline curvature has a major impact on the timing and location of precipitation. Earlier low-level convergence occurs inland of convex coastlines, and subsequent precipitation occurs earlier in simulations with curved coastlines. The presence of initial land breezes alone has little impact on subsequent precipitation. however, simulations with both coastline curvature and initial land breezes produce significantly larger peak rain rates due to nonlinear interactions.
    Schlagwort(e): Meteorology and Climatology
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Publikationsdatum: 2018-06-06
    Beschreibung: High-resolution mesoscale model simulations of the 6-7 May 2000 Missouri flash flood event were performed to test the impact of model initialization and land surface treatment on timing, intensity, and location of extreme precipitation. In this flash flood event, a mesoscale convective system (MCS) produced over 340 mm of rain in roughly 9 hours in some locations. Two different types of model initialization were employed: 1) NCEP global reanalysis with 2.5-degree grid spacing and 12-hour temporal resolution, and 2) Eta reanalysis with 40- km grid spacing and $hour temporal resolution. In addition, two different land surface treatments were considered. A simple land scheme. (SLAB) keeps soil moisture fixed at initial values throughout the simulation, while a more sophisticated land model (PLACE) allows for r interactive feedback. Simulations with high-resolution Eta model initialization show considerable improvement in the intensity of precipitation due to the presence in the initialization of a residual mesoscale convective vortex (hlCV) from a previous MCS. Simulations with the PLACE land model show improved location of heavy precipitation. Since soil moisture can vary over time in the PLACE model, surface energy fluxes exhibit strong spatial gradients. These surface energy flux gradients help produce a strong low-level jet (LLJ) in the correct location. The LLJ then interacts with the cold outflow boundary of the MCS to produce new convective cells. The simulation with both high-resolution model initialization and time-varying soil moisture test reproduces the intensity and location of observed rainfall.
    Schlagwort(e): Meteorology and Climatology
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2019-07-27
    Beschreibung: The 1993 US Midwest Flood produced record levels of flooding, in the Mississippi River Basin. This flooding resulted from repeated frontal passages and mesoscale convective complexes (MCCs) during the months of June and July. A better understanding of processes that influenced MCC development during the 1993 Flood may lead to improved forecasts of heavy precipitation and flooding. Here, we consider the impact of soil moisture on MCC development during a two-day period (June 23-24) of the 1993 US Midwest Flood. The purpose of this study is to assess the importance of soil moisture distribution on the timing, intensity, and location of heavy precipitation. In this study, the MM5-PLACE Atmosphere/Land-Surface Model is utilized. The atmospheric component consists of the Penn State/NCAR MM5 mesoscale model, and the land-surface component consists of the Goddard Parameterization for Land Atmosphere-Cloud Exchange (PLACE). Initial soil moisture is provided from two sources: 1) NCEP reanalysis, and 2) Antecedent Precipitation Index (API) using NOAA rain gauge measurements as a proxy for soil moisture. NCEP reanalysis provides coarse resolution initial soil moisture (2.5 degree), while API provides high resolution initial soil moisture (10-200 km depending on NOAA rain gauge spacing). Initial results indicate that the distribution of soil moisture has a significant impact on the timing and location of heavy precipitation during this two-day flood event. Precipitation in simulations with high resolution initial soil moisture agrees more closely with observed precipitation. These results suggest that high resolution soil moisture observations are necessary to accurately predict severe storm development, heavy precipitation, and subsequent flooding.
    Schlagwort(e): Meteorology and Climatology
    Materialart: 2001 American Meteorological Society meeting; 14-19 Jan. 2001`; Albuquerque, NM; United States
    Format: text
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2019-07-18
    Beschreibung: The onset of the southeast Asian monsoon during 1997 and 1998 was simulated with a coupled mesoscale atmospheric model (MM5) and a detailed land surface model. The rainfall results from the simulations were compared with observed satellite data from the TRMM (Tropical Rainfall Measuring Mission) TMI (TRMM Microwave Imager) and GPCP (Global Precipitation Climatology Project). The simulation with the land surface model captured basic signatures of the monsoon onset processes and associated rainfall statistics. The sensitivity tests indicated that land surface processes had a greater impact on the simulated rainfall results than that of a small sea surface temperature change during the onset period. In both the 1997 and 1998 cases, the simulations were significantly improved by including the land surface processes. The results indicated that land surface processes played an important role in modifying the low-level wind field over two major branches of the circulation; the southwest low-level flow over the Indo-China peninsula and the northern cold front intrusion from southern China. The surface sensible and latent heat exchange between the land and atmosphere modified the low-level temperature distribution and gradient, and therefore the low-level. The more realistic forcing of the sensible and latent heat from the detailed land surface model improved the monsoon rainfall and associated wind simulation. The model results will be compared to the simulation of the 6-7 May 2000 Missouri flash flood event. In addition, the impact of model initialization and land surface treatment on timing, intensity, and location of extreme precipitation will be examined.
    Schlagwort(e): Meteorology and Climatology
    Materialart: 7th Workshop on Regional Climate Simulation; Sep 27, 2004 - Sep 29, 2004; Jhong-Li; Taiwan, Province of China
    Format: text
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2019-07-18
    Beschreibung: The onset of the southeast Asian monsoon during 1997 and 1998 was simulated with a coupled mesoscale atmospheric model (MM5) and a detailed land surface model. The rainfall results from the simulations were compared with observed satellite data from the TRMM (Tropical Rainfall Measuring Mission) TMI (TRMM Microwave Imager) and GPCP (Global Precipitation Climatology Project). The simulation with the land surface model captured basic signatures of the monsoon onset processes and associated rainfall statistics. The sensitivity tests indicated that land surface processes had a greater impact on the simulated rainfall results than that of a small sea surface temperature change during the onset period. In both the 1997 and 1998 cases, the simulations were significantly improved by including the land surface processes. The results indicated that land surface processes played an important role in modifying the low-level wind field over two major branches of the circulation; the southwest low-level flow over the Indo-China peninsula and the northern cold front intrusion from southern China. The surface sensible and latent heat exchange between the land and atmosphere modified the low-level temperature distribution and gradient, and therefore the low-level. The more realistic forcing of the sensible and latent heat from the detailed land surface model improved the monsoon rainfall and associated wind simulation. The model results will be compared to the simulation of the 6-7 May 2000 Missouri flash flood event. In addition, the impact of model initialization and land surface treatment on timing, intensity, and location of extreme precipitation will be examined.
    Schlagwort(e): Meteorology and Climatology
    Materialart: 7th Workshop on Regional Climate Simulation; Oct 04, 2004 - Oct 06, 2004; Cjimg-Li; Taiwan, Province of China
    Format: text
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Publikationsdatum: 2019-07-13
    Beschreibung: This work seeks to develop cellular biosensors based on dendritic polymers. Nanoscale polymer structures less than 20 nm in diameter will be used as the basis of the biosensors. The structures will be designed to target into specific cells of an astronaut and be able to monitor health issues such as exposure to radiation. Multiple components can be assembled on the polymers including target directors, analytical devices (such as molecular probes), and reporting agents. The reporting will be accomplished through fluorescence signal monitoring, with the use of multispectral analysis for signal interpretation. These nanosensors could facilitate the success and increase the safety of extended space flight. The design and assembly of these devices has been pioneered at the Center for Biologic Nanotechnology in the University of Michigan. This period, synthesis of the test-bed biosensors continued. Studies were performed on the candidate fluorescent dyes to determine which might be suitable for the biosensor under development. Development continued on producing an artificial capillary bed as a tool for the use in the production of the fluorescence signal monitor. Work was also done on the in vitro multispectral analysis system, which uses the robotic microscope.
    Schlagwort(e): Life Sciences (General)
    Materialart: NAS2-02069-4
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2019-07-18
    Beschreibung: Cells treated with RNAlater(TradeMark) have previously been shown to contain antigenic proteins that can be visualized using Western blot analysis. These proteins seem to be stable for several months when stored in RNA stabilizer at 4 C. Antigenic protein can be recovered from cells that have been processed using an Ambion RNAqueous(Registered TradeMark) kit to remove RNA. In this set of experiments, human mixed Mullerian tumor (LNI) cells grown on the International Space Station during Expedition 3 were examined for antigenic stability after removal of RNA. The cells were stored for three months in RNAlater(TradeMark) and RNA was extracted. The RNA filtrate containing the protein was precipitated, washed, and suspended in buffer containing sodium dodecyl sulfate (SDS). Samples containing equal concentrations of protein were loaded onto SDS-polyacrylamide gels. Proteins were separated by electrophoresis and transferred by Western blot to polyvinylidene fluoride (PVDF) membrane. The Western blots were stained with an enhanced chemiluminescent ECL(Registered Trademark) Plus detection kit (Amersham) and scanned using a Storm 840 gel image analyzer (Amersham, Molecular Dynamics). ImageQuant(Registered TradeMark) software was used to quantify the densities of the protein bands. The ground control and flight LN1 cell samples showed a similar staining pattern over time with antibodies to vimentin, glyceraldehyde-3-phosphate dehydrogenase, and epithelial membrane antigens.
    Schlagwort(e): Life Sciences (General)
    Materialart: 2004 ASGSB Meeting; Nov 09, 2004 - Nov 12, 2004; Brooklyn, NY; United States
    Format: text
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 2019-08-17
    Beschreibung: Heavy rainfall occurred over the western side of Taiwan's complex terrain from August 10 to 13, 1994 after Typhoon Doug moved northward from the East China Sea into Taiwan and on towards the Yellow Sea. On August 10, most of the rainfall fell over sloped areas. The heaviest daily rainfall totals were in excess of 200 mm over southwestern as well as central Taiwan. However, not much rainfall occurred over northern Taiwan. The lack of rainfall over northern Taiwan also occurred on August 11, 12 and 13. The larger rainfall amounts shifted westward from the sloped areas on August 10 toward lower terrain on August 11. On August 12 and 13, most of the higher rainfall amounts were found over the coastal area in southwestern Taiwan. Notably, about 300 to 400 mm per day fell over the coastal area in southwest Taiwan on August 12 and 13. The distribution of rainfall amount was different on August 10 and 11 (termed as Case 1) compared to August 12 and 13 (termed as Case 2). The environmental situation and precipitation characteristics are analyzed using EC/TOGA data, ground-based radar data, surface rainfall patterns, surface wind data, and upper air soundings. Chen at al. (2001) also categorized the precipitation pattern into two types, propagating and quasi-stationary. For the propagating type of precipitation, rainrates increased or remained the same as systems went from the plains to mountainous regions. With the quasi-stationary type of precipitation, however, rainrates decreased as precipitation propagated across the plains and into the mountains. The focus of this study is to understand what causes the h1aher amounts of rainfall over Taiwan, and what factors influence where the higher amounts of rainfall will occur, over sloped areas or over coastal areas.
    Schlagwort(e): Meteorology and Climatology
    Materialart: MP-12 , MM5 Users Workshop; Jun 25, 2001 - Jun 27, 2001; Boulder, CO; United States
    Format: application/pdf
    Standort Signatur Erwartet Verfügbarkeit
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