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  • Meteorology and Climatology  (12)
  • Life Sciences (General)  (9)
  • GEOPHYSICS
  • Mice
  • 2000-2004  (14)
  • 1995-1999  (12)
  • 1
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    Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-11-01
    Description: 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〉
    Keywords: 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
    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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  • 2
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    Effects of the obese gene product on body weight regulation in ob/ob mice (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-07-28
    Description: C57BL/6J mice with a mutation in the obese (ob) gene are obese, diabetic, and exhibit reduced activity, metabolism, and body temperature. Daily intraperitoneal injection of these mice with recombinant OB protein lowered their body weight, percent body fat, food intake, and serum concentrations of glucose and insulin. In addition, metabolic rate, body temperature, and activity levels were increased by this treatment. None of these parameters was altered beyond the level observed in lean controls, suggesting that the OB protein normalized the metabolic status of the ob/ob mice. Lean animals injected with OB protein maintained a smaller weight loss throughout the 28-day study and showed no changes in any of the metabolic parameters. These data suggest that the OB protein regulates body weight and fat deposition through effects on metabolism and appetite.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelleymounter, M A -- Cullen, M J -- Baker, M B -- Hecht, R -- Winters, D -- Boone, T -- Collins, F -- New York, N.Y. -- Science. 1995 Jul 28;269(5223):540-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Amgen, Inc., Thousand Oaks, CA 91320, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7624776" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/drug effects ; Analysis of Variance ; Animals ; Blood Glucose/analysis ; Body Composition/drug effects ; Body Temperature/drug effects ; Dose-Response Relationship, Drug ; Drinking/drug effects ; Eating/*drug effects ; Energy Metabolism/drug effects ; Female ; Insulin/blood ; Leptin ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Motor Activity/drug effects ; Obesity/genetics/*physiopathology ; Oxygen Consumption/drug effects ; Proteins/genetics/*pharmacology ; Recombinant Proteins/pharmacology ; Weight Loss/*drug effects
    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
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    Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus (2000)
    In:  Other Sources
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    Publication Date: 2011-08-24
    Description: 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.
    Keywords: Life Sciences (General)
    Type: Circulation (ISSN 0009-7322); Volume 101; 8; 886-92
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  • 4
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    Melatonin and cortisol assessment of circadian shifts in astronauts before flight (1995)
    In:  Other Sources
    Details
    Publication Date: 2011-08-24
    Description: Melatonin and cortisol were measured in saliva and urine samples to assess the effectiveness of a 7-day protocol combining bright-light exposure with sleep shifting in eliciting a 12-hr phase-shift delay in eight U.S. Space Shuttle astronauts before launch. Baseline acrophases for 15 control subjects with normal sleep-wake cycles were as follows: cortisol (saliva) at 0700 (0730 in urine); melatonin (saliva) at 0130 (6-hydroxymelatonin sulfate at 0230 in urine). Acrophases of the astronaut group fell within 2.5 hr of these values before the treatment protocols were begun. During the bright-light and sleep-shifting treatments, both absolute melatonin production and melatonin rhythmicity were diminished during the first 3 treatment days; total daily cortisol levels remained constant throughout the treatment. By the fourth to sixth day of the 7-day protocol, seven of the eight crew members showed phase delays in all four measures that fell within 2 hr of the expected 11- to 12-hr shift. Although cortisol and melatonin rhythms each corresponded with the phase shift, the rhythms in these two hormones did not correspond with each other during the transition.
    Keywords: Life Sciences (General)
    Type: Journal of pineal research (ISSN 0742-3098); Volume 18; 3; 141-7
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  • 5
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    A description of the solar wind-magnetosphere coupling based on nonlinear filters (1995)
    In:  Other Sources
    Details
    Publication Date: 2011-08-24
    Description: A nonlinear filtering method is introduced for the study of the solar wind -- magnetosphere coupling and related to earlier linear techniques. The filters are derived from the magnetospheric state, a representation of the magnetospheric conditions in terms of a few global variables, here the auroral electrojet indices. The filters also couple to the input, a representation of the solar wind variables, here the rectified electric field. Filter-based iterative prediction of the indices has been obtained for up to 20 hours. The prediction is stable with respect to perturbations in the initial magnetospheric state; these decrease exponentially at the rate of 30/min. The performance of the method is examined for a wide range of parameters and is superior to that of other linear and nonlinear techniques. In the magnetospheric state representation the coupling is modeled as a small number of nonlinear equations under a time-dependent input.
    Keywords: GEOPHYSICS
    Type: Journal of Geophysical Research (ISSN 0148-0227); 100; A3; p. 3495-3512
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  • 6
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    Changes in gravity inhibit lymphocyte locomotion through type I collagen (1997)
    In:  Other Sources
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    Publication Date: 2011-08-24
    Description: Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes by ceasing locomotion through model interstitium. These in vitro investigations suggest that microgravity induces non-stress-related changes in cell function that may be critical to immunity. Preliminary analysis of locomotion in true microgravity revealed a substantial inhibition of cellular movement in Type I collagen. Thus, the rotating-wall vessel culture system provides a model for analyzing the microgravity-induced inhibition of lymphocyte locomotion and the investigation of the mechanisms related to lymphocyte movement.
    Keywords: Life Sciences (General)
    Type: In vitro cellular & developmental biology. Animal (ISSN 1071-2690); Volume 33; 5; 398-405
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  • 7
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    The Influence of Soil Moisture, Coastline Curvature, and Land-Breeze Circulations on Sea-Breeze Initiated Precipitation (2000)
    In:  CASI
    Details
    Publication Date: 2013-08-29
    Description: 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.
    Keywords: Meteorology and Climatology
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  • 8
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    Functional and cellular adaptations of rodent skeletal muscle to weightlessness (1995)
    In:  CASI
    Details
    Publication Date: 2019-06-28
    Description: This paper describes the affects of microgravity upon three key cellular levels (functional, protein, and mRNA) that are linked to one another. It is clear that at each of these levels, microgravity produces rapid and substantial alterations. One of the key challenges facing the life science community is the development of effective countermeasures that prevent the loss of muscle function as described in this paper. The development of optimal countermeasures, however, awaits a clearer understanding of events occurring at the levels of transcription, translation, and degradation.
    Keywords: Life Sciences (General)
    Type: Journal of Gravitational Physiology, Volume 2, No. 1; 39-42
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  • 9
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    High-Resolution Mesoscale Simulations of the 6-7 May 2000 Missouri Flash Flood: Impact of Model Initialization and Land Surface Treatment (2004)
    In:  CASI
    Details
    Publication Date: 2018-06-06
    Description: 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.
    Keywords: Meteorology and Climatology
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  • 10
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    Soil Moisture and Mesoscale Convective Complex Development During the 1993 US Midwest Flood: Results from the MM5-PLACE Atmosphere/Land-Surface Model (2000)
    In:  Other Sources
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    Publication Date: 2019-07-27
    Description: 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.
    Keywords: Meteorology and Climatology
    Type: 2001 American Meteorological Society meeting; 14-19 Jan. 2001`; Albuquerque, NM; United States
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