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  • 1
    Publication Date: 2005-08-16
    Description: Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor gamma (PPARgamma), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPARgamma-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Jeong-Ho -- Hwang, Eun Sook -- McManus, Michael T -- Amsterdam, Adam -- Tian, Yu -- Kalmukova, Ralitsa -- Mueller, Elisabetta -- Benjamin, Thomas -- Spiegelman, Bruce M -- Sharp, Phillip A -- Hopkins, Nancy -- Yaffe, Michael B -- CA042063/CA/NCI NIH HHS/ -- GM60594/GM/NIGMS NIH HHS/ -- GM68762/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Aug 12;309(5737):1074-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16099986" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/*cytology ; Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins/pharmacology ; Cell Differentiation ; Cell Line ; Core Binding Factor Alpha 1 Subunit ; Gene Expression Regulation, Developmental ; Humans ; Mesenchymal Stromal Cells/*cytology/physiology ; Mice ; Neoplasm Proteins/metabolism ; Oligonucleotides, Antisense ; Osteoblasts/*cytology ; Osteocalcin/genetics ; Osteogenesis ; PPAR gamma/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Proteins/chemistry/genetics/*physiology ; RNA, Small Interfering ; Transcription Factors/chemistry/genetics/metabolism/*physiology ; Transcriptional Activation ; Transfection ; Transforming Growth Factor beta/pharmacology ; Zebrafish ; Zebrafish Proteins/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-07-31
    Description: Author(s): E. Behnke, T. Benjamin, S. J. Brice, D. Broemmelsiek, J. I. Collar, P. S. Cooper, M. Crisler, C. E. Dahl, D. Fustin, J. Hall, C. Harnish, I. Levine, W. H. Lippincott, T. Moan, T. Nania, R. Neilson, E. Ramberg, A. E. Robinson, M. Ruschman, A. Sonnenschein, E. Vázquez-Jáuregui, R. A. Rivera, and L. Uplegger (COUPP Collaboration) We have directly measured the energy threshold and efficiency for bubble nucleation from iodine recoils in a CF 3 I bubble chamber in the energy range of interest for a dark matter search. These interactions cannot be probed by standard neutron calibration methods, so we develop a new technique by obs... [Phys. Rev. D 88, 021101] Published Tue Jul 30, 2013
    Keywords: Experiment
    Print ISSN: 0556-2821
    Electronic ISSN: 1089-4918
    Topics: Physics
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  • 3
    Publication Date: 2013-08-09
    Description: Author(s): Angus J. Wilkinson, Grigore Moldovan, T. Benjamin Britton, Angus Bewick, Robert Clough, and Angus I. Kirkland We report the first use of direct detection for recording electron backscatter diffraction patterns. We demonstrate the following advantages of direct detection: the resolution in the patterns is such that higher order features are visible; patterns can be recorded at beam energies below those at wh... [Phys. Rev. Lett. 111, 065506] Published Thu Aug 08, 2013
    Keywords: Condensed Matter: Structure, etc.
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 4
    Publication Date: 2014-06-10
    Description: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by extracellular plaques containing amyloid β (Aβ)-protein and intracellular tangles containing hyperphosphorylated Tau protein. Here, we describe the generation of inducible pluripotent stem cell lines from patients harboring the London familial AD (fAD) amyloid precursor protein (APP) mutation (V717I). We examine AD-relevant phenotypes following directed differentiation to forebrain neuronal fates vulnerable in AD. We observe that over differentiation time to mature neuronal fates, APP expression and levels of Aβ increase dramatically. In both immature and mature neuronal fates, the APPV717I mutation affects both β- and -secretase cleavage of APP. Although the mutation lies near the -secretase cleavage site in the transmembrane domain of APP, we find that β-secretase cleavage of APP is elevated leading to generation of increased levels of both APPsβ and Aβ. Furthermore, we find that this mutation alters the initial cleavage site of -secretase, resulting in an increased generation of both Aβ42 and Aβ38. In addition to altered APP processing, an increase in levels of total and phosphorylated Tau is observed in neurons with the APPV717I mutation. We show that treatment with Aβ-specific antibodies early in culture reverses the phenotype of increased total Tau levels, implicating altered Aβ production in fAD neurons in this phenotype. These studies use human neurons to reveal previously unrecognized effects of the most common fAD APP mutation and provide a model system for testing therapeutic strategies in the cell types most relevant to disease processes.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2014-11-08
    Description: Here, we analyse residual stress distributions obtained from various crystal systems using high resolution electron backscatter diffraction (EBSD) measurements. Histograms showing stress probability distributions exhibit tails extending to very high stress levels. We demonstrate that these extreme stress values are consistent with the functional form that should be expected for dislocated crystals. Analysis initially developed by Groma and co-workers for X-ray line profile analysis and based on the so-called “restricted second moment of the probability distribution” can be used to estimate the total dislocation density. The generality of the results are illustrated by application to three quite different systems, namely, face centred cubic Cu deformed in uniaxial tension, a body centred cubic steel deformed to larger strain by cold rolling, and hexagonal InAlN layers grown on misfitting sapphire and silicon carbide substrates.
    Print ISSN: 0003-6951
    Electronic ISSN: 1077-3118
    Topics: Physics
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  • 6
    ISSN: 0749-1581
    Keywords: 77Se NMR ; indirect detection ; selenophene ; benzeneselenol ; dimethyl selenide ; dimethyl diselenide ; selenomethionine ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 77Se was measured by inverse proton detection using multiple-quantum 1H-{77Se} correlation spectroscopy. One-and two-dimensional heteronuclear multiple quantum coherence (HMQC) experiments are reported for selenophene, benzeneselenol, dimethyl selenide, dimethyl diselenide, and D,L-selenomethionine with a range of 77Se—1H coupling constants from 9.5 to 54.2 Hz. In these compounds having protons with different 77Se—1H coupling constants the different correlations can be selectively enhanced by varying the mixing time. The enhancement for indirect versus direct 77Se detection was estimated for dimethyl selenide yielding a value close to the theoretical enhancement.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2011-08-24
    Description: The technical feasibility for providing significantly enhanced heat transport and storage as well as improved thermal control has been investigated during several Small Business Innovative Research (SBIR) programs for NASA, the United States Air Force (USAF), and the Strategic Defense Initiative Organization (SDIO) using microencapsulated phase change materials (PCMs) in both aqueous and nonaqueous two-component slurries. In the program for SDIO, novel two-component coolant fluids were prepared and successfully tested at both low (300 K) and intermediate temperatures (460 to 700 K). The two-component fluid slurries of microencapsulated PCMs included organic particles in aqueous and nonaqueous liquids, as well as microencapsulated metals that potentially could be carried by liquid metals or used as powdered heat sinks. Simulation and experimental studies showed that such active cooling systems could be designed and operated with enhancements of heat capacity that exceeded 10 times or 1000 percent that for the base fluid along with significant enhancement in the fluid's heat capacity. Furthermore, this enhancement provided essentially isothermal conditions throughout the pumped primary coolant fluid loop. The results suggest that together with much higher fluid thermal capacity, greater uniformity of temperature is achievable with such fluids, and that significant reductions in pumping power, system size, and system mass are also possible.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: In: Space nuclear power systems 1989; Proceedings of the 6th Symposium, Albuquerque, NM, Jan. 8-12, 1989. Vol. 2 (A93-20752 06-20); p. 303-306.
    Format: text
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  • 8
    Publication Date: 2013-08-31
    Description: A quick activating closure and handling system, which utilizes conical sections for locking, was developed to allow quick access to the combustor internal components of the 8 ft High Temperature Tunnel. These critical components include the existing methane spraybar, a transpiration cooled nozzle and the new liquid oxygen (LOX) injection system housed within the combustor. A substantial cost savings will be realized once the mechanism is installed since it will substantially reduce the access time and increase the time available for conducting wind tunnel tests. A need exists for more frequent inspections when the wind tunnel operates at the more severe conditions generated by using LOX in the combustor. A loads analysis and a structural (finite element) analysis were conducted to verify that the new closure system is compatible with the existing pressure shell. In addition, strain gages were placed on the pressure vessel to verify how the pressure shell reacts to transient pressure loads. A scale model of the new closure system was built to verify the operation of the conical sections in the locking mechanisms.
    Keywords: MECHANICAL ENGINEERING
    Type: The 22nd Aerospace Mechanisms Symposium,; p 99-114
    Format: application/pdf
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  • 9
    Publication Date: 2018-06-05
    Description: Physically based passive microwave precipitation retrieval algorithms require a set of relationships between satellite -observed brightness temperatures (TBs) and the physical state of the underlying atmosphere and surface. These relationships are nonlinear, such that inversions are ill ]posed especially over variable land surfaces. In order to elucidate these relationships, this work presents a theoretical analysis using TB weighting functions to quantify the percentage influence of the TB resulting from absorption, emission, and/or reflection from the surface, as well as from frozen hydrometeors in clouds, from atmospheric water vapor, and from other contributors. The percentage analysis was also compared to Jacobians. The results are presented for frequencies from 10 to 874 GHz, for individual snow profiles, and for averages over three cloud-resolving model simulations of falling snow. The bulk structure (e.g., ice water path and cloud depth) of the underlying cloud scene was found to affect the resultant TB and percentages, producing different values for blizzard, lake effect, and synoptic snow events. The slant path at a 53 viewing angle increases the hydrometeor contributions relative to nadir viewing channels. Jacobians provide the magnitude and direction of change in the TB values due to a change in the underlying scene; however, the percentage analysis provides detailed information on how that change affected contributions to the TB from the surface, hydrometeors, and water vapor. The TB percentage information presented in this paper provides information about the relative contributions to the TB and supplies key pieces of information required to develop and improve precipitation retrievals over land surfaces.
    Keywords: Geophysics
    Type: Journal of Geophysical Research - Atmospheres; Volume 116; D02213
    Format: text
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  • 10
    Publication Date: 2011-08-18
    Description: The partition coefficients between synthetic whitlockite (beta Ca-phosphate) and coexisting silicate melts are determined for the actinide elements Th, U and Pu. Experiments were performed at 1 bar pressure and 1250 C at oxygen fugacities from 10 to the -8.5 to 10 to the -0.7 bars, and partitioning was determined from trace element radiography combined with conventional electron microprobe analysis. Results show Pu to be more readily incorporated into crystalline phases than U or Th under reducing conditions, which is attributed to the observation that Pu exists primarily in the trivalent state, while U and Th are tetravalent. Corrected partition coefficients for whitlockite of 3.6, less than or equal to 0.6, 1.2, 0.5 and less than or equal to 0.002 are estimated for Pu(+3), Pu(+4), Th(+4), U(+4) and U(+6), respectively. Experiments performed at trace levels and percent levels of UO2 indicate that Si is involved in U substitution in whitlockite, and show a reduced partition coefficient at higher concentrations of U that can be explained by effects on melt structure or the fraction of tetravalent U.
    Keywords: LUNAR AND PLANETARY EXPLORATION
    Type: Geochimica et Cosmochimica Acta (ISSN 0016-7037); 47; 1695-170
    Format: text
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