Measurement of cholesterol synthesis in man by isotope kinetics of squalene.

The kinetics of the apoprotein B (apo B) of very-low-density (VLDL; d less than 1.006) and low-density (LDL; d 1.019-1.063) lipoproteins were studied in six rabbits by using radioiodinated homologous lipoproteins, before and during oral administration of mevinolin (5 mg/kg per day), a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), to explore the mechanism by which the drug reduces LDL synthesis. Before treatment LDL-apo B production greatly exceeded VLDL-apo B production in all animals, indicating that a large proportion of plasma LDL was derived from a VLDL-independent pathway. Five animals responded to mevinolin with a fall in plasma cholesterol (mean change − 53%; P less than 0.01). This was associated with a 66% decrease in LDL-apo B synthesis (P less than 0.05). In contrast, VLDL-apo B synthesis was unaffected by mevinolin. Furthermore, in all but one animal the decrement in LDL-apo B synthesis was greater than the rate of VLDL-apo B synthesis before treatment, demonstrating that mevinolin had reduced the VLDL-independent production of LDL.

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SAT-LB95 Low Density Lipoprotein Receptor and Proprotein Convertase Subtilisin/Kexin Type 9 Kinetics Using Heavy Water (2H2O) Labeling and Mass Spectrometry

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2056 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Mohamad Dandan ◽

Marc Hellerstein

Keyword(s):

Heavy Water ◽

Cholesterol Synthesis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Synthesis Rate ◽

Cholesterol Feeding ◽

High Cholesterol ◽

Cholesterol Levels ◽

Kinetics Of

Abstract Abnormally high blood cholesterol levels in low density lipoprotein (LDL) increases the risk of heart disease. Cell surface receptors such as LDL-receptors (LDLr) regulate the clearance of LDL from blood circulation. As cholesterol levels decrease, cells promote cholesterol synthesis and cholesterol uptake by increasing LDLr expression. Another regulatory protein of plasma cholesterol clearance is proprotein convertase subtilisin/kexin type 9 (PCSK9). It is secreted from the liver into circulation where it can bind to and target LDLr to the lysosome for subsequent degradation. The current model of cholesterol regulation describes how increased cholesterol content down-regulates the number of LDLr promoted by PCSK9 mediated degradation, however minimal knowledge is not known about LDLr and PCSK9 kinetics using heavy water labeling, and how cholesterol enriched diet affects LDLr and PCSK9 kinetics in vivo. Therefore, our objective(s) were to establish a method 1) to measure the kinetics of LDLr and PCSK9 via stable isotopic metabolic labeling with heavy water (2H2O) in vivo 2) to further test established models of cholesterol metabolic regulation on LDLr and PCSK9 turnover after feeding mice a cholesterol enriched diet. We hypothesize that a cholesterol enriched diet will decrease both LDLr and PCSK9 synthesis rates. In order to test this, mice were fed a cholesterol enrich diet for 1 week and metabolically labeled with heavy water (2H2O) up to 36 hours. LDLr and PCSK9 were immunoprecipitated from liver and deuterium incorporation into LDLr and PCSK9 were measured via mass spectrometry. Our results revealed high cholesterol feeding down-regulated cholesterol synthesis and LDLr fractional synthesis rate decreased from 10.0% to 6% per hour. PCSK9 concentration also decreased from 1 to 0.2 (ng/ml / total mg protein), but the synthesis rate increased from 9.0%/day in control mice to 19.5%/day in high cholesterol diet. These results suggest high cholesterol feeding increases PCSK9 synthesis that potentially depletes the intracellular pool to target LDLr to the lysosome thus decreasing LDLr turnover. This research provides a flux-based approach to measure the kinetics of LDLr and PCSK9 for a molecular based kinetic insight of their functions in physiology, disease and therapy.

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Direct observations of radiation-enhanced transformations in glass

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075543 ◽

1983 ◽

Vol 41 ◽

pp. 354-355

Author(s):

J. F. DeNatale ◽

D. G. Howitt

Keyword(s):

Glass Matrix ◽

Diffusion Mechanism ◽

Bubble Formation ◽

Silicate Glasses ◽

Phase Decomposition ◽

Direct Observations ◽

Thin Foils ◽

Oxygen Bubble ◽

Electron Energy Loss ◽

Kinetics Of

The electron irradiation of silicate glasses containing metal cations produces various types of phase separation and decomposition which includes oxygen bubble formation at intermediate temperatures figure I. The kinetics of bubble formation are too rapid to be accounted for by oxygen diffusion but the behavior is consistent with a cation diffusion mechanism if the amount of oxygen in the bubble is not significantly different from that in the same volume of silicate glass. The formation of oxygen bubbles is often accompanied by precipitation of crystalline phases and/or amorphous phase decomposition in the regions between the bubbles and the detection of differences in oxygen concentration between the bubble and matrix by electron energy loss spectroscopy cannot be discerned (figure 2) even when the bubble occupies the majority of the foil depth.The oxygen bubbles are stable, even in the thin foils, months after irradiation and if van der Waals behavior of the interior gas is assumed an oxygen pressure of about 4000 atmospheres must be sustained for a 100 bubble if the surface tension with the glass matrix is to balance against it at intermediate temperatures.

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Irradiation behavior of pyrolytic silicon carbide

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100074288 ◽

1983 ◽

Vol 41 ◽

pp. 72-73

Author(s):

R. J. Lauf

Keyword(s):

Silicon Carbide ◽

Fission Products ◽

Thermodynamics And Kinetics ◽

Neutron Fluences ◽

Fuel Particles ◽

Sic Coatings ◽

Irradiation Behavior ◽

Kinetics Of ◽

Htgr Fuel

Fuel particles for the High-Temperature Gas-Cooled Reactor (HTGR) contain a layer of pyrolytic silicon carbide to act as a miniature pressure vessel and primary fission product barrier. Optimization of the SiC with respect to fuel performance involves four areas of study: (a) characterization of as-deposited SiC coatings; (b) thermodynamics and kinetics of chemical reactions between SiC and fission products; (c) irradiation behavior of SiC in the absence of fission products; and (d) combined effects of irradiation and fission products. This paper reports the behavior of SiC deposited on inert microspheres and irradiated to fast neutron fluences typical of HTGR fuel at end-of-life.

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The Ordered Phase Formation in Ti-Al-Ga Alloys

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069193 ◽

1970 ◽

Vol 28 ◽

pp. 440-441

Author(s):

Shiro Fujishiro ◽

Harold L. Gegel

Keyword(s):

Thermal Stability ◽

High Temperature ◽

Titanium Alloys ◽

Growth Kinetics ◽

Stoichiometric Composition ◽

Good Potential ◽

Alpha Titanium ◽

Cold Rolled ◽

Kinetics Of ◽

Thermal Stability Of

Ordered-alpha titanium alloys having a DO19 type structure have good potential for high temperature (600°C) applications, due to the thermal stability of the ordered phase and the inherent resistance to recrystallization of these alloys. Five different Ti-Al-Ga alloys consisting of equal atomic percents of aluminum and gallium solute additions up to the stoichiometric composition, Ti3(Al, Ga), were used to study the growth kinetics of the ordered phase and the nature of its interface.The alloys were homogenized in the beta region in a vacuum of about 5×10-7 torr, furnace cooled; reheated in air to 50°C below the alpha transus for hot working. The alloys were subsequently acid cleaned, annealed in vacuo, and cold rolled to about. 050 inch prior to additional homogenization

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Ion Beam Induced Interfacial Reactions in Molybdenum Thin Films on Silicon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100097466 ◽

1981 ◽

Vol 39 ◽

pp. 162-163

Author(s):

L. J. Chen ◽

L. S. Hung ◽

J. W. Mayer

Keyword(s):

Ion Beam ◽

Chemical Vapor ◽

Interfacial Reactions ◽

Practical Applications ◽

Microelectronic Devices ◽

Recent Emergence ◽

Chemical Vapor Deposited ◽

Atomic Mixing ◽

Silicon Interface ◽

Kinetics Of

When an energetic ion penetrates through an interface between a thin film (of species A) and a substrate (of species B), ion induced atomic mixing may result in an intermixed region (which contains A and B) near the interface. Most ion beam mixing experiments have been directed toward metal-silicon systems, silicide phases are generally obtained, and they are the same as those formed by thermal treatment.Recent emergence of silicide compound as contact material in silicon microelectronic devices is mainly due to the superiority of the silicide-silicon interface in terms of uniformity and thermal stability. It is of great interest to understand the kinetics of the interfacial reactions to provide insights into the nature of ion beam-solid interactions as well as to explore its practical applications in device technology.About 500 Å thick molybdenum was chemical vapor deposited in hydrogen ambient on (001) n-type silicon wafer with substrate temperature maintained at 650-700°C. Samples were supplied by D. M. Brown of General Electric Research & Development Laboratory, Schenectady, NY.

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In situ study of electron beam-induced chemical vapor deposition of Au in an environmental TEM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100137653 ◽

1995 ◽

Vol 53 ◽

pp. 256-257

Author(s):

J. Drucker ◽

R. Sharma ◽

J. Kouvetakis ◽

K.H.J. Weiss

Keyword(s):

Electron Beam ◽

Chemical Vapor Deposition ◽

Vapor Deposition ◽

Quantum Effect ◽

Line Drawing ◽

Chemical Vapor ◽

Environmental Cell ◽

Engineering Changes ◽

Kinetics Of

Patterning of metals is a key element in the fabrication of integrated microelectronics. For circuit repair and engineering changes constructive lithography, writing techniques, based on electron, ion or photon beam-induced decomposition of precursor molecule and its deposition on top of a structure have gained wide acceptance Recently, scanning probe techniques have been used for line drawing and wire growth of W on a silicon substrate for quantum effect devices. The kinetics of electron beam induced W deposition from WF6 gas has been studied by adsorbing the gas on SiO2 surface and measuring the growth in a TEM for various exposure times. Our environmental cell allows us to control not only electron exposure time but also the gas pressure flow and the temperature. We have studied the growth kinetics of Au Chemical vapor deposition (CVD), in situ, at different temperatures with/without the electron beam on highly clean Si surfaces in an environmental cell fitted inside a TEM column.

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