Bibliography: leaves 105-151. / xi, 151, [47] leaves, [3] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the effect of remodelling HDL on the metabolism of apo A-I. The major focus is on the effects of CETP and LCAT in the regulation of apo A-I concentration in DHL. The effects of incubation of HDL with CETP in the presence of VLDL and/or LDL on apo A-I concentration in HDL are examined. The characterization of the dissociated apo A-I from HDL is presented. The studies demonstrate that the dissociation of apo A-I from HDL mediated by CETP is preventable and reversible in a process dependent on LCAT activity. The mechanism by which HDL apo A-I content is increased is also explored. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1997?

Thesis (Ph.D.)--Tufts University, 2004. / Adviser: Alice H. Lichtenstein. Submitted to the School of Nutrition Science and Policy. Includes bibliographical references. Access restricted to members of the Tufts University community. Also available via the World Wide Web;

This study was designed to investigate the mechanism(s) underlying the hypercatabolism of high density lipoprotein in Tangier disease (TD). Initially, the metabolism of normal HDL incubated in Tangier plasma in vitro was examined. Sufficient normal human HDL was added to TD plasma to raise the concentration of HDL-cholesterol to within normal levels. During incubation the concentration of HDL-cholesterol in the TD plasma fell by up to 50% in a time dependent manner. This was not seen in control samples treated in a similar manner. The loss of HDL-cholesterol in the TD could be completely accounted for by the loss of HDL-cholesteryl ester and was accompanied by a 2.3-fold increase in the concentration of HDL-triglyceride. These observations could not be accounted for by lecithin: cholesterol acytransferase activity, cholesteryl ester hydrolysis, or the triglyceride level in the TD plasma. However, preliminary evidence suggested that the activity of cholesteryl ester transfer protein in TD plasma is responsible for the changes in HDL-lipid composition. The resulting triglyceride-rich, cholesteryl-poor HDL was shown to have a normal affinity for the human skin fibroblast HDL receptor. However, this finding does not exclude other pathways of HDL catabolism that may contribute to the rapid turnover of modified HDL in TD plasma. The metabolism of normal HDL by TD fibroblasts and monocytes in vitro was also studied in an attempt to identify a cellular defect of HDL metabolism in TD. However, both TD fibroblasts and monocytes were normal with respect to their ability to bind/internalize and degrade normal HDL invitro. It is concluded that the hypercatabolism of normal HDL in TD involves alterations of HDL-lipid and protein composition prior to removal from the plasma component. Thus, these studies support the hypothesis that the defect in TD resides in the plasma and not in the cells of these patients. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

The high density lipoprotein (HDL) receptor Scavenger Receptor, Class B, Type I (SRBI) is a 509 amino acid integral membrane protein which has been shown to have an important role in HDL-mediated reverse cholesterol transport. SR-BI has been shown to mediate selective uptake of cholesterol, and also mediates efflux of cholesterol to HDL as seen in in vitro cell culture studies. SR-BI is abundant in the liver and steroidogenic tissues, and is also present in macrophages, which play an important role in the initial stages of atherosclerotic development. SR-BI has been shown to be protective against atherosclerosis by way of overexpression and knockout (KO) studies in murine atherosclerosis models, including low density lipoprotein receptor (LDLR) knockout mice, apolipoprotein E (ApoE) knockout mice, and human apolipoprotein B (ApoB) transgenic mice. SR-BI/LDLR double knockout (dKO) mice show a 6-fold increase in diet-induced atherosclerosis compared to LDLR single KO controls, and SR-BI/ApoE dKO mice show severe coronary occlusion, myocardial infarction, and premature death on a normal chow diet. In both, plasma total cholesterol levels are significantly elevated, and associated with abnormally large HDL particles. The majority ofSR-BI's atheroprotective effect has been shown to result from plasma cholesterol clearance by way of selective uptake in the liver. Recently, Covey et al showed that elimination of SRBI expression in macrophages of LDLR KO mice resulted in increased diet-induced atherosclerosis. To see if SR-BI in macrophages contributes to the overall atheroprotective effect of SR-BI in ApoE KO mice, presumably by mediating cellular cholesterol efflux to HDL, selective deletion ofSR-BI was induced in bone marrow derived cells of ApoE KO mice using bone marrow transplantation. Female ApoE -/recipient mice were transplanted with either SR-BI +/+ ApoE -/-or SR-BI -/- ApoE -/bone marrow from male donor mice, and fed a high fat diet for 12 weeks. This resulted in significantly increased atherosclerosis in mice transplanted with SR-BI -/- ApoE -/-bone marrow, with a concomitant decrease in cholesterol associated with HDL-sized lipoproteins. No significant differences were seen in plasma total cholesterol levels or levels of cholesterol associated with non-HDL lipoproteins. These data suggest that SRBI in macrophages contributes to SR-BI's overall protective effect against atherosclerosis, and also plays a role in the regulation ofHDL cholesterol, in ApoE deficient mice. / Thesis / Master of Science (MSc)

The effect of molecular weight on the dispersion of relatively polar montmorillonite (MMT) in non polar, unmodified high density polyethylene (HDPE) was examined. Polymer layered silicate (PLS) nanocomposites were compounded using three unmodified HDPE matrices of differing molecular weight and an organically modified MMT in concentrations ranging from 2 wt% to 8 wt% via single screw extrusion. The weight average molecular weights of the HDPE matrices used in this study ranged from 87,000 g/mol to 460,000 g/mol. X-ray diffraction (XRD), mechanical testing, dynamic mechanical thermal analysis (DMTA), as well as dynamic and capillary rheometry were performed on the nanocomposites. Nanocomposites generated from the high molecular weight (HMW) HDPE matrix exhibited increased intercalation of the MMT as shown by XRD as well as greater improvements in the Young's modulus compared to nanocomposites generated from both the low (LMW) and middle molecular weight (MMW) matrices. This was attributed to higher shear stress imparted to MMT during compounding from the more viscous matrix facilitating their separation and orientation during injection molding. DMTA showed that the torsional response of the HMW nanocomposites was not as great compared to their LMW and MMW counterparts as observed from a lower percentage enhancement in the storage modulus (Gâ ) and estimated heat distortion temperature (HDT) due to anisotropy in mechanical properties. Dynamic rheology indicated that a percolated network did not exist in any of the nanocomposites as shown by no change in the terminal behavior of Gâ upon addition of clay. / Master of Science

The passive components such as inductors and capacitors are bulky parts on circuit boards. Researchers in academia, government, and industry have been searching for ways to improve the magnetic energy density and reduce the package size of magnetic parts. The "constant-flux" concept discussed herein is leveraged to achieve high magnetic-energy density by distributing the magnetic flux uniformly, leading to inductor geometries with a volume significantly lower than that of conventional products. A relatively constant flux distribution is advantageous not only from the density standpoint, but also from the thermal standpoint via the reduction of hot spots, and from the reliability standpoint via the suppression of flux crowding. For toroidal inductors, adding concentric toroidal cells of magnetic material and distributing the windings properly can successfully make the flux density distribution uniform and thus significantly improve the power density. Compared with a conventional toroidal inductor, the constant-flux inductor introduced herein has an enclosed-winding geometry. The winding layout inside the core is configured to distribute the magnetic flux relatively uniformly throughout the magnetic volume to obtain a higher energy density and smaller package volume than those of a conventional toroidal inductor. Techniques to shape the core and to distribute the winding turns to form a desirable field profile is described for one class of magnetic geometries with the winding enclosed by the core. For a given set of input parameters such as the inductor's footprint and thickness, permeability of the magnetic material, maximum permissible magnetic flux density for the allowed core loss, and current rating, the winding geometry can be designed and optimized to achieve the highest time constant, which is the inductance divided by resistance (L/Rdc). The design procedure is delineated for the constant-flux inductor design together with an example with three winding windows, an inductance of 1.6 µH, and a resistance of 7 mΩ. The constant-flux inductor designed has the same inductance, dc resistance, and footprint area as a commercial counterpart, but half the height. The uniformity factor α is defined to reflect the uniformity level inside the core volume. For each given magnetic material and given volume, an optimal uniformity factor exists, which has the highest time constant. The time constant varies with the footprint area, inductor thickness, relative permeability of the magnetic material, and uniformity factor. Therefore, the objective for the constant-flux inductor design is to seek the highest possible time constant, so that the constant-flux inductor gives a higher inductance or lower resistance than commercial products of the same volume. The calculated time-constant-density of the constant-flux inductor designed is 4008 s/m3, which is more than two times larger than the 1463 s/m3 of a commercial product. To validate the concept of constant-flux inductor, various ways of fabrication for the core and the winding were explored in the lab, including the routing process, lasing process on the core, etching technique on copper, and screen printing with silver paste. The most successful results were obtained from the routing process on both the core and the winding. The core from Micrometals has a relative permeability of around 22, and the winding is made of copper sheets 0.5 mm thick. The fabricated inductor prototype shows a significant improvement in energy density: at the same inductance and resistance, the volume of the constant-flux inductor is two times smaller than that of the commercial counterpart. The constant-flux inductor shows great improvement in energy density and the shrinking of the total size of the inductor below that of the commercial products. Reducing the volume of the magnetic component is beneficial to most power. The study of the constant-flux inductor is currently focused on the dc analysis, and the ac analysis is the next step in the research. / Master of Science

Insulin resistance and type 2 diabetes are pathogenetically linked to increased risk of cardiovascular disease. While insulin resistance is defined by a dysregulation in hepatic insulin signaling, it is unclear how this impairment relates to the development of cardiovascular disease. Recently, there has been evidence showing that in insulin resistant individuals, cardiovascular disease is associated with a defect in reverse cholesterol transport – the cardioprotective process by which excess cholesterol is removed from the periphery, and returned to the liver for biliary excretion. Reverse cholesterol transport is facilitated by high-density lipoprotein (HDL) metabolism. Thus, malfunction in HDL turnover during reverse cholesterol transport may contribute to the buildup of atherosclerotic plaques, and subsequent cardiovascular disease in insulin resistant individuals. In this thesis, we seek to establish a better understanding of HDL metabolism and reverse cholesterol transport, as they relate to key transcription factors that mediate hepatic insulin signaling, namely the insulin-repressible forkhead transcription factors, FoxO1, FoxO3, and FoxO4 (FoxOs). We demonstrate that mice with liver-specific triple FoxO knockout (L-FoxO1,3,4) have increased HDL-cholesterol (HDL-C), associated with decreased expression of HDL-C clearance factors, scavenger receptor class B type I (SR-BI) and hepatic lipase, and defective selective uptake of HDL-cholesteryl ester by the liver. As such, we uncover a novel mechanism by which HDL-mediated reverse cholesterol transport to the liver is regulated by the hepatic insulin-->FoxO signaling pathway.

The tart cherry (Prunus cerasus) is the most significant fruit tree crop in Utah, accounting for roughly 51% of the total statewide commercial fruit acreage. In order to accommodate harvesting equipment, tart cherries are grown in conventional orchards with large trees spaced up to 5.5 meters apart. New methods of harvest are adapted to smaller trees in tighter spaced high density (HD) orchards. HD orchards bear fruit earlier in the orchard life than conventional orchards, but likely require different pruning and management strategies, which have not yet been determined for tart cherry. Experimental HD orchards were used to determine the type of renewal pruning cuts to maintain orchard productivity, and to determine whether mechanical pruning (hedging) could be used to maintain tree size. It was found that when removing branches during pruning, leaving the branch stub at least 10 cm long greatly increases the likelihood of getting adequate renewal growth. Mechanical hedging at bloom or 45 days after bloom did not change yields or fruit quality when applied to a well-pruned and maintained orchard. Spray pattern analysis in these canopies suggested that hedging creates a more consistent canopy density than unhedged HD canopies. This research provides distinct guidelines on renewal pruning of tart cherry to maintain productivity, and shows that mechanical hedging strategies can be a viable option for maintaining tree size in HD plantings without increasing pruning costs.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 138-149).

The advent of smart and wearable systems along with their Internet of Things (IoT) applications are driving unparalleled product miniaturization and multifunctional integration with computing, wireless communications, wireless healthcare, security, banking, entertainment, and navigation and others. This evolution is primarily enabled by the integration of multiple technologies such as RF, analog, digital, MEMS, sensors and optics in the same system. Integration of these heterogeneous technologies creates a new need for multiple power supply rails to provide device-specific voltage and current levels. Hence, multiple power converters, each requiring several passive components, are used to create stable power-supplies. However, state-of-art power supplies employ SMD passives that are relatively large, forcing these modules to be placed on the board far from the active IC. This leads to significantly sub-par frequency performance and poses a challenge for ultra-miniaturized and reliable power supplies. Hence, novel packaging technologies that can improve miniaturization, electrical performance and reliability at a relatively low-cost are required to address these challenges. Georgia Tech-PRC proposes 3D integration of passives and actives (3D IPAC) as doubleside thin components on ultra-thin glass substrates with through-package-vias (TPVs) to meet these requirements. This thesis focuses on a comprehensive methodology to demonstrate a 3D IPAC power module, starting with modeling, design, fabrication and characterization to validate 3D integrated ultra-thin inductors and capacitors in ultra-thin substrates. Another key focus of this thesis is to advance building block technologies such as thinfilm inductors and capacitors to achieve the target properties for 3D IPAC integration. As a first building block technology, advanced capacitor technologies were explored with high-k thinfilm barium strontium titanate dielectrics and lanthanum nickel oxide electrodes as an alternative to Cu, Ni and Pt electrodes for improved performance and cost. The BST capacitors with LNO electrodes resulted in a capacitance density of 20-30 nF/cm2 with leakage as low as nA/nF up to 3 V. A glass-compatible process was developed with crystallization temperatures less than 650 C. These capacitors with thinfilm electrodes and dielectrics can be integrated into ultra-thin interposers and packages. This can help improve the capacitor performance up to the GHz range. As a next build block, Si-nanowires were studied as high surface area electrodes for high-density capacitors. Analytical modeling was performed to understand the length of the nanowires based on the catalyst size. This modeling study was then extended to understand the cut-off frequency of the capacitors based on the RC time constant. The wires were fabricated using both chemical vapor deposition (CVD) and wet-etch processes. However, it was noticed that the wet-etch process provided more control on the geometry, density and orientation of the nanowires. Si-oxide was thermally grown on the surface of the wires. A capacitance density of 200 nF/mm2 was achieved. It was noticed that the cut-off frequency of such capacitors was limited to the lower kHz range. However, the operating frequency can be improved by simply using a highly conductive Si-substrate. The second part of the thesis focuses on inductor and capacitor integration on ultra-thin glass substrates for high-frequency power modules using the 3D IPAC approach. Analytical models were used to calculate the required passive component values based on the target frequency, ripple currents and voltages of the power module. Next, a SPICE model was used to optimize the value of the required passives based on the output parasitics. The L and C structures were then modeled using 2.5D method of moments (MOM) approach. The modeling results showed 7-8 X improvement in Q-factor when the structures were fabricated using the 3D IPAC approach relative to those fabricated on the same side of the substrate. A fabrication process flow was designed based on through-via and doubleside metallization with semi-additive patterning (SAP). The components were fabricated as thinfilms on either sides of the substrate and interconnected with through-vias. The LC network was characterized using a two-port vector network analyzer. The results showed low-pass filter response, which matched the design targets of cut-off frequencies upto 100 MHz. This study, therefore, demonstrates advanced thinfilm component technologies for ultra-high frequency power-supply. It also presents, for the first time, a 3D integrated passives and actives (3D IPAC) approach with integrated L and C for power modules.