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Papers by Ron Barrett

Active and Passive Smart Structures and Integrated Systems 2011, 2011

The paper begins with a brief historical overview of pressure adaptive materials and structures. ... more The paper begins with a brief historical overview of pressure adaptive materials and structures. By examining avian anatomy, it is seen that pressure-adaptive structures have been used successfully in the Natural world to hold structural positions for extended periods of time and yet allow for dynamic shape changes from one flight state to the next. More modern pneumatic actuators, including FAA certified autopilot servoactuators are frequently used by aircraft around the world. Pneumatic artificial muscles (PAM) show good promise as aircraft actuators, but follow the traditional model of load concentration and distribution commonly found in aircraft. A new system is proposed which leaves distributed loads distributed and manipulates structures through a distributed actuator. By using Pressure Adaptive Honeycomb (PAH), it is shown that large structural deformations in excess of 50% strains can be achieved while maintaining full structural integrity and enabling secondary flight control mechanisms like flaps. The successful implementation of pressure-adaptive honeycomb in the trailing edge of a wing section sparked the motivation for subsequent research into the optimal topology of the pressure adaptive honeycomb within the trailing edge of a morphing flap. As an input for the optimization two known shapes are required: a desired shape in cruise configuration and a desired shape in landing configuration. In addition, the boundary conditions and load cases (including aerodynamic loads and internal pressure loads) should be specified for each condition. Finally, a set of six design variables is specified relating to the honeycomb and upper skin topology of the morphing flap. A finite-element model of the pressure-adaptive honeycomb structure is developed specifically tailored to generate fast but reliable results for a given combination of external loading, input variables, and boundary conditions. Based on two bench tests it is shown that this model correlates well to experimental results. The optimization process finds the skin and honeycomb topology that minimizes the error between the acquired shape and the desired shape in each configuration.

39th AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics, and Materials Conference and Exhibit, 1998

This paper presents the bench-top testing of a piezoceramic C-block driven active flap system des... more This paper presents the bench-top testing of a piezoceramic C-block driven active flap system designed to suppress the vibrations of a helicopter rotor blade. The C-block actuators are curved benders designed to generate a larger force output than a straight bender, while providing deflections large enough to eliminate the need for external leveraging systems necessary with stack driven systems. The actuators power a balanced active flap designed to minimize the effect of air speed and rotor speed on flap deflection. Quasi-static experimentation at 1 Hz produced maximum angular flap deflections of 8.4° peak-to-peak. Dynamic tests were conducted over a 40 Hz frequency range demonstrating the ability to generate significant flap deflections both before and after the first natural frequency. Over the 40 Hz range, the flap deflections never dropped below 8° pp, with a first natural frequency of 27 Hz. The flap deflection reached a maximum value of 13.6° pp at 40 Hz. If the applied voltage is increased to the maximum allowable level, it is predicted that flap deflections as large as 20° pp can be achieved.

Structures Congress 2008, 2008

Low strength-to-weight ratios and crack-growth-inhibiting natures of fiber reinforced polymers (F... more Low strength-to-weight ratios and crack-growth-inhibiting natures of fiber reinforced polymers (FRPs) make them ideal materials to repair and strengthen fatigue-critical details in steel bridges . FRP materials can have distinct strength advantages over steel when loaded in their optimal orientation, and fiber composite materials such as graphite (carbon)-epoxy and Kevlar-epoxy can outperform steel when subjected to uniform tension (Mallick 1993). External layers of composite material can be attached to a fatigue-critical detail with the goal of providing an alternate load path, and consequently reducing the stress demand. If the reduction in the stress range is significant, it can lead to a substantial increase in the fatigue life of fatigue-prone details in steel bridge members. This technique has been studied in riveted joints with limited success in recent years . However, use of CFRP materials as a fatigue enhancement technique has proven challenging in past investigations due to localized delamination failures experienced at the bond between the steel and composite materials .

Spectrochimica Acta Part B: Atomic Spectroscopy, 2005

This paper reviews a range of instrumental microanalytical techniques for their potential in foll... more This paper reviews a range of instrumental microanalytical techniques for their potential in following the development of nanotechnology. Needs for development in secondary ion mass spectrometry (SIMS), transmission electron microscopy (TEM), Auger emission spectrometry (AES) laser mass spectrometry, X-ray photon spectroscopy are discussed as well as synchrotron-based methods for analysis. Objectives for development in all these areas for the coming 5 years are defined. Developments of instrumentation in three European synchrotron installations are given as examples of ongoing development in this field. D 2004 Published by Elsevier B.V.

Smart Materials and Structures, 2006

Page 1. Post-buckled precompressed piezoelectric flight control actuator design, development and ... more Page 1. Post-buckled precompressed piezoelectric flight control actuator design, development and demonstration This article has been downloaded from IOPscience. Please scroll down to see the full text article. 2006 Smart Mater. Struct. 15 1323 ...

The Journal of Lipid Research, 2003

Postprandial lipoprotein metabolism is impaired in hypertriglyceridemia. It is unknown how and to... more Postprandial lipoprotein metabolism is impaired in hypertriglyceridemia. It is unknown how and to what extent atorvastatin affects postprandial lipoprotein metabolism in hypertriglyceridemic patients. We evaluated the effect of 4 weeks of atorvastatin therapy (10 mg/day) on postprandial lipoprotein metabolism in 10 hypertriglyceridemic patients (age, 40 ؎ 3 years; body mass index, 27 ؎ 1 kg/m 2 ; cholesterol, 5.74 ؎ 0.34 mmol/l; triglycerides, 3.90 ؎ 0.66 mmol/l; HDL-cholesterol, 0.85 ؎ 0.05 mmol/l; and LDL-cholesterol, 3.18 ؎ 0.23 mmol/l). Patients were randomized to be studied with or without atorvastatin therapy. Postprandial lipoprotein metabolism was evaluated with a standardized oral fat load. Plasma was obtained every 2 h for 14 h. Large triglyceride-rich lipoproteins (TRLs) (containing chylomicrons) and small TRLs (containing chylomicron remnants) were isolated by ultracentrifugation, and cholesterol, triglyceride, apolipoprotein B-100 (apoB-100), apoB-48, apoC-III, and retinyl-palmitate concentrations were determined. Atorvastatin significantly ( P Ͻ 0.01) decreased fasting cholesterol ( ؊ 27%), triglycerides ( ؊ 43%), LDL-cholesterol ( ؊ 28%), and apoB-100 ( ؊ 31%), and increased HDL-cholesterol ( ؉ 19%). Incremental area under the curve (AUC) significantly ( P Ͻ 0.05) decreased for large TRL-cholesterol, -triglycerides, and -retinyl-palmitate, while none of the small TRL parameters changed. These findings contrast with the results in normolipidemic subjects, in which atorvastatin decreased the AUC for chylomicron remnants (small TRLs) but not for chylomicrons (large TRLs). We conclude that atorvastatin improves postprandial lipoprotein metabolism in addition to decreasing fasting lipid levels in hypertriglyceridemia. Such changes would be expected to improve the atherogenic profile. -Parhofer, K. G., E. Laubach, and P. H. R. Barrett. Effect of atorvastatin on postprandial lipoprotein metabolism in hypertriglyceridemic patients. J. Lipid Res. 2003 . 44: 1192-1198.

The Journal of Lipid Research, 2003

Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-1... more Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-100 (apoB-100), suggesting that cholesterol is a mediator for VLDL production. The objective of the study was to examine whether endogenous cholesterol synthesis, reflected by the lathosterol-cholesterol ratio (L-C ratio), affects the secretory rates of different VLDL subfractions. Ten healthy subjects were studied after overnight fasting. During a 10 h primed, constant infusion of 13 C-valine (15 mol/kg/h), enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL-1 and VLDL-2 by gas chromatography mass spectrometry. The synthesis rates of VLDL-1 apoB-100 and VLDL-2 apoB-100, catabolism, and transfer were estimated by compartmental analysis. Mean VLDL-1 apoB-100 pool size was 90 ؎ 15 mg, and mean VLDL-2 apoB-100 pool size was 111 ؎ 14 mg. Absolute synthesis rate of VLDL-1 apoB-100 was 649 ؎ 127 mg/day and 353 ؎ 59 mg/day for VLDL-2 apoB-100. There was a strong association between the absolute synthesis rate of VLDL-2 apoB-100 and L-C ratio ( r 2 ‫؍‬ 0.61, P Ͻ 0.01). In contrast, no correlation was observed between L-C ratio and absolute synthesis rate of VLDL-1 apoB-100 ( r 2 ‫؍‬ 0.302, P ‫؍‬ 0.09). In conclusion, these data provide additional support for an independent regulation of VLDL-1 apoB-100 and VLDL-2 apoB-100 production. Endogenous cholesterol synthesis is correlated only with the VLDL-2 apoB-100 production. -Prinsen, B.

The Journal of Lipid Research, 2006

Apolipoprotein C-III (apoC-III) is an important regulator of lipoprotein metabolism. Radioisotope... more Apolipoprotein C-III (apoC-III) is an important regulator of lipoprotein metabolism. Radioisotope and stable isotope kinetic studies show differing results in relation to the kinetics of apoC-III in HDL. Kinetic analysis of HDL apoC-III may be difficult because of its low concentration, as well as the presence of other apoproteins at higher concentration, in the HDL fraction. We used Intralipid(R) (IL), known to preferentially extract apoC proteins from plasma, as a means of extracting apoC-III from HDL before apoprotein separation by isoelectric focusing gel electrophoresis for the measurement of tracer enrichment. Protein purity was assessed by an isoleucine-to-leucine (Ile/Leu) ratio, as apoC-III contains no isoleucine. We compared apoC-III kinetics in 14 men using a bolus infusion of deuterated leucine. The Ile/Leu ratio for IL-extracted HDL (IL-HDL) apoC-III (3.0 +/- 0.7%) was not different from that of VLDL apoC-III (2.6 +/- 0.6%) but was significantly lower than that of untreated HDL apoC-III (9.0 +/- 2.9%) (P < 0.001). The isotopic enrichment curves and fractional catabolic rates (FCRs) for IL-HDL apoC-III were not different from those of VLDL apoC-III. In contrast, HDL apoC-III had significantly lower isotopic enrichments and FCRs than IL-HDL apoC-III (P < 0.001). In conclusion, this simple IL method can be used to isolate apoC-III from HDL with minimal interference from other HDL apoproteins, and it demonstrates that the kinetics of apoC-III in VLDL and HDL are similar, supporting the concept of a single kinetically homogeneous pool of apoC-III in plasma.

The Journal of Lipid Research, 2002

The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r ‫؍‬ 0.78... more The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r ‫؍‬ 0.78, P Ͻ 0.01), IDL (r ‫؍‬ 0.67, P Ͻ 0.01), and LDL (r ‫؍‬ 0.52, P Ͻ 0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apoC-III-containing lipoprotein particles in plasma by anti-apoC-III immunoaffinity chromatography. Since apoC-III does not bind biglycan directly, enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apoB and/or apoE become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apoC-III enrichment of LDL and VLDL did not increase binding. ApoC-III content may thus be a marker for lipoproteins characterized as having an increased ability to bind proteoglycans. --III content of ApoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan.

The Journal of Lipid Research, 2002

In this report, we examined the effects of naringenin on apoB kinetics in oleatestimulated HepG2 ... more In this report, we examined the effects of naringenin on apoB kinetics in oleatestimulated HepG2 cells and determined the contribution of microsomal lumen cholesteryl ester (CE) availability to apoB secretion. Pulse-chase studies of apoB secretion and intracellular degradation were analyzed by multicompartmental modeling. The model for apoB metabolism in HepG2 cells includes an intracellular compartment from which apoB can be either secreted or degraded by both rapid and slow pathways. In the presence of 0.1 mM oleic acid, naringenin (200 M) reduced the secretion of newly synthesized apoB by 52%, due to a 56% reduction in the rate constant for secretion. Intracellular degradation was significantly increased due to a selective increase in rapid degradation, while slow degradation was unaffected. Incubation with either N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) or lactacystin showed that degradation via the rapid pathway was largely proteasomal. Although these changes in apoB metabolism were accompanied by significant reductions in CE synthesis and mass, subcellular fractionation experiments comparing naringenin to specific ACAT and HMG-CoA reductase inhibitors revealed that reduced accumulation of newly synthesized CE in the microsomal lumen is not consistently associated with reduced apoB secretion. However, naringenin, unlike the ACAT and HMG-CoA reductase inhibitors, significantly reduced lumenal TG accu-

The Journal of Lipid Research, 2003

Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development... more Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development of specific inhibitors of bile acid reabsorption, potentially a new class of cholesterol-lowering agents. In the present study, we tested the hypothesis that combining the novel ASBT inhibitor, SC-435, with the HMG-CoA reductase inhibitor, atorvastatin, would potentiate reductions in LDL cholesterol (LDL-C) and LDL apolipoprotein B (apoB). ApoB kinetic studies were performed in miniature pigs fed a typical human diet and treated with the combination of SC-435 (5 mg/kg/day) plus atorvastatin (3 mg/kg/day) (SC-435 ؉ A) or a placebo. SC-435 ؉ A decreased plasma total cholesterol by 23% and LDL-C by 40%. Multicompartmental analysis (SAAM II) demonstrated that LDL apoB significantly decreased by 35% due primarily to a 45% increase in the LDL apoB fractional catabolic rate (FCR). SC-435 ؉ A significantly decreased hepatic concentrations of free cholesterol and cholesteryl ester, and increased hepatic LDL receptor mRNA consequent to increased cholesterol 7 ␣hydroxylase expression and activity. In comparison, SC-435 (10 mg/kg/day) monotherapy decreased LDL apoB by 10% due entirely to an 18% increase in LDL apoB FCR, whereas atorvastatin monotherapy (3 mg/kg/day) decreased LDL apoB by 30% due primarily to a 22% reduction in LDL apoB production.

The Journal of Lipid Research, 2006

The determination of lipolysis rates in humans in vivo requires the use of radioactive or stable ... more The determination of lipolysis rates in humans in vivo requires the use of radioactive or stable isotopic tracers

Journal of Biological Chemistry, 2009

Focal Adhesion Kinase (FAK) activity is controlled by growth factors and adhesion signals in tumo... more Focal Adhesion Kinase (FAK) activity is controlled by growth factors and adhesion signals in tumor cells. The scaffolding protein RACK1 (receptor for activated C kinases) integrates insulin-like growth factor I (IGF-I) and integrin signaling, but whether RACK1 is required for FAK function is unknown. Here we show that association of FAK with RACK1 is required for both FAK phosphorylation and dephosphorylation in response to IGF-I. Suppression of RACK1 by small interfering RNA ablates FAK phosphorylation and reduces cell adhesion, cell spreading, and clonogenic growth. Peptide array and mutagenesis studies localize the FAK binding interface to blades I-III of the RACK1 beta-propeller and specifically identify a set of basic and hydrophobic amino acids (Arg-47, Tyr-52, Arg-57, Arg-60, Phe-65, Lys-127, and Lys-130) as key determinants for association with FAK. Mutation of tyrosine 52 alone is sufficient to disrupt interaction of RACK1 with FAK in cells where endogenous RACK1 is suppressed by small interfering RNA. Cells expressing a Y52F mutant RACK1 are impaired in adhesion, growth, and foci formation. Comparative analyses of homology models and crystal structures for RACK1 orthologues suggest a role for Tyr-52 as a site for phosphorylation that induces conformational change in RACK1, switching the protein into a FAK binding state. Tyrosine 52 is further shown to be phosphorylated by c-Abl kinase, and the c-Abl inhibitor STI571 disrupts FAK interaction with RACK1. We conclude that FAK association with RACK1 is regulated by phosphorylation of Tyr-52. Our data reveal a novel mechanism whereby IGF-I and c-Abl control RACK1 association with FAK to facilitate adhesion signaling.

Journal of Aircraft, 2007

ABSTRACT The design, modeling, and testing of a morphing wing for flight control of an uninhabite... more ABSTRACT The design, modeling, and testing of a morphing wing for flight control of an uninhabited aerial vehicle is detailed. The design employed a new type of piezoelectric flight control mechanism which relied on axial precompression to magnify control deflections and forces simultaneously. This postbuckled precompressed bending actuator was oriented in the plane of the 12 % thick wing and mounted between the end of a tapered D-spar at the 40 % chord and a trailing-edge stiffener at the 98% chord. Axial precompression was generated in the piezoelectric elements by an elastic skin which covered the outside of the wing and served as the aerodynamic surface over the aft 70% of the wing chord. A two-dimensional semi-analytical model based on the Rayleigh-Ritz method of assumed modes was used to predict the static and dynamic trailing-edge deflections as a function of the applied voltage and aerodynamic loading. It was shown that static trailing-edge deflections of +/- 3.1 deg could be attained statically and dynamically through 34 Hz, with excellent correlation between theory and experiment. Wind tunnel and flight tests showed that the postbuckled precompressed morphing wing increased roll control authority on a 1.4 meter span uninhabited aerial vehicle while reducing weight, slop, part-count, and power consumption.

Journal of Aircraft, 1996

A new system for active flow control using smart vortex generators (SVG) is presented. Increments... more A new system for active flow control using smart vortex generators (SVG) is presented. Increments in C/max from modern vortex generators (VGs) are determined through wind-tunnel testing on a two-dimensional wing section. Using an optimized VG configuration, a system was built with 1) a shear-flow sensor that detected the onset and depth of stall, 2) a series of shape-memory-alloy VGs, and 3) a lift-todrag (L/D) maximizing controller. The system demonstrated a 14% increase in C /inax , a 2.7-deg rise in a,*,,, a 42% jump in L/D through the stall, and a low a C M penalty of less than 0.1%. Further testing demonstrated that the system consumed only 9.2 W of power, responded hi less than 0.8 s, and was capable of unstalling an airfoil that had exceeded o^,, by up to 3 deg.

Clinical Chemistry, 2004

Background: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (ap... more Background: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human lipoprotein metabolism. Two forms of apoB are produced from the APOB gene by a unique posttranscriptional editing process: apoB-48, which is required for chylomicron production in the small intestine, and apoB-100, required for VLDL production in the liver. In addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles. Content: The study of monogenic dyslipidemias has revealed important aspects of metabolic pathways. In this review, we discuss the regulation of apoB metabolism and examine how APOB gene defects can lead to both hypo-and hypercholesterolemia. The key clinical, metabolic, and genetic features of familial hypobetalipoproteinemia and familial ligand-defective apoB-100 are described. Summary: Missense mutations in the LDL-receptorbinding domain of apoB cause familial ligand-defective apoB-100, characterized by hypercholesterolemia and premature coronary artery disease. Other mutations in APOB can cause familial hypobetalipoproteinemia, characterized by hypocholesterolemia and resistance to atherosclerosis. These naturally occurring mutations reveal key domains in apoB and demonstrate how monogenic dyslipidemias can provide insight into biologically important mechanisms.

A parametric investigation into the use of CFRP materials to extend the fatigue life of vulnerabl... more A parametric investigation into the use of CFRP materials to extend the fatigue life of vulnerable connection details in steel bridge girders is described in this paper. CFRP overlay elements were attached to an AASHTO category E" detail and tested under cyclic loading. Several parameters were studied experimentally and analytically, including the configuration of a layer of resin used to attach the CFRP overlay to the steel, profile geometry of the composite overlay, and length of the composite overlay.

Active and Passive Smart Structures and Integrated Systems 2011, 2011

The paper begins with a brief historical overview of pressure adaptive materials and structures. ... more The paper begins with a brief historical overview of pressure adaptive materials and structures. By examining avian anatomy, it is seen that pressure-adaptive structures have been used successfully in the Natural world to hold structural positions for extended periods of time and yet allow for dynamic shape changes from one flight state to the next. More modern pneumatic actuators, including FAA certified autopilot servoactuators are frequently used by aircraft around the world. Pneumatic artificial muscles (PAM) show good promise as aircraft actuators, but follow the traditional model of load concentration and distribution commonly found in aircraft. A new system is proposed which leaves distributed loads distributed and manipulates structures through a distributed actuator. By using Pressure Adaptive Honeycomb (PAH), it is shown that large structural deformations in excess of 50% strains can be achieved while maintaining full structural integrity and enabling secondary flight control mechanisms like flaps. The successful implementation of pressure-adaptive honeycomb in the trailing edge of a wing section sparked the motivation for subsequent research into the optimal topology of the pressure adaptive honeycomb within the trailing edge of a morphing flap. As an input for the optimization two known shapes are required: a desired shape in cruise configuration and a desired shape in landing configuration. In addition, the boundary conditions and load cases (including aerodynamic loads and internal pressure loads) should be specified for each condition. Finally, a set of six design variables is specified relating to the honeycomb and upper skin topology of the morphing flap. A finite-element model of the pressure-adaptive honeycomb structure is developed specifically tailored to generate fast but reliable results for a given combination of external loading, input variables, and boundary conditions. Based on two bench tests it is shown that this model correlates well to experimental results. The optimization process finds the skin and honeycomb topology that minimizes the error between the acquired shape and the desired shape in each configuration.

39th AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics, and Materials Conference and Exhibit, 1998

This paper presents the bench-top testing of a piezoceramic C-block driven active flap system des... more This paper presents the bench-top testing of a piezoceramic C-block driven active flap system designed to suppress the vibrations of a helicopter rotor blade. The C-block actuators are curved benders designed to generate a larger force output than a straight bender, while providing deflections large enough to eliminate the need for external leveraging systems necessary with stack driven systems. The actuators power a balanced active flap designed to minimize the effect of air speed and rotor speed on flap deflection. Quasi-static experimentation at 1 Hz produced maximum angular flap deflections of 8.4° peak-to-peak. Dynamic tests were conducted over a 40 Hz frequency range demonstrating the ability to generate significant flap deflections both before and after the first natural frequency. Over the 40 Hz range, the flap deflections never dropped below 8° pp, with a first natural frequency of 27 Hz. The flap deflection reached a maximum value of 13.6° pp at 40 Hz. If the applied voltage is increased to the maximum allowable level, it is predicted that flap deflections as large as 20° pp can be achieved.

Structures Congress 2008, 2008

Low strength-to-weight ratios and crack-growth-inhibiting natures of fiber reinforced polymers (F... more Low strength-to-weight ratios and crack-growth-inhibiting natures of fiber reinforced polymers (FRPs) make them ideal materials to repair and strengthen fatigue-critical details in steel bridges . FRP materials can have distinct strength advantages over steel when loaded in their optimal orientation, and fiber composite materials such as graphite (carbon)-epoxy and Kevlar-epoxy can outperform steel when subjected to uniform tension (Mallick 1993). External layers of composite material can be attached to a fatigue-critical detail with the goal of providing an alternate load path, and consequently reducing the stress demand. If the reduction in the stress range is significant, it can lead to a substantial increase in the fatigue life of fatigue-prone details in steel bridge members. This technique has been studied in riveted joints with limited success in recent years . However, use of CFRP materials as a fatigue enhancement technique has proven challenging in past investigations due to localized delamination failures experienced at the bond between the steel and composite materials .

Spectrochimica Acta Part B: Atomic Spectroscopy, 2005

This paper reviews a range of instrumental microanalytical techniques for their potential in foll... more This paper reviews a range of instrumental microanalytical techniques for their potential in following the development of nanotechnology. Needs for development in secondary ion mass spectrometry (SIMS), transmission electron microscopy (TEM), Auger emission spectrometry (AES) laser mass spectrometry, X-ray photon spectroscopy are discussed as well as synchrotron-based methods for analysis. Objectives for development in all these areas for the coming 5 years are defined. Developments of instrumentation in three European synchrotron installations are given as examples of ongoing development in this field. D 2004 Published by Elsevier B.V.

Smart Materials and Structures, 2006

Page 1. Post-buckled precompressed piezoelectric flight control actuator design, development and ... more Page 1. Post-buckled precompressed piezoelectric flight control actuator design, development and demonstration This article has been downloaded from IOPscience. Please scroll down to see the full text article. 2006 Smart Mater. Struct. 15 1323 ...

The Journal of Lipid Research, 2003

Postprandial lipoprotein metabolism is impaired in hypertriglyceridemia. It is unknown how and to... more Postprandial lipoprotein metabolism is impaired in hypertriglyceridemia. It is unknown how and to what extent atorvastatin affects postprandial lipoprotein metabolism in hypertriglyceridemic patients. We evaluated the effect of 4 weeks of atorvastatin therapy (10 mg/day) on postprandial lipoprotein metabolism in 10 hypertriglyceridemic patients (age, 40 ؎ 3 years; body mass index, 27 ؎ 1 kg/m 2 ; cholesterol, 5.74 ؎ 0.34 mmol/l; triglycerides, 3.90 ؎ 0.66 mmol/l; HDL-cholesterol, 0.85 ؎ 0.05 mmol/l; and LDL-cholesterol, 3.18 ؎ 0.23 mmol/l). Patients were randomized to be studied with or without atorvastatin therapy. Postprandial lipoprotein metabolism was evaluated with a standardized oral fat load. Plasma was obtained every 2 h for 14 h. Large triglyceride-rich lipoproteins (TRLs) (containing chylomicrons) and small TRLs (containing chylomicron remnants) were isolated by ultracentrifugation, and cholesterol, triglyceride, apolipoprotein B-100 (apoB-100), apoB-48, apoC-III, and retinyl-palmitate concentrations were determined. Atorvastatin significantly ( P Ͻ 0.01) decreased fasting cholesterol ( ؊ 27%), triglycerides ( ؊ 43%), LDL-cholesterol ( ؊ 28%), and apoB-100 ( ؊ 31%), and increased HDL-cholesterol ( ؉ 19%). Incremental area under the curve (AUC) significantly ( P Ͻ 0.05) decreased for large TRL-cholesterol, -triglycerides, and -retinyl-palmitate, while none of the small TRL parameters changed. These findings contrast with the results in normolipidemic subjects, in which atorvastatin decreased the AUC for chylomicron remnants (small TRLs) but not for chylomicrons (large TRLs). We conclude that atorvastatin improves postprandial lipoprotein metabolism in addition to decreasing fasting lipid levels in hypertriglyceridemia. Such changes would be expected to improve the atherogenic profile. -Parhofer, K. G., E. Laubach, and P. H. R. Barrett. Effect of atorvastatin on postprandial lipoprotein metabolism in hypertriglyceridemic patients. J. Lipid Res. 2003 . 44: 1192-1198.

The Journal of Lipid Research, 2003

Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-1... more Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-100 (apoB-100), suggesting that cholesterol is a mediator for VLDL production. The objective of the study was to examine whether endogenous cholesterol synthesis, reflected by the lathosterol-cholesterol ratio (L-C ratio), affects the secretory rates of different VLDL subfractions. Ten healthy subjects were studied after overnight fasting. During a 10 h primed, constant infusion of 13 C-valine (15 mol/kg/h), enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL-1 and VLDL-2 by gas chromatography mass spectrometry. The synthesis rates of VLDL-1 apoB-100 and VLDL-2 apoB-100, catabolism, and transfer were estimated by compartmental analysis. Mean VLDL-1 apoB-100 pool size was 90 ؎ 15 mg, and mean VLDL-2 apoB-100 pool size was 111 ؎ 14 mg. Absolute synthesis rate of VLDL-1 apoB-100 was 649 ؎ 127 mg/day and 353 ؎ 59 mg/day for VLDL-2 apoB-100. There was a strong association between the absolute synthesis rate of VLDL-2 apoB-100 and L-C ratio ( r 2 ‫؍‬ 0.61, P Ͻ 0.01). In contrast, no correlation was observed between L-C ratio and absolute synthesis rate of VLDL-1 apoB-100 ( r 2 ‫؍‬ 0.302, P ‫؍‬ 0.09). In conclusion, these data provide additional support for an independent regulation of VLDL-1 apoB-100 and VLDL-2 apoB-100 production. Endogenous cholesterol synthesis is correlated only with the VLDL-2 apoB-100 production. -Prinsen, B.

The Journal of Lipid Research, 2006

Apolipoprotein C-III (apoC-III) is an important regulator of lipoprotein metabolism. Radioisotope... more Apolipoprotein C-III (apoC-III) is an important regulator of lipoprotein metabolism. Radioisotope and stable isotope kinetic studies show differing results in relation to the kinetics of apoC-III in HDL. Kinetic analysis of HDL apoC-III may be difficult because of its low concentration, as well as the presence of other apoproteins at higher concentration, in the HDL fraction. We used Intralipid(R) (IL), known to preferentially extract apoC proteins from plasma, as a means of extracting apoC-III from HDL before apoprotein separation by isoelectric focusing gel electrophoresis for the measurement of tracer enrichment. Protein purity was assessed by an isoleucine-to-leucine (Ile/Leu) ratio, as apoC-III contains no isoleucine. We compared apoC-III kinetics in 14 men using a bolus infusion of deuterated leucine. The Ile/Leu ratio for IL-extracted HDL (IL-HDL) apoC-III (3.0 +/- 0.7%) was not different from that of VLDL apoC-III (2.6 +/- 0.6%) but was significantly lower than that of untreated HDL apoC-III (9.0 +/- 2.9%) (P < 0.001). The isotopic enrichment curves and fractional catabolic rates (FCRs) for IL-HDL apoC-III were not different from those of VLDL apoC-III. In contrast, HDL apoC-III had significantly lower isotopic enrichments and FCRs than IL-HDL apoC-III (P < 0.001). In conclusion, this simple IL method can be used to isolate apoC-III from HDL with minimal interference from other HDL apoproteins, and it demonstrates that the kinetics of apoC-III in VLDL and HDL are similar, supporting the concept of a single kinetically homogeneous pool of apoC-III in plasma.

The Journal of Lipid Research, 2002

The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r ‫؍‬ 0.78... more The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r ‫؍‬ 0.78, P Ͻ 0.01), IDL (r ‫؍‬ 0.67, P Ͻ 0.01), and LDL (r ‫؍‬ 0.52, P Ͻ 0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apoC-III-containing lipoprotein particles in plasma by anti-apoC-III immunoaffinity chromatography. Since apoC-III does not bind biglycan directly, enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apoB and/or apoE become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apoC-III enrichment of LDL and VLDL did not increase binding. ApoC-III content may thus be a marker for lipoproteins characterized as having an increased ability to bind proteoglycans. --III content of ApoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan.

The Journal of Lipid Research, 2002

In this report, we examined the effects of naringenin on apoB kinetics in oleatestimulated HepG2 ... more In this report, we examined the effects of naringenin on apoB kinetics in oleatestimulated HepG2 cells and determined the contribution of microsomal lumen cholesteryl ester (CE) availability to apoB secretion. Pulse-chase studies of apoB secretion and intracellular degradation were analyzed by multicompartmental modeling. The model for apoB metabolism in HepG2 cells includes an intracellular compartment from which apoB can be either secreted or degraded by both rapid and slow pathways. In the presence of 0.1 mM oleic acid, naringenin (200 M) reduced the secretion of newly synthesized apoB by 52%, due to a 56% reduction in the rate constant for secretion. Intracellular degradation was significantly increased due to a selective increase in rapid degradation, while slow degradation was unaffected. Incubation with either N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) or lactacystin showed that degradation via the rapid pathway was largely proteasomal. Although these changes in apoB metabolism were accompanied by significant reductions in CE synthesis and mass, subcellular fractionation experiments comparing naringenin to specific ACAT and HMG-CoA reductase inhibitors revealed that reduced accumulation of newly synthesized CE in the microsomal lumen is not consistently associated with reduced apoB secretion. However, naringenin, unlike the ACAT and HMG-CoA reductase inhibitors, significantly reduced lumenal TG accu-

The Journal of Lipid Research, 2003

Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development... more Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development of specific inhibitors of bile acid reabsorption, potentially a new class of cholesterol-lowering agents. In the present study, we tested the hypothesis that combining the novel ASBT inhibitor, SC-435, with the HMG-CoA reductase inhibitor, atorvastatin, would potentiate reductions in LDL cholesterol (LDL-C) and LDL apolipoprotein B (apoB). ApoB kinetic studies were performed in miniature pigs fed a typical human diet and treated with the combination of SC-435 (5 mg/kg/day) plus atorvastatin (3 mg/kg/day) (SC-435 ؉ A) or a placebo. SC-435 ؉ A decreased plasma total cholesterol by 23% and LDL-C by 40%. Multicompartmental analysis (SAAM II) demonstrated that LDL apoB significantly decreased by 35% due primarily to a 45% increase in the LDL apoB fractional catabolic rate (FCR). SC-435 ؉ A significantly decreased hepatic concentrations of free cholesterol and cholesteryl ester, and increased hepatic LDL receptor mRNA consequent to increased cholesterol 7 ␣hydroxylase expression and activity. In comparison, SC-435 (10 mg/kg/day) monotherapy decreased LDL apoB by 10% due entirely to an 18% increase in LDL apoB FCR, whereas atorvastatin monotherapy (3 mg/kg/day) decreased LDL apoB by 30% due primarily to a 22% reduction in LDL apoB production.

The Journal of Lipid Research, 2006

The determination of lipolysis rates in humans in vivo requires the use of radioactive or stable ... more The determination of lipolysis rates in humans in vivo requires the use of radioactive or stable isotopic tracers

Journal of Biological Chemistry, 2009

Focal Adhesion Kinase (FAK) activity is controlled by growth factors and adhesion signals in tumo... more Focal Adhesion Kinase (FAK) activity is controlled by growth factors and adhesion signals in tumor cells. The scaffolding protein RACK1 (receptor for activated C kinases) integrates insulin-like growth factor I (IGF-I) and integrin signaling, but whether RACK1 is required for FAK function is unknown. Here we show that association of FAK with RACK1 is required for both FAK phosphorylation and dephosphorylation in response to IGF-I. Suppression of RACK1 by small interfering RNA ablates FAK phosphorylation and reduces cell adhesion, cell spreading, and clonogenic growth. Peptide array and mutagenesis studies localize the FAK binding interface to blades I-III of the RACK1 beta-propeller and specifically identify a set of basic and hydrophobic amino acids (Arg-47, Tyr-52, Arg-57, Arg-60, Phe-65, Lys-127, and Lys-130) as key determinants for association with FAK. Mutation of tyrosine 52 alone is sufficient to disrupt interaction of RACK1 with FAK in cells where endogenous RACK1 is suppressed by small interfering RNA. Cells expressing a Y52F mutant RACK1 are impaired in adhesion, growth, and foci formation. Comparative analyses of homology models and crystal structures for RACK1 orthologues suggest a role for Tyr-52 as a site for phosphorylation that induces conformational change in RACK1, switching the protein into a FAK binding state. Tyrosine 52 is further shown to be phosphorylated by c-Abl kinase, and the c-Abl inhibitor STI571 disrupts FAK interaction with RACK1. We conclude that FAK association with RACK1 is regulated by phosphorylation of Tyr-52. Our data reveal a novel mechanism whereby IGF-I and c-Abl control RACK1 association with FAK to facilitate adhesion signaling.

Journal of Aircraft, 2007

ABSTRACT The design, modeling, and testing of a morphing wing for flight control of an uninhabite... more ABSTRACT The design, modeling, and testing of a morphing wing for flight control of an uninhabited aerial vehicle is detailed. The design employed a new type of piezoelectric flight control mechanism which relied on axial precompression to magnify control deflections and forces simultaneously. This postbuckled precompressed bending actuator was oriented in the plane of the 12 % thick wing and mounted between the end of a tapered D-spar at the 40 % chord and a trailing-edge stiffener at the 98% chord. Axial precompression was generated in the piezoelectric elements by an elastic skin which covered the outside of the wing and served as the aerodynamic surface over the aft 70% of the wing chord. A two-dimensional semi-analytical model based on the Rayleigh-Ritz method of assumed modes was used to predict the static and dynamic trailing-edge deflections as a function of the applied voltage and aerodynamic loading. It was shown that static trailing-edge deflections of +/- 3.1 deg could be attained statically and dynamically through 34 Hz, with excellent correlation between theory and experiment. Wind tunnel and flight tests showed that the postbuckled precompressed morphing wing increased roll control authority on a 1.4 meter span uninhabited aerial vehicle while reducing weight, slop, part-count, and power consumption.

Journal of Aircraft, 1996

A new system for active flow control using smart vortex generators (SVG) is presented. Increments... more A new system for active flow control using smart vortex generators (SVG) is presented. Increments in C/max from modern vortex generators (VGs) are determined through wind-tunnel testing on a two-dimensional wing section. Using an optimized VG configuration, a system was built with 1) a shear-flow sensor that detected the onset and depth of stall, 2) a series of shape-memory-alloy VGs, and 3) a lift-todrag (L/D) maximizing controller. The system demonstrated a 14% increase in C /inax , a 2.7-deg rise in a,*,,, a 42% jump in L/D through the stall, and a low a C M penalty of less than 0.1%. Further testing demonstrated that the system consumed only 9.2 W of power, responded hi less than 0.8 s, and was capable of unstalling an airfoil that had exceeded o^,, by up to 3 deg.

Clinical Chemistry, 2004

Background: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (ap... more Background: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human lipoprotein metabolism. Two forms of apoB are produced from the APOB gene by a unique posttranscriptional editing process: apoB-48, which is required for chylomicron production in the small intestine, and apoB-100, required for VLDL production in the liver. In addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles. Content: The study of monogenic dyslipidemias has revealed important aspects of metabolic pathways. In this review, we discuss the regulation of apoB metabolism and examine how APOB gene defects can lead to both hypo-and hypercholesterolemia. The key clinical, metabolic, and genetic features of familial hypobetalipoproteinemia and familial ligand-defective apoB-100 are described. Summary: Missense mutations in the LDL-receptorbinding domain of apoB cause familial ligand-defective apoB-100, characterized by hypercholesterolemia and premature coronary artery disease. Other mutations in APOB can cause familial hypobetalipoproteinemia, characterized by hypocholesterolemia and resistance to atherosclerosis. These naturally occurring mutations reveal key domains in apoB and demonstrate how monogenic dyslipidemias can provide insight into biologically important mechanisms.

A parametric investigation into the use of CFRP materials to extend the fatigue life of vulnerabl... more A parametric investigation into the use of CFRP materials to extend the fatigue life of vulnerable connection details in steel bridge girders is described in this paper. CFRP overlay elements were attached to an AASHTO category E" detail and tested under cyclic loading. Several parameters were studied experimentally and analytically, including the configuration of a layer of resin used to attach the CFRP overlay to the steel, profile geometry of the composite overlay, and length of the composite overlay.