Polyaniline/Pt Hybrid Nanofibers: High-Efficiency Nanoelectrocatalysts for Electrochemical Devices

A simple and facile procedure to synthesize a novel hybrid nanoelectrocatalyst based on polyaniline (PANI) nanofiber-supported supra-high density Pt nanoparticles (NPs) or Pt/Pd hybrid NPs without prior PANI nanofiber functionalization at room temperature is demonstrated. This represents a new type of ID hybrid nanoelectrocatalyst with several important benefits. First, the procedure is very simple and can be performed at room temperature using commercially available reagents without the need for templates and surfactants. Second, ultra-high density small "bare" Pt NPs or Pt/Pd hybrid NPs are grown directly onto the surface of the PANI nanofiber, without using any additional linker. Most importantly, the present PANI nanofiber-supported supra-high density Pt NPs or Pt/Pd hybrid NPs can be used as a signal enhancement element for constructing electrochemical devices with high performance.

Monodisperse, submicrometer-scale platinum colloidal spheres with high electrocatalytic activity

Monodisperse, submicrometer-scale platinum (Pt) colloidal spheres were prepared through a simple direct chemical reduction of p-phenylenediamine (PPD)-chloroplatinic acid (H2PtCl6) coordination polymer colloids. It was found that the prepared Pt colloids had the similar size and morphology with their coordination polymer precursors, and the prepared Pt colloids with rough surfaces were three-dimensional (3D) structured assemblies of high-density small Pt nanoparticles. The electrochemical experiments confirmed that the prepared Pt colloids possessed a high electrocatalytic activity towards mainly four-electron reduction of dioxygen to water, making the prepared Pt colloids potential candidates for the efficient cathode material in fuel cells.

LOCALIZED ENHANCEMENTS OF Fe+10 DENSITY IN THE CORONA AS OBSERVED IN Fe xi 789.2 nm DURING THE 2006 MARCH 29 TOTAL SOLAR ECLIPSE

Habbal, Shadia Rifai; Morgan, Huw; Johnson, Judd; Arndt, Martina Belz; Daw, Adrian; Jaeggli, Sarah; Kuhn, Jeff; Mickey, Don, LOCALIZED ENHANCEMENTS OF Fe+10 DENSITY IN THE CORONA AS OBSERVED IN Fe xi 789.2 nm DURING THE 2006 MARCH 29 TOTAL SOLAR ECLIPSE, The Astrophysical Journal, Volume 663, Issue 1, pp. 598-609

Study protocol: the Adherence and Intensification of Medications (AIM) study--a cluster randomized controlled effectiveness study.

BACKGROUND: Many patients with diabetes have poor blood pressure (BP) control. Pharmacological therapy is the cornerstone of effective BP treatment, yet there are high rates both of poor medication adherence and failure to intensify medications. Successful medication management requires an effective partnership between providers who initiate and increase doses of effective medications and patients who adhere to the regimen. METHODS: In this cluster-randomized controlled effectiveness study, primary care teams within sites were randomized to a program led by a clinical pharmacist trained in motivational interviewing-based behavioral counseling approaches and authorized to make BP medication changes or to usual care. This study involved the collection of data during a 14-month intervention period in three Department of Veterans Affairs facilities and two Kaiser Permanente Northern California facilities. The clinical pharmacist was supported by clinical information systems that enabled proactive identification of, and outreach to, eligible patients identified on the basis of poor BP control and either medication refill gaps or lack of recent medication intensification. The primary outcome is the relative change in systolic blood pressure (SBP) measurements over time. Secondary outcomes are changes in Hemoglobin A1c, low-density lipoprotein cholesterol (LDL), medication adherence determined from pharmacy refill data, and medication intensification rates. DISCUSSION: Integration of the three intervention elements--proactive identification, adherence counseling and medication intensification--is essential to achieve optimal levels of control for high-risk patients. Testing the effectiveness of this intervention at the team level allows us to study the program as it would typically be implemented within a clinic setting, including how it integrates with other elements of care. TRIAL REGISTRATION: The ClinicalTrials.gov registration number is NCT00495794.

Glutamine supplementation and renal health

Gemstone Team Juiced

Recombinant Adeno-Associated Virus-Mediated Gene Therapy for Treatment of Familial Hypercholesterolemia in Rabbits

Familial hypercholesterolemia (FH) is a genetic disorder characterized by abnormally high concentrations of low-density lipoprotein-cholesterol (LDLcholesterol) in the blood that can contribute to heart disease. FH can result from a defect in the gene for the LDL receptor (LDL-R). FH patients lacking functional LDL-R may benefit from viral-mediated transfer of a functional copy of the open reading frame (ORF) of the LDL-R. Since a recombinant adeno-associated virus (rAAV) is not immunogenic and can be mass-produced, it shows promise for gene therapy applications. AAV6 and AAV8 have been shown to specifically transduce hepatocytes in several species, which normally remove the majority of LDL-cholesterol from the blood via LDL-R-mediated endocytosis. Because of the potential of rAAV to treat FH by delivery of a correct LDL-R ORF to hepatocytes, the liver specificity of these two AAV serotypes was evaluated. Additionally, rabbits were chosen as the animal model for this study because a specific strain of rabbits, Watanabe heritable hyperlipidemic (WHHL), adequately mimics the pathology of FH in humans. Exposure of rabbit liver to rAAV with the marker LacZ and subsequent inspection of liver tissue showed that AAV8 transduced rabbit liver more efficiently than AAV6. To assess the feasibility of producing a rAAV capable of transferring the LDL-R ORF to rabbit hepatocytes in vivo, rAAV8-LDL-R was mass-produced by a baculovirus system in suspension grown insect cells.

Influence of megasonic agitation on the electrodeposition of high aspect ratio blind vias

This paper presents preliminary studies in electroplating using megasonic agitation to avoid the formation of voids within high aspect ratio microvias that are used for the redistribution of interconnects in high density interconnection technology in printed circuit boards. Through this technique, uniform deposition of metal on the side walls of the vias is possible. High frequency acoustic streaming at megasonic frequencies enables the decrease of the Nernst diffusion layer down to the sub-micron range, allowing thereby conformal electrodeposition in deep grooves. This effect enables the normally convection free liquid near the surface to be agitated. Higher throughput and better control of the material properties of the deposits can be achieved for the manufacturing of embedded interconnections and metal-based MEMS. For optimal filling performance of the microvias, a full design of experiments (DOE) and a multi-physics numerical simulation have been conducted to analyse the influence of megasonic agitation on the plating quality of the microvias. Megasonic based deposition has been found to increase the deposition rate as well as improving the quality of the metal deposits.

THE ROLE OF LIPOPROTEIN(a)/APOLIPOPROTEIN(a) IN ENDOTHELIAL DYSFUNCTION: MECHANISTIC STUDIES IN VASCULAR ENDOTHELIUM

Multiple lines of evidence suggest that elevated plasma lipoprotein(a) (Lp(a)) concentrations are a significant risk factor for the development of a number of vascular diseases including coronary heart disease and stroke. Lp(a) consists of a low-density lipoprotein (LDL)-like moiety and an unique glycoprotein, apolipoprotein(a) (apo(a)), that is covalently attached to the apolipoproteinB-100 (apoB-100) component of LDL by a single disulfide bond. Many studies have suggested a role for Lp(a) in the process of endothelial dysfunction. Indeed, Lp(a) has been shown to increase both the expression of adhesion molecules on endothelial cells (EC), as well as monocyte and leukocyte chemotactic activity in these cells. We have previously demonstrated that Lp(a), through its apo(a) moiety, increases actomyosin-driven EC contraction which, as a consequence, increases EC permeability. In this thesis, we have demonstrated a role for the strong lysine-binding site in the kringle IV type 10 domain of apo(a) in increasing EC permeability, which occurs through a Rho/Rho kinase-dependent pathway. We have further validated these findings using mouse mesenteric arteries in a pressure myograph system. We also have dissected another major signaling pathway initiated by apo(a) that involves in a disruption of adherens junctions in EC. In this pathway, apo(a)/Lp(a) activates the PI3K/Akt/GSK3β-dependent pathway to facilitate nuclear translocation of beta-catenin. In the nucleus beta-catenin induced the expression of cyclooxygenase-2 (COX-2) and the secretion of prostaglandin E2 (PGE2) from the EC. Finally, we have presented data to suggest a novel inflammatory role for apo(a) in which it induces the activation of nuclear factor-kappaB through promotion of the dissociation of IkappaB from the inactive cytoplasmic complex; this allows the nuclear translocation of NFkappaB with attendant effects on the transcription of pro-inflammatory genes. Taken together, our findings may facilitate the development of new drug targets for mitigating the harmful effects of Lp(a) on vascular EC which corresponds to an early step in the process of atherogenesis.

Interactions of Lipoprotein(a) with the Plasminogen System: Mechanisms and Pathophysiological Consequences

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are associated with increased risk of atherothrombotic disease. Lp(a) is a unique lipoprotein consisting of a low density lipoprotein-like moiety covalently linked to apolipoprotein(a) (apo(a)), a homologue of the fibrinolytic proenzyme plasminogen. Apo(a) is extremely heterogeneous in size with small isoforms being independently associated with increased cardiovascular risk. Several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit tissue-type plasminogen activator (tPA)-mediated plasminogen activation on fibrin surfaces, although the mechanism of inhibition by apo(a) remains controversial. Essential to fibrin clot lysis are a number of plasmin-dependent positive feedback reactions that enhance the efficiency of plasminogen activation, including the plasmin-mediated conversion of Glu1-plasminogen to Lys78-plasminogen. Additionally, abnormal fibrin clot structures have been associated with both an increased risk of cardiovascular disease and elevated Lp(a) levels. Similarly, oxidized phospholipids have been implicated in the development of cardiovascular disease, and are not only preferentially carried by Lp(a) in the plasma but have also been shown to covalently-modify both apo(a) and plasminogen. In this thesis, we built upon the understanding of the role of apo(a) in plasminogen activation on the fibrin/degraded fibrin surface by determining that: (i) apo(a) inhibits plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion and identifying the critical domains in apo(a) responsible for this effect, (ii) apo(a) isoform size does not affect either the inhibition of tPA-mediated plasminogen activation or the inhibition of plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion, (iii) apo(a) modifies fibrin clot structure to form more dense clots with thinner fibers and reduced permeability, modifications that enhance the ability of apo(a) to inhibit tPA-mediated plasminogen activation and (iv) the phosphorus content of apo(a) affects its ability to inhibit tPA-mediated plasminogen activation and the phosphorus content of plasminogen affects its ability to be activated by tPA. By understanding these individual reactions, each of which has the potential to affect the broader fibrin clot lysis process, we have expanded our understanding of the overall effect of Lp(a)/apo(a) in the inhibition of plasminogen activation on the fibrin/degraded fibrin surface and thus broadened our understanding of how Lp(a)/apo(a) may mediate the inhibition of thrombolysis in vivo.

High-solid-content hydroxyapatite slurry for the production of bone substitute scaffolds

Key to various bone substitute scaffold production techniques is the development of free-flowing ceramic slurry with optimum theological properties. The aim is to achieve a colloidal suspension with as high a solid content as possible while maintaining a low viscosity which easily penetrates the pores of relevant sacrificial templates. The following investigation describes the optimization of a hydroxyapatite slip and demonstrates its potential application in scaffold production. Using predominantly spherical particles of hydroxyapatite of between 0.82 mu m and 16.2 mu m, coupled with a 2 wt % addition of the anionic polyelectrolyte, ammonium polyacrylate, an 80 wt % (55.9 vol %) hydroxyapatite solid loaded slip with a viscosity of approximately 126 mPa s has been developed. Its ability to infiltrate and replicate porous preforms has been shown using polyurethane foam. The enhanced particle packing achieved has allowed for the production of scaffolds with highly dense and uniform grain structures. The results represent a significant improvement in current slurry production techniques and can be utilized to develop high-density ceramic bone substitute scaffolds.

Three dimensional number density mapping in the plume of a low temperature laser ablated magnesium plasma

Simultaneous optical absorption and laser-induced fluorescence measurements have been used to map the three-dimensional number densities of ground-state ions and neutrals within a low-temperature KrF laser-produced magnesium plasma expanding into vacuum. Data is reported for the symmetry plane of the plasma, which includes the laser interaction point at a delay of 1 μs after the ∼30 ns KrF laser ablation pulse and for a laser fluence of 2 J cm−2 on target. The number density distributions of ion and neutral species within this plane indicate that two distinct regions exist within the plume; one is a fast component containing ions and neutrals at maximum densities of ∼3×1013 cm−3 and ∼4×1012 cm−3, respectively and the second is a high-density region containing slow neutral species, at densities up to ∼1×1015 cm−3.

Saturated and Trans Fatty Acids and Coronary Heart Disease

Dietary intake of both saturated and trans fatty acids has been associated with an increase in the risk of coronary heart disease (CHD). Evidence comes mainly from controlled dietary experiments with intermediate end points, such as blood lipoproteins, and from observational studies. A few small, randomized controlled trials with clinical end points have been carried out in which saturated fat was replaced with polyunsaturated fat, leading to a reduction in low-density lipoprotein cholesterol and a reduction in CHD risk. However, no such studies exist for trans fatty acids. More high-quality, randomized controlled trials on fatty acids and CHD are required, but public health recommendations to reduce intake of both saturated and trans fatty acids are appropriate based on the current evidence.

GPVI levels in platelets: relationship to platelet function at high shear

We have investigated the density of the collagen receptors glycoprotein VI (GPVI) and alpha(2)beta(1) on human platelets and their relationship to polymorphisms within the GPVI gene. GPVI levels varied 1.5-fold and showed a weak correlation (r = 0.35) with the levels of alpha(2)beta(1), which varied 3-fold. GPVI genotype had a significant effect on receptor levels with carriers of the proline 219 allele (approximately 22% of the population) having 10% lower GPVI levels than the more common serine homozygotes. GPVI and alpha(2)beta(1) levels were found to be significantly decreased on platelets from patients with myeloproliferative disorders (MPDs). In both the MPD and the control group, GPVI levels were found not to affect platelet function under high shear in whole blood. Similarly murine platelets that express up to 5-fold lower levels of GPVI showed no significant difference than controls in thrombus formation on a high-density collagen-coated surface. However platelets lacking the GPVI/Fc receptor gamma-chain (FcR gamma-chain) complex or a functional FcR gamma-chain (immunoreceptor tyrosine-based activation motif [ITAM] point mutant) exhibited severely abrogated thrombus formation at 800 s(-1) and 1500 s(-1). These results demonstrate that GPVI levels are tightly controlled and play a critical role in thrombus formation on collagen; nevertheless, a range of receptor densities can support platelet function under high shear. (C) 2003 by The American Society of Hematology.

High-resolution 14C dating of a 25,000-year lake-sediment record from equatorial East Africa

We dated a continuous, ~22-m long sediment sequence from Lake Challa (Mt. Kilimanjaro area, Kenya/Tanzania) to produce a solid chronological framework for multi-proxy reconstructions of climate and environmental change in equatorial East Africa over the past 25,000 years. The age model is based on a total of 168 AMS 14C dates on bulk-organic matter, combined with a 210Pb chronology for recent sediments and corrected for a variable old-carbon age offset. This offset was estimated by i) pairing bulk-organic 14C dates with either 210Pb-derived time markers or 14C dates on grass charcoal, and ii) wiggle-matching high-density series of bulk-organic 14C dates. Variation in the old-carbon age offset through time is relatively modest, ranging from ~450 yr during glacial and late glacial time to ~200 yr during the early and mid-Holocene, and increasing again to ~250 yr today. The screened and corrected 14C dates were calibrated sequentially, statistically constrained by their stratigraphical order. As a result their constrained calendar-age distributions are much narrower, and the calibrated dates more precise, than if each 14C date had been calibrated on its own. The smooth-spline age-depth model has 95% age uncertainty ranges of ~50–230 yr during the Holocene and ~250–550 yr in the glacial section of the record. The d13C values of paired bulk-organic and grass-charcoal samples, and additional 14C dating on selected turbidite horizons, indicates that the old-carbon age offset in Lake Challa is caused by a variable contribution of old terrestrial organic matter eroded from soils, and controlled mainly by changes in vegetation cover within the crater basin.

High-velocity features: A ubiquitous property of Type Ia supernovae

Evidence of high-velocity features (HVFs) such as those seen in the near-maximum spectra of some Type Ia supernovae (SNe Ia; e. g., SN 2000cx) has been searched for in the available SN Ia spectra observed earlier than 1 week before B maximum. Recent observational efforts have doubled the number of SNe Ia with very early spectra. Remarkably, all SNe Ia with early data ( seven in our Research Training Network sample and 10 from other programs) show signs of such features, to a greater or lesser degree, in Ca II IR and some also in the Si II lambda 6355 line. HVFs may be interpreted as abundance or density enhancements. Abundance enhancements would imply an outer region dominated by Si and Ca. Density enhancements may result from the sweeping up of circumstellar material (CSM) by the highest velocity SN ejecta. In this scenario, the high incidence of HVFs suggests that a thick disk and/or a high-density companion wind surrounds the exploding white dwarf, as may be the case in single degenerate systems. Large-scale angular fluctuations in the radial density and abundance distribution may also be responsible: this could originate in the explosion and would suggest a deflagration as the more likely explosion mechanism. CSM interaction and surface fluctuations may coexist, possibly leaving different signatures on the spectrum. In some SNe, the HVFs are narrowly confined in velocity, suggesting the ejection of blobs of burned material.