Surface Hydroxyl Chemistry of Titania- and Alumina-Based Supports: Quantitative Titration and Temperature Dependence of Surface Brønsted Acid-Base Parameters.

Surface hydroxyl groups on metal oxides play significant roles in catalyst synthesis and catalytic reactions. Despite the importance of surface hydroxyls in broader material applications, quantitative measurements of surface acid-base properties are not regularly reported. Here, we describe direct methods to quantify fundamental properties of surface hydroxyls on several titania- and alumina-based supports. Comparing commercially available anatase, rutile, P25, and P90 titania, thermogravimetric analysis (TGA) indicated that the total surface hydroxyl density varied by a factor of 2, and each surface hydroxyl is associated with approximately one weakly adsorbed water molecule. Proton-exchange site densities, determined at 25 °C with slurry acid-base titrations, led to several conclusions: (i) the intrinsic acidity/basicity of surface hydroxyls were similar regardless of the titania source; (ii) differences in the surface isoelectric point (IEP) were primarily attributable to differences in the surface concentration of acid and base sites; (iii) rutile has a higher surface concentration of basic hydroxyls, leading to a higher IEP; and (iv) P25 and P90 titania have slightly higher surface concentrationsof acidic hydroxyls relative to anatase or rutile. Temperature effects on surface acid-base properties are rarely reported yet are significant: from 5 to 65 °C, IEP values change by roughly one pH unit. The IEP changes were associated with large changes to the intrinsic acid-base equilibrium constants over this temperature range, rather than changes in the composition or concentration of the surface sites.

Prostate-Specific Membrane Antigen Targeted Pet/CT Imaging in Patients with Colon, Gastric and Pancreatic Cancer.

Current imaging modalities frequently misjudge disease stage in colorectal, gastric and pancreatic cancer. As treatment decisions are dependent on disease stage, incorrect staging has serious consequences. Previous preclinical research and case reports indicate that prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging might provide a solution to some of these challenges. This prospective clinical study aims to assess the feasibility of [18F]DCFPyL PET/CT imaging to target and visualize primary colon, gastric and pancreatic cancer. In this prospective clinical trial, patients with colon, gastric and pancreatic cancer were included and underwent both [18F]DCFPyL and [18F]FDG PET/CT scans prior to surgical resection or (for gastric cancer) neoadjuvant therapy. Semiquantitative analysis of immunohistochemical PSMA staining was performed on the surgical resection specimens, and the results were correlated to imaging parameters. The results of this study demonstrate detection of the primary tumor by [18F]DCFPyL PET/CT in 7 out of 10 patients with colon, gastric and pancreatic cancer, with a mean tumor-to-blood pool ratio (TBR) of 3.3 and mean SUVmax of 3.6. However, due to the high surrounding uptake, visual distinction of these tumors was difficult, and the SUVmax and TBR on [18F]FDG PET/CT were significantly higher than on [18F]DCFPyL PET/CT. In addition, no correlation between PSMA expression in the resection specimen and SUVmax on [18F]DCFPyL PET/CT was found. In conclusion, the detection of several gastrointestinal cancers using [18F]DCFPyL PET/CT is feasible. However, low tumor expression and high uptake physiologically in organs/background hamper the clear distinction of the tumor. As a result, [18F]FDG PET/CT was superior in detecting colon, gastric and pancreatic cancers.

Kinetics of H2 Adsorption at the Metal-Support Interface of Au/TiO2 Catalysts Probed by Broad Background IR Absorbance.

H2 adsorption on Au catalysts is weak and reversible, making it difficult to quantitatively study. We demonstrate H2 adsorption on Au/TiO2 catalysts results in electron transfer to the support, inducing shifts in the FTIR background. This broad background absorbance (BBA) signal is used to quantify H2 adsorption; adsorption equilibrium constants are comparable to volumetric adsorption measurements. H2 adsorption kinetics measured with the BBA show a lower Eapp value (23 kJ mol-1 ) for H2 adsorption than previously reported from proxy H/D exchange (33 kJ mol-1 ). We also identify a previously unreported H-O-H bending vibration associated with proton adsorption on electronically distinct Ti-OH metal-support interface sites, providing new insight into the nature and dynamics of H2 adsorption at the Au/TiO2 interface.

Water Poisons H2 Activation at the Au-TiO2 Interface by Slowing Proton and Electron Transfer between Au and Titania.

Understanding the dynamic changes at the active site during catalysis is a fundamental challenge that promises to improve catalytic properties. While performing Arrhenius studies during H2 oxidation over Au/TiO2 catalysts, we found different apparent activation energies (Eapp) depending on the feedwater pressure. This is partially attributed to changing numbers of metal-support interface (MSI) sites as water coverage changes with temperature. Constant water coverage studies showed two kinetic regimes: fast heterolytic H2 activation directly at the MSI (Eapp ∼ 25 kJ/mol) and significantly slower heterolytic H2 activation mediated by water (Eapp ∼ 45 kJ/mol). The two regimes had significantly different kinetics, suggesting a complicated mechanism of water poisoning. Density functional theory (DFT) showed water has minor effects on the reaction thermodynamics, primarily attributable to intrinsic differences in surface reactivity of different Au sites in the DFT model. The DFT model suggested significant surface restructuring of the TiO2 support during heterolytic H2 adsorption; evidence for this phenomenon was observed during in situ infrared spectroscopy experiments. A monolayer of water on the hydroxylated TiO2 surface increased the H2 dissociation activation barrier by ∼0.2 eV, in good agreement the difference in experimentally measured values. DFT calculations suggested H2 activation goes through a proton-coupled electron-transfer-like mechanism. During proton transfer to a basic support hydroxyl group, electron density is distributed through the gold nanorod and partially localized on the protonated support hydroxyl group. Water slows H2 activation by slowing this H+ transfer, forcing negative charge buildup on the Au and increasing the transition state energy.

H2 Oxidation over Supported Au Nanoparticle Catalysts: Evidence for Heterolytic H2 Activation at the Metal-Support Interface.

Water adsorbed at the metal-support interface (MSI) plays an important role in multiple reactions. Due to its importance in CO preferential oxidation (PrOx), we examined H2 oxidation kinetics in the presence of water over Au/TiO2 and Au/Al2O3 catalysts, reaching the following mechanistic conclusions: (i) O2 activation follows a similar mechanism to that proposed in CO oxidation catalysis; (ii) weakly adsorbed H2O is a strong reaction inhibitor; (iii) fast H2 activation occurs at the MSI, and (iv) H2 activation kinetics are inconsistent with traditional dissociative H2 chemisorption on metals. Density functional theory (DFT) calculations using a supported Au nanorod model suggest H2 activation proceeds through a heterolytic dissociation mechanism, resulting in a formal hydride residing on the Au and a proton bound to a surface TiOH group. This potential mechanism was supported by infrared spectroscopy experiments during H2 adsorption on a deuterated Au/TiO2 surface, which showed rapid H-D scrambling with surface hydroxyl groups. DFT calculations suggest that the reaction proceeds largely through proton-mediated pathways and that typical Brønsted-Evans Polanyi behavior is broken by introducing weak acid/base sites at the MSI. The kinetics data were successfully reinterpreted in the context of the heterolytic H2 activation mechanism, tying together the experimental and computational evidence and rationalizing the observed inhibition by physiorbed water on the support as blocking the MSI sites required for heterolytic H2 activation. In addition to providing evidence for this unusual H2 activation mechanism, these results offer additional insight into why water dramatically improves CO PrOx catalysis over Au.

CO Oxidation Kinetics over Au/TiO2 and Au/Al2O3 Catalysts: Evidence for a Common Water-Assisted Mechanism.

The mechanism of CO oxidation over supported gold catalysts has long been debated, with two prevailing mechanisms dominating the discussion: a water-assisted mechanism and a mechanism involving O-defect sites. In this study, we directly address this debate through a kinetic and mechanistic investigation of the role of water in CO oxidation over Au/TiO2 and Au/Al2O3 catalysts; the results clearly indicate a common water-assisted mechanism to be at work. Water adsorption isotherms were determined with infrared spectroscopy; the extracted equilibrium constant was essentially the same for both catalysts. Added water decreases CO adsorption on Au/TiO2, likely by blocking CO binding sites at the metal-support interface. Reaction kinetics (CO, O2, and H2O reaction orders) were essentially the same for both catalysts, as were measured O-H(D) kinetic isotope effects. These data indicate that the two catalysts operate by essentially the same mechanism under the conditions of these experiments (ambient temperature, significant amounts of water available). A reaction mechanism incorporating the kinetic and thermodynamic data and accounting for different CO and O2/COOH binding sites is proposed. The mechanism and kinetic data are treated with an active site (Michaelis-Menten) approach. This indicated that water adsorption does not significantly affect reaction rate constants, only the number of active sites available at a given water pressure. Extracted water and O2 binding constants are similar on both catalysts and consistent with previous DFT calculations. Water adsorption constants are also similar to independently determined equilibrium constants measured by IR spectroscopy. The likely roles of water, surface carbonates, and oxygen vacancies at the metal-support interface are discussed. The results definitively show that, at least in the presence of added water, O vacancies cannot play an important role in the room-temperature catalysis, and that the water-assisted mechanism is far more consistent with the preponderance of the kinetic data.

Evaluating differences in the active-site electronics of supported Au nanoparticle catalysts using Hammett and DFT studies.

Supported metal catalysts, which are composed of metal nanoparticles dispersed on metal oxides or other high-surface-area materials, are ubiquitous in industrially catalysed reactions. Identifying and characterizing the catalytic active sites on these materials still remains a substantial challenge, even though it is required to guide rational design of practical heterogeneous catalysts. Metal-support interactions have an enormous impact on the chemistry of the catalytic active site and can determine the optimum support for a reaction; however, few direct probes of these interactions are available. Here we show how benzyl alcohol oxidation Hammett studies can be used to characterize differences in the catalytic activity of Au nanoparticles hosted on various metal-oxide supports. We combine reactivity analysis with density functional theory calculations to demonstrate that the slope of experimental Hammett plots is affected by electron donation from the underlying oxide support to the Au particles.

Controlling activity and selectivity using water in the Au-catalysed preferential oxidation of CO in H2.

Industrial hydrogen production through methane steam reforming exceeds 50 million tons annually and accounts for 2-5% of global energy consumption. The hydrogen product, even after processing by the water-gas shift, still typically contains ∼1% CO, which must be removed for many applications. Methanation (CO + 3H2 → CH4 + H2O) is an effective solution to this problem, but consumes 5-15% of the generated hydrogen. The preferential oxidation (PROX) of CO with O2 in hydrogen represents a more-efficient solution. Supported gold nanoparticles, with their high CO-oxidation activity and notoriously low hydrogenation activity, have long been examined as PROX catalysts, but have shown disappointingly low activity and selectivity. Here we show that, under the proper conditions, a commercial Au/Al2O3 catalyst can remove CO to below 10 ppm and still maintain an O2-to-CO2 selectivity of 80-90%. The key to maximizing the catalyst activity and selectivity is to carefully control the feed-flow rate and maintain one to two monolayers of water (a key CO-oxidation co-catalyst) on the catalyst surface.

The critical role of water at the gold-titania interface in catalytic CO oxidation.

We provide direct evidence of a water-mediated reaction mechanism for room-temperature CO oxidation over Au/TiO2 catalysts. A hydrogen/deuterium kinetic isotope effect of nearly 2 implicates O-H(D) bond breaking in the rate-determining step. Kinetics and in situ infrared spectroscopy experiments showed that the coverage of weakly adsorbed water on TiO2 largely determines catalyst activity by changing the number of active sites. Density functional theory calculations indicated that proton transfer at the metal-support interface facilitates O2 binding and activation; the resulting Au-OOH species readily reacts with adsorbed Au-CO, yielding Au-COOH. Au-COOH decomposition involves proton transfer to water and was suggested to be rate determining. These results provide a unified explanation to disparate literature results, clearly defining the mechanistic roles of water, support OH groups, and the metal-support interface.

Alterations in plasma lecithin:cholesterol acyltransferase and myeloperoxidase in acute myocardial infarction: implications for cardiac outcome.

BACKGROUND: The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT and MPO on newly developed major adverse cardiovascular events (MACE). METHODS: Two-hundred one consecutive patients referred for acute chest pain of whom 134 had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained during 1203 (range 13-1745) days of follow-up among 185 patients. Plasma LCAT activity was measured using an exogenous substrate assay. MPO mass was assayed by chemiluminescent microparticle immunoassay. RESULTS: Plasma LCAT activity was decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI patients vs. patients with non-cardiac chest pain (p < 0.001 for both; correlation: r = -0.343, p < 0.001). MI at admission was associated independently with both lower plasma LCAT activity and higher MPO (age- and sex-adjusted odds ratio per 1 SD increment: 0.46 (95% CI, 0.31-0.68), p < 0.001 and 7.58 (95% CI, 3.34-17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95% CI, 1.15-2.19), p = 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI, 0.65-1.19), p = 0.39), predicted newly manifest MACE. CONCLUSION: In acute MI patients, plasma LCAT activity is decreased coinciding with increased MPO levels. Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac outcome.

Plasma lipoprotein-associated phospholipase A2 mass is elevated in STEMI compared to non-STEMI patients but does not discriminate between myocardial infarction and non-cardiac chest pain.

BACKGROUND: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass predicts future cardiovascular events in the non-acute setting. We tested the extent to which Lp-PLA2 is elevated in patients with acute coronary syndrome. METHODS: A total of 231 consecutive patients referred for acute chest pain participated. Of this number, 144 were diagnosed with myocardial infarction (MI; 100 were classified as MI with ST-elevation (STEMI) and 44 as MI without ST-elevation (non-STEMI)). Eighty-seven patients had non-cardiac chest pain. Plasma Lp-PLA2 mass was measured using turbidimetric immunoassay. RESULTS: Lp-PLA2 mass was not different between MI patients and patients with non-cardiac chest pain (231±72 µg/l vs.243±88 µg/l, p=0.29), and did not relate to MI in age- and sex-adjusted logistic regression analysis (odds ratio per SD increment, 0.92 (95% CI, 0.69-1.23), p=0.58). However, Lp-PLA2 mass was elevated in STEMI compared to non-STEMI patients (246±73 vs. 198±58 ng/ml, p<0.001), and independently predicted STEMI (odds ratio, 2.35 (95% CI, 1.46-3.79), p<0.001). Among MI patients maximal creatine kinase was correlated positively with Lp-PLA2 (r=0.183, p=0.034). CONCLUSIONS: In the acute setting, plasma Lp-PLA2 mass is not elevated in MI patients, although Lp-PLA2 mass appears to relate to the severity of myocardial damage.

Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: relationship with lipoprotein response to antiproteinuric treatment.

OBJECTIVE: LDL-receptor deficiency may provide a mechanism which contributes to atherogenic lipoprotein abnormalities in experimental nephrosis and in humans with glomerular proteinuria. The proprotein convertase subtilisin-kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation. We tested whether plasma PCSK9 is elevated in proteinuric states, and determined relationships of PCSK9 with lipoprotein responses to proteinuria reduction. METHODS: Thirty-nine kidney patients (e-GFR 61 ± 29 mL/min/1.73 m(2), proteinuria 1.9 [0.9-3.3] g/day; 19 on statin treatment) were studied during 2 randomized double-blind 6-week periods on either lisinopril (40 mg/day) and a regular sodium diet (194 ± 49 mmol Na+/day; baseline treatment) or lisinopril plus valsartan (320 mg/day) and a low sodium diet (102 ± 52 mmol Na(+)/day; maximal treatment), and compared to age- and sex-matched controls. Maximal treatment decreased proteinuria to 0.5 [0.3-1.1] g/day (P < 0.001). RESULTS: Plasma PCSK9 was increased at baseline in proteinuric subjects (213 [161-314] vs. 143 [113-190] ug/L in controls, P ≤ 0.001), irrespective of statin use, e-GFR and BMI. PCSK9 correlated with proteinuria at baseline (R = 0.399, P = 0.018) and at maximal antiproteinuric treatment (R = 0.525, P = 0.001), but did not decrease during proteinuria reduction (P = 0.84). Individual changes in total cholesterol (R = 0.365, P = 0.024), non-HDL cholesterol (R = 0.333, P = 0.041), and LDL cholesterol (R = 0.346, P = 0.033) were correlated positively with individual PCSK9 responses. PCSK9 at baseline independently predicted the total/HDL cholesterol ratio response to treatment (P = 0.04). CONCLUSION: Plasma PCSK9 was elevated in proteinuria, predicted lipoprotein responses to proteinuria reduction but remained unchanged after proteinuria reduction. Inhibition of the PCSK9 pathway may provide a novel treatment strategy in proteinuric subjects.

Plasma Lp-PLA(2) mass and apoB-lipoproteins that carry Lp-PLA(2) decrease after sodium.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2) ) is a novel cardiovascular risk marker, which is predominantly complexed to apolipoprotein (apo) B-containing lipoproteins in human plasma. As increasing dietary sodium intake may decrease plasma apoB-containing lipoproteins, we tested whether a sodium challenge lowers plasma Lp-PLA(2) mass, as well as the levels of apoB-containing lipoprotein particles carrying Lp-PLA(2) (apoB-Lp-PLA(2) ), employing a newly developed enzyme-linked immunosorbent assay. MATERIALS AND METHODS: In 45 women and 31 men (mean age 44 ± 14 years), plasma Lp-PLA(2) mass (turbidimetric immunoassay), the level of apoB-Lp-PLA(2) , expressed in apoB concentration and lipoproteins were measured in response to a 3-day challenge with 9 g sodium chloride tablets daily. RESULTS: Urinary sodium excretion increased from 165 ± 60 to 321 ± 70 mmol/24 h (P<0.001) after salt loading. Plasma Lp-PLA(2) mass decreased from 618 (493-719) to 588 (465-698) µg/L (P<0.001), and apoB-Lp-PLA(2) decreased from 0.276 (0.200-0.351) to 0.256 (0.189-0.328) g LDL protein/L (P=0.004) in response to the sodium challenge together with decreases in plasma total cholesterol, nonhigh-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B and the total cholesterol/HDL cholesterol ratio (P<0.01 for all). Changes in plasma Lp-PLA(2) mass were correlated positively with changes in total cholesterol, LDL cholesterol and non-HDL cholesterol (r=0.260-0.276, P<0.05 to P<0.02), whereas changes in apoB-Lp-PLA(2) were correlated positively with changes in non-HDL cholesterol and in the total cholesterol/HDL cholesterol ratio (r=0.232-0.385, P<0.05-0.01). CONCLUSION: Both plasma Lp-PLA(2) mass levels and apoB-Lp-PLA(2) decrease in response to a short-term oral sodium challenge.

Metabolic effects of high altitude trekking in patients with type 2 diabetes.

OBJECTIVE: Limited information is available regarding the metabolic effects of high altitude trekking in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirteen individuals with type 2 diabetes took part in a 12-day expedition to the summit of Mount Toubkal (altitude, 4,167 m), Morocco, after 6 months of exercise training. Energy expenditure, body weight, blood glucose, fasting insulin, lipids, and HbA(1c) were assessed. RESULTS: Training reduced fasting glucose (-0.7 ± 0.9 mmol/L, P = 0.026) and increased exercise capacity (+0.3 ± 0.3 W/kg, P = 0.005). High altitude trekking decreased fasting insulin concentrations (-3.8 ± 3.2 µU/L, P = 0.04), total cholesterol (-0.7 ± 0.8 mmol/L, P = 0.008), and LDL cholesterol (-0.5 ± 0.6 mmol/L, P = 0.007). CONCLUSIONS: High altitude trekking preceded by exercise training is feasible for patients with type 2 diabetes. It improves blood glucose, lipids, and fasting insulin concentrations, while glucose control is maintained.

Statin and fibrate combination does not additionally lower plasma cholesteryl ester transfer in type 2 diabetes mellitus.

BACKGROUND: Plasma cholesteryl ester transfer (CET) from high density lipoproteins (HDL) to very low and low density lipoproteins (VLDL+LDL) may predict (subclinical) atherosclerosis. We tested the extent to which plasma CET and cholesterol esterification (EST) are decreased by statin and fibrate combination therapy compared to statin and fibrate administration alone in type 2 diabetic patients. METHODS: Plasma CET and EST were measured by isotope assays in 14 type 2 diabetic patients, in whom a randomized placebo-controlled crossover study was carried out (8 weeks treatment with simvastatin (40 mg daily), bezafibrate (400 mg daily) and their combination). Plasma CET and EST from diabetic patients were compared with 42 non-diabetic control subjects with similar triglyceride levels. RESULTS: Plasma CET and EST were elevated in diabetic patients at baseline compared to control subjects (p < 0.01), and were correlated positively with non-HDL cholesterol and triglycerides in non-diabetic subjects and in diabetic patients at baseline (p < 0.01). Decreases in CET during combined treatment (p < 0.05) were not greater than the changes during simvastatin and bezafibrate monotherapy (p > 0.20). EST only decreased during bezafibrate therapy (p < 0.05). Changes in CET during treatment were correlated positively with changes in non-HDL cholesterol (p < 0.05) and triglycerides (p < 0.001). Changes in HDL cholesterol were related inversely to changes in CET (p < 0.05). CONCLUSIONS: Diabetes-associated plasma CET elevations are ameliorated by statin and fibrate monotherapy, but combined lipid lowering drug treatment does not additively lower CET. CET lowering likely contributes to HDL cholesterol changes during statin and fibrate administration.

Accuracy of handheld blood glucose meters at high altitude.

BACKGROUND: Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs. METHODOLOGY/PRINCIPAL FINDINGS: Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude. CONCLUSION: At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy.

Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus.

PURPOSE: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by statin or fibrate administration in patients with diabetes mellitus. METHODS: Fourteen type 2 diabetic patients participated in a placebo-controlled crossover study which included three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), and their combination. RESULTS: ApoM was decreased by 7% in response to simvastatin (P<0.05 from baseline and placebo), and remained unchanged during bezafibrate and combined simvastatin+bezafibrate administration. Plasma apoM concentrations correlated positively with apoB-containing lipoprotein measures at baseline and during placebo (P<0.02 to P<0.001), but these relationships were lost during all lipid lowering treatment periods. CONCLUSIONS: This study suggests that, even though plasma apoM is lowered by statins, apoM metabolism is to a considerable extent independent of statin- and fibrate-affected pathways involved in cholesterol homeostasis.

Patterning high surface area silica with lysozyme: adsorption kinetics, fluorescence quenching, and protein readsorption studies to evaluate the templated surface.

A method was developed for using an inexpensive and widely available protein, hen egg white lysozyme, as a patterning agent for commercial high surface area silicas. The basic patterning methodology involved spontaneous adsorption of the protein from aqueous solution, alkylation of the uncovered surface with an alkylsiloxane, and protein desorption in a slightly alkaline solution of morpholine. Adsorption kinetic studies using Bradford assays assisted in determining protein deposition conditions. These studies were generally consistent with results on more planar silica surfaces and indicated that the protein quickly and strongly adsorbs along its long axis at low surface coverages. A modified fluorescence resonance energy transfer (FRET) technique was developed and employed to evaluate protein spacing. This technique showed that the proteins are well dispersed at low coverages. Readsorption experiments show that the templated regions are robust, retaining the size and shape of the original protein templates.

A single-substrate model to interpret intra-annual stable isotope signals in tree-ring cellulose.

The carbon and oxygen stable isotope composition of wood cellulose (delta(13)C(cellulose) and delta(18)O(cellulose), respectively) reveal well-defined seasonal variations that contain valuable records of past climate, leaf gas exchange and carbon allocation dynamics within the trees. Here, we present a single-substrate model for wood growth to interpret seasonal isotopic signals collected in an even-aged maritime pine plantation growing in South-west France, where climate, soil and flux variables were also monitored. Observed seasonal patterns in delta(13)C(cellulose) and delta(18)O(cellulose) were different between years and individuals, and mostly captured by the model, suggesting that the single-substrate hypothesis is a good approximation for tree ring studies on Pinus pinaster, at least for the environmental conditions covered by this study. A sensitivity analysis revealed that the model was mostly affected by five isotopic discrimination factors and two leaf gas-exchange parameters. Modelled early wood signals were also very sensitive to the date when cell wall thickening begins (t(wt)). Our model could therefore be used to reconstruct t(wt) time series and improve our understanding of how climate influences this key parameter of xylogenesis.