Growth of vertically aligned nanowires in metal-oxide nanocomposites: kinetic Monte-Carlo modeling versus experiments.

We employ kinetic Monte-Carlo simulations to study the growth process of metal-oxide nanocomposites obtained via sequential pulsed laser deposition. Using Ni-SrTiO3 (Ni-STO) as a model system, we reduce the complexity of the computational problem by choosing a coarse-grained approach mapping Sr, Ti and O atoms onto a single effective STO pseudo-atom species. With this ansatz, we scrutinize the kinetics of the sequential synthesis process, governed by alternating deposition and relaxation steps, and analyze the self-organization propensity of Ni atoms into straight vertically aligned nanowires embedded in the surrounding STO matrix. We finally compare the predictions of our binary toy model with experiments and demonstrate that our computational approach captures fundamental aspects of self-assembled nanowire synthesis. Despite its simplicity, our modeling strategy successfully describes the impact of relevant parameters like the concentration or laser frequency on the final nanoarchitecture of metal-oxide thin films grown via pulsed laser deposition.

Nanometer-resolved quantification of mechanical response in nanoparticle-based composites.

Nanocomposites constitute an upcoming class of materials that has enormous potential within a broad range of areas, particularly with regard to mechanical applications. However, the tuning of material properties requires a full understanding of the mechanical response of the nanocomposite across all length scales. While characterization from the micro to macroscale is well established at this point, quantification of mechanical behavior at the nanoscale is still an unresolved challenge. With this background, the current work demonstrates the capabilities of quantitative contact resonance atomic force microscopy (CR-AFM) to localize and reliably characterize Ni nanoparticles that are embedded below the surface of thermally oxidized silicon thin films. Correlating these results with numerical simulations as well as high-resolution transmission electron microscopy measurements provides a comprehensive understanding of the subtle interplay between the structure and nanomechanical response of the composite.

Plasma-assisted synthesis and high-resolution characterization of anisotropic elemental and bimetallic core-shell magnetic nanoparticles.

Magnetically anisotropic as well as magnetic core-shell nanoparticles (CS-NPs) with controllable properties are highly desirable in a broad range of applications. With this background, a setup for the synthesis of heterostructured magnetic core-shell nanoparticles, which relies on (optionally pulsed) DC plasma gas condensation has been developed. We demonstrate the synthesis of elemental nickel nanoparticles with highly tunable sizes and shapes and Ni@Cu CS-NPs with an average shell thickness of 10 nm as determined with scanning electron microscopy, high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy measurements. An analytical model that relies on classical kinetic gas theory is used to describe the deposition of Cu shell atoms on top of existing Ni cores. Its predictive power and possible implications for the growth of heterostructured NP in gas condensation processes are discussed.

Plasma leptin concentrations during extended fasting and graded glucose infusions: relationships with changes in glucose, insulin, and FFA.

Despite numerous studies, the in vivo regulation of plasma leptin levels in response to nutritional factors continues to remain unclear. We investigated temporal and dose-response relationships of plasma leptin in response to physiological changes in insulin/glucose. After an overnight fast of 10 h, lean, healthy subjects were investigated for an additional 16 h of either extended fasting or one of three levels of glycemia/insulinemia induced by stepwise increasing iv glucose infusions. During extended fasting, plasma leptin values declined steadily and significantly. Plasma leptin levels remained constant at glucose concentrations between 5.8-6.5 mmol/liter, which maintained normoinsulinemia at 41.5-45.4 pmol/liter and FFA at 106-123 mg/liter, but leptin concentrations were increased at higher rates of glucose infusion (with plasma glucose rising to 8.7 mmol/liter). Concentrations of serum leptin were inversely related to FFA levels during extended fasting and at all levels of glycemia. Our data indicate that in lean healthy subjects, physiological changes in glycemia and insulinemia significantly alter plasma FFA and leptin concentrations. The increases in leptin concentrations demonstrate dose-dependent relationships that appear to relate to changes in FFA levels as well as to changes in glycemia/insulinemia.

Metabolism and distribution of [2,3-(14)C]acrolein in laying hens.

The metabolism and distribution of [2,3-(14)C]-acrolein were studied in 10 laying hens orally administered 1.09 mg/kg of body weight/day for 5 days. Eggs, excreta, and expired air were collected. The hens were killed 12-14 h after the last dose and edible tissues collected. The nature of radioactive residues was determined in tissues and eggs. All of the identified metabolites were the result of the incorporation of acrolein-derived radioactivity into normal natural products of intermediary metabolism in the hen except for 1,3-propanediol, which is a known degradation product of glycerol in bacteria.

Relationships of plasma leptin levels to changes in plasma free fatty acids in women who are lean and women who are abdominally obese.

Regulation of leptin production by the hormonal and metabolic milieu is poorly understood. Because abdominal obesity is commonly associated with elevated plasma free fatty acid (FFA) flux, we examined the effects of augmenting FFA on plasma leptin levels in women who were lean and of suppressing FFA in women with abdominal obesity. In study 1, nine subjects who were lean, after a 12-hour overnight fast, received either intravenous saline or Intralipid plus heparin to increase the plasma FFA concentration to approximately 1000 mumol/ L. After 3 hours of additional fasting, subjects underwent 3-hour hyperglycemic clamps. In study 2, seven subjects with abdominal obesity were evaluated by a similar protocol, but lipolysis and plasma FFA flux were instead maximally suppressed by acipimox. In the individuals who were lean, leptin levels were unchanged during clamping. Increasing plasma FFA reduced plasma leptin from 7.66 +/- 0.66 to 7.05 +/- 0.66 (p = 0.03), but 3 hours of hyperglycemia plus hyperinsulinemia had no additional effect on leptin levels (7.15 +/- 0.71). Basal leptin levels, 4-fold higher in the subjects with obesity, were reduced from 34.6 +/- 2.4 micrograms/L to 32.3 +/- 1.1 micrograms/L (p = 0.004) during the clamp period. When plasma FFA flux was suppressed, however, plasma leptin levels after clamped hyperglycemia/hyperinsulinemia were increased to 38.9 +/- 1.2 micrograms/L (p = 0.014 vs. time 0 and 0.001 vs. saline protocol). Changes in leptin concentrations are not correlated with changes in FFA. These results suggest that plasma FFA concentration does not regulate plasma leptin levels in basal, extended fasting, or hyperglycemic/hyperinsulinemic states.

Effects of free fatty acids and glucose on splanchnic insulin dynamics.

The mechanism of hyperinsulinemia that accompanies insulin resistance in some abdominally obese and diabetic individuals is poorly understood. Both increased secretion of insulin and decreased clearance have been demonstrated. The present study was undertaken to examine the role of free fatty acids (FFAs) and glucose in regulating splanchnic insulin dynamics in vivo. Plasma FFA levels were raised approximately twofold via an intralipid/heparin infusion in eight lean women. Insulin dynamics were assessed using the individual's C-peptide kinetic coefficients. Studies were performed in the basal state and during two levels of glycemia, 7 and 11 mmol/l. Studies were repeated using saline, and thus each subject served as her own control. Under basal conditions, raising FFA flux resulted in a modest increase in plasma insulin concentration (PIC) secondary to an increase in insulin secretion rate (ISR); however, endogenous insulin clearance (EIC) was not influenced. During the 7 mmol/l hyperglycemic clamp, maintaining a high FFA flux resulted in a 30% increase in PIC above the effect produced by glucose alone. This represents the cumulative effects of stimulation of ISR and inhibition of EIC. Clamping plasma glucose at 11 mmol/l while maintaining a high FFA flux increased PIC twofold above that produced by glucose alone. This increase in PIC was mainly due to a significant reduction in EIC without an accompanying increase in ISR (392 +/- 159 and 787 +/- 187 ml/min with and without intralipid infusion, respectively). Analysis of variance indicated that the suppressive effect of FFA on EIC was independent of the effect of glucose. The effect of the two substrates seems to be additive.

Leptin: a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African-American women.

The recently cloned adipose tissue hormone leptin has been proposed to be involved in the neuroendocrine regulation of adiposity and its metabolic sequelae. Visceral fat is known to predict reduced insulin sensitivity and associated adverse metabolic profiles. In this study, we report the first evaluation of the relationships between leptin levels and total body fat, visceral fat, and insulin sensitivity in a cohort of premenopausal African-American women. Thirty-four subjects were analyzed for total fat mass and visceral fat by dual-energy X-ray absorptiometry and computerized axial tomography, respectively. Insulin sensitivity (SI) was assessed using Bergman's minimal model. Results showed that fasting leptin levels strongly correlated with total body fat mass (r = 0.797, P < 0.001). Correlations of leptin with visceral fat (r = 0.54, P < 0.001) and SI (r = -0.419, P = 0.02) were dependent on total body fat. In conclusion, leptin levels reflect total body fat mass, and although visceral fat is known to predict reduced insulin sensitivity independently, leptin did not. Our data thus suggest that diverse mechanisms are responsible for the regulation of total body versus visceral fat distribution, with its metabolic and health risks.

Insulin-resistant lipolysis in abdominally obese hypertensive individuals. Role of the renin-angiotensin system.

Resistance to the capacity of insulin to suppress lipolysis may be an important link in the association between abdominal obesity and hypertension. Furthermore, a more active renin-angiotensin system in adipose tissue may contribute to insulin-resistant lipolysis in abdominally obese hypertensive subjects. We determined nonesterified fatty acid concentrations and turnover as well as lipid oxidation under basal conditions and during steady-state euglycemia with two levels of insulinemia (72 and 287 pmol/L) in lean normotensive, abdominally obese normotensive, and abdominally obese hypertensive subjects. To assess the role of the renin-angiotensin system in determining non-esterified fatty acid turnover, we repeated studies in the abdominally obese hypertensive subjects after double-blind random assignment to placebo or enalapril for 1 month each. The main findings were the following: (1) Nonesterified fatty acid flux was significantly higher in abdominally obese hypertensive subjects at both levels of insulinemia than in either abdominally obese normotensive or lean normotensive subjects and correlated significantly with both mean blood pressure and total systemic resistance during the higher level of insulinemia. (2) Enalapril significantly improved insulin-resistant lipolysis in the abdominally obese hypertensive subjects. The improvement in insulin suppressibility of nonesterified fatty acid flux at the high hormonal concentrations correlated positively with the magnitude of reduction in blood pressure. (3) Basal lipid oxidation and suppression in response to insulin were similarly impaired in both obese groups. Resistance to the antilipolytic actions of insulin is thus a characteristic feature in abdominally obese hypertensive subjects and may be linked to the elevated blood pressure in these individuals. A more active renin-angiotensin system may partly explain the insulin-resistant lipolysis in this form of hypertension.

Obesity hypertension is related more to insulin's fatty acid than glucose action.

Although resistance to insulin-mediated glucose disposal has emerged as a link between abdominal obesity and hypertension, abnormalities of nonesterified fatty acid metabolism may play a greater role. Analyses were performed on existing data from 17 abdominally obese subjects (11 hypertensive, 6 normotensive) to determine whether fatty acid concentration and turnover were related to blood pressure independently of hyperinsulinemia and resistance to insulin-mediated glucose disposal. Glucose utilization, fatty acid concentration, and fatty acid turnover were obtained fasting and during euglycemic hyperinsulinemia at 10 and 40 mU/m/min. Analyses were also performed on another group of 30 subjects with a wide range of risk factors who had blood pressure data as well as glucose and fatty acid measurements during an insulin tolerance test. Fatty acid concentration and turnover were markedly more resistant to suppression by insulin in obese hypertensive than in lean or obese normotensive individuals. In the 17 obese subjects, blood pressure measured at screening, in the laboratory, and over a period of 24 hours correlated significantly with fatty acid concentration and turnover but not with glucose disposal measured during the hyperinsulinemic clamp. These correlations remained significant after fasting insulin, the insulin area under the curve during an oral glucose tolerance test, and glucose disposal during the clamp were controlled for. In the second group of subjects, plasma fatty acids 15 minutes after intravenous insulin also correlated with blood pressure. These correlations remained significant after insulin and an index of sensitivity to insulin-mediated glucose disposal were statistically controlled for. The data indicate that blood pressure is related to the effects of insulin on fatty acid metabolism. The findings raise the possibility that resistance of hormone-sensitive lipase to insulin participates in elevating the blood pressure of abdominally obese hypertensive subjects by increasing fatty acid concentration and turnover.

Comparison of rat aortic, carotid & femoral artery viscoelastic properties using harmonic analysis.

Viscoelastic properties of rat (Wistar Kyota) large (6 aorta), medium (12 carotid) and small (8 femoral) in vitro artery segments, were contrasted over a wide range of static and dynamic pressures. Relationship of change in static pressure (delta dyne/mm2) to diameter (delta mm) was used to estimate a segment's incremental elasticity (KD) at each pressure level. Dynamic intravascular pressure response (Po) was recorded during swept frequency pressure (2-200 Hz; +/- 10 mm Hg) inputs as superimposed on mean pressure steps of 40, 80, 120, 160 and 200 mm Hg (P(i)). Analysis of dynamic data included Fast Fouier Transform of Po/P(i) with FANSIM (TUTSIM Products) curve fit to Bode plots. Curve fit coefficients were used to estimate properties of natural frequency (omega n) damping, viscosity and inertia. Statistical analysis employed ANOVA and SNK multiple comparison procedures. Results indicated that as step-pressure was increased diameter, KD and omega n increased proportionately in all segments. Values of KD and omega n were always highest in femoral and lowest in aortic segments. In all segments damping decreased inversely with increasing pressure while, viscosity and inertia were lowest between 80 and 160 mm Hg. These results documented distinct viscoelastic properties for the three arteries as well as, differences in their response characteristics.

Effects of obesity and gender on insulin receptor expression in liver of SHHF/Mcc-FAcp rats.

In SHHF/Mcc-FAcp rats (formerly SHR/Mcc-cp), obesity and male gender synergistically modulate hyperinsulinemia, insulin resistance and predisposition to diabetes. Our previous studies showed gender and obesity modulate hepatic cell surface insulin binding and insulin clearance additively. Hepatic insulin receptors (IR) bind insulin as a first step in insulin clearance through internalization and degradation. We hypothesize that the synergistic effects of obesity and gender on hepatic insulin binding and clearance result from interaction of these two factors on hepatic IR expression. To address IR expression in SHHF/Mcc-FAcp rats, we quantitated IR protein levels in detergent-solubilized liver homogenates by Western blotting and IR mRNA levels by a solution hybridization/RNase protection assay. Obesity reduced total hepatic IR content in males and females, 50% and 68% respectively. Male gender reduced IR protein content 24% in lean, but had no effect on IR protein content in obese rats. Neither gender nor obesity affected hepatic IR mRNA content. Thus, obesity appears to affect hepatic IR protein content and cell surface binding through post-transcriptional mechanisms; similarly, male gender in lean rats reduces IR protein levels and cell surface binding through mechanisms not involving changes in mRNA levels. In obese rats, the synergistic effects of male gender appears to involve changes in IR trafficking and consequently cell surface insulin binding and processing.

Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome.

Polycystic ovary (PCO) syndrome is strongly associated with insulin resistance and the accompanying adverse metabolic profile. To distinguish the mechanisms of this association, we determined the interactions of PCO with obesity and the influence of ameliorating direct androgenic actions via short-term treatment with the antiandrogen flutamide. Insulin sensitivity was determined by the hyperinsulinemic euglycemic clamp in groups of lean and obese PCO women and weight-matched controls. Compared with control values, insulin-mediated glucose utilization in PCO women was significantly lower in lean (1.96 +/- 0.17 v 1.24 +/- 0.10, P < .01) and obese (1.23 +/- 0.18 v 1.03 +/- 0.09 mmol/m2/min, P < .01) subjects. ANOVA indicated that the effects of obesity and androgenicity are independent and additive. In both lean and obese PCO women, treatment with flutamide for 1 or 3 months markedly improved the clinical and biochemical androgenic features, but did not significantly influence the overall insulin sensitivity. A large disparity between individuals in the response to treatment correlated significantly with a simultaneous reduction in plasma levels of dehydroepiandrosterone sulfate (DHEA-S). Thus in women, PCO and obesity exert synergistic effects on insulin resistance. The decreased insulin sensitivity is mediated via indirect androgenic actions or nonandrogenic mechanisms. In some individuals, a direct effect of androgens might have been masked by a decrease in DHEA-S levels.

Transfer function comparisons of rat aortic wall image and intravascular pressure harmonic responses.

This study examined the relationship between rat (mature Sprague-Dawley males) thoracic aortic wall and intraluminal pressure responses to a dynamic pressure input. High speed video image (Do) of outer wall area and intravascular pressure (Po) responses of the in vitro aorta were digitized and computer recorded during swept frequency pressure input (2-200 Hz; +/- 10 mm Hg) that was superimposed on static pressures from 20 to 200 mm Hg (Pi). Analysis included Fast Fourier transform (FFT) for Do/Pi and Po/Pi transfer functions and focused on comparison of coefficients from FANSIM (TUTSIM Products) polynomial equation fit to Bode plots for mean data of multiple aortas. The working hypothesis was that Do/Pi = Po/Pi. In FANSIM division by B0 of the general transfer function equality (A1s + A0)/(B2s2 + B1s + B0) yields (a1s + a0)/(b2s2 + b1s + 1); which was the form analyzed. Graphic and statistical comparisons indicated no difference for coefficients a1, a0, b2, and b1 between Do/Pi and Po/Pi. Coefficients b2, and b1 varied with change in level of static pressure. Values for a1 for both Do/Pi and Pi/Po remained relatively constant and appeared independent of static pressure. These results indicated appropriateness of the transfer function form and suggested that: b2, represented inertia of wall and intraluminal fluid mass; b1, represented wall and fluid viscosity influence; a1, represented influence of fluid viscosity and a0, represented influence of wall elasticity.

Intra-arterial pressure wave parameters modeled using electrical analogs.

An Electrical Model was developed to help identify parameters obtained from dynamic pressure data on the in vitro rat aortic artery. The data was obtained using a Multifunction Pressure Generator (MPG) and recording MPG Input Pressure (Pi) and Intraarterial Pressure (Po). Transfer functions of the form Po/Pi = (A1S+Ao)/(B2S2 + B1S+Bo) were obtained and it is necessary to link A1, Ao, B2, B1 and Bo to the Biological Parameters of Inertance (M), Vascular Resistance (R) and Compliance (C). Using the Electrical Analogs to P, M, R and C which are Voltage (V), Inductance (L), Resistance (Re), and Capacitance (Ce), an Electrical Model was built. The Electrical Model has the form Vo/Vi = (Re1S + 1/Ce)/[LS2 + (Re1 + Re2)S + 1/Ce]. Since Ao = Bo = 1 from our experimental data we multiplied the denominator and numerator by Ce to obtain Vo/Vi = (CeRe1S + 1)/[CeLS2 + Ce(Re1 + Re2)S + 1]. We then transformed our Electrical Model to its Pressure Equivalent and obtained Po/Pi = (CR2S + 1)/[CMS2 + C(R1 + R2)S + 1]. Since R2 is less than R1 + R2 we theorize that total R is composed of two viscoelastic or resistive elements R1 and R2. Using measured values of compliance it should be possible to obtain reasonable values for R1, R2 and Inertance.

Harmonic analysis of intravascular pressure response as an index of arterial wall mechanical properties.

The ability to routinely assess mechanical properties of large blood vessels, like the aorta, before an aneurysm or rupture occurs, could benefit diagnostic and therapeutic procedures and save lives. In this study, images of the wall area and intravascular pressure (IP) responses of in vitro rat aorta were recorded during swept frequency pressure input (2-200 Hz; +/- 10 mm Hg) superimposed on mean pressures from 20 to 160 mm Hg. Data analysis included Fast Fourier transform (FFT) of input and responses. Wall and IP responses were underdamped with respective resonance frequencies (Wn) that varied as a function of mean input pressure and the nonlinear nature of wall elasticity. Results indicated closely coupled wall and IP responses and suggested that the IP response may be an adequate index of wall elasticity without need of a direct measure of wall displacement. We considered results to be a key step towards development of a clinical tool which would facilitate analysis of mechanical properties of in vivo conducting vessels.

Synchronizing blood vessel response CCD imagery to swept frequency dynamic pressure signals.

Harmonic analysis of the pressure and wall responses of a blood vessel exposed to a dynamic pressure input signal required the development of a software application which could properly synchronize the data gathered by two separate microcomputers. In order to accomplish this task, the Pressure-Image Editor was developed. The first computer is used to generate a swept frequency sinusoidal dynamic pressure input signal while at the same time monitoring the resulting response pressures. The second computer is used to record the physical (visual) response of the artery to the pressure signal via a high speed CCD camera and video digitizer. Using the Pressure-Image Editor, 256 animated images along with 65,536 pressure points can be combined and synchronized based on the camera frame rate, input trigger frequency, and any internal timing delays. The Pressure-Image Editor is a object-oriented application written in C++ and includes a window based graphical user interface.