Thermal grafting of organic monolayers on amorphous carbon and silicon (111) surfaces: A comparative study

Thermally-assisted (160 °C) liquid phase grafting of linear alkene molecules has been performed simultaneously on amorphous carbon (a-C) and hydrogen passivated crystalline silicon Si(111):H surfaces. Atomically flat a-C films with a high sp³ average surface hybridization, sp³ / (sp² + sp³) = 0.62, were grown using pulsed laser deposition (PLD). Quantitative analysis of X-ray photoelectron spectroscopy, X-ray reflectometry and spectroscopic ellipsometry data show the immobilization of a densely packed (> 3 × 10¹⁴ cm^? 2) single layer of organic molecules. In contrast with crystalline Si(111):H and other forms of carbon films, no surface preparation is required for the thermal grafting of alkene molecules on PLD amorphous carbon. The molecular grafted a-C surface is stable against ambient oxidation, in contrast with the grafted crystalline silicon surface.     

Short-term hemodynamic effects of mibefradil in dogs with chronic heart failure: comparison with diltiazem

Despite the marked vasodilator and antiischemic actions of existing calcium channel blockers, their use in the treatment of patients with chronic heart failure (HF) remains highly controversial. We compared the short-term hemodynamic effects of i.v. mibefradil, a predominant T-type calcium channel blocker with only partial L-type calcium channel antagonism, and diltiazem, a selective L-type calcium channel antagonist in dogs with chronic HF. Each of three drugs namely, mibefradil, diltiazem and normal saline (as placebo control), were studied in random order (6 days between each drug intervention), in each of 8 dogs with chronic HF produced by multiple intracoronary microembolizations. Intravenous mibefradil and diltiazem were administered as a 100 micrograms/kg bolus followed by a continuous infusion of 6 and 4 micrograms/kg/min, respectively, for 15 min. Equal volumes of normal saline were administered in an identical fashion. In all instances, hemodynamics were obtained at base line and at 5, 10, 15, 30 and 60 min after bolus drug administration. Left ventriculograms were obtained at baseline, and at 15 and 60 min after bolus drug administration. Saline infusion had no effects on hemodynamic or angiographic indexes of left ventricular (LV) function. At 15 min, mibefradil caused significant increases of LV stroke volume and LV ejection fraction compared to baseline (40 +/- 5 vs. 31 +/- 3 ml, P < .05 and 41 +/- 1 vs. 28 +/- 1%, P < .05, respectively). In contrast, at 15 min, diltiazem produced no significant changes of LV stroke volume or ejection fraction compared to baseline despite reducing mean aortic pressure to the same extent as mibefradil. Short-term i.v. mibefradil improves LV function in dogs with chronic HF. The beneficial effects of mibefradil compared to diltiazem may be a consequence of T-type calcium channel selectivity resulting in a vasodilatory response that is free of negative inotropy.     

Modeling the effect of immobilization of microorganisms on the rate of biodegradation of phenol under inhibitory conditions

The main objective of this research is to model the effect of biodegradation process of phenol at high initial concentrations using a well known immobilization technique of the biomass. This work focused on testing the effect of activated carbon and clay while considering the diffusive internal mass transfer limitations. Biodegradation of phenol was performed by using enriched microorganisms from a compost of agricultural wastes. The average phenol biodegradation rate (uptake) of free biomass system was 235.3 mg g⁻¹ h⁻¹ at initial concentration range of 212-260 mg/L. However, the values for the systems of immobilized biomass in alginate and activated carbon (1 mm), alginate, activated carbon (4 mm), alginate, activated carbon and clay (1 mm) and alginate, activated carbon and clay (4 mm) were 64.9, 27.6, 27.5, and 8 mg g⁻¹ h⁻¹ respectively. The effective diffusion factors in different matrix were obtained using an intra-particle diffusion-based mathematical model. Diffusion limitation was observed when the matrix contained clay in addition to activated carbon. The diffusion coefficient was decreased from 1.6 × 10⁻⁸ to 1.2 × 10⁻⁹ cm²/s when clay was added to the matrix of 1 mm of alginate and activated carbon. Also, slight differences between the diffusion factors were observed for larger beads. The combination of clay and AC contributes to better mineralization of phenol at high concentrations. This could be attributed to the synergism of both additives.     

N,N′-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers

Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs targeting the virulence of Pectobacterium. Four N,N′-bisalkylated imidazolium salts were identified as QSIs; they were active at the μM range. In potato tuber assays, two of them were able to decrease the severity of the symptoms provoked by P. atrosepticum. This work extends the range of the QSIs acting on the Pectobacterium-induced soft-rot disease.     

Active (air-cooled) vs. passive (phase change material) thermal management of high power lithium-ion packs: Limitation of temperature rise and uniformity of temperature distribution

The effectiveness of passive cooling by phase change materials (PCM) is compared with that of active (forced air) cooling. Numerical simulations were performed at different discharge rates, operating temperatures and ambient temperatures of a compact Li-ion battery pack suitable for plug-in hybrid electric vehicle (PHEV) propulsion. The results were also compared with experimental results. The PCM cooling mode uses a micro-composite graphite–PCM matrix surrounding the array of cells, while the active cooling mode uses air blown through the gaps between the cells in the same array. The results show that at stressful conditions, i.e. at high discharge rates and at high operating or ambient temperatures (for example 40–45 °C), air-cooling is not a proper thermal management system to keep the temperature of the cell in the desirable operating range without expending significant fan power. On the other hand, the passive cooling system is able to meet the operating range requirements under these same stressful conditions without the need for additional fan power.     

Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes

BACKGROUND: Alterations in K+ channel expression and gating are thought to be the major cause of action potential remodeling in heart failure (HF). We previously reported the existence of a late Na+ current (INaL) in cardiomyocytes of dogs with chronic HF, which suggested the importance of the Na+ channel in this remodeling process. The present study examined whether this INaL exists in cardiomyocytes isolated from normal and failing human hearts. METHODS AND RESULTS: A whole-cell patch-clamp technique was used to measure ion currents in cardiomyocytes isolated from the left ventricle of explanted hearts from 10 patients with end-stage HF and from 3 normal hearts. We found INaL was activated at a membrane potential of -60 mV with maximum density (0.34+/-0.05 pA/pF) at -30 mV in cardiomyocytes of both normal and failing hearts. The steady-state availability was sigmoidal, with an averaged midpoint potential of -94+/-2 mV and a slope factor of 6.9+/-0.1 mV. The current was reversibly blocked by the Na+ channel blockers tetrodotoxin (IC50=1.5 micromol/L) and saxitoxin (IC50=98 nmol/L) in a dose-dependent manner. Both inactivation and reactivation of INaL had an ultraslow time course (tau approximately 0.6 seconds) and were independent of voltage. The amplitude of INaL was independent of the peak transient Na+ current. CONCLUSIONS: Cardiomyocytes isolated from normal and explanted failing human hearts express INaL characterized by an ultraslow voltage-independent inactivation and reactivation.     

Hemodynamic correlates of the third heart sound during the evolution of chronic heart failure

OBJECTIVES: The purpose of this study was to examine the temporal relation between the development of a third heart sound during the course of evolving heart failure and associated hemodynamic abnormalities. BACKGROUND: Although various theories have been proposed to explain the origin of the third heart sound, the exact origin of this sound remains unknown. METHODS: Studies were performed in seven dogs in which heart failure was produced by multiple sequential intracoronary micro-embolizations. Hemodynamic studies including ventriculography, pulsed wave Doppler echocardiography and intracardiac phonocardiography were performed at baseline, at the time at third heart sound was first heard and at 6 and 24 weeks after onset of the third heart sound. RESULTS: All dogs developed a third heart sound at 9 +/- 2 weeks after the initial embolization. The onset of the sound was accompanied by an increase in left ventricular chamber stiffness relative to the baseline value (0.25 +/- 0.03 vs. 0.14 +/- 0.01 mm Hg/ml) (p < 0.05) and mean deceleration of early mitral inflow velocity (1,040 +/- 90 vs. 590 +/- 40 cm/s per s) (p < 0.05). CONCLUSIONS: These data indicate that the onset of a third heart sound during the course of evolving heart failure occurs coincident with the development of increased left ventricular chamber stiffness and the manifestation of rapid deceleration of early mitral inflow velocity. These findings are consistent with a myocardial vibratory origin of this sound.     

Abnormal mitochondrial function in myocardium of dogs with chronic heart failure

Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria that include hyperplasia, reduced organelle size and compromised structural integrity. In the present study, we examined mitochondrial respiration in myocardium of 10 normal dogs and 10 dogs with chronic HF (LV ejection fraction 24+/-2%) produced by intracoronary micro-embolizations. Mitochondrial respiratory rates were determined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Basal respiratory rate (VO), respiratory rate after addition of substrates, glutamate and malate (VSUB) and state 3 respiratory rate (VADP, after addition of ADP), were measured in tissue samples from the subendocardial and subepicardial LV free wall, interventricular septum and right-ventricular free wall. No differences were observed in basal respiratory rates between normal and HF tissue, while VSUB was significantly lower in HF compared to normal. VADP was 50-60% lower in HF compared to normal tissue (P<0.001). The results indicate abnormal mitochondrial respiratory activity in myocardium of dogs with chronic HF. These findings support the concept of low myocardial energy production in HF that can contribute to the global cardiac dysfunction.     

Ventricular remodeling. Mechanisms and prevention

The changes that take place in the structure and form of the left ventricle have become closely related to increase in clinical events in patients with heart failure. These changes are included in the term remodeling and occur as a response to the initial loss of left ventricular muscle mass. The mechanisms that initiate and maintain this remodeling process have become of great importance since a variety of effective pharmacologic agents have become available. A more complete understanding of remodeling has the potential of preventing the progression of heart failure. This article considers the various aspects of left ventricular remodeling including the cardiomyocytes, the myocardial interstitium, the importance that apoptosis plays the remodeling process.     

Characterization of insulin-like growth factor binding proteins and regulation of IGFBP3 in human mesangial cells

IGF-I regulates renal growth and development. Insulin-like growth factor binding proteins (IGFBPs) are synthesized by the kidney and may modulate the local autocrine and/or paracrine actions of IGF-I. We have previously demonstrated that mesangial cells (MC) release IGF-I and IGF-binding activity; however, the specific IGFBPs produced by these cells and the factors involved in their regulation are unknown. We examined MC for expression of IGFBP-1 to -6 mRNAs and proteins. RNase protection assays using total RNA demonstrated that MC express all of the IGFBPs. [125I]IGF-I Western ligand blot of conditioned medium demonstrated that MC release IGFBPs of 24, 29, 32 kDa, and a doublet at 46 kDa, consistent with IGFBP-4, -5, -2 and -3, respectively. IGFBP species of 28 and 34 kDa were also detected. Since IGF-I and TGF-beta are implicated in glomerular hypertrophy and matrix expansion, we tested their effect on IGFBPs released by MC. IGF-I (100 ng/ml), TGF-beta (2 ng/ml) and forskolin (10(-5) M) differentially regulated the abundance of IGFBPs released in the conditioned medium in a time-dependent manner. IGF-I and TGF-beta were potent inducers of the release of IGFBP3 protein; however, TGF-beta, but not IGF-I, increased IGFBP3 mRNA levels. Recombinant IGFBP3 was tested for its effect on IGF-I-induced mitogenesis. IGFBP3 inhibited IGF-I-stimulated DNA synthesis in a dose-dependent manner with a peak effect observed at 50 nM IGFBP3. Although TGF-beta is a potent inhibitor of IGF-I-stimulated DNA synthesis, this effect is not mediated via IGFBPs. Expression of IGFBP-1 to -6 by MC suggests that these proteins may modulate IGF-I bioavailability in the glomerulus. IGF-I itself, TGF-beta and cAMP agonists may indirectly modulate the effects of IGF-I via the release of IGFBPs by MC.