Shear-Induced Detachment of Polystyrene Beads from SAM-Coated Surfaces.

In this work we experimentally and theoretically analyze the detachment of microscopic polystyrene beads from different self-assembled monolayer (SAM) surfaces in a shear flow in order to develop a mechanistic model for the removal of cells from surfaces. The detachment of the beads from the surface is treated as a thermally activated process applying an Arrhenius Ansatz to determine the activation barrier and attempt frequency of the rate determing step in bead removal. The statistical analysis of the experimental shear detachment data obtained in phosphate-buffered saline buffer results in an activation energy around 20 kJ/mol, which is orders of magnitude lower than the adhesion energy measured by atomic force microscopy (AFM). The same order of magnitude for the adhesion energy measured by AFM is derived from ab initio calculations of the van der Waals interaction energy between the polystyrene beads and the SAM-covered gold surface. We conclude that the rate determing step for detachment of the beads is the initiation of rolling on the surface (overcoming static friction) and not physical detachment, i.e., lifting the particle off the surface.

Do dielectric nanostructures turn metallic in high-electric dc fields?

Three-dimensional dielectric nanostructures have been analyzed using field ion microscopy (FIM) to study the electric dc field penetration inside these structures. The field is proved to be screened within a few nanometers as theoretically calculated taking into account the high-field impact ionization process. Moreover, the strong dc field of the order of 0.1 V/Å at the surface inside a dielectric nanostructure modifies its band structure leading to a strong band gap shrinkage and thus to a strong metal-like optical absorption near the surface. This metal-like behavior was theoretically predicted using first-principle calculations and experimentally proved using laser-assisted atom probe tomography (APT). This work opens up interesting perspectives for the study of the performance of all field-effect nanodevices, such as nanotransistor or super capacitor, and for the understanding of the physical mechanisms of field evaporation of dielectric nanotips in APT.

Disintegration of graphene nanoribbons in large electrostatic fields.

The deformation and disintegration of a graphene nanoribbon under external electrostatic fields are investigated by first principle quantum mechanical calculations to establish its stability range. Zigzag edges terminated by various functional groups are considered. By analyzing the phonon spectrum, the critical fracture field for each edge structure is obtained. It is found that different terminal groups on the zigzag graphene nanoribbons lead to different fracture patterns at different fracture fields. The failure mechanism is demonstrated to involve both the carbon bond alternation feature across the ribbon and the terminal group electronegativity.

Quantitative phase and refractive index measurements with point-source digital in-line holographic microscopy.

Point-source digital in-line holographic microscopy with numerical reconstruction is ideally suited for quantitative phase measurements to determine optical path lengths and to extract changes in refractive index within accuracy close to 0.001 on the submicrometer length scale. This is demonstrated with simulated holograms and with detailed measurements on a number of different micrometer-sized samples such as suspended drops, optical fibers, as well as organisms of biological interest such as E. coli bacteria, HeLa cells, and fibroblast cells.

Water whiskers in high electric fields.

In electrostatic fields of the order of volts per Angstrom long whiskers of up to 12 water molecules form that have been observed in the field ion microscope. Here we present a detailed analysis on the basis of the density functional theory that substantiates the earlier claims. We present whisker structures and energetics, lower and upper threshold fields, and fragmentation patterns.

Collective diffusion in two-dimensional systems: exact analysis based on the kinetic lattice gas model.

Using a gradient expansion of the local microscopic particle current, in the long-time and large-scale limit, we derive an exact analytical expression for the density and temperature dependence of the diffusivity in terms of the density dependence of correlation functions on a rectangular lattice. The latter are calculated by transfer matrix methods, generalized to an adsorbate with lateral interactions and subjected to an external field. This allows an examination of the effects of generalized hopping kinetics. Where both initial and final state interactions are involved, the Reed-Ehrlich factorization, commonly assumed, cannot apply.

High resolution Talbot self-imaging applied to structural characterization of self-assembled monolayers of microspheres.

We report the observation of the Talbot self-imaging effect in high resolution digital in-line holographic microscopy (DIHM) and its application to structural characterization of periodic samples. Holograms of self-assembled monolayers of micron-sized polystyrene spheres are reconstructed at different image planes. The point-source method of DIHM and the consequent high lateral resolution allows the true image (object) plane to be identified. The Talbot effect is then exploited to improve the evaluation of the pitch of the assembly and to examine defects in its periodicity.

Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure.

OBJECTIVES: The aim of this study was to determine the impact of nasal nocturnal oxygen therapy on respiration, sleep, exercise capacity, cognitive function and daytime symptoms in patients with congestive heart failure and Cheyne-Stokes respiration. BACKGROUND: Cheyne-Stokes respiration is common in patients with congestive heart failure and is associated with significant nocturnal oxygen desaturation and sleep disruption with arousals. Oxygen desaturations and arousals cause an increase in pulmonary artery pressure and sympathoneural activity and therefore may reduce exercise capacity. Oxygen is an effective treatment of Cheyne-Stokes respiration and should improve exercise capacity in these patients. METHODS: The study was designed as a randomized crossover, double-blind, placebo-controlled trial: 22 patients were assigned to 1 week each of nocturnal oxygen and room air. After each week, polysomnography, maximal bicycle exercise with expiratory gas analysis and trail-making test were performed, and a health assessment chart was completed. RESULTS: Nocturnal oxygen significantly reduced the duration of Cheyne-Stokes respiration (162 +/- 142 vs. 88 +/- 105 min [mean +/- SD]; p < 0.005). Sleep improved as evidenced by less stage 1 sleep and fewer arousals (20 +/- 13 vs. 15 +/- 9/h total sleep time; p < 0.05) as well as more stage 2 and slow-wave sleep; nocturnal oxygen saturation also improved. Peak oxygen consumption during exercise testing increased after oxygen treatment (835 +/- 395 vs. 960 +/- 389 ml/min; p < 0.05). Cognitive function evaluated by the trail-making test improved, but daytime symptoms in the health assessment chart did not improve significantly. CONCLUSIONS: Successful treatment of Cheyne-Stokes respiration with nocturnal nasal oxygen improves not only sleep, but also exercise tolerance and cognitive function in patients with congestive heart failure.

Myocardial enterovirus infection with left ventricular dysfunction: a benign disease compared with idiopathic dilated cardiomyopathy.

OBJECTIVES: Endomyocardial biopsy samples from patients with idiopathic dilated cardiomyopathy were screened for the presence of enterovirus genome. Patients with enterovirus-positive samples were further studied with regard to disease course, histologic variables and response to interferon-alpha treatment. BACKGROUND: Studies of patients with idiopathic dilated cardiomyopathy have reported widely divergent clinical outcomes, suggesting that there is no unique underlying pathogenetic mechanism. METHODS: Five left ventricular endomyocardial biopsy samples were screened for the presence of the enterovirus genome by an established in situ hybridization technique in combination with a histologic, histomorphometric and immunohistologic workup. The course of the disease was then prospectively followed for up to 50 months. Virus-positive patients whose condition deteriorated were treated with interferon-alpha. RESULTS: Of 77 patients, 20 (26%) had enterovirus-positive and 57 (74%) enterovirus-negative biopsy samples. During a mean follow-up period of 25.8 +/- 13.7 months, 1 patient in the enterovirus-positive group and 11 in the enterovirus-negative group died. Four patients in the enterovirus-negative group underwent heart transplantation (p < 0.05). The surviving 19 enterovirus-positive patients had a decrease in mean left ventricular end-diastolic diameter from 66 to 61 mm (p < 0.05) and a mean increase in left ventricular ejection fraction from 0.35 to 0.43 (p < 0.05). In contrast, enterovirus-negative patients had no significant change in end-diastolic diameter or left ventricular ejection fraction. Four patients in the enterovirus-positive group whose condition deteriorated were treated with a 6-month course of subcutaneous interferon-alpha (3 x 10(6) U every second day). This treatment induced hemodynamic improvement in all four patients and eliminated the persistent enteroviral infection in two. CONCLUSIONS: Enterovirus-positive patients have a better heart transplantation-free survival rate and hemodynamic course, with fewer histologic changes, than do enterovirus-negative patients. In addition, enterovirus-positive patients respond favorably to interferon-alpha treatment. These observations indicate that myocardial enteroviral infection with associated left ventricular dysfunction is a distinct disease entity with a benign course.

Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy.

There is increasing evidence that chronic enhanced exogenous or endogenous catecholamine stimulation in patients with dilated cardiomyopathy may worsen hemodynamic status and prognosis. The cause of this deterioration may lie in myocellular calcium accumulation and microcirculatory disorders. In a prospective study, the calcium channel antagonist diltiazem was given to 22 patients with dilated cardiomyopathy (60 to 90 mg three times daily) in addition to conventional therapy of digitalis, diuretics and vasodilators. Twenty-five patients received the conventional therapy and served as historical controls. Eight additional patients who were not originally included in this control group received adjunctive diltiazem treatment after initially receiving conventional therapy alone. The three patient groups were similar in all hemodynamic and anamnestic features. Only patients with reduced myofibrillar volume fraction on myocardial biopsy were included in the trial, because they could be expected to show hemodynamic deterioration. The mean survival time was 29 months in the control group, whereas no patient in the diltiazem group died over a mean follow-up period of 15.4 months (p less than 0.001). Mean left ventricular ejection fraction increased from 0.34 to 0.44 (p less than 0.001) and New York Heart Association functional class improved significantly in the diltiazem group and during the diltiazem period in the crossover patients, but deteriorated in the control group. The results suggest that adjunctive diltiazem treatment in dilated cardiomyopathy has beneficial effects on mortality, hemodynamics and symptoms.

Treatment of reperfusion injury with intracoronary calcium channel antagonists and reduced coronary free calcium concentration in regionally ischemic, reperfused porcine hearts.

The effect of intracoronary diltiazem, EGTA (ethylene-bis-(beta-aminomethylether)-N,N'-tetraacetic acid), nifedipine, verapamil and isotonic saline solution as placebo on reperfusion injury was investigated in regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally occluded for 45 min and was reperfused for 3 days. Intracoronary infusion was started immediately before reperfusion and continued during 45 min of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Apart from left ventricular end-diastolic pressure before ischemia and during 45 min of reperfusion, global hemodynamic values in the five treatment groups did not differ; in particular, calculated left ventricular oxygen consumption before and during ischemia was equally low. Intracoronary EGTA decreased coronary venous free calcium concentration to about 70% of baseline value. Infarct size was reduced from 76 +/- 10% (control group, n = 8) to 60 +/- 10% (p less than 0.01) by intracoronary diltiazem (n = 8) and to 55 +/- 15% (p less than 0.01) by intracoronary EGTA (n = 8). Insignificant reductions in infarct size were found after treatment with intracoronary verapamil (63 +/- 18%, n = 8) and intracoronary nifedipine (68 +/- 9%, n = 7). Regional systolic shortening of the risk region, which did not differ among the groups before occlusion and during ischemia, recovered to the greatest extent in the EGTA-treated pigs (p less than 0.01 compared with values in the control group). Treatment with intracoronary calcium antagonists resulted in only marginal improvement of systolic shortening.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoscintigraphy using technetium-99m-labeled anti-NCA-95 antigranulocyte antibodies as an adjunct to echocardiography in subacute infective endocarditis.

OBJECTIVES: This study was performed to assess the clinical value of immunoscintigraphy in subacute infective endocarditis. BACKGROUND: Radiolabeled granulocytes can reveal inflammatory lesions. METHODS: Using technetium-99m-labeled anti-NCA-95 anti-granulocyte antibodies, planar scintigraphy and single-photon emission computed tomography of the thorax were performed in 72 consecutive patients with suspected endocarditis. Each patient also underwent transthoracic and, if findings were negative, transesophageal echocardiography. RESULTS: Thirty-three patients were found to have endocarditis on the basis of clinical criteria (surgical confirmation in 17 patients), and the remaining 39 served as control subjects. Initial scintigraphy was true positive in 26 patients (sensitivity 79%) and false positive in 7 (specificity 82%). Echocardiography was true positive in 29 patients (sensitivity 88%) and false positive in 1 (specificity 97%). Scintigraphy was positive in the four patients with false negative echocardiography, and echocardiography was positive in the seven patients with false negative scintigraphy. Thus, the combination of scintigraphy and echocardiography yielded a sensitivity of 100% and a specificity of 82%. In 10 of the 11 patients with two to three follow-up studies, scintigraphy became negative parallel to clinical improvement, indicating decreasing floridity of the inflammatory process. CONCLUSIONS: Immunoscintigraphy in patients with subacute infective endocarditis provides valuable diagnostic information in equivocal echocardiographic findings and may be used to monitor antibiotic therapy.

Catheter ablation of ventricular tachycardia in 136 patients with coronary artery disease: results and long-term follow-up.

OBJECTIVES: This study attempted to determine the feasibility and long-term efficacy of catheter ablation by means of either radiofrequency or direct current energy in a selected group of patients with coronary artery disease. BACKGROUND: Catheter ablation of ventricular tachycardia has proved to be highly effective in patients with idiopathic and bundle branch reentrant ventricular tachycardia. In patients with coronary artery disease and recurrent sustained ventricular tachycardia resistant to medical antiarrhythmic management, the value of catheter ablation has not yet been established. METHODS: One hundred thirty-six patients with coronary artery disease and one configuration of monomorphic sustained ventricular tachycardia underwent radiofrequency (72 patients) or direct current catheter ablation (64 patients). The mapping procedure to localize an adequate site for ablation included pace mapping during sinus rhythm, endocardial activation mapping, identification of isolated mid-diastolic potentials and pacing interventions during ventricular tachycardia. RESULTS: Primary success was achieved in 102 (75%) of 136 patients (74% of 72 undergoing radiofrequency and 77% of 64 with direct current ablation). Complications were noted in 12% of patients. During a mean (+/- SD) follow-up period of 24 +/- 13 months (range 3 to 68), ventricular tachycardia recurred in 16% of patients. CONCLUSIONS: Catheter ablation of ventricular tachycardia in coronary artery disease is feasible in patients with one configuration of monomorphic sustained ventricular tachycardia. There is no significant difference with respect to the type of energy applied. The follow-up data show that in a selected group of patients with coronary artery disease, catheter ablation offers a therapy alternative.

Integration of plasmids into the bacteriophage T4 genome.

We have analyzed the integration of plasmids into the bacteriophage T4 genome via homologous recombination. As judged by genetic selection for a plasmid-borne marker, a mutation in phage gene uvsX or uvsY essentially blocked the integration of a plasmid with homology to the T4 genome but no phage replication origin (non-origin plasmid). The strict requirement for these two proteins suggests that plasmid integration can proceed via a strand-invasion reaction similar to that catalyzed in vitro by the T4-encoded strand-exchange protein (UvsX) in concert with UvsY and gp32. In contrast to the results with the non-origin plasmid, a mutation in uvsX or uvsY reduced the integration of a T4 replication origin-containing plasmid by only 3-10-fold. These results suggest that the origin-containing plasmid integrates by both the UvsXY-dependent pathway used by the non-origin plasmid and by a UvsXY-independent pathway. The origin-containing plasmid integrated into the phage genome during a uvsX- or uvsY-mutant infection of a recA-mutant host, and therefore origin-dependent integration can occur in the absence of both phage- and host-encoded strand-exchange proteins (UvsX and RecA, respectively).

Endoanaesthesia of left ventricular mechanoreceptors by steady state infusion of lignocaine and the influence of dopamine.

We recorded the afferent activity of 11 left ventricular mechanoreceptors in filaments of the vagus nerve in 10 chloralose-anaesthetised cats. The fibres showed low irregular spontaneous activity of 2.9 (0.2 to 8.4) spikes X s-1. During temporary occlusion of the left anterior descending or left main coronary artery they were activated to 19.1 (4.8 to 47.0) spikes X s-1. Intravenous infusion of 0.175 and 0.35 mg X kg-1 X min-1 lignocaine lowered heart rate and blood pressure. The spontaneous nerve fibre activity remained unchanged by the local anaesthetic, whereas the maximum activity evoked by coronary artery occlusion was reduced to 14.7 (2.6 to 34.1) and 10.9 (2.4 to 27.6) spikes X s-1. An additional infusion of 5 and 10 micrograms X kg-1 X min-1 dopamine during continued application of 0.35 mg X kg-1 X min lignocaine raised heart rate and blood pressure to control values but had only minimal effects on the response of the fibres to coronary occlusion. It is concluded that lignocaine exerts a specific endoanaesthetic effect on the left ventricular mechanoreceptors, which is not mediated by its negative inotropic side effect.

Field evaporation of insulators and semiconductors: Theoretical insights for ZnO.

We look at the new challenges associated with Atom Probe Tomography of insulators and semiconductors with regard to local fields inside and on the surface of such materials. The theoretical discovery that in high fields the band gap in these materials is drastically reduced to the point where at the evaporation field strength it vanishes will be crucial in our discussion. To understand Atom Probe results on the field evaporation of insulators and semiconductors we use density functional theory on ZnO clusters to follow the structural and electronic changes during field evaporation and to obtain potential energy curves, HOMO-LUMO gaps, field distributions, desorption pathways and fragments, dielectric constants, and polarizabilities. We also examine the effects of electric field reversal on the evaporation of ZnO and compare the results with Si.

Disintegration and field evaporation of thiolate polymers in high electric fields.

High electrostatic fields cause major changes in polymers, structural (e.g. electrostriction) and electronic (e.g. reduction of the "band gap" with final metallization). Using density functional theory we have studied field effects on amino-alkane-thiols and perfluoro-alkane-thiols adsorbed on a metal substrate. Our results agree well with the APT fragmentation spectra obtained by Stoffers, Oberdorfer and Schmitz and shed light on disintegration pathways. We demonstrate that in SAMs the HOMO/LUMO gap is again reduced as a function of the field strength and vanishes at evaporation. We also follow the field dependence of the dielectric constant and polarizability.

Recombinant Interferons beta and gamma have a higher antiviral activity than interferon-alpha in coxsackievirus B3-infected carrier state cultures of human myocardial fibroblasts.

We compared the antiviral activities of three recombinant human interferons (IFN-alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.

Expression of meta-vinculin in human coronary arteriosclerosis is related to the histological grade of plaque formation.

In the present study we demonstrate that the quantitative reduction of meta-vinculin expression parallels histological changes during the course of coronary arteriosclerosis. Immunofluorescence stainings of coronary arteries revealed that vinculin distribution resembled that of other smooth muscle-specific cytoskeletal proteins like alpha-actin, caldesmon or myosin light chain kinase in labeling smooth muscle cells brightly. Although close to arteriosclerotic plaques, the cellularity as measured by the density of nuclei was often not significantly altered. Cells of this location expressed markedly reduced amounts of vinculin, suggesting that they are smooth muscle cells of a synthetic phenotype. To determine the fractional meta-vinculin content in arteriosclerotic lesions, we performed densitometric scanning of immunoblots incubated with anti-vinculin monoclonal antibodies reacting with both meta-vinculin (150 kDa) and vinculin (130 kDa). In parallel, each tissue sample was evaluated histologically for the degree of arteriosclerotic alterations according to the morphometric atheroma score of Stratford et al. (n = 13). In type 1 lesions covering slight intimal thickening, meta-vinculin represented 36% (mean, range 35%-39%) of the total vinculin immunoreactivity. In type 2 lesions consisting of fibrous plaques of up to twice the original artery wall thickness, meta-vinculin accounted for 28% (mean, range 22%-35%) of the total vinculin content. Meta-vinculin was substantially reduced in type 3 lesions (mean 13%, range 8%-18%) which are characterized by extensive atheromatous plaques. Thus, the meta-vinculin/vinculin ratio differed significantly between early, intermediate and advanced phases of coronary arteriosclerotic plaque formation.

The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels.

Lipoprotein(a) concentrations were measured by radial immunodiffusion in a cohort of 40-60 year males who had been classified by coronary angiography as CAD+ with 50% stenosis of one or more of the major coronary arteries or CAD- with no signs of coronary lesions. Sample odds ratios were calculated as a measure of association between serum Lp(a) values and the presence of coronary artery disease. An odds ratio of 2.706 (P less than 0.001) was derived for elevated (greater than or equal to 30 mg/dl) Lp(a) levels vs low (less than 5 mg/dl) Lp(a) levels indicating a strong association between the presence of coronary artery disease and elevated Lp(a) concentrations. This association was independent of the known risk factors smoking, hypertension and diabetes as well as the serum concentrations of total triglycerides, HDL-cholesterol, alpha-Lp-cholesterol and pre-beta-Lp-cholesterol. In contrast to these variables the association between Lp(a) and coronary artery disease was dependent upon the serum concentrations of LDL-cholesterol, beta-Lp-cholesterol and total cholesterol. At concentrations below the respective median for each variable, odds ratios of between 1.42 and 1.67 were calculated whereas at concentrations above the respective medians the odds ratios ranged from 4.50 to 6.33 (P less than 0.001). Our data, therefore, suggest that increasing LDL concentrations markedly increase the risk of coronary artery disease due to elevated Lp(a) levels.