Probability distribution for heat exchange in plastic deformation.

Fluctuation theorems allow one to obtain equilibrium information from nonequilibrium experiments. The probability distribution function of the relevant magnitude measured along the irreversible nonequilibrium trajectories is an essential ingredient of fluctuation theorems. In small systems, where fluctuations can be larger than average values, probability distribution functions often deviate from being Gaussian, showing long tails, mostly exponential, and usually strongly asymmetric. Recently, the probability distribution function of the van Hove correlation function of the relevant magnitude was calculated, instead of that of the magnitude itself. The resulting probability distribution function is highly symmetric, obscuring the application of fluctuation theorems. Here, the discussion is illustrated with the help of results for the heat exchanged during plastic deformation of aluminum nanowires, obtained from molecular dynamics calculations. We find that the probability distribution function for the heat exchanged is centrally Gaussian, with asymmetric exponential tails further out. By calculating the symmetry function we show that this distribution is consistent with fluctuation theorems relating the differences between two equilibrium states to an infinite number of nonequilibrium paths connecting those two states.

Influence of Relativistic Effects on the Contact Formation of Transition Metals.

Our analysis of the contact formation processes undergone by Au, Ag, and Cu nanojunctions reveals that the distance at which the two closest atoms on a pair of opposing electrodes jump into contact is, on average, 2 times longer for Au than either Ag or Cu. This suggests the existence of a longer-range interaction between those two atoms in the case of Au, a result of the significant relativistic energy contributions to the electronic structure of this metal, as confirmed by ab initio calculations. Once in the contact regime, the differences between Au, Ag, and Cu are subtle, and the conductance of single-atom contacts for metals of similar chemical valence is mostly determined by geometry and coordination.

Graphene flakes obtained by local electro-exfoliation of graphite with a STM tip.

Graphite surfaces can be manipulated by several methods to create graphene structures of different shapes and sizes. Scanning tunneling microscopy (STM) can be used to create these structures either through mechanical contact between the tip and the surface or through electro-exfoliation. In the latter, the mechanisms involved in the process of exfoliation at an applied voltage are not fully understood. Here, we show how a graphite surface can be locally exfoliated in a systematic manner by applying an electrostatic force with a STM tip at the edge of a terrace, forming triangular flakes several nanometers in length. We demonstrate, through experiments and simulations, how these flakes are created by a two-step process: first a voltage ramp must be applied at the edge of the terrace, and then the tip must be scanned perpendicular to the edge. Ab initio electrostatic calculations reveal that the presence of charges on the graphite surface weakens the interaction between layers allowing for exfoliation at voltages in the same range as those used experimentally. Molecular dynamics simulations show that a force applied locally on the edge of a step produces triangular flakes such as those observed under STM. Our results provide new insights into surface modification that can be extended to other layered materials.

Controlled rippling of graphene via irradiation and applied strain modify its mechanical properties: a nanoindentation simulation study.

Ripples present in free standing graphene have an important influence on the mechanical behavior of this two-dimensional material. In this study, we show through nanoindentation simulations, how out-of-plane displacements can be modified by strain, resulting in softening of the membrane under compression and stiffening under tension. Irradiation also induces changes in the mechanical properties of graphene. Interestingly, compressed samples, irradiated at low doses are stiffened by the irradiation, whereas the samples under tensile strain do not show significant changes in their mechanical properties. These simulations indicate that vacancies produced by the energetic ions cannot be the ones directly responsible for this behavior. However, changes in roughness induced by the momentum transferred from the energetic ions to the membrane, can explain these differences. These results provide an alternative explanation to recent experimental observations of the stiffening of graphene under low dose irradiation, as well as the paths to tailor the mechanical properties of this material via applied strain and irradiation.

Mechanical annealing of metallic electrodes at the atomic scale.

The process of creating an atomically defined and robust metallic tip is described and quantified using measurements of contact conductance between gold electrodes and numerical simulations. Our experiments show how the same conductance behavior can be obtained for hundreds of cycles of formation and rupture of the nanocontact by limiting the indentation depth between the two electrodes up to a conductance value of approximately 5G0 in the case of gold. This phenomenon is rationalized using molecular dynamics simulations together with density functional theory transport calculations which show how, after repeated indentations (mechanical annealing), the two metallic electrodes are shaped into tips of reproducible structure. These results provide a crucial insight into fundamental aspects relevant to nanotribology or scanning probe microscopies.

Development of a risk-based methodology for estimating survival and growth of enteropathogenic Escherichia coli on iceberg-lettuce exposed at short-term storage in foodservice centers.

Ready-to-eat lettuce is a food commodity prone to contamination by pathogenic microorganisms if processing and distribution conditions as well as handling practices are not effective. A challenge testing protocol was applied to ready-to-eat iceberg-lettuce samples by inoculating different initial contamination levels (4.5, 3.5 and 2.5 log cfu/g) of Escherichia coli strain (serotype O158:H23) subsequently stored at 8, 12, 16, 20 and 24°C for 6h. A polynomial regression model for log difference (log(diff)) was developed at each inoculum level studied through the calculation of the effective static temperature (T(eff)). Furthermore, the developed model was integrated within a risk-based approach with real time/Temperature (t/T) data collected in three Spanish foodservice centers: school canteens, long-term care facilities (LTCF) and hospitals. Statistical distributions were fitted to t/T data and estimated log(diff) values were obtained as model outputs through a Monte Carlo simulation (10,000 iterations). The results obtained at static conditions indicated that the maintenance of the lettuce at 8°C slightly reduced the E. coli population from -0.4 to -0.5 log cfu/g. However, if chill chain is not maintained, E. coli can grow up to 1.1 log cfu/g at temperatures above 16°C, even at low contamination levels. Regarding log(diff) estimated in foodservice centers, very low risk was obtained (log(diff)<1.0 log cfu in all cases). Mean T(eff) values obtained in hospitals were the lowest ones (11.1°C) and no growth of E. coli was predicted in >92% of simulated cases. The results presented in this study could serve food operators to set time/Temperature requirements for ready-to-eat foods in foodservice centers, providing a scientific basis through the use of predictive modeling. These findings may also serve to food safety managers to better define the control measures to be adopted in foodservice centers in order to prevent food-borne infections.

Non-Gaussian tails in the probability distribution function of heat exchanged during isothermal stretching of aluminum and gold nanowires.

The heat exchanged upon isothermal (0.5-200 K) stretching of aluminum and gold nanowires has been calculated by means of molecular dynamics. Atoms at fixed positions with velocities randomly distributed according to Maxwell distribution were taken as initial conditions. The results clearly reveal the presence of non-Gaussian (exponential) tails in the heat probability distribution function at low temperatures, both in gold and aluminum. As temperature is raised, tails rapidly disappear.

Formation of a metallic contact: jump to contact revisited.

The transition from tunneling to metallic contact between two surfaces does not always involve a jump, but can be smooth. We have observed that the configuration and material composition of the electrodes before contact largely determine the presence or absence of a jump. Moreover, when jumps are found preferential values of conductance have been identified. Through a combination of experiments, molecular dynamics, and first-principles transport calculations these conductance values are identified with atomic contacts of either monomers, dimers, or double-bond contacts.

Comparative bioavailability of two immediate release tablets of enalapril/hydrochlorothiazide in healthy volunteers.

A bioequivalence study of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide was carried out in 20 healthy male volunteers according to a single dose, two-sequence, crossover randomized design. One washout period of nine days was observed between the two periods. Multiple samples were collected over 96 hours post-dosing. Bioavailability was evaluated on the basis of plasma concentrations of enalapril and its main active metabolite, enalaprilat and hydrochlorothiazide. Plasma samples were assayed for enalapril, enalaprilat and hydrochlorothiazide using a selective and sensitive high-performance liquid chromatography method with mass spectrometry detection (LC-MS). The pharmacokinetic parameter values of Cmax and tmax were obtained directly from plasma data, k(e) was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10), all the generally accepted tests (Schuirmann test and Wilcoxon-Tukey and Hauschke nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC(0-infinity) and with respect to rate of absorption as assessed by Cmax and tmax.

Densification of fused silica due to shock waves and its implications for 351 nm laser induced damage.

High-power 351 nm (3 ) laser pulses can produce damaged areas in high quality fused silica optics. Recent experiments have shown the presence of a densified layer at the bottom of damage initiation craters. We have studied the propagation of shock waves through fused silica using large-scale atomistic simulations since such shocks are expected to accompany laser energy deposition. These simulations show that the shocks induce structural transformations in the material that persist long after the shock has dissipated. Values of densification and thickness of densified layer agree with experimental observations. Moreover, our simulations give an atomistic description of the structural changes in the material due to shock waves and their relation to Raman spectra measurements.

The thyroid hormone down-regulates the mouse alpha-foetoprotein promoter.

The thyroid hormone (T3) was shown to down regulate the level of alpha-foetoprotein (AFP) mRNA in hepatoma cells HepG2. Recombinant plasmids containing segments from the mouse AFP gene promoter were transfected in HepG2 cells and transient expression assays showed that the T3 inhibitory effect depends on the sequence limited by positions -80 and -38, upstream from the TATA box. This sequence is able to confer T3 sensitivity to a heterologous promoter and contains a putative T3-responsive element, as well as likely CEBP- and HNF1-responsive elements. These observations suggest that T3 is a good candidate for hormonal control of the AFP gene expression and especially for the neonatal shut off of the gene.

Effects of adrenaline on ventricular function and coronary haemodynamics in relation to catecholamine handling in transplanted human hearts.

We investigated cardiovascular and coronary responses to intravenous infusions of adrenaline, which raised arterial concentrations in a stepwise fashion from basal to about 5-6 nmol.l-1, in 11 non-rejecting heart transplanted patients, and in eight intact innervated subjects. Cardiac adrenaline extraction and noradrenaline release rate were also measured. The transplanted patients showed larger increases in heart rate (36 +/- 11% vs 16 +/- 6%, P < 0.0001) and cardiac index (80 +/- 30% vs 56 +/- 19%, P < 0.05), while stroke volume increments were similar in the two groups (32 +/- 17% vs 35 +/- 13%). The study groups did not differ with respect to changes in arterial pressure, cardiac work or peripheral resistances. Coronary sinus blood flow increased to a greater extent in the transplanted group (75 +/- 35% vs 48 +/- 31%, P < 0.05) and myocardial oxygen consumption also tended to increase more in these patients (78 +/- 42% vs 48 +/- 34%, NS). Myocardial adrenaline extraction was greatly reduced in the transplant patients (-6 +/- 25% vs 64 +/- 18%, P < 0.001), while forearm adrenaline extraction was similar in the two groups (41 +/- 22% vs 40 +/- 23%, NS). Cardiac noradrenaline overflow tended to be lower in the transplanted group (12 +/- 62 vs 48 +/- 43 pmol.min-1, NS). There was a wide range of noradrenaline overflow values (-64 to 147 pmol.min-1) and definite high values in three patients. Cardiac noradrenaline overflow was not correlated to heart rate responsiveness to adrenaline. We conclude that patients with cardiac transplantation respond to adrenaline with exaggerated increases in heart rate and thus in cardiac output. High values of cardiac noradrenaline overflow are seen in some transplant recipients and may suggest reinnervation. Signs of reinnervation are not associated with consistently lower heart rate responses to beta-adrenergic stimulation.

Development of myocardial beta-adrenergic receptor density and adenylate cyclase activity after human heart transplantation.

An increase in basal heart rate caused by a lack of vagal control and chronotropic supersensitivity to epinephrine has been shown in transplanted human hearts. Prejunctional and/or postjunctional origins for this supersensitivity have been suggested, the latter involving changes in the number of myocardial beta-adrenergic receptors or in the receptor adenylate cyclase system. To directly determine the time course of change, serial determinations were performed during the first 3 months after heart transplantation. The beta-adrenergic receptor density measured by iodine 125-labelled iodocyanopindolol binding in 61 endomyocardial biopsy specimens (a mean of 6.1 +/- 0.58 biopsies from each of 10 patients) showed great intraindividual and interindividual variability (56.6 +/- 6.8 fmol/mg protein) with no mean trend toward gradually changing receptor densities. Isoproterenol-stimulated adenylate cyclase activity measured in 33 biopsy specimens (a mean of 5.5 +/- 0.67 biopsy specimens from each of six patients) varied considerably (112.5 +/- 13.8 pmol cyclic adenosine monophosphate/mg protein/min), again with no definite tendency with regard to the development over time. The beta-adrenergic receptor densities showed no statistical correlation with the degree of rejection as assessed by histologic criteria and antimyosin ration. These results suggest that in the first 3 months after heart transplantation beta-adrenergic receptor density and adenylate cyclase responses to 10 mumol/L isoproterenol do not change and that beta-adrenergic receptor density in the transplanted myocardium does not seem to be affected by the degree of rejection.

Solid-phase extraction for the high-performance liquid chromatographic determination of indomethacin, suxibuzone, phenylbutazone and oxyphenbutazone in plasma, avoiding degradation of compounds.

A solid-phase extraction method was validated for the simultaneous high-performance liquid chromatographic determination of indomethacin, suxibuzone, phenylbutazone, oxyphenbutazone and their degradation products. Indomethacin was added as internal standard to plasma samples, which were then acidified with citrate buffer and passed through a phenyl cartridge. The drugs were eluted with hexane-diethyl ether (1:1, v/v), and the organic extract was taken to dryness. The residue was dissolved in methanol and chromatographed on a C18 column with ultraviolet detection at 240 nm. The elution was isocratic with a mobile phase of 0.02 M ammonium sulphate-acetonitrile (45:55, v/v), pH 3. For indomethacin, suxibuzone, phenylbutazone and oxyphenbutazone the limit of quantitation was 0.05 microgram/ml. The linearity was checked between 0.05 and 100 micrograms/ml (r = 0.999); within this range the recovery was higher than 90% and the accuracy showed relative errors of less than 7.5%. The main advantage of this method is the avoidance of degradation by using citrate buffer instead of the usual 5 M hydrochloric acid to acidify the plasma. The method is also more specific and less time-consuming than the previously reported liquid-liquid extraction, and could possibly be automated.

Left ventricular dynamics and plasma catecholamines during isometric exercise in patients following cardiac transplantation.

Haemodynamics and plasma catecholamine responses to isometric exercise were evaluated invasively in 11 orthotopic heart transplant recipients and seven control subjects. Differences in haemodynamic responses between the two groups were already apparent after one min of handgrip at 30% of maximal voluntary contraction, and very pronounced at the end of the fourth minute. At this point transplanted patients showed smaller increments in heart rate (4.8 +/- 3.2 vs 20.4 +/- 14.1 beats.min-1, P less than 0.001), mean arterial pressure (13.7 +/- 7.2 vs 31.5 +/- 12.2 mmHg, P less than 0.001) and cardiac index (0.51 +/- 0.22 vs 1.02 +/- 0.53 L.min-1.m-2, P less than 0.01), whereas left ventricular end-diastolic pressure increased to a greater extent (8.8 +/- 4.9 vs 2.2 +/- 1.8 mmHg, P less than 0.01). Stroke volume index increased similarly (3.8 +/- 1.8 vs 2.0 +/- 3.5 ml beat-1.m-2, NS) and systemic vascular resistance remained unchanged in both groups. The slopes of the left ventricular function curves (ratio of change in left ventricular work to change in left ventricular end-diastolic pressure) indicated depressed left ventricular function in the transplanted patients. The two groups showed similar increments in mixed venous plasma norepinephrine and epinephrine indicating normal sympathoadrenal activation in the transplanted patients. In conclusion, transplanted hearts respond to handgrip with attenuated increases in heart rate, cardiac output and arterial pressure and by increasing left ventricular filling pressure, suggesting a poor contractile reserve probably due to denervation. Circulating catecholamines, especially epinephrine, probably contribute to the cardiac responses to isometric exercise.