Effective one-component model of binary mixture: molecular arrest induced by the spatially correlated stochastic dynamics.

Spatially correlated noise (SCN), i.e. the thermal noise that affects neighbouring particles in a similar manner, is ubiquitous in soft matter systems. In this work, we apply the over-damped SCN-driven Langevin equations as an effective, one-component model of the dynamics in dense binary mixtures. We derive the thermodynamically consistent fluctuation-dissipation relation for SCN to show that it predicts the molecular arrest resembling the glass transition, i.e. the critical slow-down of dynamics in the disordered phases. We show that the mechanism of singular dissipation is embedded in the dissipation matrix, accompanying SCN. We are also able to identify the characteristic length of collective dissipation, which diverges at critical packing. This novel physical quantity conveniently describes the difference between the ergodic and non-ergodic dynamics. The model is fully analytically solvable, one-dimensional and admits arbitrary interactions between the particles. It qualitatively reproduces several different modes of arrested disorder encountered in binary mixtures, including e.g. the re-entrant arrest. The model can be effectively compared to the mode coupling theory.

Thermodynamically consistent Langevin dynamics with spatially correlated noise predicting frictionless regime and transient attraction effect.

While the origins of temporal correlations in Langevin dynamics have been thoroughly researched, the understanding of spatially correlated noise (SCN) is rather incomplete. In particular, very little is known about the relation between friction and SCN. In this article, starting from the microscopic, deterministic model, we derive the analytical formula for the spatial correlation function in the particle-bath interactions. This expression shows that SCN is the inherent component of binary mixtures, originating from the effective (entropic) interactions. Further, employing this spatial correlation function, we postulate the thermodynamically consistent Langevin equation driven by the Gaussian SCN and calculate the adequate fluctuation-dissipation relation. The thermodynamical consistency is achieved by introducing the spatially variant friction coefficient, which can be also derived analytically. This coefficient exhibits a number of intriguing properties, e.g., the singular behavior for certain types of interactions. Eventually, we apply this new theory to the system of two charged particles in the presence of counter-ions. Such particles interact via the screened-charge Yukawa potential and the inclusion of SCN leads to the emergence of the anomalous frictionless regime. In this regime the particles can experience active propulsion leading to the transient attraction effect. This effect suggests a nonequilibrium mechanism facilitating the molecular binding of the like-charged particles.

Non-Gaussian polymers described by alpha-stable chain statistics: Model, effective interactions in binary mixtures, and application to on-surface separation.

The Gaussian chain model is the classical description of a polymeric chain, which provides analytical results regarding end-to-end distance, the distribution of segments around the mass center of a chain, coarse-grained interactions between two chains and effective interactions in binary mixtures. This hierarchy of results can be calculated thanks to the α stability of the Gaussian distribution. In this paper we show that it is possible to generalize the model of Gaussian chain to the entire class of α-stable distributions, obtaining the analogous hierarchy of results expressed by the analytical closed-form formulas in the Fourier space. This allows us to establish the α-stable chain model. We begin with reviewing the applications of Levy flights in the context of polymer sciences, which include: chains described by the heavy-tailed distributions of persistence length; polymers adsorbed to the surface; and the chains driven by a noise with power-law spatial correlations. Further, we derive the distribution of segments around the mass center of the α-stable chain and construct the coarse-grained interaction potential between two chains. These results are employed to discuss the model of binary mixture consisting of the α-stable chains. In what follows, we establish the spinodal decomposition condition generalized to the mixtures of the α-stable polymers. This condition is further applied to compare the on-surface phase separation of adsorbed polymers (which are known to be described with heavy-tailed statistics) with the phase separation condition in the bulk. Finally, we predict the four different scenarios of simultaneous mixing and demixing in the two- and three-dimensional systems.

Analytical theory of effective interactions in binary colloidal systems of soft particles.

While density functional theory with integral equations techniques are very efficient tools in the numerical analysis of complex fluids, analytical insight into the phenomenon of effective interactions is still limited. In this paper, we propose a theory of binary systems that results in a relatively simple analytical expression combining arbitrary microscopic potentials into effective interaction. The derivation is based on translating a many-particle Hamiltonian including particle-depletant and depletant-depletant interactions into the occupation field language, which turns the partition function into multiple Gaussian integrals, regardless of what microscopic potentials are chosen. As a result, we calculate the effective Hamiltonian and discuss when our formula is a dominant contribution to the effective interactions. Our theory allows us to analytically reproduce several important characteristics of systems under scrutiny. In particular, we analyze the following: the effective attraction as a demixing factor in the binary systems of Gaussian particles, the screening of charged spheres by ions, which proves equivalent to Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, effective interactions in the binary mixtures of Yukawa particles, and the system of particles consisting of both a repulsive core and an attractive/repulsive Yukawa interaction tail. For this last case, we reproduce the "attraction-through-repulsion" and "repulsion-through-attraction" effects previously observed in simulations.

Polymer unfolding and motion synchronization induced by spatially correlated noise.

The problem of a spatially correlated noise affecting a complex system is studied in this paper. We present a comprehensive analysis of a two-dimensional model polymer chain, driven by the spatially correlated Gaussian noise, for which we have varied the amplitude and the correlation length. The chain model is based on a bead-spring approach, enriched with a global Lennard-Jones potential and angular interactions. We show that spatial correlations in the noise inhibit the chain geometry dynamics, enhancing the preservation of the polymer shape. This is supported by the analysis of correlation functions of both the module length and angles between neighboring modules, which have been measured for the noise amplitude ranging over three orders of magnitude. Moreover, we have observed the correlation length dependent bead motion synchronization and the spontaneous polymer unfolding, resulting from an interplay between chain potentials and the spatially structured noise.

Constructive role of noise in signal transmissions by biomembrane proteins.

We discuss new examples of the constructive role of environmental fluctuations in biophysical processes, namely quantitative enhancement and qualitative sharpening of the outgoing signal in the intercellular signal transduction, e.g., in the synaptic links. An experimental check in a chemical flow reactor is suggested.

Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia.

OBJECTIVES: To assess the effects of aspirin compared with simvastatin on thrombin generation in hypercholesterolemic men, and to establish whether the reduction of elevated blood cholesterol by simvastatin would affect the action of aspirin on thrombin formation. BACKGROUND: Aspirin inhibits thrombin formation, but its performance is blunted in hypercholesterolemia. By virtue of altering lipid profile, statins could be expected to influence thrombin generation. METHODS: Thirty-three men, aged 34 to 61 years, with minimal or no clinical symptoms, serum total cholesterol >6.5 mmol/liter and serum triglycerides <4.6 mmol/liter, completed the study consisting of three treatment phases. First, they received 300 mg of aspirin daily for two weeks (phase I), which was then replaced by simvastatin at the average dose of 24 mg/d for three months (phase II). In phase III, aspirin, 300 mg/day, was added for two weeks to simvastatin, the dose of which remained unchanged. Thrombin generation was assessed: 1) in vivo, by measuring levels of fibrinopeptide A (FPA) and prothrombin fragment 1+2 (F1+2) in venous blood; and 2) ex vivo, by monitoring the rates of increase of FPA and F1+2 in blood emerging from standardized skin incisions of a forearm. A mathematical model was used to describe the kinetics of thrombin formation at the site of microvascular injury. RESULTS: Two-week treatment with aspirin had no effect on thrombin markers in vivo, while ex vivo it depressed the total amount of thrombin formed, though not the reaction rate. After simvastatin treatment, serum cholesterol decreased by 31% and LDL cholesterol by 42%, while thrombin generation became markedly depressed. In venous blood, FPA was significantly reduced. Concomitantly, the initial thrombin concentration and total amount of thrombin generated decreased significantly. Addition of aspirin to simvastatin (phase III) had no further effect on any of these parameters. CONCLUSIONS: In men with hypercholesterolemia, lowering serum cholesterol level by a three-month simvastatin treatment is accompanied by a marked reduction of thrombin generation both at basal conditions in venous blood and after activation of hemostasis by microvascular injury. Once blood cholesterol became reduced, adding aspirin to simvastatin did not enhance dampening of thrombin formation.

Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia.

Recent evidence indicates that aspirin inhibits thrombin generation in clotting blood. We noticed that this effect was less pronounced in patients with hypercholesterolemia. The aim of the study was to prove this observation. The effects of aspirin on thrombin generation were evaluated in (1) 46 healthy volunteers, 2 hours after ingestion of a single, 500-mg dose and (2) 28 survivors of myocardial infarction who took 300 mg aspirin/d for 2 weeks. In both populations, two well-matched subgroups were distinguished, using a serum cholesterol level of 6.2 mmol/L (240 mg/dL) and an LDL cholesterol level of 4.0 mmol/L (155 mg/dL) as borderline. Thrombin generation was monitored ex vivo in blood emerging from a skin microvasculature injury and additionally, in a single-dose study in vitro in recalcified plasma. Aspirin depressed thrombin generation in the group of subjects with serum cholesterol < 6.2 mmol/L and LDL cholesterol < 4.0 mmol/L but not in the group with high blood cholesterol levels. Inhibitory effects of aspirin were more pronounced after the 2-week treatment than after a single dose. There was a significant correlation between total serum cholesterol or LDL cholesterol and total amount of thrombin generated after aspirin treatment. In subjects with high blood cholesterol levels, thrombin generation was not affected by aspirin. Blunting of aspirin action in hypercholesterolemia might be explained by (1) alterations in platelet lipid-protein matrix that render their membrane proteins less accessible for acetylation by aspirin and (2) changes in composition and structure of plasma lipoproteins that diminish the chance of aspirin to interact with prothrombin.

Serum immunoglobulin E and sudden cardiac arrest during myocardial infarction.

BACKGROUND: While studying the immunological response to acute myocardial infarction (AMI) we noticed that patients who on admission had a high serum immunoglobulin E (IgE) level were less likely to die suddenly. This observation seemed to deserve verification since atopic patients whose production of IgE was excessive had been reported to have depressed haemostatic platelet function and impaired thrombinogenesis. METHODS: We measured levels of serum IgE in 386 patients with AMI at the time of admission to the coronary care unit. Patients were divided into two groups, depending on the presence (n = 55) or absence (n = 331) of sudden cardiac arrest. The two groups did not differ with respect to age, sex, or risk factors for coronary artery disease. RESULTS: The mean level of serum IgE was significantly higher in the group without sudden cardiac arrest than in the group with this complication. In a separate study we found that high serum IgE levels were associated with delayed thrombin generation in the clotting blood of survivors of myocardial infarction. CONCLUSION: Early determination of serum IgE levels might help to detect patients at risk of sudden cardiac arrest during myocardial infarction. Patients with high serum IgE levels might be protected against sudden cardiac death through the depression of clot formation because of the late appearance of thrombin in their coronary arteries.

Antiplatelet drugs and generation of thrombin in clotting blood.

Platelets participate in formation of thrombin through secretion of coagulation factors and by providing a catalytic surface on which prothrombinase complex is assembled. We studied the effects of four antiplatelet drugs on thrombin formation in healthy volunteers. Thrombin generation was monitored both in vitro--in recalcified plasma--and ex vivo--in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. A mathematical model has been developed to describe the latter reaction. It is based on estimation of the rate of increase in fibrinopeptide A (FPA), a specific marker of thrombin activity, in blood emerging from skin incisions. Two hours after the ingestion of 500 mg of aspirin, thrombin formation became significantly impaired both in vitro and ex vivo. In contrast, 2 hours after the oral administration of placebo, indomethacin 50 mg, or OKY-046 (a thromboxane synthase inhibitor) 400 mg, thrombinogenesis remained unaltered. Ticlopidine, studied either 3 hours after 500 mg oral administration, or after 5 days of intake at a daily dose of 500 mg, had no effect on thrombin generation. Thus, aspirin, contrary to other antiplatelet drugs, depresses thrombin formation in clotting blood, a phenomenon that might be of clinical relevance. It is suggested that aspirin exerts this effect by acetylating prothrombin and/or macromolecules of platelet membrane.

A mathematical model describing consequences of abnormally high levels of epidermal growth factor receptor on the proliferation of neoplastic cells.

Recent laboratory and clinical data suggest that some human neoplasms exhibit unusually high levels of cell-surface receptors for epidermal growth factor, and that this abnormality is associated with rapid cellular proliferation and poor prognosis. We propose that the existence of an abnormally high number of mitogen receptors is not merely correlated with rapid proliferation but is pathophysiologically responsible for such behavior. Cells with high levels of mitogen receptors may be rendered 'hypersensitive' to mitogenic stimuli, and hence may be stimulated to divide even when ambient mitogen concentrations are at a low 'background' level, insufficient to prompt the division of cells with a normal number of receptors. To investigate this hypothesis further, we have developed a mathematical model that describes proliferative behavior of cells as a function of mitogen concentration and receptor number. The model enables us to simulate the proliferative behavior of cells with various receptor levels at various mitogen concentrations and predicts a growth advantage associated with excess mitogen receptors. Computer simulations based on the model are consistent with previously published experimental data. This work provides support for the view that overexpression of genes encoding normal growth factor receptors can contribute to the inappropriate proliferation of neoplastic cells.

Intralipid alterations in pulmonary prostaglandin metabolism and gas exchange.

To assess the role of Intralipid as a prostaglandin (PG) precursor, we infused Intralipid into 40 rabbits with long-term arterial and venous catheters; 24 other rabbits received a control saline infusion. One-half of the rabbits in both experimental and control groups had oleic acid-damaged lungs, and at least 5 in each of the 4 groups (Intralipid/saline in normal/damaged lungs) received indomethacin. Two vasodilating PGs (E2 and 6KF1 alpha) and one vasoconstricting PG (F2 alpha) were measured. Triglyceride levels increased significantly in all Intralipid groups, averaging 580 mg/dl. Intralipid-related alterations in PG levels and arterial oxygen tension (PaO2) were significant only in the lung-damaged group. The mean (+/- sem) decrease in PaO2 was 12 +/- 1.5 torr (p less than .001). For both vasodilating PGs, Intralipid infusion increased the pulmonary arteriovenous gradients for PG E2 and PG 6KF1 alpha by 960 pg/ml (p less than .05) and 697 pg/ml (p less than .10), respectively. Both the PaO2 decrease and the vasodilating PG increases were blocked by indomethacin. In summary, Intralipid infusion in lung-damaged rabbits increased pulmonary production of vasodilating PGs and associated hypoxemia, presumably caused by an unblocking of hypoxic vasoconstriction and resultant increase in intrapulmonary right-to-left shunt.

Experimental effects of chloral hydrate in ventilatory response to hypoxia and hypercarbia.

The effect of chloral hydrate (CH)-induced sleep on inspiratory drive has not been systematically assessed. To determine the effects of CH on the ventilatory responses to hypercarbia and to hypoxia, nine unanesthetized adult rabbit with chronic tracheostomy were studied. We compared awake ventilatory measurements before CH to non-REM sleep assessments at 30, 60, 90, and 120 min after administration of 250 mg/kg of CH. There were no significant differences between any of these assessment intervals for respiratory rate, PACO2, PAO2, tidal volume (VT), minute volume, Ti/Ttot, or VT/Ti. Hypercarbic ventilatory response to slopes were not diminished at any of the CH-sleep intervals compared to the awake mean slope. In addition, the ventilatory response to hypoxia at PAO2=70 mm Hg (V70) and the hypoxic response slope demonstrated no significant decrease at any of the CH-sleep intervals. In summary, absence of any significant decrease in either hypercarbic or hypoxic ventilatory response after CH administration indicates absence of any CH effect on chemical inspiratory drive.

Indomethacin inhibition of intralipid-induced lung dysfunction.

Intralipid-related pulmonary alterations have been attributed to hyperlipemia. To better quantitate and explain these alterations, Intralipid (0.4 gm/kg over one hour) was infused into three groups of rabbits and saline into a fourth group. Group I had normal lung function; Groups II-IV were pretreated with oleic acid and Group III also received indomethacin. Serum triglyceride (TG) levels, arterial (a) and end-tidal (A) PCO2 and PO2 were measured at baseline and then hourly for six hours. There was no ventilatory deterioration in Group I despite a peak TG level of 638 mg/dl. In Group II there was an Intralipid-related PaO2 decrease of 11-13 mmHg (p less than .01) and a delta AaPO2 increase of 16 mmHg (p less than .01); both returned to baseline without significant TG normalization. Since indomethacin prevented these PaO2 and delta AaPO2 changes despite a significant TG increase, the effects of Intralipid appear not to be TG-related but rather to be related to PG-mediated alterations in pulmonary vasomotor tone. Our results are most consistent with a net increase in vasodilating prostaglandins and resultant hypoxemia secondary to unblocking of baseline hypoxic vasoconstriction.

The effect of overdistention of the lung on pulmonary function in beagle puppies.

The removal of one lung from a beagle puppy results in minimal interference with lung function or the arterial gases. The removal of air from the empty pleural cavity results in a shift of the mediastinum and overdistention of the contralateral lung. An immediate decrease in the PO2 and increase in the PCO2 is seen. Significant increase in the alveolar-arterial CO2 gradient reflected marked increase in dead space ventilation. Biopsies of the overdistended lung demonstrated emphysema and disruption of alveoli. These changes may explain some of the deterioration of lung function and the complication of contralateral pneumothorax following repair of a Bochdalek diaphragmatic hernia. Our study suggests that the mediastinum should be stabilized in the midline after repair of a diaphragmatic hernia or after a pneumonectomy in an infant or small child.