Stationary and Transient Fluctuation Theorems for Effective Heat Fluxes between Hydrodynamically Coupled Particles in Optical Traps.

We experimentally study the statistical properties of the energy fluxes between two trapped Brownian particles, interacting through dissipative hydrodynamic coupling, and submitted to an effective temperature difference ΔT, obtained by random forcing the position of one trap. We identify effective heat fluxes between the two particles and show that they satisfy an exchange fluctuation theorem in the stationary state. We also show that after the sudden application of a temperature gradient ΔT, the total hot-cold flux satisfies a transient exchange fluctuation theorem for any integration time, whereas the total cold-hot flux only does it asymptotically for long times.

Heat flux and entropy produced by thermal fluctuations.

We report an experimental and theoretical analysis of the energy exchanged between two conductors kept at different temperature and coupled by the electric thermal noise. Experimentally we determine, as functions of the temperature difference, the heat flux, the out-of-equilibrium variance, and a conservation law for the fluctuating entropy, which we justify theoretically. The system is ruled by the same equations as two Brownian particles kept at different temperatures and coupled by an elastic force. Our results set strong constraints on the energy exchanged between coupled nanosystems held at different temperatures.

Efficiency at maximum power of interacting molecular machines.

We investigate the efficiency of systems of molecular motors operating at maximum power. We consider two models of kinesin motors on a microtubule: for both the simplified and the detailed model, we find that the many-body exclusion effect enhances the efficiency at maximum power of the many-motor system, with respect to the single motor case. Remarkably, we find that this effect occurs in a limited region of the system parameters, compatible with the biologically relevant range.

On the surface tension of fluctuating quasi-spherical vesicles.

We calculate the stress tensor for a quasi-spherical vesicle and we thermally average it in order to obtain the actual, mechanical, surface tension tau of the vesicle. Both closed and poked vesicles are considered. We recover our results for tau by differentiating the free energy with respect to the proper projected area. We show that tau may become negative well before the transition to oblate shapes and that it may reach quite large negative values in the case of small vesicles. This implies that spherical vesicles may have an inner pressure lower than the outer one.

Pathways of mechanical unfolding of FnIII(10): low force intermediates.

We study the mechanical unfolding pathways of the FnIII(10) domain of fibronectin by means of an Ising-like model, using both constant force and constant velocity protocols. At high forces and high velocities our results are consistent with experiments and previous computational studies. Moreover, the simplicity of the model allows us to probe the biologically relevant low force regime, where we predict the existence of two intermediates with very close elongations. The unfolding pathway is characterized by stochastic transitions between these two intermediates.

Work distribution in manipulated single biomolecules.

We consider the relation between the microscopic and effective descriptions of the unfolding experiment on a model polypeptide. We evaluate the probability distribution function of the work performed by Monte Carlo simulations and compare it with that obtained by evaluating the work distribution generating function on an effective Brownian motion model tailored to reproduce exactly the equilibrium properties. The agreement is satisfactory for fast protocols, but deteriorates for slower ones, hinting at the existence of processes on several time scales even in such a simple system.

Equilibrium properties and force-driven unfolding pathways of RNA molecules.

The mechanical unfolding of a simple RNA hairpin and of a 236-base portion of the Tetrahymena thermophila ribozyme is studied by means of an Ising-like model. Phase diagrams and free energy landscapes are computed exactly and suggest a simple two-state behavior for the hairpin and the presence of intermediate states for the ribozyme. Nonequilibrium simulations give the possible unfolding pathways for the ribozyme, and the dominant pathway corresponds to the experimentally observed one.

Equilibriumlike fluctuations in some boundary-driven open diffusive systems.

There exist some boundary-driven open systems with diffusive dynamics whose particle current fluctuations exhibit universal features that belong to the Edwards-Wilkinson universality class. We achieve this result by establishing a mapping, for the system fluctuations, to an equivalent open yet equilibrium-diffusive system. We discuss the possibility of observing dynamic phase transitions using the particle current as a control parameter.

Work and heat probability distribution of an optically driven Brownian particle: theory and experiments.

We analyze the equations governing the evolution of distributions of the work and the heat exchanged with the environment by a manipulated stochastic system, by means of a compact and general derivation. We obtain explicit solutions for these equations for the case of a dragged Brownian particle in a harmonic potential. We successfully compare the resulting predictions with the outcomes of experiments, consisting of dragging a micron-sized colloidal particle through water with a laser trap.

Fluctuation relations for a driven Brownian particle.

We consider a driven Brownian particle, subject to both conservative and nonconservative applied forces, whose probability evolves according to the Kramers equation. We derive a general fluctuation relation, expressing the ratio of the probability of a given Brownian path in phase space with that of the time-reversed path, in terms of the entropy flux to the heat reservoir. This fluctuation relation implies those of Seifert, Jarzynski, and Gallavotti-Cohen in different special cases.

Theoretical description of effective heat transfer between two viscously coupled beads.

We analytically study the role of nonconservative forces, namely viscous couplings, on the statistical properties of the energy flux between two Brownian particles kept at different temperatures. From the dynamical model describing the system, we identify an energy flow that satisfies a fluctuation theorem both in the stationary and in transient states. In particular, for the specific case of a linear nonconservative interaction, we derive an exact fluctuation theorem that holds for any measurement time in the transient regime, and which involves the energy flux alone. Moreover, in this regime the system presents an interesting asymmetry between the hot and cold particles. The theoretical predictions are in good agreement with the experimental results already presented in our previous article [Imparato et al., Phys. Rev. Lett. 116, 068301 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.068301], where we investigated the thermodynamic properties of two Brownian particles, trapped with optical tweezers, interacting through a dissipative hydrodynamic coupling.

Accurate noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with chronic failure heart failure.

OBJECTIVES: This study was undertaken to explore further the relationship between Doppler-derived parameters of pulmonary flow and pulmonary vascular resistance (PVR) and to determine whether PVR could be accurately estimated noninvasively from Doppler flow velocity measurements in patients with chronic heart failure. BACKGROUND: The assessment of PVR is of great importance in the management of patients with heart failure. However, because of the inconclusive and conflicting data available, Doppler estimation of PVR is still considered unreliable. METHODS: Simultaneous Doppler echocardiographic examination and right heart catheterization were performed in 63 consecutive sinus rhythm heart failure patients with severe left ventricular systolic dysfunction. Hemodynamic PVR was calculated with the standard formula. The following Doppler variables on pulmonary flow and tricuspid regurgitation velocity curve were correlated with PVR: maximal systolic flow velocity, pre-ejection period (PEP), acceleration time (AcT), ejection time, total systolic time (TT), velocity time integral, and right atrium-ventricular gradient. RESULTS: At univariate analysis, all variables except maximal systolic flow velocity and velocity time integral showed a significant, although weak, correlation with PVR. The best correlation found was between AcT and PVR (r = -0.68). By regression analysis, only PEP, AcT and TT entered into the final equation, with a cumulative r = 0.87. When the function (PEP/AcT)/TT was correlated with PVR, the correlation coefficient further improved to 0.96. Of note, this function prospectively predicted PVR (r = 0.94) after effective unloading manipulations. CONCLUSIONS: The analysis of Doppler-derived pulmonary systolic flow is a reliable and accurate tool for estimating and monitoring PVR in patients with chronic heart failure due to left ventricular systolic dysfunction.

Independent and incremental prognostic value of Doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction.

OBJECTIVES: This study sought to investigate the relative and incremental prognostic value of demographic, historical, clinical, echocardiographic and mitral Doppler variables in patients with left ventricular systolic dysfunction. BACKGROUND: The prognostic value of diastolic abnormalities as assessed by mitral Doppler echocardiography has yet to be defined. METHOD: A total of 508 patients with left ventricular ejection fraction < or = 35% were followed up for a mean (+/- SD) period of 29 +/- 11 months. RESULTS: During the follow-up period, 148 patients (29.1%) were admitted to the hospital for congestive heart failure, and 100 patients (19.7%) died. By Cox model analysis, Doppler-derived mitral deceleration time of early filling < or = 125 ms (relative risk [RR] 1.93, 95% confidence interval [CI] 1.4 to 3.7), New York Heart Association functional class III or IV (RR 1.49, 95% CI 1.4 to 2.3), ejection fraction < or = 25% (RR 1.85, 95% CI 1.6 to 2.9), third heart sound (RR 2.06, 95% CI 1.8 to 3.2), age > 60 years (RR 1.95, 95% CI 1.8 to 3.1) and left atrial area > 18 cm2 (RR 1.73, 95% CI 1.6 to 2.7) were all found to be independent and additional predictors of all-cause mortality, and deceleration time was the single best predictor (chi-square 37.80). When all these significant variables were analyzed in hierarchic order, after age, functional class, third sound, ejection fraction and left atrial area, deceleration time still added significant prognostic information (global chi-square from 9.2 to 104.7). Also, deceleration time was the strongest independent predictor of hospital admission for congestive heart failure (RR 4.88, 95% CI 3.7 to 6.9) and cumulative events (congestive heart failure or all-cause mortality, or both; RR 2.44, 95% CI 2.0 to 3.8) in both symptomatic and asymptomatic patients. CONCLUSIONS: Deceleration time of early filling is a powerful independent predictor of poor prognosis in patients with left ventricular systolic dysfunction, whether symptomatic or asymptomatic. A short (< or = 125 ms) deceleration time by mitral Doppler echocardiography adds important prognostic information compared with other clinical, functional and echocardiographic variables.

Doppler-derived mitral deceleration time of early filling as a strong predictor of pulmonary capillary wedge pressure in postinfarction patients with left ventricular systolic dysfunction.

OBJECTIVES: The aim of this study was to investigate the correlations between Doppler-derived transmitral flow velocity variables and pulmonary capillary wedge pressure in patients with severe left ventricular systolic dysfunction. BACKGROUND: Abnormal relaxation and increased chamber stiffness have opposing effects on the left ventricular filling pattern. When both abnormalities are present at the same time, as often occurs in patients with systolic dysfunction, the ability of Doppler recording to assess diastolic function and predict left ventricular filling pressure may be significantly compromised. METHOD: Pulmonary capillary wedge pressure and Doppler transmitral flow velocity profile were simultaneously recorded in 140 postinfarction patients with ejection fraction < or = 35%. RESULTS: Correlation between the ratio of mitral peak flow velocity in early diastole to peak flow velocity in late diastole (E/A ratio) and pulmonary capillary wedge pressure was weak (r = 0.65). Although the specificity of E/A > or = 2 in predicting > or = 20 mm Hg in pulmonary capillary wedge pressure was high (99%), its sensitivity was low (43%). Conversely, a very close negative correlation was found between mitral deceleration time of early filling and pulmonary capillary wedge pressure (r = -0.90). Sensitivity and specificity of < or = 120 ms in deceleration time in predicting > or = 20 mm Hg in pulmonary capillary wedge pressure were 100% and 99%, respectively. CONCLUSIONS: Doppler-derived mitral deceleration time of early filling provides a simple and accurate means of estimating pulmonary capillary wedge pressure that is particularly useful in patients with a normal or normalized mitral flow velocity pattern.

Reversible restrictive left ventricular diastolic filling with optimized oral therapy predicts a more favorable prognosis in patients with chronic heart failure.

OBJECTIVES: We sought to assess whether in clinically stable patients with chronic heart failure (CHF) the prolongation (i.e., increase) of an initially short (< or = 125 ms) Doppler transmitral deceleration time (DT) of early filling obtained with long-term optimal oral therapy predicts a more favorable prognosis. BACKGROUND: It has been recently demonstrated that transmitral early DT is a powerful independent predictor of poor prognosis in patients with left ventricular dysfunction. However, DT may change over time according to loading conditions and medical treatment. METHOD: One hundred forty-four patients with CHF and a short DT (< or = 125 ms) underwent repeat Doppler echocardiographic study 6 months after the initial examination, while clinically stable with optimal oral therapy, and were then followed up for a mean period of 26 +/- 7 months. RESULTS: After 6 months, DT had not changed in 80 patients (group 1), whereas it was significantly prolonged (> 125 ms) in the remaining 64 patients (group 2). Baseline Doppler echocardiographic features were similar in the two groups. No changes were found after 6 months in group 1, whereas group 2 showed a slight but significant (p < 0.01) reduction in end-systolic volume, an improvement in left ventricular ejection fraction (p < 0.01) and a decrease (p < 0.01) in the degree of tricuspid regurgitation. During follow-up, 37% of patients in group 1 experienced cardiac death versus 11% in group 2 (p < 0.0005). By Cox model analysis, prolongation of a short DT emerged as the single best predictor of survival (chi-square 15.70). CONCLUSIONS: The prolongation of an initially short DT obtained with long-term optimal oral therapy predicts a more favorable outcome in clinically stable patients with CHF.

Long-term physical training and left ventricular remodeling after anterior myocardial infarction: results of the Exercise in Anterior Myocardial Infarction (EAMI) trial. EAMI Study Group.

OBJECTIVES: The aim of this multicenter randomized study was to investigate whether long-term physical training would influence left ventricular remodeling after anterior myocardial infarction. BACKGROUND: Exercise is currently recommended for patients after myocardial infarction; however, the effects of long-term physical training on ventricular size and remodeling still have to be defined. METHODS: Patients with no contraindications to exercise were studied 4 to 8 weeks after anterior Q wave myocardial infarction and 6 months later by echocardiography at rest and bicycle ergometric testing. After the initial study, patients were randomly allocated to a 6-month exercise training program (n = 49) or a control group (n = 46). A computerized system was used to derive echocardiographic variables of ventricular size, function and topography. RESULTS: After 6 months, a significant (p < 0.01) increase in work capacity (from 4,596 +/- 1,246 to 5,508 +/- 1,335 kp-m) was observed only in the training group, whereas global ventricular size, regional dilation and shape distortion did not change in either the control or the training group. However, compared with patients with an ejection fraction > 40%, patients with an ejection fraction < or = 40% had more significant (p < 0.001) ventricular enlargement at entry and demonstrated further (p < 0.01) global and regional dilation after 6 months, in both the control and the training group (end-diastolic volume from 77 +/- 14 to 85 +/- 17 ml/m2 in the control group and from 74 +/- 11 to 77 +/- 15 ml/m2 in the training group; regional dilation from 46 +/- 18% to 57 +/- 21% in the control group and from 42 +/- 18% to 44 +/- 26% in the training group). Ventricular size and topography did not change in patients with an ejection fraction > 40%. CONCLUSIONS: Patients with poor left ventricular function 1 to 2 months after anterior myocardial infarction are prone to further global and regional dilation. Exercise training does not appear to influence this spontaneous deterioration. Thus, postinfarction patients without clinical complications, even those with a large anterior infarction, may benefit from long-term physical training without any additional negative effect on ventricular size and topography.

Residual exertional ischemia and unfavorable left ventricular remodeling in patients with systolic dysfunction after anterior myocardial infarction.

OBJECTIVES: This study investigated whether exercise-induced myocardial ischemia influences left ventricular remodeling after anterior myocardial infarction. BACKGROUND: The effects of acute and recurrent ischemia on ventricular function are well established. However, to our knowledge the role of exertional ischemia in the remodeling response after infarction has not been investigated. METHODS: Ninety-one patients with a first anterior Q wave myocardial infarction were studied at 5 weeks by rest echocardiography and exercise scintigraphy. The echocardiographic examination was repeated 6 months later. On the basis of the presence and extent of reversible perfusion defects on exercise scintigraphy, patients were assigned to groups with no exertional ischemia (group 1, n = 20 [22%], mild to moderate ischemia (group 2, n = 45 [49%]) and severe exertional ischemia (group 3, n = 26 [29%]). RESULTS: Initial left ventricular volumes were similar, and no differences were found among the three groups in the remodeling response over the 6-month period of the study. However, patients in groups 2 and 3 with an ejection fraction < or = 40% showed significant (p < 0.01) ventricular enlargement over time, which was similar between the two groups (end-diastolic volume [mean +/- SD] from 74 +/- 13 to 80 +/- 17 ml/m2 in group 2 and from 72 +/- 11 to 81 +/- 19 ml/m2 in group 3; regional dilation from 42 +/- 16% to 52 +/- 22% in group 2 and from 38 +/- 18% to 46 +/- 27% in group 3). In contrast, ventricular dimensions did not change in group 1 patients with an ejection fraction < or = 40% as well as in patients in all three groups with an ejection fraction > 40%. CONCLUSIONS: Exercise-induced myocardial ischemia may contribute to progressive ventricular enlargement in patients with poor left ventricular function after a large anterior myocardial infarction.

Work-probability distribution in systems driven out of equilibrium.

We derive the differential equation describing the time evolution of the work probability distribution function of a stochastic system which is driven out of equilibrium by the manipulation of a parameter. We consider both systems described by their microscopic state or by a collective variable which identifies a quasiequilibrium state. We show that the work probability distribution can be represented by a path integral, which is dominated by "classical" paths in the large system size limit. We compare these results with simulated manipulation of mean-field systems. We discuss the range of applicability of the Jarzynski equality for evaluating the system free energy using these out-of-equilibrium manipulations. Large fluctuations in the work and the shape of the work distribution tails are also discussed.

Thermal transport in out-of-equilibrium quantum harmonic chains.

We address the problem of heat transport in a chain of coupled quantum harmonic oscillators, exposed to the influences of local environments of various nature, stressing the effects that the specific nature of the environment has on the phenomenology of the transport process. We study in detail the behavior of thermodynamically relevant quantities such as heat currents and mean energies of the oscillators, establishing rigorous analytical conditions for the existence of a steady state, whose features we analyze carefully. In particular, we assess the conditions that should be faced to recover trends reminiscent of the classical Fourier law of heat conduction and highlight how such a possibility depends on the environment linked to our system.

Effects of nitroglycerin by technetium-99m sestamibi tomoscintigraphy on resting regional myocardial hypoperfusion in stable patients with healed myocardial infarction.

Myocardial sestamibi uptake reflects regional flow distribution and cellular integrity; however, some segments showing reduced tracer uptake at rest may consist of viable, although hypoperfused, myocardium. It is speculated that the administration of nitroglycerin (NTG) before the sestamibi injection would improve the tracer uptake in resting hypoperfused regions. Thirty-six stable patients with previous myocardial infarction (56 +/- 2 years; mean ejection fraction 42 +/- 2%), in whom perfusion defects could be seen at resting sestamibi tomography, repeated the scintigraphic study 2 to 6 days later, receiving NTG (0.3 to 0.6 mg sublingually) before the tracer injection. The size of the tracer uptake defect was quantified from circumferential profiles in 3 short-axis slices by integrating the area below the lower normal limit (mean -2 SD). After NTG, the mean perfusion defect significantly decreased (from 6,324 +/- 619 to 5,365 +/- 516, p < 0.01). The defect was reduced beyond the reproducibility limits in 20 patients (56%, group 1) and was unchanged or increased in 16 (44%, group 2). The resting sestamibi defect size was comparable between the 2 groups. The average percent reduction of the perfusion defect after NTG was 29 +/- 4% (range 7 to 74).(ABSTRACT TRUNCATED AT 250 WORDS)