Fluctuations of entropy production in turbulent thermal convection

We report on a numerical experiment performed to analyze fluctuations of the entropy production in turbulent thermal convection, a physical configuration that represents here a prototypical case of an out-of-equilibrium dissipative system. We estimate the entropy production from instantaneous measurements of the local temperature and velocity fields sampled along the trajectory of a large number of point-wise Lagrangian tracers. The entropy production is characterized by large fluctuations and becomes often negative. This represents a sort of "finite-time" violation of the second principle of thermodynamics, since the direction of the energy flux is opposite to that prescribed by the external gradient. We clearly show that the fluctuations of entropy production observed in the present system verify the fluctuation relation (FR), even though the system is time-irreversible

Negative Pressure Wound Therapy applied to a cholecystoparietal fistula: How to treat a rare complication of a common condition - a case report

A cholecystoparietal fistula is an uncommon complication of gallstone disease as a result of neglected gallbladder disease).The subcutaneous abdominal wall abscess, derived from this condition, might be wide and hard to treat, especially in elderly and debilitated patients. The best management of cholecystoparietal fistula depends on its etiology and may require medical, surgical, or endoscopic treatment. Negative Pressure Wound Therapy (NPWT) is a valuable support therapy that can improve the prognosis of the disease and the patient’s outcome. We report the case of an 89-year-old female patient affected by a spontaneous cholecystoparietal fistula with a wide abdominal wall abscess treated by a one-stage surgical approach combined with NPWT over the resulting skin loss

Heat transfer in drop-laden turbulence

Heat transfer by large deformable drops in a turbulent flow is a complex and rich in physics system, in which drops deformation, breakage and coalescence influence the transport of heat. We study this problem coupling direct numerical simulations (DNS) of turbulence, with a phase-field method for the interface description. Simulations are run at fixed shear Reynolds and Weber numbers. To evaluate the influence of microscopic flow properties, like momentum/thermal diffusivity, on macroscopic flow properties, like mean temperature or heat transfer rates, we consider four different values of the Prandtl number, which is the momentum to thermal diffusivity ratio: Pr=1, Pr=2, Pr=4 and Pr=8. The drops volume fraction is Phi=5.4% for all cases. Drops are initially warmer than the turbulent carrier fluid, and release heat at different rates, depending on the value of Pr, but also on their size and on their own dynamics (topology, breakage, drop-drop interaction). Computing the time behavior of the drops and carrier fluid average temperatures, we clearly show that an increase of Pr slows down the heat transfer process. We explain our results by a simplified phenomenological model: we show that the time behavior of the drops average temperature is self similar, and a universal behavior can be found upon rescaling by t/Pr^2/3

Harnessing the Therapeutic Potential of Antibodies Targeting Connexin Hemichannels

Connexin hemichannels have been implicated in pathology-promoting conditions, including inflammation, numerous widespread human diseases, including cancer and diabetes, and several rare diseases linked to pathological point mutations

Cues to opening mechanisms from in silico electric field excitation of cx26 hemichannel and in vitro mutagenesis studies in HeLa transfectans

Connexin channels play numerous essential roles in virtually every organ by mediating solute exchange between adjacent cells, or between cytoplasm and extracellular milieu. Our understanding of the structure-function relationship of connexin channels relies on X-ray crystallographic data for human connexin 26 (hCx26) intercellular gap junction channels. Comparison of experimental data and molecular dynamics simulations suggests that the published structures represent neither fully-open nor closed configurations. To facilitate the search for alternative stable configurations, we developed a coarse grained (CG) molecular model of the hCx26 hemichannel and studied its responses to external electric fields. When challenged by a field of 0.06 V/nm, the hemichannel relaxed toward a novel configuration characterized by a widened pore and an increased bending of the second transmembrane helix (TM2) at the level of the conserved Pro87. A point mutation that inhibited such transition in our simulations impeded hemichannel opening in electrophysiology and dye uptake experiments conducted on HeLa tranfectants. These results suggest that the hCx26 hemichannel uses a global degree of freedom to transit between different configuration states, which may be shared among the whole connexin family

Mitochondrial Thioredoxin System as a Modulator of Cyclophilin D Redox State

The mitochondrial thioredoxin system (NADPH, thioredoxin reductase, thioredoxin) is a major redox regulator. Here we have investigated the redox correlation between this system and the mitochondrial enzyme cyclophilin D. The peptidyl prolyl cis-trans isomerase activity of cyclophilin D was stimulated by the thioredoxin system, while it was decreased by cyclosporin A and the thioredoxin reductase inhibitor auranofin. The redox state of cyclophilin D, thioredoxin 1 and 2 and peroxiredoxin 3 was measured in isolated rat heart mitochondria and in tumor cell lines (CEM-R and HeLa) by redox Western blot analysis upon inhibition of thioredoxin reductase with auranofin, arsenic trioxide, 1-chloro-2,4-dinitrobenzene or after treatment with hydrogen peroxide. A concomitant oxidation of thioredoxin, peroxiredoxin and cyclophilin D was observed, suggesting a redox communication between the thioredoxin system and cyclophilin. This correlation was further confirmed by i) co-immunoprecipitation assay of cyclophilin D with thioredoxin 2 and peroxiredoxin 3, ii) molecular modeling and iii) depleting thioredoxin reductase by siRNA. We conclude that the mitochondrial thioredoxin system controls the redox state of cyclophilin D which, in turn, may act as a regulator of several processes including ROS production and pro-apoptotic factors release

Towards the ultimate regime in Rayleigh–Darcy convection

Numerical simulations are used to probe Rayleigh-Darcy convection in fluid-saturated porous media towards the ultimate regime. The present three-dimensional dataset, up to Rayleigh-Darcy number Ra = 80 × 10 3 , suggests that the appropriate scaling of the Nusselt number is Nu = 0.0081 Ra +0.067 Ra 0.61 , fitting the computed data for Ra & 10 3 . Extrapolation of current predictions to the ultimate linear regime yields the asymptotic law Nu = 0.0081 Ra, about 16% less than indicated in previous studies. Upon examination of the flow structures near the boundaries, we confirm previous indications of small flow cells hierarchically nesting into supercells, and we show evidence that the supercells at the boundary are the footprints of the megaplumes that dominate the interior part of the flow. The present findings pave the way for more accurate modeling of geophysical systems, with special reference to geological CO 2 sequestration

A Human-Derived Monoclonal Antibody Targeting Extracellular Connexin Domain Selectively Modulates Hemichannel Function

Connexin hemichannels, which are plasma membrane hexameric channels (connexons) composed of connexin protein protomers, have been implicated in a host of physiological processes and pathological conditions. A number of single point pathological mutations impart a "leaky" character to the affected hemichannels, i.e., make them more active or hyperactive, suggesting that normal physiological condition could be recovered using selective hemichannel inhibitors. Recently, a human-derived monoclonal antibody named abEC1.1 has been shown to inhibit both wild type and hyperactive hemichannels composed of human (h) connexin 26 (hCx26) subunits. The aims of this work were (1) to characterize further the ability of abEC1.1 to selectively modulate connexin hemichannel function and (2) to assess its in vitro stability in view of future translational applications. In silico analysis of abEC1.1 interaction with the hCx26 hemichannel identified critically important extracellular domain amino acids that are conserved in connexin 30 (hCx30) and connexin 32 (hCx32). Patch clamp experiments performed in HeLa DH cells confirmed the inhibition efficiency of abEC1.1 was comparable for hCx26, hCx30 and hCx32 hemichannels. Of note, even a single amino acid difference in the putative binding region reduced drastically the inhibitory effects of the antibody on all the other tested hemichannels, namely hCx30.2/31.3, hCx30.3, hCx31, hCx31.1, hCx37, hCx43 and hCx45. Plasma membrane channels composed of pannexin 1 were not affected by abEC1.1. Finally, size exclusion chromatography assays showed the antibody does not aggregate appreciably in vitro. Altogether, these results indicate abEC1.1 is a promising tool for further translational studies

Digital twin for civil engineering systems: an exploratory review for distributed sensing updating

We live in an environment of ever-growing demand for transport networks, which also have ageing infrastructure. However, it is not feasible to replace all the infrastructural assets that have surpassed their service lives. The commonly established alternative is increasing their durability by means of Structural Health Monitoring (SHM)-based maintenance and serviceability. Amongst the multitude of approaches to SHM, the Digital Twin model is gaining increasing attention. This model is a digital reconstruction (the Digital Twin) of a real-life asset (the Physical Twin) that, in contrast to other digital models, is frequently and automatically updated using data sampled by a sensor network deployed on the latter. This tool can provide infrastructure managers with functionalities to monitor and optimize their asset stock and to make informed and data-based decisions, in the context of day-to-day operative conditions and after extreme events. These data not only include sensor data, but also include regularly revalidated structural reliability indices formulated on the grounds of the frequently updated Digital Twin model. The technology can be even pushed as far as performing structural behavioral predictions and automatically compensating for them. The present exploratory review covers the key Digital Twin aspects—its usefulness, modus operandi, application, etc.—and proves the suitability of Distributed Sensing as its network sensor component.This research was funded by Fondazione CARITRO Cassa di Risparmio di Trento e Rovereto, grant number 2021.0224.Peer ReviewedPostprint (published version