Numerical solution of the eXtended Pom-Pom model for viscoelastic free surface flows

In this paper we present a finite difference method for solving two-dimensional viscoelastic unsteady free surface flows governed by the single equation version of the eXtended Pom-Pom (XPP) model. The momentum equations are solved by a projection method which uncouples the velocity and pressure fields. We are interested in low Reynolds number flows and, to enhance the stability of the numerical method, an implicit technique for computing the pressure condition on the free surface is employed. This strategy is invoked to solve the governing equations within a Marker-and-Cell type approach while simultaneously calculating the correct normal stress condition on the free surface. The numerical code is validated by performing mesh refinement on a two-dimensional channel flow. Numerical results include an investigation of the influence of the parameters of the XPP equation on the extrudate swelling ratio and the simulation of the Barus effect for XPP fluids

Seleno-functionalization of quercetin improves the non-covalent inhibition of mpro and its antiviral activity in cells against sars-cov-2

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro ) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 µM and 8 µM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Prostaglandin E2 Regulates AMPA Receptor Phosphorylation and Promotes Membrane Insertion in Preoptic Area Neurons and Glia during Sexual Differentiation

Sexual differentiation of the rodent brain is dependent upon the organizing actions of the steroid hormone, estradiol. In the preoptic area, a brain region critical for the expression of adult reproductive behavior, there are twice as many dendritic spine synapses per unit length on newborn male neurons compared to female neurons and this sex difference correlates with the expression of adult male copulatory behavior. The sex difference in the POA is achieved via estradiol's upregulation of the membrane-derived lipid signaling molecule prostaglandin E2 (PGE2); PGE2 is necessary and sufficient to masculinize both dendritic spine density and adult sexual behavior in rats. We have previously shown that PGE2 activates EP2 and EP4 receptors which increases protein kinase A (PKA) activity and that masculinized dendritic spine density and sex behavior are both dependent upon PKA as well as activation of AMPA type glutamate receptors. In the current experiments, we build upon this signaling cascade by determining that PGE2 induces phosphorylation of the AMPA receptor subunit, GluR1, which leads to increased AMPA receptor insertion at the membrane. Treating female pups on the day of birth with PGE2 induced the phosphorylation of GluR1 at the PKA-sensitive site within 2 hours of treatment, an effect that was blocked by co-administration of the PKA/AKAP inhibitor, HT31 with PGE2. Brief treatment of mixed neuronal/glial POA cultures with PGE2 or the cAMP/PKA stimulator, forskolin, increased membrane associated GluR1 in both neurons and glia. We speculate that PGE2 induced increases in AMPA receptor associated with the membrane underlies our previously observed increase in dendritic spine density and is a critical component in the masculinization of rodent sex behavior

Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization

Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate

A finite difference technique for simulating unsteady viscoelastic free surface flows

This work is concerned with the development of a numerical method capable of simulating viscoelastic free surface flow of an Oldroyd-B fluid. The basic equations governing the flow of an Oldroyd-B fluid are considered. A novel formulation is developed for the computation of the non-Newtonian extra-stress components on rigid boundaries. The full free surface stress conditions are employed. The resulting governing equations are solved by a finite difference method on a staggered grid, influenced by the ideas of the marker-and-cell (MAC) method. Numerical results demonstrating the capabilities of this new technique are presented for a number of problems involving unsteady free surface flows

On the transport through polymer layer and porous arterial wall in drug-eluting stents

The safety and efficacy of drug-eluting stents are strongly influenced by the transport of the antiproliferative/anti-inflammatory drugs in the arterial wall. Dissolution in the polymer coating and specific binding in the artery wall play an important role in the process. We consider the model of dissolution, transport and binding of sirolimus on an axisymmetric domain representing the polymer coating layer and the porous artery wall in the vicinity of a stent strut. We employ the FEM on an unstructured mesh to discretize the governing equations. We employ a nonlinear dissolution model for the dynamics in the coating, and a nonlinear saturable binding model that includes both specific and non-specific binding in the arterial wall as separate phases, as proposed by McGinty and Pontrelli (J Math Chem 54:967–976, 2016). The arterial wall is considered an anisotropic porous media, and the flow is considered to be governed by Darcy flow. The permeability in the polymer coating is considered to be very small, but finite. The endothelium lamina, where present, is modelled as a no-flow boundary. The effect of slow and fast release polymers is considered, showing that the time evolution of the process can be efficiently controlled by the polymer diffusion coefficient. In fact, an order of magnitude decrease in the polymer diffusion coefficient results in an order of magnitude increase in the time of drug delivery. It is estimated that 52–54% of the sirolimus mass actually diffuses into the arterial wall. However, the spatial distribution of the sirolimus is greatly influenced by the flow and the arterial wall properties, being therefore susceptible to patient health conditions

Dizocilpine infusion has a different effect in the development of morphine and cocaine sensitization: behavioral and neurochemical aspects

6noreservedThe stimulation of glutamate receptors plays a relevant role in the development of behavioral sensitization to psychostimulants, while less clear results have been obtained on their role in morphine sensitization. We addressed this issue by comparing the development of cocaine and morphine sensitization under a continuous s.c. infusion of the N-methyl-D-aspartate (NMDA) antagonist dizocilpine (0.1 mg/kg/24 h). Moreover, we studied the expression of NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunits in discrete limbic areas of rats sensitized to morphine or cocaine with or without the concomitant dizocilpine infusion. It was observed that dizocilpine infusion did not prevent the development of morphine sensitization, while it prevented the development of tolerance to morphine-induced analgesia. Finally, morphine-sensitized animals did not present any modification in the subunit expression of glutamate receptors in the brain areas examined. In agreement with previous results, we found that dizocilpine infusion prevented the development of cocaine sensitization. Moreover, we observed that rats sensitized to cocaine presented a significant increase in the levels of GLUR1, NR1 and NR2B, in the nucleus accumbens, and of NR2B in the hippocampus compared to control animals. Such modifications were absent in rats administered cocaine under dizocilpine infusion. We conclude that: (i) morphine sensitization is a neuroadaptive phenomenon which does not appear to require NMDA receptor activity in order to develop; (ii) cocaine sensitization is clearly dependent on NMDA receptor activity, as dizocilpine infusion prevented the occurrence of glutamate receptors modifications as well as the development of sensitization.mixedSCHEGGI, S.; MANGIAVACCHI, S.; MASI, F.; GAMBARANA, C.; TAGLIAMONTE, A.; DE MONTIS, M.G.Scheggi, S.; Mangiavacchi, S.; Masi, F.; Gambarana, C.; Tagliamonte, A.; DE MONTIS, M. G