Aggregation and breakup of colloidal particle aggregates in shear flow: A combined Monte Carlo - Stokesian dynamics approach

A method for the simulation of aggregation and breakup processes in colloidal particle suspensions is presented. The method combines a Monte Carlo algorithm to determine, on the basis of probabilistic considerations, the sequence of aggregation and breakup events, and a Discrete Element Method, built in the framework of Stokesian dynamics and contact mechanics, to accurately reproduce them. Liquid-solid suspensions subject to a uniform shear stress are investigated. The model is seen to be able to reproduce the typical dynamic steady state which is observed in colloidal suspensions under severe shearing, in which the effects of aggregation and breakup balance each other. The structural properties of the aggregates and the dynamics of the aggregation and breakup phenomena are characterized in detail. Both fragmentation and erosion are seen to contribute to the breakup process, which is characterized by an exponent similar to the one reported in the literature for compact clusters

CFD-DEM characterization and population balance modelling of a dispersive mixing process

This work investigates the breakup dynamics of solid agglomerates in a polymer compounding operation, by using computational fluid dynamics (CFD) simulations together with discrete element method (DEM) simulations. CFD simulations are used to compute the flow field and the shear stress distribution inside a 2D section of a typical internal mixer for polymer compounding. DEM simulations are instead used to predict the mechanical response of the agglomerates and to detect the critical viscous shear stress needed to induce breakup. DEM breakup data and viscous stress distributions are correlated by a first–time passage–statistics and used to calibrate a population balance model. The work returned detailed insights into the flow field characteristics and into the dispersive mixing kinetics. The simulation strategy herein reported can be adapted to study generic solid–liquid disperse flows in which the breakup of the solid phase is found at the core of the system behaviour

Evidence for a GABAergic system in rodent and human testis: Local GABA production and GABA receptors

The major neurotransmitter of the central nervous system, gamma-aminobutyric acid (GABA), exerts its actions through GABA(A), GABA(B) and GABA(C) receptors. GABA and GABA receptors are, however, also present in several non-neural tissues, including the endocrine organs pituitary, pancreas and testis. In the case of the rat testis, GABA appears to be linked to the regulation of steroid synthesis by Leydig cells via GABA(A) receptors, but neither testicular sources of GABA, nor the precise nature of testicular GABA receptors are fully known. We examined these points in rat, mouse, hamster and human testicular samples. RT-PCR followed by sequencing showed that the GABA-synthesizing enzymes glutamate decarboxylase (GAD) 65 and/or GAD67, as well as the vesicular GABA transporter vesicular inhibitory amino acid transporter (VIAAT/VGAT) are expressed. Testicular GAD in the rat was shown to be functionally active by using a GAD assay, and Western blot analysis confirmed the presence of GAD65 and GAD67. Interstitial cells, most of which are Leydig cells according to their location and morphological characteristics, showed positive immunoreaction for GAD and VIAAT/VGAT proteins. In addition, several GABA(A) receptor subunits (alpha1-3, beta1-3, gamma1-3), as well as GABAB receptor subunits R1 and R2, were detected by RT-PCR. Western blot analysis confirmed the results for GABA(A) receptor subunits beta2/3 in the rat, and immunohistochemistry identified interstitial Leydig cells to possess immunoreactive GABA(A) receptor subunits beta2/3 and alpha1. The presence of GABA(A) receptor subunit alpha1 mRNA in interstitial cells of the rat testis was further shown after laser microdissection followed by RT-PCR analysis. In summary, these results describe molecular details of the components of an intratesticular GABAergic system expressed in the endocrine compartment of rodent and human testes. While the physiological significance of this peripheral neuroendocrine system conserved throughout species remains to be elucidated, its mere presence in humans suggests the possibility that clinically used drugs might be able to interfere with testicular function. Copyright (C) 2003 S. Karger AG, Basel

A CFD-DEM approach to study the breakup of fractal agglomerates in an internal mixer

In this work we present a method to investigate the breakup of filler agglomerates in an internal mixer during a compounding operation. The method employs computational fluid dynamics (CFD) simulations along with discrete element method (DEM) simulations. CFD simulations are performed to compute the flow field inside a 2D section of a typical batch internal mixer with two tangential rotors. During the CFD simulation, we assume the filler agglomerates to behave as tracer particles, carried passively by the flow. The trajectory of the tracers, together with the experienced velocity gradients, are fed to a DEM code, built in the framework of Stokesian dynamics. The code computes the mechanical response of the agglomerates along the trajectory, from which it is finally possible to ascertain the occurrence of breakup. Simulations are performed to evaluate the robustness of the method on two different rotor speed ratio conditions and varying agglomerate strength

Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

Prostaglandin F2α (PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2α synthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2α biosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2α but expressed different biosynthetic isozymes. In chromaffin cells, PGF2α secretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2α secretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2α release and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2α receptor was only detected in chromaffin cells, making medulla the primary target of PGF2α action. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2α repressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2α may be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cell-specific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal

Numerical Modelling of a Lab-scale Reactor for Microalgae Growth

In this paper we present the results of a numerical modelling work aimed at predicting the kinetics of microalgae production in a lab-scale photobioreactor. The experimental equipment is composed of a flat-plate bioreactor exposed to the light irradiation, and of a tank equipped with a hydraulic pump to secure the culture circulation. The numerical model addresses both the hydrodynamics of the experimental equipment and the kinetics of the relevant bio-chemical reactions. The hydrodynamics of the reactor was modelled as the one of a plug flow with a longitudinal dispersion, whereas the hydrodynamics of the tank was modelled as a cascade of continuous flow stirred tank reactors. The gaseous species transfer from the liquid free surface to the atmosphere was also considered. The relevant bio-chemical processes involved were modelled using common first-order rate expressions for the microalgae growth, and the effect of both thermal and photosynthetic phenomena, as well as the inhibition effects induced by substrate limitation and oxygen excess, have been taken into account. A calibration procedure has been conducted and showed that the model is able to reproduce with a satisfactorily degree of accuracy the experimental results, thus paving the way for its use as a production forecasting tool

Response of shear-activated nanotherapeutic particles in a clot-obstructed blood vessel by CFD-DEM simulations

In recent years, targeted drug delivery systems have been regarded as a promising solution to enhance the efficiency of treatments against clots in blood vessels. In this context, shear-activated nanotherapeutics (SANTs) have been recently proposed. These are micrometric clusters of polymeric nanoparticles coated with a clot lysing agent. These drug carriers are stable under normal blood flow conditions, but they can be designed to undergo breakup right on the clot in response to the local increase in the hydrodynamic stress caused by the lumen restriction, effectively concentrating the active agent at the point of need. The aim of this work is to investigate the mechanical response of three potential drug carrier morphologies to the pathological flow field stress, typically encountered in obstructed blood vessels. Computational fluid dynamics simulations have been used to compare the viscous stress in arterial obstructions with the one in a microfluidic device, suitable for in vitro experimental tests. Discrete element method simulations built upon Stokesian dynamics were conducted to estimate the tensile stress distribution acting inside isostatic, random close packing, and hollow drug carriers. The results herein presented constitute a platform for a future experimental campaign and aim at establishing SANTs as a robust and broadly applicable targeting strategy