Modelling and simulation of counter-current and confined jet reactors for hydrothermal synthesis of nano-materials

A confined jet mixer and a counter-current mixer for the continuous hydrothermal flow synthesis of TiO2 nano-materials under supercritical water conditions have been investigated using computational fluid dynamics (CFD). The fluid flow and heat transfer behaviour, including velocity and temperature profiles in both reactor configurations, are studied using the CFD tool ANSYS Fluent. The tracer concentration profiles are also simulated via solving species equations from which the mixing behaviour in the reactors is examined. A combined CFD and population balance model is used to predict the size distribution. The predicted temperature distributions for both reactors were found to be in good agreement with experimentally measured data. Detailed comparison of the hydrodynamic and thermal behaviours, and particle size distributions between the two reactors helped in the identification of key factors that affect the reactor performance, and also provided suggestions for reactor design optimisation and scale-up

Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines

Objective - Although inflammation is a recognized feature of atherosclerosis, the impact of inflammation on cellular cholesterol homeostasis is unclear. This study focuses on the molecular mechanisms by which inflammatory cytokines disrupt low-density lipoprotein (LDL) receptor regulation.Methods and Results - IL-1 beta enhanced transformation of vascular smooth muscle cells into foam cells by increasing uptake of unmodified LDL via LDL receptors and by enhancing cholesterol esterification as demonstrated by Oil Red O staining and direct assay of intracellular cholesterol concentrations. In the absence of IL-1 beta, a high concentration of LDL decreased LDL receptor promoter activity, mRNA synthesis and protein expression. However, IL-1 beta enhanced LDL receptor expression, overriding the suppression usually induced by a high concentration of LDL and inappropriately increasing LDL uptake. Exposure to IL-1 beta also caused overexpression of the sterol regulatory element binding protein ( SREBP) cleavage-activating protein ( SCAP), and enhanced its translocation from the endoplasmic reticulum to the Golgi, where it is known to cleave SREBP, thereby enhancing LDL receptor gene expression.Conclusions - These observations demonstrate that IL-1 beta disrupts cholesterol-mediated LDL receptor feedback regulation, permitting intracellular accumulation of unmodified LDL and causing foam cell formation. The implication of these findings is that inflammatory cytokines may contribute to intracellular LDL accumulation without previous modification of the lipoprotein

Analytical technology aided optimization and scale-up of impinging jet mixer for reactive crystallization process

Reactive crystallization is widely used in the manufacture of active pharmaceutical ingredients (APIs). Since APIs often have low solubility, traditional stirred tank reactors and the route of process operation and control using metastable zone width are not effective. The current work investigated the integration of an impinging jet mixer and a stirred tank crystallizer that can take advantage of both the reaction and crystallization characteristics, the focus being on design optimization and scale-up using process analytical techniques based on the Fourier transform Infrared spectroscopy and Focused Beam Reflectance Measurement, as well as X-ray diffraction and particle imaging Morphologi G3. The parameters for process operation and design of the impinging jet mixer were optimized. The research was carried out with reference to the manufacture of an antibiotic, sodium cefuroxime, firstly in a 1L reactor, then a 10L reactor. The crystals produced showed higher crystallinity, narrower size distribution, higher stability and purity

Seed Recipe Design for Batch Cooling Crystallization with Application to l-Glutamic Acid

In this paper, a seed recipe design is proposed for batch cooling crystallization to obtain the desired product attributes including product yield and product size distribution, based on simulation studies and experiments on β-l-glutamic acid (β-LGA) crystallization. The impact of seed recipe on product attributes is investigated based on the population balance model (PBM) simulations with respect to the size-dependent growth of crystals. It is found that the product yield is primarily affected by the seed loading ratio (SLR) and the batch time, but less affected by the mean size and variance of seeds. Smaller seeds could improve the product yield, and in contrast, larger seeds facilitate the growth into larger crystals but require a larger SLR to ensure the product yield. By introducing an objective function for optimization with the above PBM, a seed recipe design is given for obtaining the desired product attributes as above-mentioned. In addition, it is found that washing seeds by the solvent is necessary to ensure seed quality for quantitative seed recipe design and implementation, by comparing three different seed preparation methods. Simulation tests and experiments well demonstrate the effectiveness of the proposed seed recipe design for seeded batch cooling crystallization

The enhancement of TiO?photocatalytic activity by hydrogen thermal treatment

Author name used in this publication: H. LiuAuthor name used in this publication: X. Z. Li2002-2003 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Topographic influences on transient harbor oscillations excited by N-waves

The main objective of this paper is to comprehensively study influences of the variation of the bottom profile inside the harbor on the transient harbor oscillations excited by normally-incident N-waves. The specific physical phenomena investigated consist of wave profile evolution, maximum runup, relative wave energy distribution and total wave energy inside the harbor. A series of numerical experiments are implemented using a fully nonlinear Boussinesq model, FUNWAVE-TVD. Results show that when the harbor is subjected to the leading-elevation N-waves (LEN waves), the evolution of the maximum free surface elevation during the wave shoaling process inside the harbor coincides well with Green's law overall. When the incident wave amplitude is small, the maximum runup inside the harbor is almost only determined by the incident wave amplitude. As the incident wave amplitude increases, effects of the bottom profile on the maximum runup closely depend on both the incident wave type and amplitude. As the mean water depth inside the harbor decreases, the relative wave energy distribution tends to become more uniform, regardless of the incident wave amplitude and type. Finally, the variation trend of the total wave energy with the bottom profile is found to depend on the incident wave amplitude

Novel impinging jet and continuous crystallizer design for rapid reactive crystallization of pharmaceuticals

Reactive crystallization is an important operation in the pharmaceutical industry for the production of the active pharmaceutical ingredients (APIs), but has not been as widely studied as cooling or anti-solvent crystallization. Reactive crystallization has many unique features that make them different from cooling or anti-solvent crystallization, even leading to some concepts and methods not directly applicable to the former. Literature survey reveals that previous research on reactive crystallization has mainly been conducted for inorganic materials which are known to be simpler than crystallization of organic molecules. The focus of this research project was to carry out research on the process design and optimization of organic reactive crystallization. The objective was to research on novel crystallizer designs that suit and take advantages of the features of reactive crystallization, and on advanced modeling and optimization techniques with the aim of manufacturing high quality products. Process analytical technology was used as a supporting tool to achieve the above stated objectives. The results showed that by using novel impinging jet design, the product had uniform size distribution and superior crystallinity. In addition, continuous process design can achieve a greater amount of product handling and reduce the batch-to-batch variation

Development of a stereo imaging system for three-dimensional shape measurement of crystals

Despite the availability of various Process Analytical Technologies (PAT) for measuring other particle properties, their inherit limitations for the measurement of crystal shape have been restricted. This has impacted, in turn, on the development and implementation of optimisation, monitoring and control of crystal shape and size distributions within particle formulation and processing systems In recent years, imaging systems have shown to be a very promising PAT technique for the measurement of crystal growth, but still essentially limited as a technique only to provide two-dimensional information. The idea of using two synchronized cameras to obtain 3D crystal shape was mentioned previously (Chem Eng Sci 63(5) 1171-1184, 2008) but no quantitative results were reported. In this paper, a methodology which can directly image the full three-dimensional shape of crystals has been developed. It is based on the mathematical principle that if the two-dimensional images of an object are obtained from two different angles, the full three-dimensional crystal shape can be reconstructed. A proof of concept study has been carried out to demonstrate the potentials in using the system for the three-dimensional measurement of crystals

Caspase 3/ROCK1 pathway mediates high glucose-induced platelet microparticles shedding

Background: Platelet microparticles (PMPs) are closely associated with diabetic macrovascular complications. This study aimed to explore the underlying mechanisms of high glucose-induced PMPs generation. Methods: Washed platelets, obtained from the plasma of healthy male Sprague-Dawley rats, were incubated with high glucose. PMPs were isolated using gradient centrifugation and counted by flow cytometry. Expression and activity of ROCK1 and caspase3 were evaluated by real-time PCR, Western blotting, and activity assay kit. Results: High glucose enhanced PMPs shedding in the presence of collagen. The mRNA and protein levels of ROCK1, but not ROCK2, were increased in platelets incubated with high glucose. Y-27632, an inhibitor of ROCK, blocked the increased PMPs shedding induced by high glucose. Expression and activity of caspase3 were elevated in platelets under the high glucose conditions. Z-DVED-FMK, a caspase3 inhibitor, inhibited ROCK1 activity and decreased the PMPs generation under high glucose. Conclusion: High glucose increased PMPs shedding via caspase3-ROCK1 signal pathway

Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis

BACKGROUND: Our previous study demonstrated that the disruption of cholesterol homeostasis promotes tubulointerstitial injury in diabetic nephropathy (DN). This study aimed to further investigate the effects of gut microbiota dysbiosis on this process and explored its potential mechanism. METHODS: Diabetic rats treated with broad-spectrum oral antibiotics or faecal microbiota transplantation (FMT) from the healthy donor group and human kidney 2 (HK-2) cells stimulated with sodium acetate were used to observe the effects of gut microbiota on cholesterol homeostasis. The gut microbiota distribution was measured by 16S rDNA sequencing with faeces. Serum acetate level was examined by gas chromatographic analysis. Protein expression of G protein coupled receptor 43 (GPR43) and molecules involved in cholesterol homeostasis were assessed by immunohistochemical staining, immunofluorescence staining, and Western Blotting. RESULTS: Depletion of gut microbiota significantly attenuated albuminuria and tubulointerstitial injury. Interestingly, serum acetate levels were also markedly decreased in antibiotics-treated diabetic rats and positively correlated with the cholesterol contents in kidneys. An in vitro study demonstrated that acetate significantly increased cholesterol accumulation in HK-2 cells, which was caused by increased expression of proteins mainly modulating cholesterol synthesis and uptake. As expected, FMT effectively decreased serum acetate levels and alleviated tubulointerstitial injury in diabetic rats through overriding the disruption of cholesterol homeostasis. Furthermore, GPR43 siRNA treatment blocked acetate-mediated cholesterol homeostasis dysregulation in HK-2 cells through decreasing the expression of proteins governed cholesterol synthesis and uptake. CONCLUSIONS: Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy