Experiments and modelling of biomass pulverisation in swirling and non-swirling bluff body-stabilised turbulent annular flows

Deeper insights into particle loading have practical significance in applications particularly when this affects fuel-oxidiser mixing and flame stabilisation, as occurs in pulverised fuel (biomass) combustion systems. The underlying particle flow and dispersion characteristics not only play a crucial role in controlling overall combustion performance but can also impact emissions. A fundamental understanding of particle flow dynamics and dispersion behaviour for raw pulverised biomass, under non-swirling and swirling conditions need further systematic investigation to better understand the interplay between swirling and non-swirling bluff-body stabilised recirculation zones and particles emitted from a centralised jet. This work uses Particle Image Velocimetry (PIV) with three-dimensional multi-phase simulations based on the Discrete Phase Model (DPM) and Reynolds Stress Model (RSM) to investigate the flow and dispersion characteristics in confined flows typical of many practical combustors. Raw pulverised biomass-laden is introduced through a central turbulent jet (Rej = 4500 and 7800) and also subjected to turbulent annular flows (Res = 35,500), both non-swirling (S = 0) and swirling conditions (S = 0.3). Simulations are first validated against Constant Temperature Anemometry (CTA) resolved inlet boundary conditions and flow field PIV data under similar conditions. Results show that when a pulverised biomass-laden central jet interacts with a surrounding turbulent annular flow (non-swirling, swirling) the presence of a bluff-body based recirculating zone (BB-RZ) leads to biomass particle entrainment (pick up) and their recirculation over the bluff-body before being dispersed further downstream. Under non-swirling conditions, a significant 35% decrease in the mean particle axial velocity is measured coupled with an even more substantive 177% increase in turbulent fluctuation along the centreline. These findings are indicative of intense upstream (x/D ≈ 0.64) turbulent mixing and more intense particle dispersion into a BB-RZ. For swirling annular flow conditions near the end of the BB-RZ, the interaction between a biomass-laden central jet and the annular flow is comparatively weaker in the upstream region relative to non-swirling conditions. However, swirl significantly enhances downstream particle dispersion and lateral spread as reflected by a 254% hike in the mean particle radial velocity. Numerical predictions show that for the same particle loading ratio, but different (higher and lower) Reynolds number of a central particle-laden jet (i.e., the carrier gas), the conditions at relatively lower central jet Reynolds number allow better particle recirculation in BB-RZ as well as enhancing downstream lateral particle dispersion and entrainment, compared to a higher Reynolds number in the central jet. Outcomes from this investigation may have implications on the design and operation of pulverised (solid) fuel combustors if operated on renewably sourced biomass rather than traditional fossil fuels

COMPARISON OF IRON STORES IN HEALTHY INDIVIDUALS AND PATIENTS WITH ISCHAEMIC HEART DISEASE

ABSTRACT Excess body iron has been linked to atherosclerosis owing to its pro-oxidative properties. However, inconsistent results have emerged from the epidemiological studies linking iron status and the risk of cardiovascular diseases (CVD). Objective of the present study is to compare iron stores of healthy individuals and patients with ischaemic heart disease (IHD). A total of 137 subjects were included in the study, 90 patients of IHD and 47 healthy subjects with no history of IHD as controls. We compared body iron stores of patients and controls. Serum ferritin, serum transferrin receptor (sTfR) and sTfR/ferritin ratio were used as measures of body iron stores. Our results revealed that mean serum ferritin concentration of cases was significantly higher than controls. Moreover, mean sTfR and sTfR/ferritin ratio of controls was significantly higher than the patients. We conclude from our results that IHD patients have higher iron stores than healthy subjects suggesting a possible association between high iron stores and the risk of IHD

Inhibition of CNS remyelination by the presence of semaphorin 3A

Failure of oligodendrocyteprecursor cell (OPC)differentiationhasbeen recognized asthe leading causeforthefailure ofmyelin regenerationin diseases such as multiple sclerosis (MS). One explanation for the failure of OPC differentiation in MS is the presence of inhibitory molecules in demyelinatedlesions.Sofaronly afewinhibitory substrateshavebeenidentifiedinMSlesions.Semaphorin3A (Sema3A), a secretedmemberof the semaphorin family, can act as repulsive guidance cue for neuronal and glial cells in the CNS. Recent studies suggest that Sema3A is also expressedin activeMSlesions.However,theimplicationof Sema3A expressioninMSlesions remainsunclear asOPCs are commonlypresentin chronic demyelinated lesions. In the present study we identify Sema3A as a potent, selective, and reversible inhibitor of OPC differentiation in vitro. Furthermore, we show that administration of Sema3A into demyelinating lesions in the rat CNS results in a failure of remyelination. Our results imply an important role for Sema3A in the differentiation block occurring in MS lesions

Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD

Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopmental disorders (NDD), including those falling within the autism spectrum disorders (ASD). A key question is whether this correlation between genetics and clinical presentation at the level of the patient can be translated to the cell phenotypes arising from the neurodevelopment of patient induced pluripotent stem cells (iPSCs). Here, we examine how iPSCs derived from ASD patients with an associated CNV inform our understanding of the genetic and biological mechanisms underlying the aetiology of ASD. We consider selection of genetically characterised patient iPSCs; use of appropriate control lines; aspects of human neurocellular biology that can capture in vitro the patient clinical phenotype; and current limitations of patient iPSC-based studies. Finally, we consider how future research may be enhanced to maximise the utility of CNV patients for research of pathological mechanisms or therapeutic targets

In Vitro Release Studies of Diclofenac Potassium Tablet from Pure and Blended Mixture of Hydrophilic and Hydrophobic Polymers

The purpose of the present study was to evaluate the effect of pure and blended mixtures, with different compositions of hydroxy propyl methyl cellulose (HPMC) and carnauba wax (CW) on the release of diclofenac potassium from matrix tablets. Fifteen different matrix tablet formulations were prepared by direct compression process by using Carver Hydraulic laboratory press having 13 mm flat dies set at constant pressure. The paddle dissolution apparatus II (Curio DL 2020) was used to assess the dissolution of drug in phosphate buffer, pH 7.4 for 8 h. The release data was fitted to different release models. Zoom stereo micrography was done to evaluated the release mechanism of drug from polymers. The interaction of polymer mixture and different ratios of drug in polymer mixture was determined by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The type and content of polymer in the matrix system influenced the release characteristics. Higher polymeric content in the matrix decreased the drug release rate because of increased tortuosity and decreased porosity. Retardation of drug release from pure carnauba was higher as compared to that with pure HPMC matrices. The polymers blends controlled drug release pattern effectively. The drug released showed better linearity with Higuchi release kinetics. The Korsmeyer equation revealed n value ranged from 0.388-0.627 or non - Fickian transport mechanism of drug release was predominant. The FTIR and DSC suggested that there were no chemical interaction between drug and polymers.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Inhibition of phosphodiesterase-4 promotes oligodendrocyte precursor cell differentiation and enhances CNS remyelination

The increasing effectiveness of new disease-modifying drugs that suppress disease activity in multiple sclerosis has opened up opportunities for regenerative medicines that enhance remyelination and potentially slow disease progression. Although several new targets for therapeutic enhancement of remyelination have emerged, few lend themselves readily to conventional drug development. Here, we used transcription profiling to identify mitogen-activated protein kinase (Mapk) signalling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signalling by elevation of intracellular levels of cyclic adenosine monophosphate (cAMP) using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolysing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination. These data reveal a novel approach to therapeutic enhancement of remyelination amenable to pharmacological intervention and hence with significant potential for translation

Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling

Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS–PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination

Inhibition of phosphodiesterase‐4 promotes oligodendrocyte precursor cell differentiation and enhances CNS

The increasing effectiveness of new disease-modifying drugs that suppress disease activity in multiple sclerosis has opened up opportunities for regenerative medicines that enhance remyelination and potentially slow disease progression. Although several new targets for therapeutic enhancement of remyelination have emerged, few lend themselves readily to conventional drug development. Here, we used transcription profiling to identify mitogen-activated protein kinase (Mapk) signalling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signalling by elevation of intracellular levels of cyclic adenosine monophosphate (cAMP) using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolysing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination. These data reveal a novel approach to therapeutic enhancement of remyelination amenable to pharmacological intervention and hence with significant potential for translation

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia

From Crossref journal articles via Jisc Publications RouterBackground Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. Methods We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. Results The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). Conclusions In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.11pubpub