Active Vaccination With EMMPRIN-Derived Multiple Antigenic Peptide (161-MAP) Reduces Angiogenesis in a Dextran Sodium Sulfate (DSS)-Induced Colitis Model

Ulcerative colitis (UC) is an autoimmune disease that affects the colon and shares many clinical and histological features with the dextran sulfate sodium (DSS)-induced colitis model in mice. Angiogenesis is a critical component in many autoimmune diseases, as well as in the DSS-induced colitis model, and is it partially mediated by EMMPRIN, a multifunctional protein that can induce the expression of both the potent pro-angiogenic vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). We asked whether targeting EMMPRIN by active vaccination, using a novel, specific epitope in the protein, synthesized as a multiple antigenic peptide (MAP), could trigger beneficial effects in the DSS-induced colitic C57BL/6J mice. Mice were vaccinated with four boost injections (50 μg each) of either 161-MAP coding for the EMMPRIN epitope or the scrambled control peptide (Scr-MAP) emulsified in Freund's adjuvant. We show that male mice that were vaccinated with 161-MAP lost less weight, demonstrated improved disease activity indices (DAI), had reduced colitis histological score, and their colons were longer in comparison to mice vaccinated with the Scr-MAP. The 161-MAP vaccination also reduced serum and colon levels of EMMPRIN, colon concentrations of VEGF, MMP-9, and TGFβ, and vessel density assessed by CD31 staining. A similar effect was observed in female mice vaccinated with 161-MAP, including weight loss, colitis histological score, colon length, colon levels of EMMPRIN and colon concentrations of VEGF. However, for female mice, the changes in DAI values, EMMPRIN serum levels, and MMP-9 and TGFβ colon concentrations did not reach significance. We conclude that our strategy of alleviating autoimmunity in this model through targeting angiogenesis by actively vaccinating against EMMPRIN was successful and efficient in reducing angiogenesis

Evaluating Mixed-Initiative Procedural Level Design Tools using a Triple-Blind Mixed-Method User Study

Results from a triple-blind mixed-method user study into the effectiveness of mixed-initiative tools for the procedural generation of game levels are presented. A tool which generates levels using interactive evolutionary optimisation was designed for this study which (a) is focused on supporting the designer to explore the design space and (b) only requires the designer to interact with it by designing levels. The tool identifies level design patterns in an initial hand-designed map and uses that information to drive an interactive optimisation algorithm. A rigorous user study was designed which compared the experiences of designers using the mixed-initiative tool to designers who were given a tool which provided completely random level suggestions. The designers using the mixed-initiative tool showed an increased engagement in the level design task, reporting that it was effective in inspiring new ideas and design directions. This provides significant evidence that procedural content generation can be used as a powerful tool to support the human design process

Protective effect of Nigella sativa against paracetamol induced hepatic and renal damages

Background: Non-steroidal anti-inflammatory drugs are very commonly used as an analgesic, antipyretic, anti-inflammatory, and antiplatelet agent. They have significant adverse effect on liver and kidney besides damaging stomach. Their effect on liver and kidney are of serious concern. Hence, we have decided to study the preventive effect of Nigella sativa against paracetamol induced hepatic and renal damages.Methods: Ethanolic and aqueous extracts of N. sativa were prepared with the help of Soxhlet’s apparatus. Totally, 36 wistar albino rats (150-200 g) of either sex were divided into six groups of six each. Group I was administered with distilled water, Group II-VI were treated with paracetamol 750 mg/kg i.p. Group III-VI were test groups also treated with N. sativa aqueous extract (200 and 400 mg/kg p.o) and ethanolic extract (200 and 400 mg/kg p.o), respectively. The treatment was given daily for 7 days and on 8th all the rats were sacrificed and the blood was analyzed for hepatic and renal function tests and tissue was preserved for histopathological examination.Results: Paracetamol administration caused a marked hepatic and renal damage, which is evidenced by the increase in liver and renal function test parameters in the negative control group. N.sativa extracts prevented this damage. The protective was seen maximum in ethanolic extract followed by the aqueous extract in dose-dependent manner.Conclusion: Ethanolic extract showed significant protection against paracetamol-induced and renal damage

Clinical evaluation of efficacy and safety of α-keto analogs of essential amino acids supplementation in patients of chronic kidney disease

Background: The objective was to evaluate the efficacy and safety of α-keto analogs of essential amino acids (KAA) as a supplement in chronic kidney disease (CKD).Methods: A prospective comparative study was conducted in patients of CKD of a tertiary care center of North India. Patients were randomly divided into two interventional groups. Group I (control) was advised conservative management and placebo while Group II (KAA) given conservative management along with KAA (600 mg, thrice daily) for 12 weeks. Hemogram, renal function tests, lipid profiles were done, and adverse effects were recorded at 0, 4, 8, and 12 weeks of treatment.Results: There was progressive improvement in clinical features in both groups after 12 weeks of treatment, but KAA group showed more marked improvement as compared with the control group. Both groups showed gradual improvement in the biochemical parameters as compared to their pre-treated values, which was more marked in KAA supplemented group. There was a reduction in blood glucose, blood urea, serum creatinine, and 24 h total urine protein. There was an increase in hemoglobin, 24 h total urine volume and glomerular filtration rate. KAA group showed significant (p<0.05) improvement in lipid profiles as compared with the control group. There was no statistical difference in two groups with respect to side-effects (p>0.05).Conclusion: KAA supplementation along with conservative management is efficacious and safe in preventing the progression of disease in patients of CKD

Macrophages and Neutrophils: Regulation of the Inflammatory Microenvironment in Autoimmunity and Cancer.

No abstract available

Shape optimisation using Computational Fluid Dynamics and Evolutionary Algorithms

This is the author accepted manuscript.Optimisation of designs using Computational Fluid Dynamics (CFD) are frequently performed across many fields of research, such as the optimisation of an aircraft wing to reduce drag, or to increase the efficiency of a heat exchanger. General optimisation strategies involves altering design variables with a view to improve appropriate objective function(s). Often the objective function(s) are non-linear and multi-modal, and thus polynomial time algorithms for solving such problems may not be available. In such cases, applying Evolutionary Algorithms (EAs - a class of stochastic global optimisation techniques inspired from natural evolution) may locate good solutions within a practical time frame. The traditional CFD design optimisation process is often based on a ‘trial-and-error type approach. Starting from an initial geometry, Computational Aided Design changes are introduced manually based on results from a limited number of design iterations and CFD analyses. The process is usually complex, time-consuming and relies heavily on engineering experience, thus making the overall design procedure inconsistent, i.e. different ‘best’ solutions are obtained from different designers. [...]This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) grant (reference number: EP/M017915/1) for the University of Exeter’s College of Engineering, Mathematics, and Physical Sciences

Automatic shape optimisation of the turbine-99 draft tube

This is the author accepted manuscript.INTRODUCTION The performance of a hydraulic reaction turbine is significantly affected by the efficiency of its draft tube. Factors which impede the tube’s performance include the geometrical shape (profile), and velocity distribution at the inflow. So far, the design of draft tubes has been improved through experimental observations resulting in empirical formulae or ‘rules of thumb’. The use of Computational Fluid Dynamics (CFD) in this design process has only been a recent addition due to its robustness and cost-effectivenesses with increasing availability to computational power. The flexibility of CFD, allowing for comprehensive analysis of complex profiles, is especially appealing for optimising the design. Hence, there is a need for developing an accurate and reliable CFD approach together with an efficient optimisation strategy. Flows through a turbine draft tube are characterised as turbulent with a range of flow phenomena, e.g. unsteadiness, flow separation, and swirling flow. With the aim of improving the techniques for analysing such flows, the turbomachinery community have proposed a standard test case in the form of the Turbine-99 draft tube [1]. Along with this standard geometry, with the aim of simulating the swirling inflow, an additional runner proposed by Cervantes [2] is included in the present work. The draft tube geometry is shown in Fig.1. The purpose of this abstract is to outline the framework developed to achieve the automated shape optimisation of this draft tube.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) grant (reference number: EP/M017915/1) for the University of Exeters College of Engineering, Mathematics, and Physical Sciences

EVALUATION OF EFFICACY AND SAFETY OF NIGELLA SATIVA OIL SUPPLEMENTATION IN PATIENTS OF CHRONIC KIDNEY DISEASE

ABSTRACTObjective: To evaluate efficacy and safety of add-on therapy of Nigella sativa oil in patients of stage 3 and 4 of chronic kidney disease (CKD).Materials and Methods: The study was conducted in a tertiary care center of north India in stage 3 and 4 patients of CKD. It was a prospective,comparative, and open label study. Patients were randomly divided into two interventional groups. Group I (Control) received conservativemanagement of CKD while Group II (Test) received conservative management along with N. sativa oil (2.5 mL, per orally, once daily) for 12 weeks.Hemogram and renal function tests were done, and adverse events were recorded at 0, 6, and 12 weeks of treatment.Results: After 12 weeks of treatment, there was a progressive improvement in clinical features and biochemical parameters in both the groups, but itwas more marked in the test group compared to control group. Both groups showed gradual improvement in the biochemical parameters as comparedto their pre-treated values which were more marked in N. sativa oil supplemented group. There was a reduction in blood glucose, blood urea, serumcreatinine, and 24-hr total urine protein. There was an increase in hemoglobin, 24-hr total urine volume, and glomerular filtration rate.Conclusion: N. sativa oil supplementation along with conservative management is efficacious and safe in averting the progression of disease in stage 3and 4 patients of CKD.Keywords: Chronic kidney disease, Nigella sativa oil, End-stage renal disease, Glomerular filtration rate

Role of rhubarb and α-keto analogues of essential amino acids supplementation in halting progression of chronic kidney disease

Background: Chronic kidney disease (CKD) is an emerging chronic disease due to rapidly increasing incidence of diabetes and hypertension worldwide. Newer drugs are being searched which can stop nephron damage and are cost effective. This study was undertaken to compare the efficacy and safety profile of rhubarb and α-keto analogues of essential amino acids supplementation in patients of chronic kidney disease.Methods: A prospective comparative study was conducted in patients of chronic kidney disease attending Renal Clinic of a tertiary care centre. Randomization of patients was done into three interventional groups: conservative management along with placebo was given in first group (Control); conservative management along with Rhubarb capsule (350 mg, thrice daily) was given in second group (Rhubarb) and conservative management along with α-keto analogues of essential amino acids (600 mg, thrice daily) was given in third group (KAA). The treatment was given for 12 weeks. Clinical and biochemical parameters were assessed at 0, 4, 8 and 12 weeks of treatment.Results: Patients of all three groups showed gradual improvement in clinical features and biochemical parameters as compared to their pre-treated values which was more marked in KAA supplemented group. There was reduction in: fasting blood glucose (12.51%, 19.15% and 20.78%), PPBG (14.80%, 19.00% and 20.89%), serum creatinine (25.00%, 30.54% and 39.52%), blood urea (25.55%, 33.64% and 38.09%), and 24-hour total urine protein (TUP) (19.80%, 30.18% and 38.34%) in Group I, II and III respectively. There was increase in: haemoglobin level (12.64%, 14.99% and 19.77%), 24-hour total urine volume (TUV) (19.41%, 28.82% and 33.32%) and GFR (22.6%, 46.5% and 49.2%) in Group I, II and III respectively. Rhubarb and KAA supplementations were safe and well-tolerated.Conclusions: KAA is more effective than Rhubarb as add on therapy with conservative management in patients of chronic kidney disease