Electrosprayed Janus Particles for Combined Photo-Chemotherapy

This work is a proof of concept study establishing the potential of electrosprayed Janus particles for combined photodynamic therapy-chemotherapy. Sub-micron-sized particles of polyvinylpyrrolidone containing either an anti-cancer drug (carmofur) or a photosensitiser (rose bengal; RB), and Janus particles containing both in separate compartments were prepared. The functional components were present in the amorphous form in all the particles, and infrared spectroscopy indicated that intermolecular interactions formed between the different species. In vitro drug release studies showed that both carmofur and RB were released at approximately the same rate, with dissolution complete after around 250 min. Cytotoxicity studies were undertaken on model human dermal fibroblasts (HDF) and lung cancer (A549) cells, and the influence of light on cell death explored. Formulations containing carmofur as the sole active ingredient were highly toxic to both cell lines, with or without a light treatment. The RB formulations were non-toxic to HDF when no light was applied, and with photo-treatment caused large amounts of cell death for both A549 and HDF cells. The Janus formulation containing both RB and carmofur was non-toxic to HDF without light, and only slightly toxic with the photo-treatment. In contrast, it was hugely toxic to A549 cells when light was applied. The Janus particles are thus highly selective for cancer cells, and it is hence proposed that such electrosprayed particles containing both a chemotherapeutic agent and photosensitiser have great potential in combined chemotherapy/photodynamic therapy

Experimental and CFD analysis of the wake characteristics of tidal turbines

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.This paper investigates the accuracy of the Computational Fluid Dynamics (CFD) based Immersed Body Force (IBF) turbine modelling method for predicting the flow characteristics of a Momentum-Reversal-Lift type of tidal turbine. This empirically-based CFD model has been developed based on the actuator disc method enhanced with additional features to mimic the effect of the complex blade motion on the downstream wake, without the high computational costs of explicitly modelling the dynamic blade motion. The model has been calibrated against the flow characteristics data obtained from experiment and found to perform well, although there are few inconsistencies in the flow patterns which show some of the limitations of the IBF model compared to a full dynamic blade motion simulation. However, given the complexity and computational cost of modelling the detailed blade motion the limitations of the IBF model are acceptable and will be useful especially for optimisation of arrays of devices where there is a significant computational demand.We would like to thank EPSRC for providing the funding under project number EP/J010138/1, as part of the Supergen Marine research program and the IFREMER personnel of Boulogne-sur-Mer for their assistance and advice during the experimental trials

Solid lipid nanoparticles self-assembled from spray dried microparticles

We report the self-assembly of anti-cancer drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When the spray dried microparticles are added to water, the PVP matrix dissolves and the GTS and drug self-assemble into SLNs. The SLNs provide a non-toxic delivery platform for both hydrophobic (indomethacin) and hydrophilic (5-fluorouracil) drugs. They show extended release profiles over more than 24 h, and in permeation studies the drug cargo is seen to accumulate inside cancer cells. This overcomes major issues with achieving local intestinal delivery of these active ingredients, in that IMC permeates well and thus will enter the systemic circulation and potentially lead to side effects, while 5-FU remains in the lumen of the small intestine and will be secreted without having any therapeutic benefit. The SLN formulations are as effective as the pure drugs in terms of their ability to induce cell death. Our approach represents a new and simple route to the fabrication of SLNs: by assembling these from spray-dried microparticles on demand, we can circumvent the low storage stability which plagues SLN formulations

European 1 MW, 170 GHz CW Gyrotron Prototype for ITER - long-pulse operation at KIT -

The upgraded EU 1 MW, 170 GHz continuous wave (CW) industrial prototype gyrotron (TH1509U) for Electron Cyclotron Resonance Heating and Current Drive (ECRH&CD) in ITER was tested at the Karlsruhe Institute of Technology (KIT). The gyrotron surpassed the performance of the previous TH1509 tube. In particular, TH1509U delivered (i) 0.9 MW in 180 s pulses (max. pulse length of the KIT test stand) and (ii) more than 1 MW at a pulse length limited to 40 s, due to a problem with the test stand cooling circuit at that time. In addition, it was possible to demonstrate gyrotron operation at (iii) 0.5 MW in 1600 s pulses

Two-loop Corrections to the B to pi Form Factor from QCD Sum Rules on the Light-Cone and |V(ub)|

We calculate the leading-twist O(alphas^2 beta0) corrections to the B to pi transition form factor f+(0) in light-cone sum rules. We find that, as expected, there is a cancellation between the O(alphas^2 beta0) corrections to fB f+(0) and the large corresponding corrections to fB, calculated in QCD sum rules. This suggests the insensitivity of the form factors calculated in the light-cone sum rules approach to this source of radiative corrections. We further obtain an improved determination of the CKM matrix element |V(ub)|, using latest results from BaBar and Belle for f+(0)|V(ub)|.Comment: 18 pages, 3 figure

Mapping the disease-specific LupusQoL to the SF-6D

Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Two-Year Longitudinal Analysis of a Cluster Randomized Trial of Physical Activity Promotion by General Practitioners

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Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations