Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range

Empirical Bayesian Mixture Models for Medical Image Translation

Automatically generating one medical imaging modality from another is known as medical image translation, and has numerous interesting applications. This paper presents an interpretable generative modelling approach to medical image translation. By allowing a common model for group-wise normalisation and segmentation of brain scans to handle missing data, the model allows for predicting entirely missing modalities from one, or a few, MR contrasts. Furthermore, the model can be trained on a fairly small number of subjects. The proposed model is validated on three clinically relevant scenarios. Results appear promising and show that a principled, probabilistic model of the relationship between multi-channel signal intensities can be used to infer missing modalities -- both MR contrasts and CT images.Comment: Accepted to the Simulation and Synthesis in Medical Imaging (SASHIMI) workshop at MICCAI 201

Asymmetric Image-Template Registration

Authors Manuscript received: 2010 May 4. 12th International Conference, London, UK, September 20-24, 2009, Proceedings, Part IA natural requirement in pairwise image registration is that the resulting deformation is independent of the order of the images. This constraint is typically achieved via a symmetric cost function and has been shown to reduce the effects of local optima. Consequently, symmetric registration has been successfully applied to pairwise image registration as well as the spatial alignment of individual images with a template. However, recent work has shown that the relationship between an image and a template is fundamentally asymmetric. In this paper, we develop a method that reconciles the practical advantages of symmetric registration with the asymmetric nature of image-template registration by adding a simple correction factor to the symmetric cost function. We instantiate our model within a log-domain diffeomorphic registration framework. Our experiments show exploiting the asymmetry in image-template registration improves alignment in the image coordinates.NAMIC (NIH NIBIB NAMIC U54-EB005149)NAC (NIH NCRR NAC P41- RR13218)mBIRN (NIH NCRR mBIRN U24-RR021382)NIH NINDS (R01-NS051826 Grant)National Science Foundation (U.S.) (CAREER Grant 0642971)NIBIB (R01 EB001550)NIBIB (R01EB006758)NCRR (R01 RR16594-01A1)NCRR (P41-RR14075)NINDS (R01 NS052585-01)Singapore. Agency for Science, Technology and Researc

Building generic anatomical models using virtual model cutting and iterative registration

Article deposited according to publisher policy posted on SHERPA/RoMEO, 30/07/2010.YesFunding provided by the Open Access Authors Fund

Use of atmospheric plasma treatment to improve adhesion properties of sodium ionomer sheets

“NOTICE: this is the author’s version of a work that was accepted for publication in Surface and Coatings Technology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Surface and Coatings Technology, [VOL 218, (MAR 15 2013)] DOI10.1016/j.surfcoat.2012.12.016¨[EN] Polyolefins are characterized by having a low surface energy due to their non-polar nature, in the case of some ionomers, the base component is a polyolefin, thus relative poor adhesion properties are expected. As is widely known, for many industrial applications, such as coatings, paintings and formation of adhesive bonds, a high surface energy is required in order to provide good surface adhesion; for this reason the use of ionomers in these applications requires a previous surface treatment. In this paper surface treatment by atmospheric plasma has been used to provide surface activation to polyolefin-based sodium ionomers in order to improve their low intrinsic adhesion properties. This work has focused on the analysis of the influence of main process variables such as treatment rate and distance between nozzle and substrate to observe the improvement of adhesion properties at ionomer-polycarbonate adhesion joints subjected to shear and T-peel tests. After plasma treatment, T-peel force has increased six times it original value at most aggressive plasma parameters. Regarding on shear force, at same aggressive conditions of plasma treatment we achieved an increase of ten times its value of the shear sample without surface treatment, and its phenomenon can be seen in SEM pictures. (C) 2012 Elsevier B.V. All rights reserved.This work is part of the project IPT-310000-2010-037, "ECOTEXCOMP: Research and development of textile structures useful as reinforcement of composite materials with marked ecological character" funded by the "Ministerio de Ciencia e Innovacion", with an aid of 189540.20 euros, within the "Plan Nacional de Investigacion Cientifica, Desarrollo e InnovacionTecnologica 2008-2011" and funded by the European Union through FEDER funds, Technology Fund 2007-2013, Operational Programme on R + D + i for and on behalf of the companies. Also Generalitat Valenciana ref.: ACOMP/2012/087 is acknowledged for financial support. J.M. Espana wants to thank the Polytechnic University of Valencia (UPV) for their financial support through an FPI-UPV grant.España Giner, JM.; Boronat Vitoria, T.; García Sanoguera, D.; López Martínez, J.; Balart Gimeno, RA. (2013). Use of atmospheric plasma treatment to improve adhesion properties of sodium ionomer sheets. Surface and Coatings Technology. 218:1-6. https://doi.org/10.1016/j.surfcoat.2012.12.016S1621

Improving mechanical performance of thermoplastic adhesion joints by atmospheric plasma

Polyethylene (PE) is characterized by low surface energy as a consequence of its non-polar nature. This characteristic is responsible for poor adhesion properties on polyethylene substrates. It is well known that some industrial applications such as coating, painting and formation of adhesion joints require high surface energy to promote good anchorages, so that, the use of polyethylene in these applications needs a previous surface treatment. In this work atmospheric plasma has been used to promote surface activation on polyethylene substrates for improved adhesion properties. The work has been focused on analyzing the influence of some variables (treatment rate and nozzle-sample distance) on mechanical performance of PE¿PE adhesion joints subjected to shear and T-peel tests.This work is a part of the project IPT-310000-2010-037, ''ECO-TEXCOMP: Research and development of textile structures useful as reinforcement of composite materials with marked ecological character.'' funded by the "Ministerio de Ciencia e Innovacion", with an aid of 189540.20 euros, within the "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica 2008-2011" and funded by the European Union through FEDER funds, Technology Fund 2007-2013, Operational Programme on R + D + i for and on behalf of the companies. Also, microscopy services at UPV are acknowledged for SEM and AFM support.Fombuena, V.; Balart Gimeno, JF.; Boronat, T.; Sánchez-Nácher, L.; García-Sanoguera, D. (2013). Improving mechanical performance of thermoplastic adhesion joints by atmospheric plasma. Materials and Design. 47:49-56. doi:10.1016/j.matdes.2012.11.031S49564

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Intricate Correlation between Body Posture, Personality Trait and Incidence of Body Pain: A Cross-Referential Study Report

OBJECTIVE: Occupational back pain is a disorder that commonly affects the working population, resulting in disability, health-care utilization, and a heavy socioeconomic burden. Although the etiology of occupational pain remains largely unsolved, anecdotal evidence exists for the contribution of personality and posture to long-term pain management, pointing to a direct contribution of the mind-body axis. In the current study, we have conducted an extensive evaluation into the relationships between posture and personality. METHOD: We have sampled a random population of 100 subjects (50 men and 50 women) in the age range of 13-82 years based on their personality and biomechanical profiles. All subjects were French-Canadian, living in Canada between the Québec and Sorel-Tracy areas. The Biotonix analyses and report were used on the subjects being tested in order to distinguish postural deviations. Personality was determined by using the Myers-Briggs Type Indicator questionnaire. RESULTS: We establish a correlation between ideal and kyphosis-lordosis postures and extraverted personalities. Conversely, our studies establish a correlative relationship between flat back and sway-back postures with introverted personalities. CONCLUSION: Overall, our studies establish a novel correlative relationship between personality, posture and pain

Cross-Talk between Signaling Pathways Can Generate Robust Oscillations in Calcium and cAMP

BACKGROUND:To control and manipulate cellular signaling, we need to understand cellular strategies for information transfer, integration, and decision-making. A key feature of signal transduction is the generation of only a few intracellular messengers by many extracellular stimuli. METHODOLOGY/PRINCIPAL FINDINGS:Here we model molecular cross-talk between two classic second messengers, cyclic AMP (cAMP) and calcium, and show that the dynamical complexity of the response of both messengers increases substantially through their interaction. In our model of a non-excitable cell, both cAMP and calcium concentrations can oscillate. If mutually inhibitory, cross-talk between the two second messengers can increase the range of agonist concentrations for which oscillations occur. If mutually activating, cross-talk decreases the oscillation range, but can generate 'bursting' oscillations of calcium and may enable better filtering of noise. CONCLUSION:We postulate that this increased dynamical complexity allows the cell to encode more information, particularly if both second messengers encode signals. In their native environments, it is unlikely that cells are exposed to one stimulus at a time, and cross-talk may help generate sufficiently complex responses to allow the cell to discriminate between different combinations and concentrations of extracellular agonists