289 research outputs found

    Breast Cancer: Modelling and Detection

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    This paper reviews a number of the mathematical models used in cancer modelling and then chooses a specific cancer, breast carcinoma, to illustrate how the modelling can be used in aiding detection. We then discuss mathematical models that underpin mammographic image analysis, which complements models of tumour growth and facilitates diagnosis and treatment of cancer. Mammographic images are notoriously difficult to interpret, and we give an overview of the primary image enhancement technologies that have been introduced, before focusing on a more detailed description of some of our own recent work on the use of physics-based modelling in mammography. This theoretical approach to image analysis yields a wealth of information that could be incorporated into the mathematical models, and we conclude by describing how current mathematical models might be enhanced by use of this information, and how these models in turn will help to meet some of the major challenges in cancer detection

    Explaining rain forest diversity

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    This group, which is concerned with the applications of mathematics to agricultural science, was formed in 1970 and has since met at approximately yearly intervals in London for one-day meetings. The thirty-third meeting of the group, chaired by Professor P. K. Maini of the Mathematical Institute, University of Oxford, was held in the Kohn Centre at the Royal Society, 6 Carlton House Terrace, London on Friday, 6 April 2001 when the following papers were read

    Computer-Assisted Precision Surgery in the Ear

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    Chirurgische Eingriffe am Ohr stellen aufgrund der komplexen Anatomie und der GrössenverhĂ€ltnisse der beteiligten anatomischen Strukturen eine Herausforderung fĂŒr den HNO-Chirurgen dar. In diesem Beitrag wird ein Ansatz fĂŒr die roboterbasierte Navigation zur HörgerĂ€teimplantation vorgestellt. Insbesondere wird auf die Möglichkeit des FrĂ€sens von Implantatlagern im Felsenbein eingegangen. Je prĂ€ziser ein Implantat im SchĂ€del verankert werden kann, desto einfacher ist der chirurgischen Ablauf. Weiterhin, profitieren Patienten von verkĂŒrzten Operationszeiten und weniger schmerzhaften Eingriffen.Traditional surgical procedures involving the implantation of artificial hearing devices in the inner ear are challenging due to the size and complexity of anatomical structures within the temporal bone. To date, no stereotactic instrument guidance technology providing the necessary levels of accuracy is available. This work presents an approach to robot assisted implantation of hearing devices. Specifically, the robot system was used to milla cavity to for a direct acoustical stimulation implant. As the precision of such cavities increases, so also can future implant generations improve in terms of size, complexity and cost effectiveness. Additionally, patients themselves would profit from shorter procedure times and less painful interventions

    Reproducible model development in the Cardiac Electrophysiology Web Lab

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    The modelling of the electrophysiology of cardiac cells is one of the most mature areas of systems biology. This extended concentration of research effort brings with it new challenges, foremost among which is that of choosing which of these models is most suitable for addressing a particular scientific question. In a previous paper, we presented our initial work in developing an online resource for the characterisation and comparison of electrophysiological cell models in a wide range of experimental scenarios. In that work, we described how we had developed a novel protocol language that allowed us to separate the details of the mathematical model (the majority of cardiac cell models take the form of ordinary differential equations) from the experimental protocol being simulated. We developed a fully-open online repository (which we termed the Cardiac Electrophysiology Web Lab) which allows users to store and compare the results of applying the same experimental protocol to competing models. In the current paper we describe the most recent and planned extensions of this work, focused on supporting the process of model building from experimental data. We outline the necessary work to develop a machine-readable language to describe the process of inferring parameters from wet lab datasets, and illustrate our approach through a detailed example of fitting a model of the hERG channel using experimental data. We conclude by discussing the future challenges in making further progress in this domain towards our goal of facilitating a fully reproducible approach to the development of cardiac cell models

    Hydrodynamic dispersion within porous biofilms

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    Many microorganisms live within surface-associated consortia, termed biofilms, that can form intricate porous structures interspersed with a network of fluid channels. In such systems, transport phenomena, including flow and advection, regulate various aspects of cell behavior by controlling nutrient supply, evacuation of waste products, and permeation of antimicrobial agents. This study presents multiscale analysis of solute transport in these porous biofilms. We start our analysis with a channel-scale description of mass transport and use the method of volume averaging to derive a set of homogenized equations at the biofilm-scale in the case where the width of the channels is significantly smaller than the thickness of the biofilm. We show that solute transport may be described via two coupled partial differential equations or telegrapher's equations for the averaged concentrations. These models are particularly relevant for chemicals, such as some antimicrobial agents, that penetrate cell clusters very slowly. In most cases, especially for nutrients, solute penetration is faster, and transport can be described via an advection-dispersion equation. In this simpler case, the effective diffusion is characterized by a second-order tensor whose components depend on (1) the topology of the channels' network; (2) the solute's diffusion coefficients in the fluid and the cell clusters; (3) hydrodynamic dispersion effects; and (4) an additional dispersion term intrinsic to the two-phase configuration. Although solute transport in biofilms is commonly thought to be diffusion dominated, this analysis shows that hydrodynamic dispersion effects may significantly contribute to transport

    Preventing the Selection of "Deaf Embryos" Under the Human Fertilisation and Embryology Act 2008:Problematizing Disability?

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    Section 14(4) of the Human Fertilisation and Embryology Act 2008 imposes – within the general licensing conditions listed in the Human Fertilisation and Embryology Act 1990 – a prohibition to prevent the selection and implantation of embryos for the purpose of creating a child who will be born with a “serious disability.” This article offers a perspective that demonstrates the problematic nature of the consultation, review, and legislative reform process surrounding s 14(4). The term “serious disability” is not defined within the legislation, but we highlight the fact that s 14(4) was passed with the case of selecting deaf children in mind. We consider some of the literature on the topic of disability and deafness, which, we think, casts some doubt on the view that deafness is a “serious disability.” The main position we advance is that the lack of serious engagement with alternative viewpoints during the legislative process was unsatisfactory. We argue that the contested nature of deafness necessitates a more robust consultation process and a clearer explanation and defence of the normative position that underpins s 14(4)

    Winnow based identification of potent hERG inhibitors in silico: comparative assessment on different datasets

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    RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Peer Reviewe

    Rapid Characterization of hERG Channel Kinetics II: Temperature Dependence

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    © 2019 Biophysical Society Ion channel behavior can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in voltage-dependent ion channel kinetics (rates of opening, closing, inactivating, and recovery) are commonly represented with Q10 coefficients or an Eyring relationship. In this article, we assess the validity of these representations by characterizing channel kinetics at multiple temperatures. We focus on the human Ether-à-go-go-Related Gene (hERG) channel, which is important in drug safety assessment and commonly screened at room temperature so that results require extrapolation to physiological temperature. In Part I of this study, we established a reliable method for high-throughput characterization of hERG1a (Kv11.1) kinetics, using a 15-second information-rich optimized protocol. In this Part II, we use this protocol to study the temperature dependence of hERG kinetics using Chinese hamster ovary cells overexpressing hERG1a on the Nanion SyncroPatch 384PE, a 384-well automated patch-clamp platform, with temperature control. We characterize the temperature dependence of hERG gating by fitting the parameters of a mathematical model of hERG kinetics to data obtained at five distinct temperatures between 25 and 37°C and validate the models using different protocols. Our models reveal that activation is far more temperature sensitive than inactivation, and we observe that the temperature dependency of the kinetic parameters is not represented well by Q10 coefficients; it broadly follows a generalized, but not the standardly-used, Eyring relationship. We also demonstrate that experimental estimations of Q10 coefficients are protocol dependent. Our results show that a direct fit using our 15-s protocol best represents hERG kinetics at any given temperature and suggests that using the Generalized Eyring theory is preferable if no experimental data are available to derive model parameters at a given temperature
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