178,124 research outputs found
Evasion of tumours from the control of the immune system: consequences of brief encounters
No full textIn this work a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. Specifically, attention is focused on the interactions between cytotoxic T-lymphocytes (CTLs) and tumour cells in a small, avascular multicellular tumour. At this stage of the disease the CTLs and the tumour cells are considered to be in a state of dynamic equilibrium or cancer dormancy. The precise biochemical and cellular mechanisms by which CTLs can control a cancer and keep it in a dormant state are still not completely understood from a biological and immunological point of view. The mathematical model focuses on the spatio-temporal dynamics of tumour cells, immune cells, chemokines and ``chemo-repellors'' in an immunogenic tumour. The CTLs and tumour cells are assumed to migrate and interact with each other in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation of the lymphocytes and consequently the survival of the tumour cells. In the latter case, we assume that each tumour cell which survives its ``brief encounter'' with the CTLs undergoes certain beneficial phenotypic changes. We explore the dynamics of the model under these assumptions and show that the process of immuno-evasion can arise as a consequence of these encounters. We also briefly discuss the evolutionary features of our model, by framing them in the recent quasi-Lamarckian theories
Modeling the emergence of phenotypic heterogeneity in vascularized tumors
No full textWe present a mathematical study of the emergence of phenotypic heterogeneity in vascularized tumors. Our study is based on formal asymptotic analysis and numerical simulations of a system of nonlocal parabolic equations that describes the phenotypic evolution of tumor cells and their nonlinear dynamic interactions with the oxygen, which is released from the intratumoral vascular network. Numerical simulations are carried out both in the case of arbitrary distributions of intratumor blood vessels and in the case where the intratumoral vascular network is reconstructed from clinical images obtained using dynamic optical coherence tomography. The results obtained support a more in-depth theoretical understanding of the eco-evolutionary process which underpins the emergence of phenotypic heterogeneity in vascularized tumors. In particular, our results offer a theoretical basis for empirical evidence indicating that the phenotypic properties of cancer cells in vascularized tumors vary with the distance from the blood vessels, and establish a relation between the degree of tumor tissue vascularization and the level of intratumor phenotypic heterogeneity
The Free Church army chaplain 1830-1930.
No full textThe study traces the efforts of English Nonconformists to provide
chaplains for their adherents in the British Army. Unrecognised
by the War Office, and opposed by the Church of England, the
Wesleyan Methodists persisted in providing an unpaid civilian
ministry until, by stages, they secured partial recognition in
1862 and 1881. The respect earned by volunteer Wesleyan civilian
chaplains, who accompanied the troops on most colonial and
imperial expeditions in the last quarter of the century,
culminating in the Boer War, prompted the War Office in 1903 to
offer them a number of commissioned chaplaincies. The Wesleyans
declined the offer. Although they had earlier, and after
anguished debate, accepted State payment of chaplains, they were
not prepared to accept military control of them.
In the Great War, Wesleyan chaplains were nevertheless obliged to
accept temporary commissions. Congregationalists, Baptists,
Primitive and United Methodists, through a United Board, provided
another stream of chaplains. With the political help of Lloyd
George, both sets of Nonconformists secured equitable treatment
at the hands of the Church of England and, through an
Interdenominational Committee, gained positions of considerable
influence over chaplaincy policy. In the field, remarkably for
the age, they joined with Presbyterians and Roman Catholics in a
single chain of command. By 1918, over 500 Wesleyan and United
Board commissioned chaplains were engaged. After the war, as the price of retaining their newly won standing
and influence, both the Wesleyans and the United Board
denominations accepted permanent commissions for their chaplains
and their absorption within a unified Chaplains Department.
Acceptability was secured through willingness to compromise on
voluntaryism and conformity to the State
A study of role conflict in a changing society with special reference to some twentieth century problems
No full textThis thesis arises out of a very practical and personal need to identify, examine and possibly resolve any role conflict that might be experienced by the military chaplain in the performance of his religious and military duties. It endeavours to trace the dilemma against a background of certain military and political activities and in the light of some theological comment to arrive at some form of modus Vivendi whereby those who legitimately take up arms in the defence of their country are not without the ministry and help of those who, in ordination, have taken up the profession of Jesus Christ. The history of the military chaplain is traced from the early days of his acceptance by society to the time when he begins to feel rejected and serious doubts are being raised as to his ability to serve both God and Caesar. In an attempt to discover if there is any support or even understanding for his peculiar and specialised ministry the relationship between Church and State is examined and analysed. The role of the chaplain in both war and peace is studied with particular reference to the nuclear deterrent debate, Northern Ireland and its problems and of course the two great world wars of the twentieth century. Questions are asked of many chaplains in an attempt to discover if the conflict is in any sense destructive of their ministry or indeed oreative. In the end the role of the military chaplain is seen to be but a microcosmic .reflection of the paradoxical role that is continually being experienced by all Christians in their attempts to establish the Kingdom of God in a world which is far from perfect
Mechanical Models of Pattern and Form in Biological Tissues: The Role of Stress–Strain Constitutive Equations
No full textMechanical and mechanochemical models of pattern formation in biological tissues have been used to study a variety of biomedical systems, particularly in developmental biology, and describe the physical interactions between cells and their local surroundings. These models in their original form consist of a balance equation for the cell density, a balance equation for the density of the extracellular matrix (ECM), and a force-balance equation describing the mechanical equilibrium of the cell-ECM system. Under the assumption that the cell-ECM system can be regarded as an isotropic linear viscoelastic material, the force-balance equation is often defined using the Kelvin–Voigt model of linear viscoelasticity to represent the stress–strain relation of the ECM. However, due to the multifaceted bio-physical nature of the ECM constituents, there are rheological aspects that cannot be effectively captured by this model and, therefore, depending on the pattern formation process and the type of biological tissue considered, other constitutive models of linear viscoelasticity may be better suited. In this paper, we systematically assess the pattern formation potential of different stress–strain constitutive equations for the ECM within a mechanical model of pattern formation in biological tissues. The results obtained through linear stability analysis and the dispersion relations derived therefrom support the idea that fluid-like constitutive models, such as the Maxwell model and the Jeffrey model, have a pattern formation potential much higher than solid-like models, such as the Kelvin–Voigt model and the standard linear solid model. This is confirmed by the results of numerical simulations, which demonstrate that, all else being equal, spatial patterns emerge in the case where the Maxwell model is used to represent the stress–strain relation of the ECM, while no patterns are observed when the Kelvin–Voigt model is employed. Our findings suggest that further empirical work is required to acquire detailed quantitative information on the mechanical properties of components of the ECM in different biological tissues in order to furnish mechanical and mechanochemical models of pattern formation with stress–strain constitutive equations for the ECM that provide a more faithful representation of the underlying tissue rheology
A hybrid discrete-continuum approach to model Turing pattern formation
No full textSince its introduction in 1952, with a further refinement in 1972 by Gierer and Meinhardt, Turing's (pre-)pattern theory (the chemical basis of morphogenesis) has been widely applied to a number of areas in developmental biology, where evolving cell and tissue structures are naturally observed. The related pattern formation models normally comprise a system of reaction-diffusion equations for interacting chemical species (morphogens), whose heterogeneous distribution in some spatial domain acts as a template for cells to form some kind of pattern or structure through, for example, differentiation or proliferation induced by the chemical pre-pattern. Here we develop a hybrid discrete-continuum modelling framework for the formation of cellular patterns via the Turing mechanism. In this framework, a stochastic individual-based model of cell movement and proliferation is combined with a reaction-diffusion system for the concentrations of some morphogens. As an illustrative example, we focus on a model in which the dynamics of the morphogens are governed by an activator-inhibitor system that gives rise to Turing pre-patterns. The cells then interact with the morphogens in their local area through either of two forms of chemically-dependent cell action: Chemotaxis and chemically-controlled proliferation. We begin by considering such a hybrid model posed on static spatial domains, and then turn to the case of growing domains. In both cases, we formally derive the corresponding deterministic continuum limit and show that that there is an excellent quantitative match between the spatial patterns produced by the stochastic individual-based model and its deterministic continuum counterpart, when sufficiently large numbers of cells are considered. This paper is intended to present a proof of concept for the ideas underlying the modelling framework, with the aim to then apply the related methods to the study of specific patterning and morphogenetic processes in the future
The elastic spiral phase pipe
No full textThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordWe design a device for the passive mode conversion of guided, axisymmetric, ultrasonic waves in hollow elastic pipes into arbitrary non-axisymmetric flexural waves that have a constant angular profile along the pipe axis. To achieve this we create an elastic analogue to optical spiral phase plates—the elastic spiral phase pipe. Three possible configurations of the elastic spiral phase pipe are presented which allow the efficient generation of non-axisymmetric flexural waves from an axisymmetric, longitudinal forcing. The theory leverages the dispersive nature of the guided elastic waves that are supported in pipes through a defined relative refractive index. As such we include a spectral collocation method used to aid the design of the elastic spiral phase pipe that is corroborated with numerical simulations and then experimentally verified.Engineering and Physical Sciences Research Council (EPSRC)European Union Horizon 2020Royal Commission for the Exhibition of 185
The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity
No full textWe present here a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of abiotic components of the tumour microenvironment in mediating phenotypic selection of cancer cells. Numerical simulations are performed both on the 3D geometry of an in silico multicellular tumour spheroid and on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography. The results obtained show that inhomogeneities in the spatial distribution of oxygen, currently observed in solid tumours, can promote the creation of distinct local niches and lead to the selection of different phenotypic variants within the same tumour. This process fosters the emergence of stable phenotypic heterogeneity and supports the presence of hypoxic cells resistant to cytotoxic therapy prior to treatment. Our theoretical results demonstrate the importance of integrating spatial data with ecological principles when evaluating the therapeutic response of solid tumours to cytotoxic therapy
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A paper entitled Highlights of Address made by the National Chaplain
No full textA paper entitled Highlights of Address made by the National Chaplain. No mention of an author or a date is found
A stochastic individual-based model to explore the role of spatial interactions and antigen recognition in the immune response against solid tumours
No full textSpatial interactions between cancer and immune cells, as well as the recognition of tumour antigens by cells of the immune system, play a key role in the immune response against solid tumours. The existing mathematical models generally focus only on one of these key aspects. We present here a spatial stochastic individual-based model that explicitly captures antigen expression and recognition. In our model, each cancer cell is characterised by an antigen profile which can change over time due to either epimutations or mutations. The immune response against the cancer cells is initiated by the dendritic cells that recognise the tumour antigens and present them to the cytotoxic T cells. Consequently, T cells become activated against the tumour cells expressing such antigens. Moreover, the differences in movement between inactive and active immune cells are explicitly taken into account by the model. Computational simulations of our model clarify the conditions for the emergence of tumour clearance, dormancy or escape, and allow us to assess the impact of antigenic heterogeneity of cancer cells on the efficacy of immune action. Ultimately, our results highlight the complex interplay between spatial interactions and adaptive mechanisms that underpins the immune response against solid tumours, and suggest how this may be exploited to further develop cancer immunotherapies
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