Colorectal Cancer Through Simulation and Experiment

Colorectal cancer has continued to generate a huge amount of research interest over several decades, forming a canonical example of tumourigenesis since its use in Fearon and Vogelstein’s linear model of genetic mutation. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical biology and computer-based modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the ‘Hallmarks of Cancer’ has been extended in recent times and provides an excellent basis for future research. We present a timely summary of the literature relating to colorectal cancer, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. We conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that mathematical and computational modelling can provide

Civil engineering status report for the ATLAS & CMS worksites

Construction work on the civil engineering contracts at Point 1 and Point 5 started in 1998. The new surface buildings and underground structures are necessary to accommodate the ATLAS and CMS detectors for the LHC Project. The principal underground works at both points consist of two new shafts, two caverns along with a number of small connection tunnels and galleries. At Point 1, the works are 90% complete. Most of the surface buildings as well as the shafts and one of the two new caverns have been completed, and the construction of the second cavern is well underway. At Point 5, the works are 70% complete. Most of the surface buildings as well as the shafts and the pillar have been completed. With excavation of the two large caverns complete, the concreting of the final linings has started. The aim of this paper is to present the status of the civil engineering on these worksites and in particular the challenges encountered constructing the experimental caverns

On-lattice agent-based simulation of populations of cells within the open-source chaste framework

Over the years, agent-based models have been developed that combine cell division and reinforced random walks of cells on a regular lattice, reaction-diffusion equations for nutrients and growth factors and ordinary differential equations (ODEs) for the subcellular networks regulating the cell cycle. When linked to a vascular layer, this multiple scale model framework has been applied to tumour growth and therapy. Here we report on the creation of an agent-based multiscale environment amalgamating the characteristics of these models within a Virtual Pysiological Human (VPH) Exemplar Project. This project enables re-use, integration, expansion and sharing of the model and relevant data. The agent-based and reactiondiffusion parts of the multiscale model have been implemented and are available for download as part of the latest public release of Chaste (“Cancer, Heart and Soft Tissue Environment”), (http://www.cs.ox.ac.uk/chaste/) version 3.1, part of the VPH Toolkit (http://toolkit.vph-noe.eu/). The environment functionalities are verified against the original models, in addition to extra validation of all aspects of the code. In this work, we present the details of the implementation of the agent-based environment, including the system description, the conceptual model, the development of the simulation model and the processes of verification and validation of the simulation results. We explore the potential use of the environment by presenting exemplar applications of the “what if” scenarios that can easily be studied in the environment. These examples relate to tumour growth, cellular competition for resources and tumour responses to hypoxia. We conclude our work by summarising the future steps for the expansion of the current system

Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues

The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to PDE-based continuum methods, although formal relationships between the discrete and continuum frameworks remain to be established. For crystal mechanics, the discrete-to-continuum bridge is often made by assuming that local atom displacements can be mapped homogeneously from the mesoscale deformation gradient, an assumption known as the Cauchy-Born rule (CBR). Although the CBR does not hold exactly for non-crystalline materials, it may still be used as a first order approximation for analytic calculations of effective stresses or strain energies. In this work, our goal is to investigate numerically the applicability of the CBR to 2-D cellular-scale models by assessing the mechanical behaviour of model biological tissues, including crystalline (honeycomb) and non-crystalline reference states. The numerical procedure consists in precribing an affine deformation on the boundary cells and computing the position of internal cells. The position of internal cells is then compared with the prediction of the CBR and an average deviation is calculated in the strain domain. For centre-based models, we show that the CBR holds exactly when the deformation gradient is relatively small and the reference stress-free configuration is defined by a honeycomb lattice. We show further that the CBR may be used approximately when the reference state is perturbed from the honeycomb configuration. By contrast, for vertex-based models, a similar analysis reveals that the CBR does not provide a good representation of the tissue mechanics, even when the reference configuration is defined by a honeycomb lattice. The paper concludes with a discussion of the implications of these results for concurrent discrete/continuous modelling, adaptation of atom-to-continuum (AtC) techniques to biological tissues and model classification

Resumption of mass accretion in RS Oph

The latest outburst of the recurrent nova RS Oph occurred in 2006 February. Photometric data presented here show evidence of the resumption of optical flickering, indicating re-establishment of accretion by day 241 of the outburst. Magnitude variations of up to 0.32 mag in V band and 0.14 mag in B band on time-scales of 600–7000 s are detected. Over the two-week observational period, we also detect a 0.5 mag decline in the mean brightness, from V≈ 11.4 to 11.9, and record B≈ 12.9 mag. Limits on the mass accretion rate of [inline image] are calculated, which span the range of accretion rates modelled for direct wind accretion and Roche lobe overflow mechanisms. The current accretion rates make it difficult for thermonuclear runaway models to explain the observed recurrence interval, and this implies average accretion rates are typically higher than seen immediately post-outburst

Solute transport within porous biofilms: diffusion or dispersion?

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 behaviour by controllling 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 biofilmscale. We show that solute transport may be described via two coupled partial differential equations for the averaged concentrations, or telegrapher’s equations. These models are particularly relevant for chemical species, 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 characterised 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 dispersion effects may significantly contribute to transport

Parenting Practices of Resident Fathers: The Role of Marital and Biological Ties

This paper uses data from the Fragile Families and Child Wellbeing Study to examine differences in the parenting behaviors of resident biological and social fathers on measures of engagement, shared responsibility, and cooperation in parenting. Regression, difference-in-difference, and decomposition techniques are used. Results suggest that biological and social fathers differ significantly on most parenting measures (and in some unexpected ways), but that a considerable portion of these differences can be explained by differences in the background characteristics of the individuals and families in each group. Additionally, the analyses reveal a stronger link between marriage and higher-quality parenting behaviors for social-father families than for biological-father families.

The interplay between tissue growth and scaffold degradation in engineered tissue constructs

In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation.\ud \ud In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (i) differential interactions between cells and the supporting scaffold and their associated ECM, (ii) scaffold degradation, and (iii) mechanotransduction-regulated cell proliferation and ECM deposition.\ud \ud Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability for implantation in vivo

The SSS phase of RS Ophiuchi observed with Chandra and XMM-Newton I.: Data and preliminary Modeling

The phase of Super-Soft-Source (SSS) emission of the sixth recorded outburst of the recurrent nova RS Oph was observed twice with Chandra and once with XMM-Newton. The observations were taken on days 39.7, 54.0, and 66.9 after outburst. We confirm a 35-sec period on day 54.0 and found that it originates from the SSS emission and not from the shock. We discus the bound-free absorption by neutral elements in the line of sight, resonance absorption lines plus self-absorbed emission line components, collisionally excited emission lines from the shock, He-like intersystem lines, and spectral changes during an episode of high-amplitude variability. We find a decrease of the oxygen K-shell absorption edge that can be explained by photoionization of oxygen. The absorption component has average velocities of -1286+-267 km/s on day 39.7 and of -771+-65 km/s on day 66.9. The wavelengths of the emission line components are consistent with their rest wavelengths as confirmed by measurements of non-self absorbed He-like intersystem lines. We have evidence that these lines originate from the shock rather than the outer layers of the outflow and may be photoexcited in addition to collisional excitations. We found collisionally excited emission lines that are fading at wavelengths shorter than 15A that originate from the radiatively cooling shock. On day 39.5 we find a systematic blue shift of -526+-114 km/s from these lines. We found anomalous He-like f/i ratios which indicates either high densities or significant UV radiation near the plasma where the emission lines are formed. During the phase of strong variability the spectral hardness light curve overlies the total light curve when shifted by 1000sec. This can be explained by photoionization of neutral oxygen in the line of sight if the densities of order 10^{10}-10^{11} cm^{-3}.Comment: 16 pages, 10 figures, 4 tables. Accepted by ApJ; v2: Co-author Woodward adde

Causal structure of the entanglement renormalization ansatz

We show that the multiscale entanglement renormalization ansatz (MERA) can be reformulated in terms of a causality constraint on discrete quantum dynamics. This causal structure is that of de Sitter space with a flat spacelike boundary, where the volume of a spacetime region corresponds to the number of variational parameters it contains. This result clarifies the nature of the ansatz, and suggests a generalization to quantum field theory. It also constitutes an independent justification of the connection between MERA and hyperbolic geometry which was proposed as a concrete implementation of the AdS-CFT correspondence