Optimal finite element modelling and efficient reconstruction in non-linear 3D electrical resistance tomography

Electrical Impedance Tomography can provide images with well-defined characteristics using a fully non-linear reconstruction process when appropriate constraints are imposed on the solution to allow the ill-posed inverse problem to be solved. Using appropriate finite element discretizations for forward solution and inverse problem offers additional advantages in the image reconstruction process, such as (a) inclusion of prior knowledge, (b) generic model templating to adapt to, for example, individual head shapes, and (c) obtaining accurate results without unnecessary computational overhead. We have developed an efficient 3D non-linear reconstruction algorithm based on a regularized inverse conjugate gradient solver which incorporates (a) local image smoothness constraints, and (b) a number of optimisations which reduce the computing power required to obtain an accurate solution. We show results from applying this to various problems which arise in medical resistivity reconstruction given only surface potential measurements and demonstrate the importance of the FE discretization. Keywords: 3D non-linear electrical impedance tomography, FE template modelling, optimal finite element meshes, 3D visualization, FE discretization

Efficient non-linear 3D electrical tomography reconstruction

Non-linear electrical tomography imaging can be performed efficiently if certain optimisations are applied to the computational reconstruction process. We present a 3D non-linear reconstruction algorithm based on a regularized conjugate gradient solver and discuss the optimisations which we incorporated to allow for an efficient and accurate reconstruction. In particular, the application of image smoothness constraints or other regularization techniques and auto-adaptive mesh refinement are highly relevant. We demonstrate the results of applying this algorithm to the reconstruction of a simulated material distribution in a cubic volume

The method of Glowinski and Pironneaufor the unsteady stokes problem

AbstractThe unsteady Stokes problem, i.e., the Stokes problem with a constant multiple of the velocity included in the velocity-pressure equation, is often central to methods used to solve the nonstationary Navier-Stokes equations and the equations governing viscoelastic flows. The Glowinski-Pironneau finite-element method for the Stokes problem decomposes the problem into a series of Poisson's equations, providing a potentially efficient approach for large problems in two or three dimensions. The goal of this paper is to present a complete development and analysis of the Glowinski-Pironneau method for the unsteady Stokes problem, along with numerical results which confirm the analytical estimates

Efficient non-linear 3D electrical tomography and finite element optimizations for functional source imaging

An essential factor in functional source imaging is the accurate knowledge of the conducitvity dostribution inside the body. Current models for electrophysiological forward and inverse problems use tabulated conductivity values obtained from experiments. This article shows how EIT-derived conductivities can be used in EEG reconstructions of a head slice

Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH) arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA) analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR) at high frequency (>10%). Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains). Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver gene

Footrot and interdigital dermatitis in sheep: Farmer satisfaction with current management, their ideal management and sources used to adopt new strategies

The aims of this research were to identify management practices that sheep farmers currently use to treat and prevent footrot in sheep and whether they consider that these are successful management tools and to find out how sheep farmers would ideally like to manage footrot in their flock. Over 90% of lameness in sheep in the UK is caused by Dichelobacter nodosus, which presents clinically as interdigital dermatitis (ID) alone or with separation of hoof horn (FR). A questionnaire was sent to 265 farmers to investigate their current management and their satisfaction with current management of the spectrum of clinical presentations of footrot. Farmers were also asked their ideal management of footrot and their interest in, and sources of information for, change. Approximately 160 farmers responded. Farmers satisfied with current management reported a prevalence of lameness ≤5%. These farmers caught and treated lame sheep within 3 days of first seeing them lame, and treated sheep with FR and ID with parenteral antibacterials. Farmers dissatisfied with their management reported a prevalence of lameness >5%. These farmers practised routine foot trimming, footbathing and vaccination against footrot. Whilst 89% of farmers said they were satisfied with their management of FR over 34% were interested in changing management. Farmers identified veterinarians as the most influential source for new information. Farmers reported that ideally they would control FR by culling/isolating lame sheep, sourcing replacements from non-lame parents, trimming feet less, using antibacterial treatments less and using vaccination more. Footbathing was a commonly used management that was linked with dissatisfaction and that also was listed highly as an ideal management. Consequently, some of the ideal managements are in agreement with our understanding of disease control (culling and isolation, sourcing healthy replacements) but others are in contrast with our current knowledge of management and farmers self-reporting of satisfaction of management of footrot (less use of antibacterial treatment, more footbathing and vaccination). One explanation for this is the theory of cognitive dissonance where belief follows behaviour, i.e. farmers report that they believe an ideal which is what they are currently doing, even if the management is sub-optimal

Molecular scale contact line hydrodynamics of immiscible flows

From extensive molecular dynamics simulations on immiscible two-phase flows, we find the relative slipping between the fluids and the solid wall everywhere to follow the generalized Navier boundary condition, in which the amount of slipping is proportional to the sum of tangential viscous stress and the uncompensated Young stress. The latter arises from the deviation of the fluid-fluid interface from its static configuration. We give a continuum formulation of the immiscible flow hydrodynamics, comprising the generalized Navier boundary condition, the Navier-Stokes equation, and the Cahn-Hilliard interfacial free energy. Our hydrodynamic model yields interfacial and velocity profiles matching those from the molecular dynamics simulations at the molecular-scale vicinity of the contact line. In particular, the behavior at high capillary numbers, leading to the breakup of the fluid-fluid interface, is accurately predicted.Comment: 33 pages for text in preprint format, 10 pages for 10 figures with captions, content changed in this resubmissio

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

Search for the Rare Decay KL --> pi0 ee

The KTeV/E799 experiment at Fermilab has searched for the rare kaon decay KL--> pi0ee. This mode is expected to have a significant CP violating component. The measurement of its branching ratio could support the Standard Model or could indicate the existence of new physics. This letter reports new results from the 1999-2000 data set. One event is observed with an expected background at 0.99 +/- 0.35 events. We set a limit on the branching ratio of 3.5 x 10^(-10) at the 90% confidence level. Combining the results with the dataset taken in 1997 yields the final KTeV result: BR(KL --> pi0 ee) < 2.8 x 10^(-10) at 90% CL.Comment: 4 pages, three figure