Enabling research with human embryonic and fetal tissue resources

Congenital anomalies are a significant burden on human health. Understanding the developmental origins of such anomalies is key to developing potential therapies. The Human Developmental Biology Resource (HDBR), based in London and Newcastle, UK, was established to provide embryonic and fetal material for a variety of human studies ranging from single gene expression analysis to large-scale genomic/transcriptomic studies. Increasingly, HDBR material is enabling the derivation of stem cell lines and contributing towards developments in tissue engineering. Use of the HDBR and other fetal tissue resources discussed here will contribute to the long-term aims of understanding the causation and pathogenesis of congenital anomalies, and developing new methods for their treatment and prevention

Stokes-Doppler coherence imaging for ITER boundary tomography

An optical coherence imaging system is presently being designed for impurity transport studies and other applications on ITER. The wide variation in magnetic field strength and pitch angle (assumed known) across the field of view generates additional Zeeman-polarization-weighting information that can improve the reliability of tomographic reconstructions. Because background reflected light will be somewhat depolarized analysis of only the polarized fraction may be enough to provide a level of background suppression. We present the principles behind these ideas and some simulations that demonstrate how the approach might work on ITER. The views and opinions expressed herein do not necessarily reflect those of the ITER Organization

Human TBX22 expression and protein-DNA interactions

Cleft palate is one of the most common birth abnormalities. Figures published in 2006 by the American Centres for Disease Control and Prevention, report the incidence of those born in the United States with a cleft palate without the presence of a cleft lip (CPI) to be 6.39 for every 10000 in the three years between 1999 to 2001 and for cleft lip in association with a cleft palate (CLP) to be even greater - 10.48 per 10000 live births. In 2001, Braybrook and colleagues reported that mutations in the TBX22 gene cause X-linked cleft palate (CPX), a disease characterised by a cleft of the secondary palate and is often seen in association with ankyloglossia (tongue-tie) (Braybrook et al. 2001). A cleft of the secondary palate arises as a consequence of disturbance to correct development during palatogenesis: an anomaly in palatal shelf growth; delayed or failed shelf elevation; defective shelf fusion or a failure of medial edge epithelium cell death. This thesis reveals that the expression of TBX22 during these key developmental events in human embryos is consistent with the phenotype seen in CPX. To enable an investigation for TBX22 target genes, a DNA binding sequence is determined for the TBX22 protein. This sequence is used to generate a generic TBX22 DNA binding site, the presence of which is screened for in promoter regions, defined as 2kb upstream of transcription start sites. 132 genes were selected as candidate TBX22 targets on the basis that they underlie human disorders that include a cleft palate. The screen shows that 28 of these genes have at least one perfect or near perfect match to the generic TBX22 DNA binding site. Of these, only two both contained a perfect TBX22 generic DNA binding site and mouse mutants also had cleft palates: SUMO1 and MSX1. Interaction between SUMO1 and TBX22 has already been shown (Andreou et al. 2007). This study investigated MSX1 as a downstream target of TBX22 using a luciferase reporter gene construct in vitro. The results showed that in the presence of TBX22, the luciferase signal was reduced and support MSX1 being a downstream target gene of TBX22. These findings further the understanding of the molecular networks regulating craniofacial development. Unravelling these complex interactions is crucial to identifying the mechanisms of oro-facial clefting, important steps towards improved methods of counselling, treatment and prevention of these common birth disorders.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Towards a unified linear kinetic transport model with the trace ion module for EIRENE

Linear kinetic Monte Carlo particle transport models are frequently employed in fusion plasma simulations to quantify atomic and surface effects on the main plasma flow dynamics. Separate codes are used for transport of neutral particles (incl. radiation) and charged particles (trace impurity ions). Integration of both modules into main plasma fluid solvers provides then self consistent solutions, in principle. The required interfaces are far from trivial, because rapid atomic processes in particular in the edge region of fusion plasmas require either smoothing and resampling, or frequent transfer of particles from one into the other Monte Carlo code. We propose a different scheme here, in which despite the inherently different mathematical form of kinetic equations for ions and neutrals (e.g. Fokker-Planck vs. Boltzmann collision integrals) both types of particle orbits can be integrated into one single code. We show that the approximations and shortcomings of this "single sourcing" concept (e.g., restriction to explicit ion drift orbit integration) can be fully tolerable in a wide range of typical fusion edge plasma conditions, and be overcompensated by the code-system simplicity, as well as by inherently ensured consistency in geometry (one single numerical grid only) and (the common) atomic and surface process modulesComment: 15 pages, 7 figure

Detachment evolution on the TCV tokamak

Divertor detachment in the TCV tokamak has been investigated through experiments and modelling. Density ramp experiments were carried out in ohmic heated L-mode pulses with the ion ∇B drift directed away from the primary X-point, similar to previous studies . Before the roll-over in the ion current to the outer strike point, C III and Dα emission from the outer leg recede slowly from the strike point toward the X-point, at a rate of ∼2.0 × 10-19 m/m-3 along the magnetic field as the electron temperature along the leg reduces with increasing density. Around the onset of detachment, the upstream density profile and outer target Dα profiles broaden, possibly leading to an increase in radiation in the SOL by increased interaction between the SOL and the carbon tiles lining the outer wall. The plasma conditions upstream and at various locations along the detached outer divertor leg have been characterised, and the consistency of this data has been checked with the interpretive OSM-EIRENE-DIVIMP suite of codes and are broadly found to be consistent with measured Dγ/Dα emissivity profiles along the detached outer divertor leg