Prospects for computational steering of evolutionary computation

Currently, evolutionary computation (EC) typically takes place in batch mode: algorithms are run autonomously, with the user providing little or no intervention or guidance. Although it is rarely possible to specify in advance, on the basis of EC theory, the optimal evolutionary algorithm for a particular problem, it seems likely that experienced EC practitioners possess considerable tacit knowledge of how evolutionary algorithms work. In situations such as this, computational steering (ongoing, informed user intervention in the execution of an otherwise autonomous computational process) has been profitably exploited to improve performance and generate insights into computational processes. In this short paper, prospects for the computational steering of evolutionary computation are assessed, and a prototype example of computational steering applied to a coevolutionary algorithm is presented

Indium(III) promoted oxidative P-P coupling of silylphosphines

The reaction of indium(III) salts with Ph2PSiMe3 and PhP(SiMe3)2 gives rise to a one- and two-electron reductive P-P coupling respectively, with the formation of new P-P bonds resulting in the preparation of (Ph2P)2 and the cyclicoligophosphane compounds (PhP)4 and (PhP)6

Developmental counterpart of the Wilms Tumour cancer stem cell

Wilms tumour (WT; more correctly known as nephroblastoma) is an important childhood renal cancer. The WT cancer stem cell (CSC) has been identified as being a neural cell adhesion molecule-1+ (NCAM1) and aldefluor+ sub-population of tumour cells that can recapitulate the characteristic histology of WT when only 200 cells were used to seed the tumour in vivo. The aim was to explore the relationship between normal nephron progenitor cells and the WT cancer stem cell, with the hypothesis that the CSC has a normal developmental cell counterpart and when this is transformed by cancer-causing mutations it initiates WT. We show that ALDH1A2 is responsible for the aldefluor activity seen both in CSCs and normal embryonic kidneys, and that NCAM1 and ALDH1A2 are expressed in different cell lineages in the normal developing mouse kidney. Ncam1 expression is found in the Six2-positive nephrogenic progenitor cells, whereas Aldh1a2 is expressed in the Foxd1- positive stromal lineage. When we conditionally knock-out Wt1 in mice (the classical WT-causing mutation) we find that NCAM1 and ALDH1A2 become present in the same cells, as in the CSCs. Similar results are seen when using a Six2-Cre, suggesting that the origin of the CSC is the NCAM1+ nephrogenic lineage. We conclude that the Wilms tumour initiating mutation is directly responsible for the co-expression of the two WT CSC markers in the same cells. The construction of an mCherry fluorescence expressing vector with inducible Cre for insertion at the Ncam1 locus will allow future lineage tracing of the developmental equivalent of the CSC and conditional knock-out of other WT associated genes. In addition, pilot data is presented for the production of WT-like pseudo-tumours in NOD/SCID mice

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network

Complementary role of cardiac CT in the assessment of aortic valve replacement dysfunction

Aortic valve replacement is the second most common cardiothoracic procedure in the UK. With an ageing population, there are an increasing number of patients with prosthetic valves that require follow-up. Imaging of prosthetic valves is challenging with conventional echocardiographic techniques making early detection of valve dysfunction or complications difficult. CT has recently emerged as a complementary approach offering excellent spatial resolution and the ability to identify a range of aortic valve replacement complications including structural valve dysfunction, thrombus development, pannus formation and prosthetic valve infective endocarditis. This review discusses each and how CT might be incorporated into a multimodal cardiovascular imaging pathway for the assessment of aortic valve replacements and in guiding clinical management