A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion.

Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unknown. Here we use a Cancer rainbow (Crainbow) modelling system for fluorescently barcoding somatic mutations and directly visualizing the clonal expansion and spread of oncogenes. Crainbow shows that mutations of ß-catenin (Ctnnb1) within the intestinal stem cell results in widespread expansion of oncogenes during perinatal development but not in adults. In contrast, mutations that extrinsically disrupt the stem cell microenvironment can spread in adult intestine without delay. We observe the rapid spread of premalignant clones in Crainbow mice expressing oncogenic Rspondin-3 (RSPO3), which occurs by increasing crypt fission and inhibiting crypt fixation. Crainbow modelling provides insight into how somatic mutations rapidly spread and a plausible mechanism for predetermining the intratumor heterogeneity found in colon cancers

The BBC, Austerity and Broadcasting the 1948 Olympic Games

Based on original archive research, including papers held in the BBC Written Archives Centre, and interviews with those involved, this paper analyses the historical importance for the BBC of the 1948 Games as the first publicly televised Olympics. In particular, the paper addresses the management of operations by the Head of Outside Broadcasting at the BBC, Seymour Joly de Lotbiniere. De Lotbiniere had been an important figure in the development of outside broadcasting commentaries during the inter-war period and was given the task of organising the radio and television coverage of the London Games in 1948. The paper examines the technical, operational and ideological issues raised by the event for the BBC and its legacy for the development of live televised outside broadcasts from sport. The analysis suggests the BBC’s ability to host international broadcasters became a matter of prestige and its forays into television a sign of its emerging post-War modernity

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN

An appropriate tool for entrepreneurial learning in SMEs? The case of the 20Twenty Leadership Programme

The 20Twenty Leadership Programme was developed by Cardiff Metropolitan University as an executive education programme to be delivered within South Wales to small businesses. It is funded by the European Social Fund (ESF) and administered by the Welsh European Funding Office and has the key aim of developing SME’s growth potential via a range of leadership and management skills, including a focus on ‘soft’ skills. The focus of this paper is to place the 20Twenty Leadership Programme within the wider context of entrepreneurship policy and SME training initiatives in particular, and then to examine the rationale and delivery methods of the Programme in relation to these. It also reflects on the Programme’s success (or otherwise) to date where possible. Finally, the paper seeks to suggest fruitful areas of further research both in terms of the 20Twenty Leadership Programme itself, but also with regard to evaluation in relation to other parallel programmes, and to SME training initiatives more generally

Proteotypic classification of spontaneous and transgenic mammary neoplasms

INTRODUCTION: Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation. METHODS: Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV). RESULTS: On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1. CONCLUSIONS: Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm

Segmenting and labeling query sequences in a multidatabase environment

When gathering information from multiple independent data sources, users will generally pose a sequence of queries to each source, combine (union) or cross-reference (join) the results in order to obtain the information they need. Furthermore, when gathering information, there is a fair bit of trial and error involved, where queries are recursively refined according to the results of a previous query in the sequence. From the point of view of an outside observer, the aim of such a sequence of queries may not be immediately obvious. We investigate the problem of isolating and characterizing subsequences representing coherent information retrieval goals out of a sequence of queries sent by a user to different data sources over a period of time. The problem has two sub-problems: segmenting the sequence into subsequences, each representing a discrete goal; and labeling each query in these subsequences according to how they contribute to the goal. We propose a method in which a discriminative probabilistic model (a Conditional Random Field) is trained with pre-labeled sequences. We have tested the accuracy with which such a model can infer labels and segmentation on novel sequences. Results show that the approach is very accurate (> 95% accuracy) when there are no spurious queries in the sequence and moderately accurate even in the presence of substantial noise (∼70% accuracy when 15% of queries in the sequence are spurious). © 2011 Springer-Verlag

Dense Antihydrogen: Its Production and Storage to Envision Antimatter Propulsion

We discuss the possibility that dense antihydrogen could provide a path towards a mechanism for a deep space propulsion system. We concentrate at first, as an example, on Bose-Einstein Condensate (BEC) antihydrogen. In a Bose-Einstein Condensate, matter (or antimatter) is in a coherent state analogous to photons in a laser beam, and individual atoms lose their independent identity. This allows many atoms to be stored in a small volume. In the context of recent advances in producing and controlling BECs, as well as in making antihydrogen, this could potentially provide a revolutionary path towards the efficient storage of large quantities of antimatter, perhaps eventually as a cluster or solid.Comment: 12 pages, 3 figure