Biochemical studies of the tracheobronchial epithelium.

Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. In brief, formidable strides have been made in biochemistry specific to this important target tissue, despite the inability to acquire tracheobronchial epithelium in large quantities

Large scale deployment of molecular docking application on computational grid infrastructures for combating malaria

PCSVInternational audienceComputational grids are solutions for several biological applications like virtual screening or molecular dynamics where large amounts of computing power and storage are required. The WISDOM project successfully deployed virtual screening at large scale on EGEE grid infrastructures in the summer 2005 and achieved 46 million dockings in 45 days, which is equivalent to 80 CPU years. WISDOM is one good example of a successful deployment of an embarrassingly parallel application. In this paper, we describe the improvements in our deployment. We screened ZINC database against four targets implicated in malaria. During more than 2 months and a half, we have achieved 140 million dockings, representing an average throughput of almost 80,000 dockings per hour. This was made possible by the availability of thousands of CPUs through different infrastructures worldwide. Through the acquired experience, the WISDOM production environment is evolving to enable an easy and fault-tolerant deployment of biological tool

Growth, profits and technological choice: The case of the Lancashire cotton textile industry

Using Lancashire textile industry company case studies and financial records, mainly from the period just before the First World War, the processes of growth and decline are re-examined. These are considered by reference to the nature of Lancashire entrepreneurship and the impact on technological choice. Capital accumulation, associated wealth distributions and the character of Lancashire business organisation were sybiotically linked to the success of the industry before 1914. However, the legacy of that accumulation in later decades, chronic overcapacity, formed a barrier to reconstruction and enhanced the preciptious decline of a once great industry

XML-structured documents: Retrievable units and inheritance

We consider the retrieval of XML-structured documents, and of passages from such documents, defined as elements of the XML structure. These are considered from the point of view of passage retrieval, as a form of document retrieval. A retrievable unit (an element chosen as defining suitable passages for retrieval) is a textual document in its own right, but may inherit information from the other parts of the same document. Again, this inheritance is defined in terms of the XML structure. All retrievable units are mapped onto a common field structure, and the ranking function is a standard document retrieval function with a suitable field weighting. A small experiment to demonstrate the idea, using INEX data, is described

A Golf Programme for People with Severe and Enduring Mental Health Problems

This article reports a pioneering golf programme for people with severe and enduring mental health problems. Following a discussion of the problems and possibilities of golf as a form of physical activity for this group, we outline the structure, organisation, and ethos of the golf programme. Through an analysis of qualitative case study data collected during the programme, we discuss the response to the programme from service users and mental health professionals. We conclude by highlighting aspects of the programme which were critical to its success and offering suggestions for further initiatives in this area