Local network-based measures to assess the inferability of different regulatory networks

The purpose of this study is to compare the inferability of various synthetic as well as real biological regulatory networks. In order to assess differences we apply local network-based measures. That means, instead of applying global measures, we investigate and assess an inference algorithm locally, on the level of individual edges and subnetworks. We demonstrate the behaviour of our local network-based measures with respect to different regulatory networks by conducting large-scale simulations. As inference algorithm we use exemplarily ARACNE. The results from our exploratory analysis allow us not only to gain new insights into the strength and weakness of an inference algorithm with respect to characteristics of different regulatory networks, but also to obtain information that could be used to design novel problem-specific statistical estimators.

York; Shadows in Siberia According to Kapuscinski

Two poems

Barriers to student computer usage: staff and student perceptions

Ensuring that all graduates are able to exploit new technologies is a primary goal of all UK universities and a variety of assumptions have underpinned policies designed to promote this goal, This paper explores some of these assumptions through the findings of a. longitudinal study involving a cohort of over 800 university students. The study adopted a student perspective to examine the factors affecting their use of computers over a three year period. Unsurprisingly, the results indicated that situational factors (e.g. access, training and time) influence the extent to which students use computers, but a disparity was found in the importance attributed to these factors by the academic staff, who focused on the needs of their department, and by the students, who focused on their individual needs. Results suggest that increased attention to a student perspective may lead to improved strategic planning in students' use of computers.

Reading the Irishwoman: Studies in Cultural Encounter and Exchange, 1714-1960

In 1700 few Irishwomen were literate. Most lived in a rural environment, rarely encountered a book or a play or ventured much beyond their own domestic space. By 1960 literacy was universal, all Irishwomen attended primary school, had access to a variety of books, magazines, newspapers and other forms of popular media and the wider world was now part of their every-day life. This study seeks to examine the cultural encounters and exchanges inherent in this transformation. It analyses reading and popular and consumer culture as sites of negotiation of gender roles. This is not an exhaustive treatment of the theme but focusses on three key points of cultural encounter: the Enlightenment, emigration and modernism. The writings and intellectual discourse generated by the Enlightenment was one of the most influential forces shaping western society. It set the agenda for scientific, political and social thought for the eighteenth and nineteenth centuries. The migration of peoples to north America was another key historical marker in the development of the modern world. Emigration altered and shaped American society as well as the lives of those who remained behind. By the twentieth century, aesthetic modernism suspicious of enlightenment rationalism and determined to produce new cultural forms developed in a complex relationship with the forces of industrialisation, urbanisation and social change. This study analyses the impact of these three key forces in Western culture on changing roles and perceptions of Irish women from 1700 to 1960.

The Ectocarpus genome and the independent evolution of multicellularity in brown algae

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related(1). These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae(2-5), closely related to the kelps(6,7) (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic(2) approaches to explore these and other(4,5) aspects of brown algal biology further.

Combining bio- and chemo-catalysis: from enzymes to cells, from petroleum to biomass

In the future, biomass will continue to emerge as a viable source of chemicals. The development of new industries that utilize bio-renewables provides opportunities for innovation. For example, bio- and chemo-catalysts can be combined in 'one pot' to prepare chemicals of commercial value. This has been demonstrated using isolated enzymes and whole cells for a variety of chemical transformations. The one-pot approach has been successfully adopted to convert chemicals derived from biomass, and, in our opinion, it has an important role to play in the design of a more sustainable chemical industry. To implement new one-pot bio- and chemo-catalytic processes, issues of incompatibility must be overcome; the strategies for which are discussed in this opinion article.

Suez 1956: A European Intervention

This article does not analyse events in the Middle East. It is concerned with the structural background of the Suez Crisis. The Cold War bargain of 1949-50, and thus the Western bloc architecture, was challenged in 1956 and 1962-63. The Suez Crisis and the SKYBOLT Affair are classic examples of intra-bloc conflict. This article focuses on inter-allied conflict during the Suez Crisis. The crisis year 1956 witnessed a European challenge to the bipolar order of the Cold War. It is the hypothesis of this article that the mystique of the Suez Crisis unravels, if the events are interpreted as a clash of conflicting world views. The article attempts to enhance our understanding of the crisis by exploring the impact of the formation of a European core on the transatlantic pluralistic security community. The article will thus re-evaluate the architectural debate within the Western partial system. It is the aim to shed new light on the almost unexplored European foreign-policy co-operation within the Western European Union (WEU) in the crisis year 1956

Development and validation of a method for the confirmation of nicarbazin in chicken liver and eggs using LC-electrospray MS-MS according to the revised EU criteria for veterinary drug residue analysis

A method is described for the quantitative confirmation of 4,4'-dinitrocarbanilide (DNC), the marker residue for nicarbazin in chicken liver and eggs. The method is based on LC coupled to negative ion electrospray MS-MS of tissue extracts prepared by liquid-liquid extraction. The [M-H](-) ion at m/z 301 is monitored along with two transition ions at m/z 137 and 107 for DNC and the [M-H](-) ion at m/z 309 for the internal standard, d(8)-DNC. The method has been validated according to the new EU criteria for the analysis of veterinary drug residues at 100, 200 and 300 mug kg(-1) in liver and at 10, 30 and 100 mug kg(-1) in eggs. Difficulties concerning the application of the new analytical limits, namely the decision limit (CC) and the detection capability (CC) to the determination of DNC in both liver and eggs are discussed.

New prognostic markers, determined using gene expression analyses, reveal two distinct subtypes of chronic myelomonocytic leukaemia patients

Chronic myelomonocytic leukaemia (CMML) is a heterogeneous haematopoietic disorder characterized by myeloproliferative or myelodysplastic features. At present, the pathogenesis of this malignancy is not completely understood. In this study, we sought to analyse gene expression profiles of CMML in order to characterize new molecular outcome predictors. A learning set of 32 untreated CMML patients at diagnosis was available for TaqMan low-density array gene expression analysis. From 93 selected genes related to cancer and cell cycle, we built a five-gene prognostic index after multiplicity correction. Using this index, we characterized two categories of patients with distinct overall survival (94% vs. 19% for good and poor overall survival, respectively; P = 0.007) and we successfully validated its strength on an independent cohort of 21 CMML patients with Affymetrix gene expression data. We found no specific patterns of association with traditional prognostic stratification parameters in the learning cohort. However, the poor survival group strongly correlated with high-risk treated patients and transformation to acute myeloid leukaemia. We report here a new multigene prognostic index for CMML, independent of the gene expression measurement method, which could be used as a powerful tool to predict clinical outcome and help physicians to evaluate criteria for treatments.

The Emergence of Rural Support Organisations in the UK and Canada: Providing Support for Patrilineal Family Farming

A certain type of rural support has emerged since agricultural restructuring of the 1980s. The article draws on research from the UK and Canada to suggest that support in both countries is derived from a patrilineal culture that still dominates family farming in both countries. Such a way of life, it is argued, involves the majority of farming men and women across generations working increasingly hard to ensure farm survival in order to facilitate an overall pattern of farm succession via the male or ‘patrilineal’ line. The article begins by providing a conceptualisation of patrilineal family farming drawing on insights from gender-informed work on farming identities, political-economy approaches from agricultural geography and the cultural turn in rural studies. This section will provide theoretical direction for discussion of the research findings. Here the article presents a discussion of the context to and typologies of organisations that emerged and five key findings derived from research conducted with members of the organisations in the UK and Canada. This assists in developing the argument that the emergent organisations are responding to and supporting this way of life and highlights some of the potential implications of doing so. The article has two aims. Firstly, it suggests that family farming in the UK and Canada continues to be predominantly structured by a way of life transmitted across generations which has the overall prerequisite of maintaining farm survival to enable patrilineal succession. Secondly, it suggests that a particular type of support for farming families emerged as a response to perceived threats to this way of life and provides evidence of its enduring nature.

Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy

BACKGROUND & AIMS:
Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large panel of GC cell lines. We tested if these subtypes might be associated with differences in patient survival times and responses to various standard-of-care cytotoxic drugs.
METHODS:
We analyzed gene expression profiles for 37 GC cell lines to identify intrinsic GC subtypes. These subtypes were validated in primary tumors from 521 patients in 4 independent cohorts, where the subtypes were determined by either expression profiling or subtype-specific immunohistochemical markers (LGALS4, CDH17). In vitro sensitivity to 3 chemotherapy drugs (5-fluorouracil, cisplatin, oxaliplatin) was also assessed.
RESULTS:
Unsupervised cell line analysis identified 2 major intrinsic genomic subtypes (G-INT and G-DIF) that had distinct patterns of gene expression. The intrinsic subtypes, but not subtypes based on Lauren's histopathologic classification, were prognostic of survival, based on univariate and multivariate analysis in multiple patient cohorts. The G-INT cell lines were significantly more sensitive to 5-fluorouracil and oxaliplatin, but more resistant to cisplatin, than the G-DIF cell lines. In patients, intrinsic subtypes were associated with survival time following adjuvant, 5-fluorouracil-based therapy.
CONCLUSIONS:
Intrinsic subtypes of GC, based on distinct patterns of expression, are associated with patient survival and response to chemotherapy. Classification of GC based on intrinsic subtypes might be used to determine prognosis and customize therapy.

European Law and New Health Technologies

Health is a matter of fundamental importance in European societies, both as a human right in itself, and as a factor in a productive workforce and therefore a healthy economy. New health technologies promise improved quality of life for patients suffering from a range of diseases, and the potential for the prevention of incidence of disease in the future. At the same time, new health technologies pose significant challenges for governments, particularly in relation to ensuring the technologies are safe, effective, and provide appropriate value for (public) money.

To guard against the possible dangers arising from new health technologies, and to maximize the benefits, all European governments regulate their development, marketing, and public financing. In addition, several international institutions operating at European level, in particular the European Union, the Council of Europe, and the European Patent Office, have become involved in the regulation of new health technologies. They have done so both through traditional 'command and control' legal measures, and through other regulatory mechanisms, including guidelines, soft law, 'steering' through redistribution of resources, and private or quasi-private regulation.

This collection analyses European law and its relationships with new health technologies. It uses interdisciplinary insights, particularly from law but also drawing on regulation theory, and science and technology studies, to shed new light on some of the key defining features of the relationships and especially the roles of risk, rights, ethics, and markets. The collection explores the way in which European law's engagement with new health technologies is to be legitimized, and discusses the implications for biological or biomedical citizenship.

Patterns of cough in the clinic

Current guidelines for the management of cough highlight the value of a taking a careful history to establish specific features of the cough in particular its duration, typical triggers or aggravants and associated symptoms. Unfortunately the diagnostic yield from a history alone is poor and there is a need to understand the pattern of clinical cough in a more precise way. As the technology to record cough in ambulatory settings becomes more sophisticated so the possibility that precise measurement of the cough frequency, intensity and acoustic characteristics may offer diagnostically valuable information in individual patients becomes a reality. In this article the current knowledge of the clinical patterns of cough is discussed and the potential for new technology to record cough patterns in a meaningful way is considered.

Aminopeptidases of malaria parasites:new targets for chemotherapy

Novel targets for new drug development are urgently required to combat malaria, a disease that puts half of the world's population at risk. One group of enzymes identified within the genome of the most lethal of the causative agents of malaria, Plasmodium falciparum, that may have the potential to become new targets for antimalarial drug development are the aminopeptidases. These enzymes catalyse the cleavage of the N-terminal amino acids from proteins and peptides. P. falciparum appears to encode for at least nine aminopeptidases, two neutral aminopeptidases, one aspartyl aminopeptidase, one aminopeptidase P, one prolyl aminopeptidase and four methionine aminopeptidases. Recent advances in our understanding of these genes and their protein products are outlined in this review, including their potential for antimalarial drug development.

Handwritten undergraduate case reports

Background: This article describes a 'back to the future' approach to case 'write-ups', with medical students producing handwritten instead of word-processed case reports during their clinical placements. Word-processed reports had been found to have a number of drawbacks, including the inappropriate use of 'cutting and pasting', undue length and lack of focus. Method: We developed a template to be completed by hand, based on the hospital 'clerking-in process', and matched this to a new assessment proforma. An electronic survey was conducted of both students and assessors after the first year of operation to evaluate impact and utility. Results: The new template was well received by both students and assessors. Most students said they preferred handwriting the case reports (55.6%), although a significant proportion (44.4%) preferred the word processor. Many commented that the template enabled them to effectively learn the structure of a case history and to improve their history-taking skills. Most assessors who had previously marked case reports felt the new system represented an improvement. The average time spent marking each report fell from 23.56 to 16.38minutes using the new proforma. Discussion: Free text comments from the survey have led to the development of a more flexible case report template better suited to certain specialties (e.g. dermatology). This is an evolving process and there will be opportunities for further adaptation as electronic medical records become more common in hospital. © Blackwell Publishing Ltd 2012.