Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model.

MOTIVATION: Combinatorial interactions of transcription factors with cis-regulatory elements control the dynamic progression through successive cellular states and thus underpin all metazoan development. The construction of network models of cis-regulatory elements, therefore, has the potential to generate fundamental insights into cellular fate and differentiation. Haematopoiesis has long served as a model system to study mammalian differentiation, yet modelling based on experimentally informed cis-regulatory interactions has so far been restricted to pairs of interacting factors. Here, we have generated a Boolean network model based on detailed cis-regulatory functional data connecting 11 haematopoietic stem/progenitor cell (HSPC) regulator genes. RESULTS: Despite its apparent simplicity, the model exhibits surprisingly complex behaviour that we charted using strongly connected components and shortest-path analysis in its Boolean state space. This analysis of our model predicts that HSPCs display heterogeneous expression patterns and possess many intermediate states that can act as 'stepping stones' for the HSPC to achieve a final differentiated state. Importantly, an external perturbation or 'trigger' is required to exit the stem cell state, with distinct triggers characterizing maturation into the various different lineages. By focusing on intermediate states occurring during erythrocyte differentiation, from our model we predicted a novel negative regulation of Fli1 by Gata1, which we confirmed experimentally thus validating our model. In conclusion, we demonstrate that an advanced mammalian regulatory network model based on experimentally validated cis-regulatory interactions has allowed us to make novel, experimentally testable hypotheses about transcriptional mechanisms that control differentiation of mammalian stem cells. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cruciferous vegetables and cancer risk in a network of case-control studies.

Background Cruciferous vegetables have been suggested to protect against various cancers, though the issue is open to discussion. To further understand their role, we analyzed data from a network of case-control studies conducted in Italy and Switzerland. Patients and methods The studies included a total of 1468 cancers of the oral cavity/pharynx, 505 of the esophagus, 230 of the stomach, 2390 of the colorectum, 185 of the liver, 326 of the pancreas, 852 of the larynx, 3034 of the breast, 367 of the endometrium, 1031 of the ovary, 1294 of the prostate, 767 of the kidney, and 11 492 controls. All cancers were incident, histologically confirmed; controls were subjects admitted to the same network of hospitals as cases for a wide spectrum of acute nonneoplastic conditions. Results The multivariate odds ratio (OR) for consumption of cruciferous vegetables at least once a week as compared with no/occasional consumption was significantly reduced for cancer of the oral cavity/pharynx (OR = 0.83), esophagus (OR = 0.72), colorectum (OR = 0.83), breast (OR = 0.83), and kidney (OR = 0.68). The OR was below unity, but not significant, for stomach (OR = 0.90), liver (OR = 0.72), pancreatic (OR = 0.90), laryngeal (OR = 0.84), endometrial (OR = 0.93), ovarian (OR = 0.91), and prostate (OR = 0.87) cancer. Conclusion This large series of studies provides additional evidence of a favorable effect of cruciferous vegetables on several common cancers.

Distinction of males of the Lutzomyia intermedia (Lutz & Neiva, 1912) species complex by ratios between dimensions and by an artificial neural network (Diptera: Psychodidae, Phlebotominae)

The females of the two species of the Lutzomyia intermedia complex can be easily distinguished, but the males of each species are quite similar. The ratios between the extra-genital and the genital structures of L. neivai are larger than those of L. intermedia s. s., according to ANOVA. An artificial neural network was trained with a set of 300 examples, randomly taken from a sample of 358 individuals. The input vectors consisted of several ratios between some structures of each insect. The model was tested on the remaining 58 insects, 56 of which (96.6%) were correctly identified. This ratio of success can be considered remarkable if one takes into account the difficulty of attaining comparable results using traditional statistical techniques.

Productivity and human capital: a business-level analysis

This paper aims to analyse the impact of human capital on business productivity, focusing the analysis on the possible effect of the complementarity that exists between human capital and new production technologies, particularly advanced manufacturing technologies (AMTs) for the specific case of small and medium enterprises (SMEs) in Catalonia. Additionally, following the theory of skill-biased technological change, the paper analyses whether technological change produces bias exclusively in the skills required for managers, or whether the bias extends to the skills required of production staff. With this objective, we have compared the possible existence of complementarity between AMTs and the level of human capital for different occupational groups. The results confirm the complementary relationship between human capital and new production technologies. The results by occupational group confirm that to maximise the productivity of new technologies, skilled staff are needed both in management and production, with managers and professionals as well as skilled operatives playing a vital role. Keywords: human capital, process technologies, complementarity, business productivity. (JEL D24, J24, O30).

Regulatory federalism in network industries

Report for the scientific sojourn at the UC Berkeley, USA, from march until july 2008. This document starts by surveying the literature on economic federalism and relating it to network industries. The insights and some new developments (which focus on the role of interjurisdictional externalities, multiple objectives and investment incentives) are used to analyze regulatory arrangements in telecommunications and energy in the EU and the US. In the long history of vertically integrated monopolies in telecommunications and energy, there was a historical trend to move regulation up in the vertical structure of government, at least form the local level to the state or nation-state level. This move alleviated the pressure on regulators to renege on the commitment not to expropriate sunk investments, although it did not eliminate the practice of taxation by regulation that was the result of multiple interest group action. Although central or federal policy making is more focused and especialized and makes it difficult for more interest groups to organize, it is not clear that under all conditions central powers will not be associated with underinvestment. When technology makes the introduction of competition in some segments possible, the possibilities for organizing the institutional architechture of regulation expand. The central level may focus on structural regulation and the location of behavioral regulation of the remaining monopolists may be resolved in a cooperative way or concentrated at the level where the relevant spillovers are internalized.

Organizational form and business performance

This project deals with the generation of profitability and the distribution of its benefits. Inspired by Davis (1947, 1955), we define profitability as the ratio of revenue to cost. Profitability is not as popular a measure of business financial performance as profit, the difference between revenue and cost. Regardless of its popularity, however, profitability is surely a useful financial performance measure. Our primary objective in this project is to identify the factors that generate change in profitability. One set of factors, which we refer to as sources, consists of changes in quantities and prices of outputs and inputs. Individual quantity changes aggregate to the overall impact of quantity change on profitability change, which we call productivity change. Individual price changes aggregate to the overall impact of price change on profitability change, which we call price recovery change. In this framework profitability change consists exclusively of productivity change and price recovery change. A second set of factors, which we refer to as drivers, consists of phenomena such as technical change, change in the efficiency of resource allocation, and the impact of economies of scale. The ability of management to harness these factors drives productivity change, which is one component of profitability change. Thus the term sources refers to quantities and prices of individual outputs and inputs, whose changes influence productivity change or price recovery change, either of which influences profitability change. The term drivers refers to phenomena related to technology and management that influence productivity change (but not price recovery change), and hence profitability change.

Department of Health and Children Business Plan 2001

Department of Health and Children Business Plan 2001 Download the Report here

Department of Health and Children Business Plan 2002

The framework within which the Office of the CMO will operate for 2002 is that of the Departmentâ?Ts corporate implementation plan for the Strategy. The Office will contribute to the achievement of the objectives of the Department with regard to the Strategy, by participating in  relevant agreed activities so as to achieve the first national goal of better health for everybody.The stakeholders identified in the Strategy consultation process are those with whom appropriate linkages and communications need to be  established and managed if the Strategy is to be implemented effectively. Download document here

Department of Health and Children Business Plan 2003

Department of Health and Children Business Plan 2003 The National Health Strategy â?oQuality and Fairness: A Health System for Youâ?Âù is based on a whole-system approach to health matters. It recognises the role of stakeholders such as the public, community and voluntary bodies, health service providers, statutory and non-statutory bodies, other Government Departments and international bodies in working together to produce a world-class health system and a healthier population. Click here to download PDF 2.5mb

Department of Health and Children Business Plan 2003

Click here to download PDF

Department of Health and Children business plan 2004

Click here to download PDF

Integració d'un business intelligence en un ERP

Aquest projecte mostra la importància que pot tenir un sistema basat en Business Intelligence, dins d’una empresa o organització, donant una eina per augmentar la competitivitat, treballant les dades que s’obtenen dels diferents sistemes de gestió que hi ha dins l’empresa. Aquest gran nombre de dades històriques les transformarem per formar una base de dades de qualitat, i les explorarem per tal d’extreure’n informació útil en format gràfic, per ajudar a la pressa de decisions per part dels directius.

The Rare Cancer Network: achievements from 1993 to 2012.

The Rare Cancer Network (RCN), founded in 1993, performs research involving rare tumors that are not common enough to be the focus of prospective study. Over 55 studies have either been completed or are in progress.The aim of the paper is to present an overview of the 30 studies done through the RCN to date, organized by disease site. Five studies focus on breast pathology, including sarcoma, lymphoma, phyllodes tumor, adenoid cystic carcinoma, and ductal carcinoma in situ in young women. Three studies on prostate cancer address prostatic small cell carcinoma and adenocarcinoma of young and elderly patients. Six studies on head and neck cancers include orbital and intraocular lymphoma, mucosal melanoma, pediatric nasopharyngeal carcinoma, olfactory neuroblastoma, and mucosa-associated lymphoid tissue lymphoma of the salivary glands. There were 4 central nervous system studies on patients with cerebellar glioblastoma multiforme, atypical and malignant meningioma, spinal epidural lymphoma and myxopapillary ependymoma. Outside of these disease sites, there is a wide variety of other studies on tumors ranging from uterine leiomyosarcoma to giant cell tumors of the bone. The studies done by the RCN represent a wide range of rare pathologies that were previously only studied in small series or case reports. With further growth of the RCN and collaboration between members our ability to analyze rare tumors will increase and result in better understanding of their behavior and ultimately help direct research that may improve patient outcomes.