Characteristic bimodal profiles of RNA polymerase II at thousands of active mammalian promoters.

BACKGROUND: In mammals, ChIP-seq studies of RNA polymerase II (PolII) occupancy have been performed to reveal how recruitment, initiation and pausing of PolII may control transcription rates, but the focus is rarely on obtaining finely resolved profiles that can portray the progression of PolII through sequential promoter states. RESULTS: Here, we analyze PolII binding profiles from high-coverage ChIP-seq on promoters of actively transcribed genes in mouse and humans. We show that the enrichment of PolII near transcription start sites exhibits a stereotypical bimodal structure, with one peak near active transcription start sites and a second peak 110 base pairs downstream from the first. Using an empirical model that reliably quantifies the spatial PolII signal, gene by gene, we show that the first PolII peak allows for refined positioning of transcription start sites, which is corroborated by mRNA sequencing. This bimodal signature is found both in mouse and humans. Analysis of the pausing-related factors NELF and DSIF suggests that the downstream peak reflects widespread pausing at the +1 nucleosome barrier. Several features of the bimodal pattern are correlated with sequence features such as CpG content and TATA boxes, as well as the histone mark H3K4me3. CONCLUSIONS: We thus show how high coverage DNA sequencing experiments can reveal as-yet unnoticed bimodal spatial features of PolII accumulation that are frequent at individual mammalian genes and reminiscent of transcription initiation and pausing. The initiation-pausing hypothesis is corroborated by evidence from run-on sequencing and immunoprecipitation in other cell types and species.

Regional value added in Italy over the long run (1891-2001): linking indirect estimates with official figures, and implications

This paper presents value added estimates for the Italian regions, in benchmark years from 1891 until 1951, which are linked to those from official figures available from 1971 in order to offer a long-term picture. Sources and methodology are documented and discussed, whilst regional activity rates and productivity are also presented and compared. Thus some questions are briefly reconsidered: the origins and extent of the north-south divide, the role of migration and regional policy in shaping the pattern of regional inequality, the importance of social capital, and the positioning of Italy in the international debate on regional convergence, where it stands out for the long run persistence of its disparities.

Desarrollo de un sistema integrado de navegación inercial: interfície IMU + FPGA

Els sistemes automatitzats que requereixen d’un control d’estabilitat o moviment es poden trobar cada cop en més àmbits. Aplicacions UAV o de posicionament global són les més comunes per aquest tipus de sistemes, degut a que necessiten d’un control de moviment molt precís. Per a dur a terme aquest procés s’utilitzen unitats de mesura inercial, que mitjançant acceleròmetres i giroscopis degudament posicionats, a més a més d’una correcció del possible error que puguin introduir aquests últims, proporcionen una acceleració i una velocitat angular de les quals es pot extreure el camí efectuat per aquestes unitats. La IMU, combinada amb un GPS i mitjançant un filtre de Kalman, proporcionen una major exactitud , a més d’un punt de partida (proporcionat per el GPS), un recorregut representable en un mapa y, en el cas de perdre la senyal GPS, poder seguir adquirint dades de la IMU. Aquestes dades poden ser recollides i processades per una FPGA, que a la vegada podem sincronitzar amb una PDA per a que l’usuari pugui veure representat el moviment del sistema. Aquest treball es centra en el funcionament de la IMU i l’adquisició de dades amb la FPGA. També introdueix el filtre de Kalman per a la correcció de l’error dels sensors.

Anatomic shoulder arthroplasty: consequences of humeral head malposition

Purpose Third generation anatomic total shoulder prostheses offer a wide range of adaptability (size, thickness, retroversion and offset of the humeral head, cervico-diaphyseal angle) in order to reproduce anatomy and biomechanics of the shoulder as normal as possible. The large variability of the implants may also induce malposition. Our goal was to analyse the consequences of a humeral head malposition, which is one of the most frequent placement errors. Material and Methods A 3D finite element model of the glenohumeral joint, including the rotator cuff muscles and the deltoid, was used with the Aequalis anatomic prosthesis. Active abduction was simulated. Three humeral head placements were compared : anatomic positioning (A), 5 mm inferior positioning (B), 5 mm superior positioning (C). The effect of humeral head malposition was evaluated through the following quantities : the range of motion free of impingements, the glenohumeral contact pattern, and the stress within the polyethylene and the cement. Results Inferior positioning (B) of the humeral head produced a superior impingement before 90° of abduction, an inferior eccentric contact point on the glenoid, and 165% increase of cement stress. Superior positioning (C) of the humeral head produced a postero-superior eccentric contact point on the glenoid, 300% increase of glenohumeral contact pressure, 450% increase of polyethylene stress, and 207% increase of cement stress. Conclusion Malposition of the humeral head of anatomic prostheses induces biomechanical consequences that may preclude the glenoid survival. Particular attention must be paid to reproduce the humeral anatomy as normal as possible.

A fully echo-guided trans-apical aortic valve implantation.

The trans-apical aortic valve implantation (TA-AVI) is an established technique for high-risk patients requiring aortic valve replacement. Traditionally, preoperative (computed tomography (CT) scan, coronary angiogram) and intra-operative imaging (fluoroscopy) for stent-valve positioning and implantation require contrast medium injections. To preserve the renal function in elderly patients suffering from chronic renal insufficiency, a fully echo-guided trans-catheter valve implantation seems to be a reasonable alternative. We report the first successful TA-AVI procedure performed solely under trans-oesophageal echocardiogram control, in the absence of contrast medium injections.

Apport de la systématique dans l'amélioration de la compréhension des systèmes de prise en compte des risques en entreprise

La gestion des risques est souvent appréhendée par l'utilisation de méthodes linéaires mettant l'accent sur des raisonnements de positionnement et de type causal : à tel événement correspond tel risque et telle conséquence. Une prise en compte des interrelations entre risques est souvent occultée et les risques sont rarement analysés dans leurs dynamiques et composantes non linéaires. Ce travail présente ce que les méthodes systémiques et notamment l'étude des systèmes complexes sont susceptibles d'apporter en matière de compréhension, de management et d'anticipation et de gestion des risques d'entreprise, tant sur le plan conceptuel que de matière appliquée. En partant des définitions relatives aux notions de systèmes et de risques dans différents domaines, ainsi que des méthodes qui sont utilisées pour maîtriser les risques, ce travail confronte cet ensemble à ce qu'apportent les approches d'analyse systémique et de modélisation des systèmes complexes. En mettant en évidence les effets parfois réducteurs des méthodes de prise en compte des risques en entreprise ainsi que les limitations des univers de risques dues, notamment, à des définitions mal adaptées, ce travail propose également, pour la Direction d'entreprise, une palette des outils et approches différentes, qui tiennent mieux compte de la complexité, pour gérer les risques, pour aligner stratégie et management des risques, ainsi que des méthodes d'analyse du niveau de maturité de l'entreprise en matière de gestion des risques. - Risk management is often assessed through linear methods which stress positioning and causal logical frameworks: to such events correspond such consequences and such risks accordingly. Consideration of the interrelationships between risks is often overlooked and risks are rarely analyzed in their dynamic and nonlinear components. This work shows what systemic methods, including the study of complex systems, are likely to bring to knowledge, management, anticipation of business risks, both on the conceptual and the practical sides. Based on the definitions of systems and risks in various areas, as well as methods used to manage risk, this work confronts these concepts with approaches of complex systems analysis and modeling. This work highlights the reducing effects of some business risk analysis methods as well as limitations of risk universes caused in particular by unsuitable definitions. As a result this work also provides chief officers with a range of different tools and approaches which allows them a better understanding of complexity and as such a gain in efficiency in their risk management practices. It results in a better fit between strategy and risk management. Ultimately the firm gains in its maturity of risk management.

Análisis, desarrolo y posicionamiento de una web 2.0

Anàlisi i desenvolupament d’una web 2.0 per taxistes, en forma de xarxa social, on puguin participar activament, anunciar la venda de les seves llicències de taxi amb informació detallada i trobin publicitat d’empreses del sector que ofereixen ofertes i promocions dels seus serveis o productes gràcies a les eines que ofereix la web a les empreses subscrites. Optimització de la web pels principals motors de cerca d’ Internet.

IPH response to DSD consultation on proposed changes to the law regulating sale and supply of alcohol

This consultation was intended to test public opinion on proposed changes to the law regulating the sale of alcohol in Northern Ireland. The proposed changes relate to-    regulating the sale of alcohol in supermarkets and off-sales premises-    regulating the sale of alcohol in pubs and other on-sales premises-    regulating private member clubs-    codes of practice Key points from IPH response -    IPH welcomes the opportunity to submit our views on this review of regulations related to the sale and supply of alcohol in Northern Ireland. IPH notes that the reduction of alcohol-related harm is a stated aim of the review. -    International evidence clearly supports the role of regulation of the sale and supply of alcohol in reducing alcohol consumption and in reducing alcohol-related harm. -    The consultation document does not present any meaningful estimation of the scale or nature of potential positive or negative effects on alcohol-related harm arising from the proposed changes. On this basis, IPH recommends that a Health Impact Assessment should be conducted on the proposed regulations. -    IPH shares the concerns raised in respect of increases in the number of people drinking at home and the availability of large volumes of low cost alcohol in supermarkets. In this regard, we welcome the proposals to enhance the regulation of sale of alcohol in mixed trading premises by more stringent structural separation measures and restricted advertising. -    IPH wishes to emphasise the importance of the work underway to explore the introduction of minimum unit pricing of alcohol on the island of Ireland as this measure will be significant in enhancing the proposals on regulating sale of alcohol in mixed trading premises -    In light of evidence of increased alcohol consumption and harm associated with increased hours and days of sale of alcohol, IPH does not support the proposal to introduce additional late opening hours or extended drinking up time.

IPH response to Department of Health (UK) Standardised Packaging of Tobacco Products

Enhanced tobacco control policies and programmes are an important component of any strategic approach to improving population health and tackling health inequalities. The consultation on standardised packaging of tobacco products in the UK is particularly timely in view of the recent publication of the Ten Year Tobacco Strategy for Northern Ireland (DHSSPS, 2012). In this strategy the Department expressed its support for the introduction of further measures to reduce the influence of tobacco advertising and promotion upon children e.g. the introduction of plain packaging for cigarettes and hand rolling tobacco.  IPH key points •    The extent of tobacco-related harm across the island of Ireland and across the UK is unacceptable. Increasingly comprehensive and effective tobacco-control interventions are required. •    IPH recommends the adoption of option 2: require standardised packaging of tobacco products. •    IPH acknowledges that as plain packaging has not yet been introduced in any country, it is not possible at this time to accurately forecast the extent and nature of this intervention on population level health outcomes in the UK context. •    The proposed approach appears comprehensive in addressing the direct and indirect ways in which elements of tobacco packaging can promote brand appeal and can portray impressions in respect of tobacco-related harm. Consideration should be given to include specific provisions relating to roll-your-own (RYO) tobacco packaging. Any approach needs to be regularly reviewed to take into account attempts to bypass restrictions and evaluate responses in respect of consumer choices. •    IPH considers that the introduction of plain packaging has the potential to support the achievement of the goals set out in the Ten Year Tobacco Control Strategy for Northern Ireland ( DHSSPS, 2012). •    Among children in Northern Ireland who reported trying their first cigarette, around one quarter were aged 11 or under and three quarters were 14 or under when they did so (DHSSPS, 2012).  The very young age of these children is concerning on many levels including their susceptibility to sophisticated branding and marketing techniques linked to tobacco packaging.

IPH response to Broadcasting Authority of Ireland (BAI): General and Children's Commercial Communications Codes (June 2012)

IPH submitted their views on the Draft BAI General and Commercial Communications Code. IPH previously submitted views to the BAI in the first phase of consultation (Oct 2011). The final code will regulate the advertising of food and non-alcoholic beverages that are high in fat, salt or sugar on Irish television channels. The submission sets out approaches to appropriate scheduling and content restrictions as well as to possible exemptions.