Optimization strategies for fast detection of positive selection on phylogenetic trees.

MOTIVATION: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution. RESULTS: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total).Availability and implementation: ftp://ftp.vital-it.ch/tools/FastCodeML/. CONTACT: selectome@unil.ch or nicolas.salamin@unil.ch.

Public health impact of statin prescribing strategies based on JUPITER Modeling study from a population-based study.

OBJECTIVE: To evaluate the public health impact of statin prescribing strategies based on the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin Study (JUPITER). METHODS: We studied 2268 adults aged 35-75 without cardiovascular disease in a population-based study in Switzerland in 2003-2006. We assessed the eligibility for statins according to the Adult Treatment Panel III (ATPIII) guidelines, and by adding "strict" (hs-CRP≥2.0mg/L and LDL-cholesterol <3.4mmol/L), and "extended" (hs-CRP≥2.0mg/L alone) JUPITER-like criteria. We estimated the proportion of CHD deaths potentially prevented over 10years in the Swiss population. RESULTS: Fifteen % were already taking statins, 42% were eligible by ATPIII guidelines, 53% by adding "strict", and 62% by adding "extended" criteria, with a total of 19% newly eligible. The number needed to treat with statins to avoid one CHD death over 10years was 38 for ATPIII, 84 for "strict" and 92 for "extended" JUPITER-like criteria. ATPIII would prevent 17% of CHD deaths, compared with 20% for ATPIII+"strict" and 23% for ATPIII + "extended" criteria (+6%). CONCLUSION: Implementing JUPITER-like strategies would make statin prescribing for primary prevention more common and less efficient than it is with current guidelines.

Stratégies destinées a optimiser l'utilisation des antibiotiques en réanimation [Strategies targeted at optimising antimicrobial therapy in critically ill patients]

Antibiotics are widely used in critical care and adequate empirical treatments has a significant impact on the outcome of many patients. Most nosocomial infections may be due to multidrug-resistant pathogens and requires empirical borad spectrum coverage before identification of the etiologic agents. This is associated with overuse of antibiotics which contributes to the further increase in multidrug-resistances. In this context, new strategies targeted at antibiotic control, such as guidelines and de-escalation are needed to control this evolution.

Ego identity in adolescence: preliminary validation of a French short-form of the EIPQ

Following the seminal work on personal identity of Erikson, Marcia's identity status model has been one of the most enduring paradigms. The Ego Identity Process Questionnaire (EIPQ; Balistreri, Busch-Rossnagel, & Geissinger, 1995) is a widely used measure of identity status. The purpose of this study was to evaluate the factor structure and the reliability of a French version of the EIPQ. The hypothesized structures were not confirmed. In light of the failed attempts to validate the original version, an alternative short-form version of the EIPQ (EIPQ-SF), maintaining the integrity of the original model, was developed in one sample and cross-validated in another sample. Additionally, theoretically consistent associations between the EIPQ-SF dimensions and self-esteem confirmed convergent validity. Globally, the results indicated that the French short-version of the EIPQ might be a useful instrument for the assessment of the identity statuses in adolescence and emerging adulthood.

Pasture characteristics of Italian ryegrass and milk production under different management strategies

The objective of this work was to assess the effects of the sward structure of Italian ryegrass (Lolium multiflorum), during the first grazing cycle, on its morphological and bromatological characteristics throughout the growing season, and on the performance of dairy cows. The treatments consisted of two structures obtained as a function of canopy-light interception: high-light interception (HLI) and low-light interception (LLI), with different pre-grazing heights in the first grazing cycle. Pasture was managed under rotational grazing with a herbage allowance not below 30 kg dry matter (DM) per cow per day. Three grazing cycles, with a grazing interval of 30 days, were evaluated. Pre-grazing herbage mass was greater (2,240 vs. 1,656 kg ha-1 DM), but the proportion of leaf blades was smaller (0.35 vs. 0.43) for HLI swards. Neutral detergent fiber (NDF) content and organic matter digestibility (OMD) were similar between treatments in the first grazing cycle, but in the second and third ones NDF was greater, and OMD lower, for the HLI swards. Milk yields were greater for cows grazing LLI swards (19.4 vs. 21.1 kg per day). Initial grazing with 90% of light interception promotes greater nutritional value in the subsequent cycles.

Tapping the innovation potential of corporate engagement with stakeholders

Summary This dissertation explores how stakeholder dialogue influences corporate processes, and speculates about the potential of this phenomenon - particularly with actors, like non-governmental organizations (NGOs) and other representatives of civil society, which have received growing attention against a backdrop of increasing globalisation and which have often been cast in an adversarial light by firms - as a source of teaming and a spark for innovation in the firm. The study is set within the context of the introduction of genetically-modified organisms (GMOs) in Europe. Its significance lies in the fact that scientific developments and new technologies are being generated at an unprecedented rate in an era where civil society is becoming more informed, more reflexive, and more active in facilitating or blocking such new developments, which could have the potential to trigger widespread changes in economies, attitudes, and lifestyles, and address global problems like poverty, hunger, climate change, and environmental degradation. In the 1990s, companies using biotechnology to develop and offer novel products began to experience increasing pressure from civil society to disclose information about the risks associated with the use of biotechnology and GMOs, in particular. Although no harmful effects for humans or the environment have been factually demonstrated even to date (2008), this technology remains highly-contested and its introduction in Europe catalysed major companies to invest significant financial and human resources in stakeholder dialogue. A relatively new phenomenon at the time, with little theoretical backing, dialogue was seen to reflect a move towards greater engagement with stakeholders, commonly defined as those "individuals or groups with which. business interacts who have a 'stake', or vested interest in the firm" (Carroll, 1993:22) with whom firms are seen to be inextricably embedded (Andriof & Waddock, 2002). Regarding the organisation of this dissertation, Chapter 1 (Introduction) describes the context of the study, elaborates its significance for academics and business practitioners as an empirical work embedded in a sector at the heart of the debate on corporate social responsibility (CSR). Chapter 2 (Literature Review) traces the roots and evolution of CSR, drawing on Stakeholder Theory, Institutional Theory, Resource Dependence Theory, and Organisational Learning to establish what has already been developed in the literature regarding the stakeholder concept, motivations for engagement with stakeholders, the corporate response to external constituencies, and outcomes for the firm in terms of organisational learning and change. I used this review of the literature to guide my inquiry and to develop the key constructs through which I viewed the empirical data that was gathered. In this respect, concepts related to how the firm views itself (as a victim, follower, leader), how stakeholders are viewed (as a source of pressure and/or threat; as an asset: current and future), corporate responses (in the form of buffering, bridging, boundary redefinition), and types of organisational teaming (single-loop, double-loop, triple-loop) and change (first order, second order, third order) were particularly important in building the key constructs of the conceptual model that emerged from the analysis of the data. Chapter 3 (Methodology) describes the methodology that was used to conduct the study, affirms the appropriateness of the case study method in addressing the research question, and describes the procedures for collecting and analysing the data. Data collection took place in two phases -extending from August 1999 to October 2000, and from May to December 2001, which functioned as `snapshots' in time of the three companies under study. The data was systematically analysed and coded using ATLAS/ti, a qualitative data analysis tool, which enabled me to sort, organise, and reduce the data into a manageable form. Chapter 4 (Data Analysis) contains the three cases that were developed (anonymised as Pioneer, Helvetica, and Viking). Each case is presented in its entirety (constituting a `within case' analysis), followed by a 'cross-case' analysis, backed up by extensive verbatim evidence. Chapter 5 presents the research findings, outlines the study's limitations, describes managerial implications, and offers suggestions for where more research could elaborate the conceptual model developed through this study, as well as suggestions for additional research in areas where managerial implications were outlined. References and Appendices are included at the end. This dissertation results in the construction and description of a conceptual model, grounded in the empirical data and tied to existing literature, which portrays a set of elements and relationships deemed important for understanding the impact of stakeholder engagement for firms in terms of organisational learning and change. This model suggests that corporate perceptions about the nature of stakeholder influence the perceived value of stakeholder contributions. When stakeholders are primarily viewed as a source of pressure or threat, firms tend to adopt a reactive/defensive posture in an effort to manage stakeholders and protect the firm from sources of outside pressure -behaviour consistent with Resource Dependence Theory, which suggests that firms try to get control over extemal threats by focussing on the relevant stakeholders on whom they depend for critical resources, and try to reverse the control potentially exerted by extemal constituencies by trying to influence and manipulate these valuable stakeholders. In situations where stakeholders are viewed as a current strategic asset, firms tend to adopt a proactive/offensive posture in an effort to tap stakeholder contributions and connect the organisation to its environment - behaviour consistent with Institutional Theory, which suggests that firms try to ensure the continuing license to operate by internalising external expectations. In instances where stakeholders are viewed as a source of future value, firms tend to adopt an interactive/innovative posture in an effort to reduce or widen the embedded system and bring stakeholders into systems of innovation and feedback -behaviour consistent with the literature on Organisational Learning, which suggests that firms can learn how to optimize their performance as they develop systems and structures that are more adaptable and responsive to change The conceptual model moreover suggests that the perceived value of stakeholder contribution drives corporate aims for engagement, which can be usefully categorised as dialogue intentions spanning a continuum running from low-level to high-level to very-high level. This study suggests that activities aimed at disarming critical stakeholders (`manipulation') providing guidance and correcting misinformation (`education'), being transparent about corporate activities and policies (`information'), alleviating stakeholder concerns (`placation'), and accessing stakeholder opinion ('consultation') represent low-level dialogue intentions and are experienced by stakeholders as asymmetrical, persuasive, compliance-gaining activities that are not in line with `true' dialogue. This study also finds evidence that activities aimed at redistributing power ('partnership'), involving stakeholders in internal corporate processes (`participation'), and demonstrating corporate responsibility (`stewardship') reflect high-level dialogue intentions. This study additionally finds evidence that building and sustaining high-quality, trusted relationships which can meaningfully influence organisational policies incline a firm towards the type of interactive, proactive processes that underpin the development of sustainable corporate strategies. Dialogue intentions are related to type of corporate response: low-level intentions can lead to buffering strategies; high-level intentions can underpin bridging strategies; very high-level intentions can incline a firm towards boundary redefinition. The nature of corporate response (which encapsulates a firm's posture towards stakeholders, demonstrated by the level of dialogue intention and the firm's strategy for dealing with stakeholders) favours the type of learning and change experienced by the organisation. This study indicates that buffering strategies, where the firm attempts to protect itself against external influences and cant' out its existing strategy, typically lead to single-loop learning, whereby the firm teams how to perform better within its existing paradigm and at most, improves the performance of the established system - an outcome associated with first-order change. Bridging responses, where the firm adapts organisational activities to meet external expectations, typically leads a firm to acquire new behavioural capacities characteristic of double-loop learning, whereby insights and understanding are uncovered that are fundamentally different from existing knowledge and where stakeholders are brought into problem-solving conversations that enable them to influence corporate decision-making to address shortcomings in the system - an outcome associated with second-order change. Boundary redefinition suggests that the firm engages in triple-loop learning, where the firm changes relations with stakeholders in profound ways, considers problems from a whole-system perspective, examining the deep structures that sustain the system, producing innovation to address chronic problems and develop new opportunities - an outcome associated with third-order change. This study supports earlier theoretical and empirical studies {e.g. Weick's (1979, 1985) work on self-enactment; Maitlis & Lawrence's (2007) and Maitlis' (2005) work and Weick et al's (2005) work on sensegiving and sensemaking in organisations; Brickson's (2005, 2007) and Scott & Lane's (2000) work on organisational identity orientation}, which indicate that corporate self-perception is a key underlying factor driving the dynamics of organisational teaming and change. Such theorizing has important implications for managerial practice; namely, that a company which perceives itself as a 'victim' may be highly inclined to view stakeholders as a source of negative influence, and would therefore be potentially unable to benefit from the positive influence of engagement. Such a selfperception can blind the firm from seeing stakeholders in a more positive, contributing light, which suggests that such firms may not be inclined to embrace external sources of innovation and teaming, as they are focussed on protecting the firm against disturbing environmental influences (through buffering), and remain more likely to perform better within an existing paradigm (single-loop teaming). By contrast, a company that perceives itself as a 'leader' may be highly inclined to view stakeholders as a source of positive influence. On the downside, such a firm might have difficulty distinguishing when stakeholder contributions are less pertinent as it is deliberately more open to elements in operating environment (including stakeholders) as potential sources of learning and change, as the firm is oriented towards creating space for fundamental change (through boundary redefinition), opening issues to entirely new ways of thinking and addressing issues from whole-system perspective. A significant implication of this study is that potentially only those companies who see themselves as a leader are ultimately able to tap the innovation potential of stakeholder dialogue.

Studies toward new anti-cancer strategies based on alpha-mannosidase inhibition.

Changes in the glycosylation pattern of cellular glycoproteins constitute a hallmark in human cancer and influence tumor progression, suggesting that inhibitors of selected glycosidases may control cancer progression. Following the studies on swainsonine, a natural inhibitor of Golgi alpha-mannosidase II, which highlighted the inhibition of cellular mannosidases as a potential innovative approach for the treatment of cancer, several dihydroxylated pyrrolidines and analogues were developed as new potent inhibitors of alpha-mannosidases II able to induce antiproliferative effects in human cancer cells.

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui.

Stocking densities and feeding strategies in shrimp and tilapia polyculture in tanks

The objective of this work was to evaluate the performance of Pacific marine shrimp (Litopenaeus vannamei) and tilapia (Oreochromis niloticus), in a polyculture in tanks subjected to different stocking densities and feeding strategies, in comparison with monoculture. Two experiments were performed, at the same time, in a completely randomized design with three treatments and four replicates each. Treatments for experiment I were: monoculture with 10 shrimp per m² (10S:0T); polyculture with 10 shrimp and 0.5 tilapia per m² (10S:0.5T); and polyculture with 10 shrimp and 1 tilapia per m² (10S:1T). Shrimp was the main crop, and feed was provided based on shrimp biomass. Treatments for experiment II were: monoculture with 2 tilapia per m² (2T:0S); polyculture with 2 tilapia and 2.5 shrimp per m² (2T:2.5S); and polyculture with 2 tilapia and 5 shrimp per m² (2T:5S). Tilapia was the main crop, and feed was provided based on fish requirements. In the experiment I, tilapia introduction to shrimp culture resulted in lower shrimp growth and poor feed conversion rate. In experiment II, shrimp introduction to tilapia culture did not interfere with fish performance. Polyculture is more efficient with the combination of 2 tilapia and 2.5 or 5 shrimp per m² and feed based on fish requirements.

Toward a novel forensic intelligence model: systematic profiling of false identity documents

False identity documents represent a serious threat through their production and use in organized crime and by terrorist organizations. The present-day fight against this criminal problem and threats to national security does not appropriately address the organized nature of this criminal activity, treating each fraudulent document on its own during investigation and the judicial process, which causes linkage blindness and restrains the analysis capacity. Given the drawbacks of this case-by-case approach, this article proposes an original model in which false identity documents are used to inform a systematic forensic intelligence process. The process aims to detect links, patterns, and tendencies among false identity documents in order to support strategic and tactical decision making, thus sustaining a proactive intelligence-led approach to fighting identity document fraud and the associated organized criminality. This article formalizes both the model and the process, using practical applications to illustrate its powerful capabilities. This model has a general application and can be transposed to other fields of forensic science facing similar difficulties.

The Arcuated Lintel and the "Serlian Motif". Imperial Identity, Architectural and Symbolic Interactions in Ancient Rome

Essay on the origin, use and development of the arcuated lintel in ancient Rome and the configuration of the so– called ‘Serlian motif’. These architectural elements will be related to the architecture of prestige on its technical, functional, visual and symbolic sphere. Its depictions, in addition to buildings, can offer a rich repertory of images that speak about the relations between visual culture, religion and power. Furthermore, the analyzed motifs will become important elements of the Western cultural legacy for centuries. The analysis of these events will contribute to the comprehension of the role played by some resources of ancient Rome architecture of prestige and its success

Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases.

Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.

Forensic processing of false identity and travel documents to produce intelligence: a novel approach to assist in fighting organized crime

The production and use of false identity and travel documents in organized crime represent a serious and evolving threat. However, a case-by-case perspective, thus suffering from linkage blindness and a limited analysis capacity, essentially drives the present-day fight against this criminal problem. To assist in overcoming these limitations, a process model was developed using a forensic perspective. It guides the systematic analysis and management of seized false documents to generate forensic intelligence that supports strategic and tactical decision-making in an intelligence-led policing approach. The model is articulated on a three-level architecture that aims to assist in detecting and following-up on general trends, production methods and links between cases or series. Using analyses of a large dataset of counterfeit and forged identity and travel documents, it is possible to illustrate the model, its three levels and their contribution. Examples will point out how the proposed approach assists in detecting emerging trends, in evaluating the black market's degree of structure, in uncovering criminal networks, in monitoring the quality of false documents, and in identifying their weaknesses to orient the conception of more secured travel and identity documents. The process model proposed is thought to have a general application in forensic science and can readily be transposed to other fields of study.

Strategies and tools for preventing neurotoxicity: to test, to predict and how to do it

A change in paradigm is needed in the prevention of toxic effects on the nervous system, moving from its present reliance solely on data from animal testing to a prediction model mostly based on in vitro toxicity testing and in silico modeling. According to the report published by the National Research Council (NRC) of the US National Academies of Science, high-throughput in vitro tests will provide evidence for alterations in"toxicity pathways" as the best possible method of large scale toxicity prediction. The challenges to implement this proposal are enormous, and provide much room for debate. While many efforts address the technical aspects of implementing the vision, many questions around it need also to be addressed. Is the overall strategy the only one to be pursued? How can we move from current to future paradigms? Will we ever be able to reliably model for chronic and developmental neurotoxicity in vitro? This paper summarizes four presentations from a symposium held at the International Neurotoxicology Conference held in Xi"an, China, in June 2011. A. Li reviewed the current guidelines for neurotoxicity and developmental neurotoxicity testing, and discussed the major challenges existing to realize the NCR vision for toxicity testing. J. Llorens reviewed the biology of mammalian toxic avoidance in view of present knowledge on the physiology and molecular biology of the chemical senses, taste and smell. This background information supports the hypothesis that relating in vivo toxicity to chemical epitope descriptors that mimic the chemical encoding performed by the olfactory system may provide a way to the long term future of complete in silico toxicity prediction. S. Ceccatelli reviewed the implementation of rodent and human neural stem cells (NSCs) as models for in vitro toxicity testing that measures parameters such as cell proliferation, differentiation and migration. These appear to be sensitive endpoints that can identify substances with developmental neurotoxic potential. C. Sun ol reviewed the use of primary neuronal cultures in testing for neurotoxicity of environmental pollutants, including the study of the effects of persistent exposures and/or in differentiating cells, which allow recording of effects that can be extrapolated to human developmental neurotoxicity.

Growth strategies of international companies in the emerging markets of South-East Europe

Työn tarkoituksena oli tutkia niitä tekijöitä jotka ovat vaikuttaneet kansainvälisten yritysten myynnin kasvuun Romaniassa, Bulgariassa, Serbiassa ja Sloveniassa. Tutkimusta varten haastateltiin neljää kansainvälisen yrityksen edustajaa sekä 16 kansainvälisen kaupan ammattilaista. Työn akateemisena viitekehyksenä käytettiin keskeisiä kansainvälisen liiketoiminnan teorioita sekä myynnin strategista viitekehystä. Johtopäätöksenä katsotaan, että menestyvillä yrityksillä on selvä kansainvälistymis-strategia, kansainvälinen organisaatio, konsultoiva myyntityyli ja resursseja investoida koulutukseen. Tarkastelun alla olevista maista etenkin Romaniasta ja Bulgarista löytyy liiketoiminta potentiaalia. Tutkimuksen johtopäätökset perustuvat laadullisiin ja määrällisiin tutkimusmenetelmiin ja ne on tarkoitettu palvemaan Tikkurila Oy:tä. Tutkimustuloksia on myös mahdollista soveltaa laajemmin samanlaisessa tutkimusympäristössä, kunhan tutkittavan liiketoimintaympäristön erityispiirteet ovat otetttu huomioon