Silanisation de polysaccharides en milieu liquide ionique et réactivité d’un organoalkoxysilane vis-à-vis de nucléophiles simples : vers des hydrogels injectables pour l’ingénierie tissulaire du cartilage

Tissue engineering is a real challenge for the treatment of cartilage pathologies. In this field, biomimetic hydrogels based on natural polymers are among the most commonly used matrices. A hydrogel made of silanized hydroxypropylmethylcellulose (HPMC-Si) is especially promising because it can be injected in cartilaginous lesions by minimally invasive surgery. However, the current synthesis of HPMC-Si is limited by the insolubility of hydroxypropylmethylcellulose (HPMC). This thesis work was focused on finding new synthesis conditions for the design of HPMC-Si hydrogel. In order to obtain a complete solubilization of HPMC and to improve its functionalization by the (3-glycidyloxypropyl) trimethoxysilane (GPTMS), the use of ionic liquids (IL), which are excellent solvents for polysaccharides, was undertaken. The beginning of this study was first devoted to the selection of an IL and then to the development of new reaction conditions. With these new conditions, higher silicon rates were obtained for HPMC modified in ionic liquid medium, however no hydrogel could be formed. The second part was therefore devoted to the synthesis of GPTMS 13C. Indeed, thanks to this radiolabeling, a structural characterization by 13C NMR of the HPMC-Si could be achieved. Finally, the reactivity in organic solvents of three organosilanes, including the GPTMS, was investigated toward nucleophiles representing the common functions found in natural polymers (e.g. -NH2, -OH, -SH). The results of this thesis have provided insights into the GPTMS reactivity in organic medium and thus paves the way to new conditions for the silanization of polysaccharides.

An Information Theoretic Approach to Automatic Query Expansion

International audience

Conceptual guidelines for the international expansion of SMEs from Curaçao

Internationalization and moving to new markets can create many opportunities for small businesses across the globe, but also presents a number of new challenges they will face, which may influence their competitive advantage in the global market -- Present paper aims to provide an internationalization guide for SMEs from Curaçao -- Also the determinants that can impact internationalization will be discussed -- In this paper, three widely researched internationalization models form the basis of the theoretical perspectives of this paper; the traditional Uppsala model, the Network model and the Linkage, Leverage and Learning model

Decline and re-expansion of an amphibian with high prevalence of chytrid fungus

The disease chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is a key driver of global amphibian declines. While chytridiomycosis can cause extinction, many susceptible species persist after an initial period of decline, albeit with reduced abundance and distribution. Emerging evidence indicates that amphibian abundance can recover within remnant populations, but to date, the capacity of amphibian populations to re-expand into historically occupied habitat has received limited research attention. We surveyed 145 sites in 2011 and 2012 to determine if populations of the whistling tree frog (Litoria verreauxii verreauxii) have re-expanded compared with historical data from 1975-1976, 1990 and 1996. L. v. verreauxii underwent a major range contraction likely caused by chytridiomycosis between the first two time periods. Populations have recently re-expanded, with 39 new sites colonised despite high prevalence of Bd. We suspect that changes in disease dynamics have resulted in the increased coexistence of L. v. verreauxii and Bd. Habitat attributes at sites that retained frogs for the duration of the study indicate that high quality habitat may contribute to buffering against population level effects of Bd. Colonised sites had more coarse woody debris, suggesting a possible habitat management strategy to encourage range expansion for this species. Given sufficient time and adequate source populations in high quality habitat, it is possible that other amphibian species may re-expand from chytridiomycosis-induced declines. This provides an impetus for the protection of historical, but currently unoccupied amphibian habitats and highlights the importance of maintaining high quality habitat to help species survive novel shocks such as pandemic diseases.

Air pollution and infant mortality: evidence from the expansion of natural gas infrastructure

We examine the impact of widespread adoption of natural gas as a source of fuel on infant mortality in Turkey, using variation across provinces and over time in the intensity of natural gas utilisation. Our estimates indicate that the expansion of natural gas infrastructure has resulted in a significant decrease in the rate of infant mortality. Specifically, a one-percentage point increase in natural gas intensity – measured by the rate of subscriptions to natural gas services – would cause the infant mortality rate to decrease by 4%, which would translate into approximately 348 infant lives saved in 2011 alone.

Enhanced Ex Vivo expansion of human hematopoietic progenitors on native and spin coated acellular matrices prepared from bone marrow stromal cells

The extracellular microenvironment in bone marrow (BM) is known to regulate the growth and differentiation of hematopoietic stem and progenitor cells (HSPC). We have developed cell-free matrices from a BM stromal cell line (HS-5), which can be used as substrates either in native form or as tissue engineered coatings, for the enhanced ex vivo expansion of umbilical cord blood (UCB) derived HSPC. The physicochemical properties (surface roughness, thickness, and uniformity) of native and spin coated acellular matrices (ACM) were studied using scanning and atomic force microscopy (SEM and AFM). Lineage-specific expansion of HSPC, grown on these substrates, was evaluated by immunophenotypic (flow cytometry) and functional (colony forming) assays. Our results show that the most efficient expansion of lineage-specific HSPC occurred on spin coated ACM. Our method provides an improved protocol for ex vivo HSPC expansion and it offers a system to study the in vivo roles of specific molecules in the hematopoietic niche that influence HSPC expansion.

Impact of oxygen levels on human hematopoietic stem and progenitor cell expansion

Oxygen levels are an important variable during the in vitro culture of stem cells. There has been increasing interest in the use of low oxygen to maximize proliferation and, in some cases, effect differentiation of stem cell populations. It is generally assumed that the defined pO2 in the incubator reflects the pO2 to which the stem cells are being exposed. However, we demonstrate that the pO2 experienced by cells in static culture can change dramatically during the course of culture as cell numbers increase and as the oxygen utilization by cells exceeds the diffusion of oxygen through the media. Dynamic culture (whereby the cell culture plate is in constant motion) largely eliminates this effect, and a combination of low ambient oxygen and dynamic culture results in a fourfold increase in reconstituting capacity of human hematopoietic stem cells compared with those cultured in static culture at ambient oxygen tension. Cells cultured dynamically at 5% oxygen exhibited the best expansion: 30-fold increase by flow cytometry, 120-fold increase by colony assay, and 11% of human CD45 engraftment in the bone marrow of NOD/SCID mice. To our knowledge, this is the first study to compare individual and combined effects of oxygen and static or dynamic culture on hematopoietic ex vivo expansion. Understanding and controlling the effective oxygen tension experienced by cells may be important in clinical stem cell expansion systems, and these results may have relevance to the interpretation of low oxygen culture studies.

Multiple dispersal vectors drive range expansion in an invasive marine species

The establishment and subsequent spread of invasive species is widely recognised as one of the most threatening processes contributing to global biodiversity loss. This is especially true for marine and estuarine ecosystems, which have experienced significant increases in the number of invasive species with the increase in global maritime trade. Understanding the rate and mechanisms of range expansion is therefore of significant interest to ecologists and conservation managers alike. Using a combination of population genetic surveys, eDNA plankton sampling and hydrodynamic modelling we examined the patterns of introduction of the predatory Northern Pacific seastar (Asterias amurensis) and pathways of secondary spread within southeast Australia. Genetic surveys across the invasive range reveal some genetic divergence between the two main invasive regions and no evidence of ongoing gene flow; a pattern that is consistent with the establishment of the second invasive region via a human-mediated translocation event. In contrast hydrodynamic modelling combined with eDNA plankton sampling demonstrated that the establishment of range expansion populations within a region is consistent with natural larval dispersal and recruitment. Our results suggest that both anthropogenic and natural dispersal vectors have played an important role in the range expansion of this species in Australia. The multiple modes of spread combined with high levels of fecundity and a long larval duration in A. amurensis suggests it is likely to continue its range expansion and significantly impact Australian marine ecosystems.

Pirates, Exiles, and Empire: English Seamen, Atlantic Expansion, and Jamaican Settlement, 1558-1658

A life of piracy offered marginal men a profession with a degree of autonomy, despite the brand of “outlaw” and the fear of prosecution. At various times throughout history, governments and crowned heads suspended much of their piracy prosecution, licensing men to work as “privateers” for the state, supplementing naval forces. This practice has a long history, but in sixteenth-century England, Elizabeth I (1558-1603) significantly altered this tradition. Recognizing her own weakness in effectively prosecuting these men and the profit they could contribute to the government, Elizabeth began incorporating pirates into the English naval corps in peacetime—not just in war. This practice increased English naval resources, income, and presence in the emerging Atlantic World, but also increased conflict with the powerful Spanish empire. By 1605, making peace with Spain, James VI/I (1603-1625) retracted Elizabeth’s privateering promotion, prompting an emigration of English seamen to the American outposts they had developed in the previous century. Now exiles, no longer beholden to the Crown, seamen reverted back to piracy. The Carolinas and Jamaica served as bases for these rover communities. In 1650, the revolutionary leader Oliver Cromwell (1649-1658) once again recognized the merits of such policies. Determined to demonstrate his authority and solidify his rule, Cromwell offered citizenship and state support to Caribbean exiles in exchange for their aiding of his navy in the taking of Spanish Jamaica. Official chartering of Port Royal, Jamaica served as reward for these men’s efforts and as the culmination of a century-long cycle of piracy legislation, creating one of England’s most lucrative colonies in the middle of a traditionally Spanish Caribbean empire. Through legal and diplomatic records, correspondence, and naval and demographic records from England and Spain, this dissertation explores early modern piracy/privateering policy and its impact on the development of the Atlantic World. European disputes and imperial competition converged in these piracy debates with significant consequences for the definitions of criminality and citizenship and for the development of Atlantic empire.

Standardised tobacco packaging:a health policy case study of corporate conflict expansion and adaptation

Objectives: To investigate opposition to standardised tobacco packaging in the UK. To increase understanding of how transnational corporations are adapting to changes in their access to policymakers precipitated by Article 5.3 of the Framework Convention on Tobacco Control (FCTC). Design: Case study web-based documentary analysis, using NVivo V.10. Examination of relationships between opponents of standardised packaging and transnational tobacco companies (TTCs) and of the volume, nature, transparency and timing of their activities. Setting: UK standardised packaging policy debate 2011-2013. Participants: Organisations selected on basis of opposition to, or facilitation thereof, standardised tobacco packaging in the UK; 422 associated documents. Results: Excluding tobacco manufacturing and packaging companies (n=12), 109 organisations were involved in opposing standardised packaging, 82 (75%) of which had a financial relationship with 1 or more TTC. These 82 organisations (43 actively opposing the measure, 39 facilitating opposition) were responsible for 60% of the 404 activities identified, including the majority of public communications and research production. TTCs were directly responsible for 28% of total activities, predominantly direct lobbying, but also financially underwrote third party research, communication, mass recruitment and lobbying. Active organisations rarely reported any financial relationship with TTCs when undertaking opposition activities. Conclusions: The multifaceted opposition to standardised packaging was primarily undertaken by third parties with financial relationships with major tobacco manufacturers. Low levels of transparency regarding these links created a misleading impression of diverse and widespread opposition. Countries should strengthen implementation of Article 5.3 of the FCTC by systematically requiring conflict of interest declarations from all organisations participating in political or media debates on tobacco control.

Le journalisme informatique au Québec : Expansion du journalisme ou nouveau territoire professionnel?

Le journalisme informatique est une pratique émergente qui consiste en l’emploi de méthodes et d’outils empruntés au domaine de l’informatique dans la cueillette, le traitement, l’analyse ou la présentation en ligne de l’information, dans le respect des valeurs fondamentales du journalisme (Diakopoulos, 2010). Cette recherche caractérise le journalisme informatique tel qu’il se pratique au Québec en 2015 au moyen d’une série d’entrevues semi-dirigées avec 30 participants : des praticiens, bien sûr, mais aussi des responsables des principales entreprises de presse où le journalisme informatique est pratiqué ou a été pratiqué, ainsi que des professionnels de l’informatique afin d’avoir un point de vue extérieur. Elle met notamment en relief deux attitudes à l’égard de cette pratique, attitudes qui s’expriment par un travail-frontière. Il y a, d’une part, les tenants d’une ségrégation entre le journalisme et l’informatique, et, d’autre part, les partisans d’une hybridation entre les deux disciplines. Pour ces derniers, le journalisme informatique occupe un territoire professionnel distinct, à la frontière du journalisme et de l’informatique. Cette recherche décrit de façon détaillée les motivations, les compétences et les activités des journalistes informatiques québécois et fait valoir qu’ils participent à une certaine « re-professionnalisation » du journalisme. Mots-clés : journalisme; informatique; technologie; journalisme informatique; journalisme de données; datajournalisme; journalisme assisté par ordinateur; professionnalisme; identité professionnelle; compétences professionnelles; travail-frontière; innovation en journalisme; Canada; Québec

Déterminants de la distribution subcellulaire et tissulaire de médicaments cationiques lysosomotropiques et leur effet antiprolifératif

La concentration des médicaments cationiques dans les compartiments acides de la cellule est bien connue. Nous avons tenté d’expliquer davantage certains aspects encore inconnus au sujet de cette réaction cellulaire. En premier lieu, nous avons étudié l’accumulation subcellulaire et in vivo d’un médicament cationique fluorescent, la quinacrine, dans un modèle murin. L’accumulation cellulaire de la quinacrine dans les fibroblastes dermiques de souris induisait une inhibition du flux autophagique, ainsi qu’une lysosomogénèse. L’administration de la quinacrine in vivo démontrait une distribution hétérogène et une augmentation autophagique et lysosomale dans les poumons. En deuxième lieu, l’effet cytostatique et cytotoxique d’une série de médicaments cationiques lysosomotropiques furent étudiés dans une série de lignées cellulaires. Une série de 6 triéthylamines substituées furent choisies afin d’étudier davantage l’effet cytostatique de l’ion trapping. L’accumulation du marqueur autophagique LC3 II, le marqueur apoptotique PARP1, la cytotoxicité, le cycle cellulaire et la fonction endocytose furent étudiés plus en détails dans la lignée tumorale U937. Chacun des médicaments cationiques démontrait un effet antiprolifératif significatif, mais aucun signe de cytotoxicité n’était observé à certains niveaux de concentrations. Un cotraitement avec les inhibiteurs de cholestérol, β-cyclodextrine et lovastatine, renversait partiellement l’effet antiprolifératif des amines. L’intensité de l’effet antiprolifératif induit par les médicaments cationiques est clairement prédite par leur puissance de l’inhibition du flux autophagique et par la liposolubilité. L’accumulation tissulaire de la quinacrine et l’effet cytostatique prédit par l’inhibition du flux autophagique et par la liposolubilité des amines substituées offre des possibilités d’application dans le domaine de l’oncologie et de la pharmacocinétique des nombreux médicaments concernés.