Surface Modification of Polydimethylsiloxane via Combined Aminolysis and Alcoholysis Generating Cell Adhesive and Antifouling Properties

Abstract Polydimethylsiloxane (PDMS) is an elastomeric polymer frequently used as implant material, for flexible tubing and in microfluidic devices. The pronounced hydrophobic surface of this unique material impedes many applications where a good wetting behavior is required. Consequentially, various ways of surface modifications have been used to introduce new properties. Plasma treatment is the most popular technique in this respect, but is not generally applicable, especially if hardly accessible surfaces are to be modified. A novel wet‐chemistry‐based modification scheme yielding an amino‐functionalized PDMS surface using a combined alcoholysis/aminolysis reaction is presented. Biological applications are exemplified by the conjugation of the RGD peptide, or polyethylene glycol (PEG) and heparin, yielding surfaces with cell‐adhesive or nonthrombogenic properties, respectively. The effect of subsequent conjugation with an adhesive peptide is tested in cell culture. Additionally, two antifouling surfaces generated by coupling heparin and polyethylene glycol respectively are shown to improve the materials resistance to platelet adhesion drastically while simultaneously preventing hydrophobic recovery of the PDMS surface. The findings provide a versatile means of surface functionalization of PDMS substrates and is suitable for many biomedical applications

Surface Modification of Polytetrafluoroethylene and Polycaprolactone Promoting Cell-Selective Adhesion and Growth of Valvular Interstitial Cells

Tissue engineering concepts, which are concerned with the attachment and growth of specific cell types, frequently employ immobilized ligands that interact preferentially with cell types of interest. Creating multicellular grafts such as heart valves calls for scaffolds with spatial control over the different cells involved. Cardiac heart valves are mainly constituted out of two cell types, endothelial cells and valvular interstitial cells. To have control over where which cell type can be attracted would enable targeted cell settlement and growth contributing to the first step of an engineered construct. For endothelial cells, constituting the outer lining of the valve tissue, several specific peptide ligands have been described. Valvular interstitial cells, representing the bulk of the leaflet, have not been investigated in this regard. Two receptors, the integrin α9β1 and CD44, are known to be highly expressed on valvular interstitial cells. Here, we demonstrate that by covalently grafting the corresponding peptide and polysaccharide ligand onto an erodible, polycaprolactone (PCL), and a non-degradable, polytetrafluoroethylene (PTFE), polymer, surfaces were generated that strongly support valvular interstitial cell colonization with minimal endothelial cell and reduced platelet adhesion. The technology for covalent binding of corresponding ligands is a key element towards tissue engineered cardiac valves for in vitro applications, but also towards future in vivo application, especially in combination with degradable scaffold material

Analytical modelling of a lateral dual gate MESFET for integrated circuit in SiC

International audienceThis paper presents a static analytical model derived from a lateral dual gate MESFET in SiC for which the gates have the particularity to be of different physical nature: the first gate is a Schottky barrier and the second gate is a bipolar junction. In order to build a design-kit dedicated to simulation, a spice model has been developed that includes an analytical model of the MESFET which takes into account especially the influence of the both gates on the channel conductivity. The model provides results with a good agreement with experimental measurements and continuous optimization processes allow having a better matching

Reprogramming for cardiac regeneration

Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle. Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades. The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here

L'identification électronique par RFID chez les volailles

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Topsoil characteristics of forests and lawns along an urban–rural gradient in the Paris region (France)

International audienceUrban soils are a crucial component of urban ecosystems, especially in public green spaces, because of the ecosystem services they provide (e.g. public recreation, urban cooling or water infiltration). In this study, we describe the chemical, physical and hydrostructural characteristics of 180 forest and lawn surface soil samples, taken along an urban-rural gradient in the Paris region. This was done in order to identify how these soils have been affected by urbanization. Forests and lawns are the main vegetation types found in this region and represent 21% and 22.2% of the territory's surface area, respectively. Many of the properties of urban forest soils differed from those of other sites (e.g. texture, organic carbon content, total nitrogen and carbonate contents), possibly because the urban forests are much older than the lawns and because of the legacy of the historical management of soils in this region (Haussmann period). Urban lawn soils were more compacted than urban forests, probably due to higher foot traffic. The effects of urbanization were, at times, confounded with other factors (e.g. sandier texture of urban forests), which suggests that surface soil characteristics were influenced by past urban planning. Finally, this study constitutes a baseline analysis for the monitoring of soil quality in the region

Céramiques languedociennes du haut Moyen Age (VIIe-XIe s.) : Etudes micro-régionales et essai de synthèse

International audienceRéunissant les contributions d'une vingtaine d'auteurs, cette étude présente un premier bilan sur la vaisselle en usage en Languedoc du VIIe au XIe s. Le mobilier est présenté sous forme de notices décrivant les contextes de découverte et proposant un essai de datation. L'étude s'achève par une tentative de synthèse dans la double perspective de la typo-chronologie et de la diffusion des productions. L'identification de plusieurs zones de production et l'approche de leurs aires de diffusion tendent à révéler l'existence d'un commerce régional, image venant contredire la vision traditionnelle d'un monde rural replié sur lui-même

Échanges et consommation

International audienceAls die Wissenschaftler zu Beginn der 80iger Jahre des 20. Jahrhunderts begannen sich vermehrt der Spätantike zu widmen, bestand eines der Hauptprobleme in der Datierung des Fundmaterials -Vorbedingung für jeglichen Fortschritt bei den Studien. In der Provence und im Languedoc machte die Studiengruppe CATHMA (Céramique de l’Antiquité tardive et du haut Moyen Âge) sich dies zur Aufgabe. Sie allein verbucht für sich an die fünfzehn Untersuchungen, die die Ausarbeitung eines typochronologischen Referenzrahmens zum Ziel hatten. Die Studien wurden von dem Grabungsboom dieser Jahre, sowohl in den Städten als auch auf dem Land begleitet, sie basierten demzufolge auf den neuesten Entdeckungen und steuerten im Gegenzug zur Verfeinerung der chronologischen Rahmen bei. Diese stratigraphisch dokumentierten Grabungen trugen wesentlich zu dem Aufschwung bei. Eine erste Auflage des Dictionnaire des Céramiques antiques räumte den spätantiken Keramikformen Südfrankreichs und den mediterranen Importwaren großen Raum ein, doch das Werk •unvollständig und inzwischen vergriffen •muss auf den neuesten Stand gebracht und neuaufgelegt werden, da die Erkenntnisse seitdem fortwährend aktualisiert wurden. Auch in der Region Rhône-Alpes konnte von einer Arbeitsgruppe ein typochronologischer Rahmen erarbeitet werden. Darüber hinaus wurden vor kürzerem und in einem weitergefassten geographischen Rahmen mehrere Untersuchungen zum Thema Schmuck durchgeführt. Diese Untersuchungen in Frankreich selbst wurden durch Studien in mehreren Regionen des Mittelmeerraumes von Tunesien bis in den Vorderen Orient ergänzt, wo zahlreiche Werkstätten, in denen Amphoren, Geschirr oder Glas hergestellt worden war, lokalisiert oder unter Berücksichtigung moderner Untersuchungstechniken erneut untersucht wurden. So können wir heute, zumindest bis zum 6. Jahrhundert, Datierungen mit einer Spanne von nur 50 oder sogar nur 25 Jahren vorschlagen. Danach werden die Bezugspunkte seltener und es steht noch viel Arbeit an, insbesondere um durch den systematischen Einsatz der Radiokarbondatierung zahlreiche Elemente zu untermauern und genauer zu bestimmen. Diese Verfeinerung der chronologischen Kriterien kennzeichnete eine entscheidende Etappe, die es den Studien ermöglichte die Phase der approximativen Interpretationen hinter sich zu lassen. Über die chronologischen Feinheiten hinaus, die die keramologischen Studien ermöglichten, ging es im Grunde viel mehr darum, sich die Frage nach der Verbreitung der Importe aus fernen Regionen und der regionalen Produkte zu stellen, und deren Vordringen und Zurückweichen zu verfolgen. So wird nach und nach eine Geschichte des Warentauschs erkennbar, die von den vorgefassten Meinungen und Verallgemeinerungen von einer rückläufigen Wirtschaft am Ende des Altertums nicht berücksichtigt wird.With the expansion of research on Late Antiquity in the early 80’, the question of the datation of finds was a task that could not be escaped, for the advancement of these studies. In Provence and Languedoc, on the credit of the CATHMA programme (Céramique de l’Antiquité tardive et du haut Moyen Âge) which had this ambition, about fifteen reports have been devoted to the finalization of a typochronological reference pattern. In connection with the development of urban excavations, and as well in the countryside, this activity could use new discoveries and in turn help to work out a fine dating pattern. The stratigraphical data given by these excavations constituted a decisive step. A preliminary Dictionnaire des Céramiques antiques gave a large place to these Late southern productions and to Mediterranean imports. The book is not complete and now out-of-print; it should be published again and reactualized with important new evidence. A collective project has been working also in Rhône-Alpes on a chronological typopological reference system and more recently several surveys, on a larger area, were carried out on adornments. This research had effects in several Mediterranean areas. From Tunisia to the Near East amphorae and pottery fabrics and glass workshops have been located or re-examined with the help of new methods of study. Consequently, from now on, it is possible to propose fine datations up to 50 years, even within a quarter of a century, at least until the 6th century. Markers get poor afterwards and there is still much to do, especially to confirm and determine a number of points, due to systematic radiocarbone datation. This improvement of chronological criteras allow to escape approximative interpretations. Outside pottery studies bringing precise datation, more basically one had to examine the distribution of distant imports as of regional products and to follow their ebb and flow. Thus a history of trade is gradually emerging, avoiding presuppositions and stereotypes of a weakened economy in Late Antiquity.Au début des années 1980, lorsque les recherches sur l’Antiquité tardive commencèrent à se développer, le problème de datation des vestiges matériels constituait une tâche incontournable, conditionnant tout avancement des études. En Provence et Languedoc, ce fut l’ambition du groupe CATHMA (Céramique de l’Antiquité tardive et du haut Moyen Âge), à l’actif duquel on compte une quinzaine d’études consacrées à l’élaboration d’un cadre de référence typochronologique. Cette activité accompagnait l’essor des chantiers de fouille, tant en ville qu’à la campagne, se nourrissait des découvertes les plus récentes et contribuait en retour à l’affinement des cadres de datation. Livrant une documentation stratigraphique, ces chantiers marquèrent une étape cruciale de cet essor. Un premier essai de Dictionnaire des Céramiques antiques donnait une large place à ces productions tardo-antiques du Midi ainsi qu’aux importations méditerranéennes mais l’ouvrage, incomplet et désormais épuisé, devra être réédité avec de substantielles mises à jour, imposées par l’affinement régulier des connaissances. En Rhône-Alpes aussi, une entreprise collective permit d’élaborer un cadre de référence chronotypologique, tandis que plus récemment et sur une plus grande aire géographique se développèrent plusieurs enquêtes sur le mobilier de parure. Ces recherches métropolitaines trouvèrent par la suite leurs prolongements dans plusieurs régions méditerranéennes, de la Tunisie au Proche-Orient où de nombreux ateliers, d’amphore, de vaisselle ou de verrerie, furent localisés ou revisités à la faveur des nouvelles techniques d’étude. Ainsi peut-on désormais proposer des datations allant parfois jusqu’au demi-siècle, voire même au quart de siècle près, tout au moins jusqu’au vie s. Les repères faiblissent ensuite et il reste beaucoup à faire, notamment pour étayer et préciser encore de nombreux éléments grâce à la systématisation des dates par radiocarbone. Cet affinement des critères chronologiques a marqué une étape décisive pour sortir les études des interprétations approximatives. Au-delà des raffinements chronologiques autorisés par les études céramologiques, il s’agissait, bien plus fondamentalement, de s’interroger sur la diffusion des importations lointaines autant que des productions régionales, d’en suivre le flux et le reflux. Ainsi apparaît peu à peu une histoire des échanges qui échappe aux présupposés et aux stéréotypes d’une économie en repli à la fin de l’Antiquité

Les princes et le pouvoir au Moyen Âge

La Bretagne ducale illustre l'ambiguïté d'une grande principauté, quasi rivale du royaume, et d'un prince qui se voudrait roi et qui s'arroge maint attribut de la souveraineté. Mais ailleurs, de I'Empire germanique à la péninsule ibérique, des principautés françaises au Milanais, surgissent des questions autour du thème fondamental du pouvoir, de ses fins et de ses moyens. Idéologie, hommes et finances, lignage, pays et peuple, image que veut donner le prince par ses tenues et ses résidences, rapports avec ses sujets, ses villes, sa noblesse et ses clercs, tels sont quelques-uns des points de vue que l'on trouvera présentés dans cet ouvrage. S'il n'est d'histoire que d'histoire de l'homme, dans sa chair comme dans ses comportements, le thème du prince et de son pouvoir dépasse de loin la sécheresse toute descriptive d'une histoire institutionnelle, pour devenir celle d'un homme mû tout entier par une ambition qu'il se doit de satisfaire au sein d'un « pays » et d'un peuple, qui lui en accordent ou non les moyens. Dépourvu de tout signe sacré et de tout attribut de souveraineté, le prince médiéval est le plus souvent étranger à la genèse monarchique de l'État moderne

Modulation of SLFN11 induces changes in DNA Damage response in breast cancer

Abstract Background Lack of Schlafen family member 11 (SLFN11) expression has been recently identified as a dominant genomic determinant of response to DNA damaging agents in numerous cancer types. Thus, several strategies aimed at increasing SLFN11 are explored to restore chemosensitivity of refractory cancers. In this study, we examined various approaches to elevate SLFN11 expression in breast cancer cellular models and confirmed a corresponding increase in chemosensitivity with using the most successful efficient one. As oncogenic transcriptomic downregulation is often driven by methylation of the promotor region, we explore the demethylation effect of 5-aza-2′-deoxycytidine (decitabine), on the SLFN11 gene. Since SLFN11 has been reported as an interferon inducible gene, and interferon is secreted during an active anti-tumor immune response, we investigated the in vitro effect of IFN-γ on SLFN11 expression in breast cancer cell lines. As a secondary approach to pick up cross talk between immune cells and SLFN11 expression we used indirect co-culture of breast cancer cells with activated PBMCs and evaluated if this can drive SLFN11 upregulation. Finally, as a definitive and specific way to modulate SLFN11 expression we implemented SLFN11 dCas9 (dead CRISPR associated protein 9) systems to specifically increase or decrease SLFN11 expression. Results After confirming the previously reported correlation between methylation of SLFN11 promoter and its expression across multiple cell lines, we showed in-vitro that decitabine and IFN-γ could increase moderately the expression of SLFN11 in both BT-549 and T47D cell lines. The use of a CRISPR-dCas9 UNISAM and KRAB system could increase or decrease SLFN11 expression significantly (up to fivefold), stably and specifically in BT-549 and T47D cancer cell lines. We then used the modified cell lines to quantify the alteration in chemo sensitivity of those cells to treatment with DNA Damaging Agents (DDAs) such as Cisplatin and Epirubicin or DNA Damage Response (DDRs) drugs like Olaparib. RNAseq was used to elucidate the mechanisms of action affected by the alteration in SLFN11 expression. In cell lines with robust SLFN11 promoter methylation such as MDA-MB-231, no SLFN11 expression could be induced by any approach. Conclusion To our knowledge this is the first report of the stable non-lethal increase of SLFN11 expression in a cancer cell line. Our results show that induction of SLFN11 expression can enhance DDA and DDR sensitivity in breast cancer cells and dCas9 systems may represent a novel approach to increase SLFN11 and achieve higher sensitivity to chemotherapeutic agents, improving outcome or decreasing required drug concentrations. SLFN11-targeting therapies might be explored pre-clinically to develop personalized approaches