Adressage et contrôle de nanosources optiques par plasmonique intégrée ou fibrée

Surface plasmon polariton (SPP) can confine light on subwavelength dimensions. Since they are not diffraction limited, they are of great interest for addressing and controlling optical nanosources. For example, a metal nanowire defines 1D plasmonic waveguide with a great potential for either addressing or coupling quantum emitters. Therefore, SPP opens great opportunities for integrated optical applications. However, SPP suffer from ohmic losses that jeopardize the applications of plasmonic components. In this context, we study the possibilities provided by an hybrid plasmonic-photonicstructure to couple efficiently an emitter to a fiber mode. Such a structure paves the way for fibered single photon nanosource or high resolution optical probe. In this thesis manuscript, we first study the coupling rate between a fluorescent molecule and a metallic nanowire thanks to Green’s dyad formalism. This leads us to distinguish the different relaxation channels and the enhancement of the energy transferred into the plasmonic guided mode by optimizing the shape of the guide (crystalline nano-wire,slow modes). Then, we investigate the energy propagation in a metal coated taperedoptical fiber. Finally, we achieve an optimal configuration for which more than 50% of the energy emitted by a quantum emitter laid on a substrat is transferred into an optical fiber.Les plasmons polaritons de surface, modes supportés par des nanostructures métalliques permettent de confiner la lumière à des échelles sub-longueurs d’onde. En s’affranchissant de la limite de diffraction, ces modes constituent des pistes intéressantes pour l’adressage et le contrôle de nanosources optiques (molécules, boites quantiques...). Par exemple, un nanofil métallique constitue un guide plasmonique unidimensionnel qui permet d’exciter une nanosource ou encore de coupler deux émetteurs avec des applications possibles pour la réalisation de composants nano-optiques intégrés. En revanche, la perte d’énergie dans le métal diminue la portée de ces dispositifs. Une stratégie consiste donc à travailler sur une configuration hybride : plasmonique et fibre optique, pour coupler efficacement l’émission de la nanosource à un mode de fibre. Ceci ouvre la voie à la réalisation d’une nanosource fibrée de manipulation aisée pouvant être utilisée comme source de photon unique pour la cryptographie quantique ou plus simplement comme une sonde de champ proche optique haute résolution.Après une étude des principaux canaux de relaxation d’une molécule fluorescente à proximité d’un guide plasmonique, nous discutons de l’optimisation du couplage entre l’émetteur et le guide plasmonique en jouant sur sa forme et la longueur d’onde d’émission. Ensuite, nous nous intéressons au comportement d’une structure hybride composée d’une fibre optique étirée et métallisée. Enfin, nous montrons que l’optimisation du transfert d’énergie d’une molécule fluorescente en présence de cette structure permet de collecter plus de 50% de l’énergie lumineuse d’un nano-émetteur posé sur un substrat vers une fibre optique par le truchement d’un plasmon

Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future

Incorporation of resident macrophages in engineered tissues: multiple cell type response to microenvironment controlled macrophage-laden gelatin hydrogels

The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, we developed an in-vitro model of interaction between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, Naive THP-1 monocytes, endothelial cells, and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. In order to mimic resident macrophages, THP-1 cells were encapsulated in the presence or absence of IL-4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in secretion of both pro and anti-inflammatory cytokines compared to M2 stimulation. We demonstrated that there is a distinct effect of encapsulated macrophages on the behavior of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation

Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation

The function of soft tissues is intricately linked to their connections with the other systems of the body such as circulation, nervous system, and immune system. The presence of resident macrophages in tissues provides a means to control tissue homeostasis and also a way to react to the physical/biological insults and tissue damage. Thus, incorporation of resident macrophage like phenotype-controlled macrophages in engineered tissues can improve their fidelity as model tissues and also improve their rate of integration and facilitate the resolution of inflammation for regenerative medicine applications. Herein, we demonstrate two potential ways to immunoassist the remodeling process of engineered soft tissues in three-dimensional (3-D) gelatin based hydrogels containing fibroblasts and/or endothelial cells: (i) with supplementation of interleukin-4 (IL-4) in the presence of macrophages and (ii) in tri-culture via naive monocytes or differentiated macrophages. The presence of IL-4 had a proliferative effect on fibroblasts, with a significant boosting effect on proliferation and cytokine secretion in the presence of differentiated macrophages with an upregulation of activin, interleukin-1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), creating a more stimulating microenvironment. The addition of IL-4 in endothelial cell/macrophage co-culture configuration improved the organization of the sprout-like structures, with a boost in proliferation at day 1 and with an upregulation of IL-6 and IL-1RA at the earliest stage in the presence of differentiated macrophages creating a favorable microenvironment for angiogenesis. In tri-culture conditions, the presence of monocytes or macrophages resulted in a denser tissue-like structure with highly remodeled hydrogels. The presence of differentiated macrophages had a boosting effect on the angiogenic secretory microenvironment, such as IL-6 and IL-8, without any additional cytokine supplementation. The presence of fibroblasts in combination with endothelial cells also had a significant effect on the secretion of angiopoietin. Our results demonstrate that incorporation of macrophages in a resident macrophage function and their phenotype control have significant effects on the maturation and cytokine microenvironment of 3-D multiple cell type-laden hydrogels, which can be harnessed for better integration of implantable systems and for more physiologically relevant in vitro tissue models with an immune component

Increased birth rank of homosexual males: disentangling the older brother effect and sexual antagonism hypothesis

Male homosexual orientation remains a Darwinian paradox, as there is no consensus on its evolutionary (ultimate) determinants. One intriguing feature of homosexual men is their higher male birth rank compared to heterosexual men. This can be explained by two non-exclusive mechanisms: an antagonistic effect (AE), implying that more fertile women have a higher chance of having a homosexual son and to produce children with a higher mean birth rank, or a fraternal birth effect (FBOE), where each additional older brother increases the chances for a male embryo to develop a homosexual orientation due to an immunoreactivity process. However, there is no consensus on whether both FBOE and AE are present in human populations, or if only one of these mechanisms is at play with its effect mimicking the signature of the other mechanism. An additional sororal birth order effect (SBOE) has also recently been proposed. To clarify this situation, we developed theoretical and statistical tools to study FBOE and AE independently or in combination, taking into account all known sampling biases. These tools were applied on new individual data, and on various available published data (two individual datasets, and all relevant aggregated data). Support for FBOE was apparent in aggregated data, with the FBOE increasing linearly with fertility. The FBOE was also supported in two individual datasets. An SBOE is generated when sampling in presence of FBOE, suggesting that controlling for FBOE is required to avoid artefactual SBOE. AE was not supported in individual datasets, including the analysis of the extended maternal family. The evolutionary implications of these findings are discussed

Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation

The immediate tissue microenvironment of implanted biomedical devices and engineered tissues is highly influential on their long term fate and efficacy. The creation of a long-term anti-inflammatory microenvironment around implants and artificial tissues can facilitate their integration. Macrophages are highly plastic cells that define the tissue reactions on the implanted material. Local control of macrophage phenotype by long-term fixation of their healing activities and suppression of inflammatory reactions are required to improve implant acceptance. Herein, we describe the development of a cytokine cocktail (M2Ct) that induces stable M2-like macrophage phenotype with significantly decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine secretion profile. The positive effect of the M2Ct was shown in an in vitro wound healing model; where M2Ct facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have shown that the M2Ct phenotype is stable for 12 days. However, in the absence of M2Ct in the medium macrophages underwent rapid pro-inflammatory re-programming upon IFNg stimulation. Therefore, loading and release of the cytokine cocktail from a self-standing, transferable gelatin/tyraminated hyaluronic acid based release system was developed to stabilize macrophage phenotype for in vivo applications in implantation and tissue engineering. The M2Ct cytokine cocktail retained its anti-inflammatory activity in controlled release conditions. Our data indicate that the direct application of a potent M2 inducing cytokine cocktail in a transferable release system can significantly improve the long term functionality of biomedical devices by decreasing pro-inflammatory cytokine secretion and increasing the rate of wound healing

Il meticciato nell'Italia contemporanea. Storia, memorie e cultura di massa.

L'idea diffusa degli "italiani brava gente" e della diversit\ue0 della nostra storia rispetto alla storia USA, segnata da razzismo istituzionale, si fonda sul silenziamento del passato coloniale e razzista italiano. Il ripudio della categoria di razza da parte dell'Italia repubblicana e la smentita scientifica dell'esistenza biologica della categoria non hanno cancellato la presenza della razza, formazione storico-culturale che paradossalmente esiste e non esiste. Priva di referenti oggettivi nella realt\ue0, la razza produce in essa effetti significativi, opera sia come categoria sociale e strumento di esclusione, sia come costruzione simbolica e istanza identitaria. A fronte del silenziamento del meticciato storico nell'uso pubblico della storia e nella memoria nazionali del secondo dopoguerra, il saggio sottolinea la presenza diffusa del meticciato nei prodotti della cultura di massa italiani contemporanei e ne indaga i significati con gli strumenti degli studi critici sulla razza e in prospettiva comparata tra Italia e Stati Uniti