86 research outputs found

    Low-loss, compact, spot-size-converter based vertical couplers for photonic integrated circuits

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    Funding: (i) European Union Horizon H2020 Programme (H2020-ICT27-2015, COSMICC No. 688516). (ii) European Union Research Council (ERC) starting grant 337508.In recent years, the monolithic integration of new materials such as SiN, Ge and LiNbO3 on silicon (Si) has become important to the Si photonics community due to the possibility of combining the advantages of both material systems. However, efficient coupling between the two different layers is challenging. In this work, we present a spot size converter based on a two-tier taper structure to couple the optical mode adiabatically between Si and SiN. The fabricated devices show a coupling loss as low as 0.058 dB  ±  0.01 dB per transition at 1525 nm. The low coupling loss between the Si to SiN, and vice versa, reveals that this interlayer transition occurs adiabatically for short taper lengths (<200 µm). The high refractive index contrast between the Si and SiN is overcome by matching the optical impedance. The proposed two-tier taper structure provides a new platform for optoelectronic integration and a route towards 3D photonic integrated circuits.PostprintPeer reviewe

    Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

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    Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects

    Human Bone Marrow-Derived Stem Cells Acquire Epithelial Characteristics through Fusion with Gastrointestinal Epithelial Cells

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    Bone marrow-derived mesenchymal stem cells (MSC) have the ability to differentiate into a variety of cell types and are a potential source for epithelial tissue repair. Several studies have demonstrated their ability to repopulate the gastrointestinal tract (GIT) in bone marrow transplanted patients or in animal models of gastrointestinal carcinogenesis where they were the source of epithelial cancers. However, mechanism of MSC epithelial differentiation still remains unclear and controversial with trans-differentiation or fusion events being evoked. This study aimed to investigate the ability of MSC to acquire epithelial characteristics in the particular context of the gastrointestinal epithelium and to evaluate the role of cell fusion in this process. In vitro coculture experiments were performed with three gastrointestinal epithelial cell lines and MSC originating from two patients. After an 8 day coculture, MSC expressed epithelial markers. Use of a semi-permeable insert did not reproduce this effect, suggesting importance of cell contacts. Tagged cells coculture or FISH on gender-mismatched cells revealed clearly that epithelial differentiation resulted from cellular fusion events, while expression of mesenchymal markers on fused cells decreased over time. In vivo cell xenograft in immunodeficient mice confirmed fusion of MSC with gastrointestinal epithelial cells and self-renewal abilities of these fused cells. In conclusion, our results indicate that fusion could be the predominant mechanism by which human MSC may acquire epithelial characteristics when in close contact with epithelial cells from gastrointestinal origin . These results could contribute to a better understanding of the cellular and molecular mechanisms allowing MSC engraftment into the GIT epithelium

    Reciprocal influence of the p53 and the hypoxic pathways

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    When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1α stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1α and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed

    Long cavity photonic crystal laser in FDML operation using an akinetic reflective filter

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    A novel configuration of a Fourier domain mode locked (FDML) laser based on silicon photonics platform is presented in this work that exploits the narrowband reflection spectrum of a photonic crystal (PhC) cavity resonator. Configured as a linear Fabry-Perot laser, forward biasing of a p-n junction on the PhC cavity allowed for thermal tuning of the spectrum. The modulation frequency applied to the reflector equalled the inverse roundtrip time of the long cavity resulting in stable FDML operation over the swept wavelength range. An interferometric phase measurement measured the sweeping instantaneous frequency of the laser. The silicon photonics platform has potential for very compact implementation, and the electro-optic modulation method opens the possibility of modulation speeds far beyond those of mechanical filters

    Yersinia effector protein (YopO)-mediated phosphorylation of host gelsolin causes calcium-independent activation leading to disruption of actin dynamics.

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    Pathogenic Yersinia bacteria cause a range of human diseases. To modulate and evade host immune systems, these yersiniae inject effector proteins into host macrophages. One such protein, the serine/threonine kinase YopO (YpkA in Yersinia pestis), uses monomeric actin as bait to recruit and phosphorylate host actin polymerization-regulating proteins, including the actin-severing protein gelsolin, to disrupt actin filaments and thus impair phagocytosis. However, the YopO phosphorylation sites on gelsolin and the consequences of YopO-mediated phosphorylation on actin remodeling have yet to be established. Here we determined the effects of YopO-mediated phosphorylation on gelsolin and identified its phosphorylation sites by mass spectrometry. YopO phosphorylated gelsolin in the linker region between gelsolin homology domains G3 and G4, which, in the absence of calcium, are compacted but adopt an open conformation in the presence of calcium, enabling actin binding and severing. Using phosphomimetic and phosphodeletion gelsolin mutants, we found that YopO-mediated phosphorylation partially mimics calcium-dependent activation of gelsolin, potentially contributing to a reduction in filamentous actin and altered actin dynamics in phagocytic cells. In summary, this work represents the first report of the functional outcome of serine/threonine phosphorylation in gelsolin regulation and provides critical insight into how YopO disrupts normal gelsolin function to alter host actin dynamics and thus cripple phagocytosis
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