203 research outputs found

    Iron oxidation at low temperature (260–500 C) in air and the effect of water vapor

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    The oxidation of iron has been studied at low temperatures (between 260 and 500 C) in dry air or air with 2 vol% H2O, in the framework of research on dry corrosion of nuclear waste containers during long-term interim storage. Pure iron is regarded as a model material for low-alloyed steel. Oxidation tests were performed in a thermobalance (up to 250 h) or in a laboratory furnace (up to 1000 h). The oxide scales formed were characterized using SEM-EDX, TEM, XRD, SIMS and EBSD techniques. The parabolic rate constants deduced from microbalance experiments were found to be in good agreement with the few existing values of the literature. The presence of water vapor in air was found to strongly influence the transitory stages of the kinetics. The entire structure of the oxide scale was composed of an internal duplex magnetite scale made of columnar grains and an external hematite scale made of equiaxed grains. 18O tracer experiments performed at 400 C allowed to propose a growth mechanism of the scale

    The functional characteristics of optogenetic gene therapy for vision restoration

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    Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with a complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally degenerated mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration

    A systematic comparison of optogenetic approaches to visual restoration

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    During inherited retinal degenerations (IRDs), vision is lost due to photoreceptor cell death; however, a range of optogenetic tools have been shown to restore light responses in animal models. Restored response characteristics vary between tools and the neuronal cell population to which they are delivered: the interplay between these is complex, but targeting upstream neurons (such as retinal bipolar cells) may provide functional benefit by retaining intraretinal signal processing. In this study, our aim was to compare two optogenetic tools: mammalian melanopsin (hOPN4) and microbial red-shifted channelrhodopsin (ReaChR) expressed within two subpopulations of surviving cells in a degenerate retina. Intravitreal adeno-associated viral vectors and mouse models utilising the Cre/lox system restricted expression to populations dominated by bipolar cells or retinal ganglion cells and was compared with non-targeted delivery using the chicken beta actin (CBA) promoter. In summary, we found bipolar-targeted optogenetic tools produced faster kinetics and flatter intensity-response relationships compared with non-targeted or retinal-ganglion-cell-targeted hOPN4. Hence, optogenetic tools of both mammalian and microbial origins show advantages when targeted to bipolar cells. This demonstrates the advantage of bipolar-cell-targeted optogenetics for vision restoration in IRDs. We therefore developed a bipolar-cell-specific gene delivery system employing a compressed promoter with the potential for clinical translation

    Formulation, characterisation and flexographic printing of novel Boger fluids to assess the effects of ink elasticity on print uniformity

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    Model elastic inks were formulated, rheologically characterised in shear and extension, and printed via flexography to assess the impact of ink elasticity on print uniformity. Flexography is a roll-to-roll printing process with great potential in the mass production of printed electronics for which understanding layer uniformity and the influence of rheology is of critical importance. A new set of flexo-printable Boger fluids was formulated by blending polyvinyl alcohol and high molecular weight polyacrylamide to provide inks of varying elasticity. During print trials, the phenomenon of viscous fingering was observed in all prints, with those of the Newtonian ink exhibiting a continuous striping in the printing direction. Increasing elasticity significantly influenced this continuity, disrupting it and leading to a quantifiable decrease in the overall relative size of the printed finger features. As such, ink elasticity was seen to have a profound effect on flexographic printing uniformity, showing the rheological tuning of inks may be a route to obtaining specific printed features

    ON-bipolar cell gene expression during retinal degeneration: Implications for optogenetic visual restoration.

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    PURPOSE: Retinal bipolar cells survive even in the later stages of inherited retinal degenerations (IRDs) and so are attractive targets for optogenetic approaches to vision restoration. However, it is not known to what extent the remodelling that these cells undergo during degeneration affects their function. Specifically, it is unclear if they are free from metabolic stress, receptive to adeno-associated viral vectors, suitable for opsin-based optogenetic tools and able to propagate signals by releasing neurotransmitter. METHODS: Fluorescence activated cell sorting (FACS) was performed to isolate labelled bipolar cells from dissociated retinae of litter-mates with or without the IRD mutation Pde6brd1/rd1 selectively expressing an enhanced yellow fluorescent protein (EYFP) as a marker in ON-bipolar cells. Subsequent mRNA extraction allowed Illumina® microarray comparison of gene expression in bipolar cells from degenerate to those of wildtype retinae. Changes in four candidate genes were further investigated at the protein level using retinal immunohistochemistry over the course of degeneration. RESULTS: A total of sixty differentially expressed transcripts reached statistical significance: these did not include any genes directly associated with native primary bipolar cell signalling, nor changes consistent with metabolic stress. Four significantly altered genes (Srm2, Slf2, Anxa7 & Cntn1), implicated in synaptic remodelling, neurotransmitter release and viral vector entry had immunohistochemical staining colocalising with ON-bipolar cell markers and varying over the course of degeneration. CONCLUSION: Our findings suggest relatively few gene expression changes in the context of degeneration: that despite remodelling, bipolar cells are likely to remain viable targets for optogenetic vision restoration. In addition, several genes where changes were seen could provide a basis for investigations to enhance the efficacy of optogenetic therapies

    The role of venture capitalists in the regional innovation ecosystem : a comparison of networking patterns between private and publicly backed venture capital funds

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    This paper empirically examines the development of social networks among venture capitalists and other professionals of the regional innovation ecosystem. Using an online survey of venture capitalists, the article considers their networking behaviour, focusing particularly on the distinction between those employed by private and those employed by publicly backed venture capital funds, and on the composition and spatial search of their networks. It investigates whether the frequency of interaction between venture capitalists and other members of the innovation ecosystem is associated with the nature of the venture capital funds. The paper provides the first detailed investigation of the relationship between different types of venture capitalists and other players of the innovation ecosystem such as universities incubators, research institutes, and business support organisations. The results show that there are distinctive differences within the two seemingly similar professional groups (private and public venture capitalists), and public dependence of the venture capital fund is strongly and significantly associated with higher volumes of interactions. The more publicly dependent a fund is, the more it interacts with other players of the innovation system. This finding has important implications for both academics and practitioners and suggests that publicly backed funds have a wider role to play in mobilising the different players of the regional innovation ecosystem

    Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

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    Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

    Customised bifurcating networks for mapping polymer dynamics in shear flows

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    Understanding the effect of varying shear stresses on individual polymer dynamics is important for applications such as polymer flooding, polymer induced drag reduction, or the design of DNA separation devices. In all cases, the individual polymer response to varying shear flows needs to be understood. A biomimetic design rule was recently proposed for bifurcating networks of rectangular channels of constant depth. These customised microfluidic geometries represent an elegant option to investigate, in a single device, multiple well-controlled shear stresses. Here, we present the first experimental realisation of such customised microfluidic networks, consisting of a series of rectangular microchannels with varying cross-sections, and we demonstrate their potential for testing polymer dynamics. We used microfluidic geometries optimised for both Newtonian and power-law fluids of constant or increasing average wall shear stress. The experimental model systems were tested using particle tracking velocimetry to confirm the theoretically predicted flow fields for shear-thinning xanthan gum solutions and a Newtonian fluid. Then, λ-DNA molecules were used as an example of shear sensitive polymers to test the effect of distinct shear stress distributions on their extension. By observing the conformation of individual molecules in consecutive channels, we demonstrate the effect of the varying imposed stresses. The results obtained are in good agreement with previous studies of λ-DNA extension under shear flow, validating the bifurcating network design. The customised microfluidic networks can thus be used as platforms for the investigation of individual polymer dynamics, in a large range of well-controlled local and cumulative shear stresses, using a single experiment

    Mycorrhization of fagaceae forests within mediterranean ecosystems

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    Mediterranean Fagaceae forests are valuable due to their ecological and socioeconomic aspects. Some profitable plant species, such as Castanea (timber and chestnut), Quercus (timber and cork), and Fagus (timber), encounter in this habitat the excellent edaphoclimatic conditions to develop. All Fagaceae plants are commonly associated to ECM fungal species, which are found in these forests in quite stable communities, mainly enriched in Russulaceae and Telephoraceae species. Currently, the Mediterranean Basin is considered as one of the global biodiversity hotspots, since many of their endemic plant species are not found elsewhere and are now under threat. Due to climate changing and introduction of disease agents, Fagaceae forests are facing an adaptation challenge to both biotic and abiotic threats. Although ECM communities are highly disturbed by climate factors and tree disease incidence, they could play an important role in increasing water availability to the plant and also improving plant tree defense against pathogens. Recent advances, namely, on genomics and transcriptomics, are providing tools for increasing the understanding of Fagaceae mycorrhization process and stress responses to biotic and abiotic stresses. Such studies can provide new information for the implementation of the most adequate management policies for protecting threaten Mediterranean forests.info:eu-repo/semantics/publishedVersio

    Contribution of spatially explicit models to climate change adaptation and mitigation plans for a priority forest habitat

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    Climate change will impact forest ecosystems, their biodiversity and the livelihoods they sustain. Several adaptation and mitigation strategies to counteract climate change impacts have been proposed for these ecosystems. However, effective implementation of such strategies requires a clear understanding of how climate change will influence the future distribution of forest ecosystems. This study uses maximum entropy modelling (MaxEnt) to predict environmentally suitable areas for cork oak (Quercus suber) woodlands, a socio-economically important forest ecosystem protected by the European Union Habitats Directive. Specifically, we use two climate change scenarios to predict changes in environmental suitability across the entire geographical range of the cork oak and in areas where stands were recently established. Up to 40 % of current environmentally suitable areas for cork oak may be lost by 2070, mainly in northern Africa and southern Iberian Peninsula. Almost 90 % of new cork oak stands are predicted to lose suitability by the end of the century, but future plantations can take advantage of increasing suitability in northern Iberian Peninsula and France. The predicted impacts cross-country borders, showing that a multinational strategy, will be required for cork oak woodland adaptation to climate change. Such a strategy must be regionally adjusted, featuring the protection of refugia sites in southern areas and stimulating sustainable forest management in areas that will keep long-term suitability. Afforestation efforts should also be promoted but must consider environmental suitability and land competition issues
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