51 research outputs found

    The Electrode-Ferroelectric Interface as the Primary Constraint on Endurance and Retention in HZO-Based Ferroelectric Capacitors

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    Ferroelectric hafnium-zirconium oxide is one of the most relevant CMOS-compatible materials for next-generation, non-volatile memory devices. Nevertheless, performance reliability remains an issue. With TiN electrodes (the most reported electrode material), Hf-Zr-based ferroelectric capacitors struggle to provide reliable retention due to electrode-ferroelectric interface interactions. Although Hf-Zr-based ferroelectric capacitors are fabricated with other electrodes, the focus is predominantly directed toward obtaining a large ferroelectric response. The impact of the electrodes on data retention for these ferroelectrics remains underreported and greater insight is needed to improve device reliability. Here, a comprehensive set of electrodes are evaluated with emphasis on the core ferroelectric memory reliability metrics of endurance, retention, and imprint. Metal-ferroelectric-metal capacitors comprised of a Hf0.5Zr0.5O2 layer deposited between different combinations of nitride (TiN, TiAlN, and NbN), pure metal (W), and oxide (MoO2, RuO2, and IrO2) top and bottom electrodes are fabricated for the investigation. From the electrical, physical, and structural analysis, the low reactivity of the electrode with the ferroelectric is found to be key for improved reliability of the ferroelectric capacitor. This understanding of interface properties provides necessary insight for the broad implementation of Hf-Zr-based ferroelectrics in memory technology and, overall, boosts the development of next-generation memories

    Insights from Amphioxus into the Evolution of Vertebrate Cartilage

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    Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

    Ovatoxin-a and Palytoxin Accumulation in Seafood in Relation to Ostreopsis cf. ovata Blooms on the French Mediterranean Coast

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    Dinoflagellates of the genus Ostreopsis are known to cause (often fatal) food poisoning in tropical coastal areas following the accumulation of palytoxin (PLTX) and/or its analogues (PLTX group) in crabs, sea urchins or fish. Ostreopsis spp. occurrence is presently increasing in the northern to north western Mediterranean Sea (Italy, Spain, Greece and France), probably in response to climate change. In France, Ostreopsis. cf. ovata has been associated with toxic events during summer 2006, at Morgiret, off the coast of Marseille, and a specific monitoring has been designed and implemented since 2007. Results from 2008 and 2009 showed that there is a real danger of human poisoning, as these demonstrated bioaccumulation of the PLTX group (PLTX and ovatoxin-a) in both filter-feeding bivalve molluscs (mussels) and herbivorous echinoderms (sea urchins). The total content accumulated in urchins reached 450 µg PLTX eq/kg total flesh (summer 2008). In mussels, the maximum was 230 µg eq PLTX/kg (summer 2009) compared with a maximum of 360 µg found in sea urchins during the same period at the same site. This publication brings together scientific knowledge obtained about the summer development of Ostreopsis spp. in France during 2007, 2008 and 2009

    The caveolae‐associated coiled‐coil protein, NECC2, regulates insulin signalling in Adipocytes

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    Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane‐binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2 (NECC2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC2 expression increased during adipogenesis. Furthermore, NECC2 co‐immunoprecipitated with caveolin‐1 (CAV1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC2 overexpression enhanced insulin‐activated Akt phosphorylation, whereas NECC2 downregulation impaired insulin‐induced phosphorylation of Akt and ERK2. Finally, an up‐regulation of NECC2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.La disfunción de los adipocitos en la obesidad se asocia comúnmente con la alteración de la señalización de la insulina en los adipocitos y la resistencia a la insulina. La señalización de la insulina se ha asociado con las caveolas, que están recubiertas por grandes complejos de proteínas de caveolina y cavina, junto con proteínas con propiedades de remodelación y unión a la membrana. Aquí, analizamos la regulación y la función de un componente de las caveolas involucrado en la señalización del factor de crecimiento en las células neuroendocrinas, la proteína 2 neuroendocrina de espiral larga (NECC 2 ) , en los adipocitos. Los estudios en células 3T3‐L1 mostraron que la expresión de NECC 2 aumentó durante la adipogénesis. Además, NECC 2 co‐inmunoprecipitado con caveolina‐1 ( CAV1) y mostró un patrón de distribución similar al de los componentes de las caveolas adipocitarias, CAV 1, Cavin1, el receptor de insulina y la actina cortical. Curiosamente, la sobreexpresión de NECC 2 mejoró la fosforilación de Akt activada por insulina, mientras que la regulación negativa de NECC 2 perjudicó la fosforilación de Akt y ERK 2 inducida por insulina . resistencia a la insulina. Este efecto también se observó en adipocitos 3T3‐L1 expuestos a hiperglucemia/hiperinsulinemia. En general, el presente estudio identifica NECC2 como un componente de las caveolas de los adipocitos que se regula en respuesta a la obesidad y las complicaciones metabólicas asociadas, y respalda la contribución de esta proteína como un andamio molecular que modula la transducción de señales de insulina en estos microdominios de membrana

    Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

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    International audienceThe worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary car-cinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low-and high-grade lung neuroendocrine neoplasms

    The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

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    Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk).We make site-level summary data available alongside this article. The full database will be publicly available in 2015

    Transitions from reproductive systems governed by two self-incompatible Loci to one in fungi.

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    Self-incompatibility (SI), a reproductive system broadly present in plants, chordates, fungi, and protists, might be controlled by one or several multiallelic loci. How a transition in the number of SI loci can occur and the consequences of such events for the population's genetics and dynamics have not been studied theoretically. Here, we provide analytical descriptions of two transition mechanisms: linkage of the two SI loci (scenario 1) and the loss of function of one incompatibility gene within a mating type of a population with two SI loci (scenario 2). We show that invasion of populations by the new mating type form depends on whether the fitness of the new type is lowered, and on the allelic diversity of the SI loci and the recombination between the two SI loci in the starting population. Moreover, under scenario 1, it also depends on the frequency of the SI alleles that became linked. We demonstrate that, following invasion, complete transitions in the reproductive system occurs under scenario 2 and is predicted only for small populations under scenario 1. Interestingly, such events are associated with a drastic reduction in mating type number

    The Genomic Signature of Population Reconnection Following Isolation: From Theory to HIV

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    Ease of worldwide travel provides increased opportunities for organisms not only to colonize new environments but also to encounter related but diverged populations. Such events of reconnection and secondary contact of previously isolated populations are widely observed at different time scales. For example, during the quaternary glaciation, sea water level fluctuations caused temporal isolation of populations, often to be followed by secondary contact. At shorter time scales, population isolation and reconnection of viruses are commonly observed, and such events are often associated with epidemics and pandemics. Here, using coalescent theory and simulations, we describe the temporal impact of population reconnection after isolation on nucleotide differences and the site frequency spectrum, as well as common summary statistics of DNA variation. We identify robust genomic signatures of population reconnection after isolation. We utilize our development to infer the recent evolutionary history of human immunodeficiency virus 1 (HIV-1) in Asia and South America, successfully retrieving the successive HIV subtype colonization events in these regions. Our analysis reveals that divergent HIV-1 subtype populations are currently admixing in these regions, suggesting that HIV-1 may be undergoing a process of homogenization, contrary to popular belief
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