106 research outputs found

    Polytype control of spin qubits in silicon carbide

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    Crystal defects can confine isolated electronic spins and are promising candidates for solid-state quantum information. Alongside research focusing on nitrogen vacancy centers in diamond, an alternative strategy seeks to identify new spin systems with an expanded set of technological capabilities, a materials driven approach that could ultimately lead to "designer" spins with tailored properties. Here, we show that the 4H, 6H and 3C polytypes of SiC all host coherent and optically addressable defect spin states, including spins in all three with room-temperature quantum coherence. The prevalence of this spin coherence shows that crystal polymorphism can be a degree of freedom for engineering spin qubits. Long spin coherence times allow us to use double electron-electron resonance to measure magnetic dipole interactions between spin ensembles in inequivalent lattice sites of the same crystal. Together with the distinct optical and spin transition energies of such inequivalent spins, these interactions provide a route to dipole-coupled networks of separately addressable spins.Comment: 28 pages, 5 figures, and supplementary information and figure

    MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma

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    Half of high-risk neuroblastoma patients have MYCN amplification. Here, the authors show that MYCN induces fatty acid uptake and synthesis to support neuroblastoma and inhibition of a fatty acid transporter impairs tumor progression in preclinical models.Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and pharmacological SLC27A2 inhibition selectively suppresses tumor growth, prolongs animal survival, and exerts synergistic anti-tumor effects when combined with conventional chemotherapies in multiple preclinical NB models. This study identifies FA uptake as a critical metabolic dependency for MYCN-amplified tumors. Inhibiting FA uptake is an effective approach for improving current treatment regimens

    O projecto INTERFRUTA II e o seu papel no desenvolvimento da fruticultura na ilha Terceira

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    I Congresso de Fruticultura e Viticultura. Angra do Heroísmo 17-19 Abril 2008.Trabalho de investigação desenvolvido no projecto INTERFRUTA II, financiado pelo programa INTERREG III-B (05/MAC/3.1/A4).O Projecto INTERFRUTA II é um projecto desenvolvido nas Ilhas da Madeira, Tenerife (Canárias) e Terceira (Açores) destinado a contribuir para a promoção da fruticultura e viticultura nestas três regiões insulares, procurando uma melhoria dos conhecimentos sobre as culturas de macieiras, bananeiras, castanheiros e vinha. Englobando um estudo integrado que envolve a climatologia, fenologia, pedologia, problemas fitossanitários, pragas-chave e a fauna auxiliar presente nas parcelas estudadas, distribuídas pela zona Norte e Sul da Ilha, aplicando técnicas que contribuam decisivamente para o conhecimento e procura de soluções inovadoras que conduzam ao acréscimo do rendimento dos produtores e a uma menor utilização e aplicação de pesticidas. Para atingir estes objectivos numa fase inicial realizaram-se 160 inquéritos aos produtores e foi possível a identificação, através de SIG, das áreas de produção frutícola da Ilha. Para a análise dos factores climáticos ao nível da parcela, foram instaladas estações meteorológicas de leitura automática. Na parte relativa ao estudo da fenologia e produção para além da caracterização foi avaliado o impacto da polinização na taxa de vingamento dos frutos de macieira. Dentro dos problemas fitossanitários, na identificação das pragas-chave de cada cultura foi utilizada a observação visual de órgãos predefinidos e a monitorização através de armadilhas com feromona sexual e utilizadas placas cromotrópicas com cola. Nos fungos foi utilizada a observação visual e na prospecção de vírus e fitoplasmas utilizaram-se técnicas moleculares (ELISA) e PCR. Na prospecção da fauna auxiliar foi a técnica dos batimentos (ou pancadas) e a armadilha Malaise. Foi também realizado o levantamento das plantas auxiliares de produção e feita a sua identificação. Nas pragas-chave de cada uma das culturas, centrou-se a investigação sobre as mais importantes. A mosca-do-Mediterrâneo (C. capitata Wied.) foi uma delas, onde com o objectivo da sua monitorização, recorrendo aos SIG, foi montada uma rede de armadilhas em toda a ilha. Na bananeira, centrou-se todo o trabalho no gorgulho-da-bananeira (Cosmopolites sordidus Germar) e nas tripes. No castanheiro, no bichado-da-castanha (Cydia splendana Hubner) tendo sido avaliados os prejuízos que causa e conhecida a sua curva de voo através da sua monitorização usando armadilhas com feromona sexual. Na vinha, o míldio é a doença que mais contribuiu para a diminuição da produção de uva para vinho. Nas macieiras, os principais problemas decorrem da presença de aranhiço vermelho (Panonychus ulmi Koch), traça-oriental (Cydia molesta) e bichado (Cydia pomonella L.). Para a recolha e divulgação de toda a informação foi construída uma página Web do projecto, disponível na Internet (www.interfuta.angra.uac.pt) e uma base de dados fitossanitários de diagnóstico da Macaronésia (PROFITOMAC) para a identificação de todos os problemas que afectam estas culturas nos três arquipélagos em que o projecto de desenvolve. No âmbito das actividades do projecto foram ainda realizados alguns cursos de formação de curta duração para técnicos e produtores

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Unexpected differential metabolic responses of Campylobacter jejuni to the abundant presence of glutamate and fucose

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    Introduction: Campylobacter jejuni is the leading cause of foodborne bacterial enteritis in humans, and yet little is known in regard to how genetic diversity and metabolic capabilities among isolates affect their metabolic phenotype and pathogenicity. Objectives: For instance, the C. jejuni 11168 strain can utilize both l-fucose and l-glutamate as a carbon source, which provides the strain with a competitive advantage in some environments and in this study we set out to assess the metabolic response of C. jejuni 11168 to the presence of l-fucose and l-glutamate in the growth medium. Methods: To achieve this, untargeted hydrophilic liquid chromatography coupled to mass spectrometry was used to obtain metabolite profiles of supernatant extracts obtained at three different time points up to 24 h. Results: This study identified both the depletion and the production and subsequent release of a multitude of expected and unexpected metabolites during the growth of C. jejuni 11168 under three different conditions. A large set of standards allowed identification of a number of metabolites. Further mass spectrometry fragmentation analysis allowed the additional annotation of substrate-specific metabolites. The results show that C. jejuni 11168 upon l-fucose addition indeed produces degradation products of the fucose pathway. Furthermore, methionine was faster depleted from the medium, consistent with previously-observed methionine auxotrophy. Conclusions: Moreover, a multitude of not previously annotated metabolites in C. jejuni were found to be increased specifically upon l-fucose addition. These metabolites may well play a role in the pathogenicity of this C. jejuni strain.</p

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts. Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context

    Unexpectedly good spellers too. Associations and dissociations in reading and spelling French

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