75 research outputs found

    A global transcriptional network connecting noncoding mutations to changes in tumor gene expression.

    Get PDF
    Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration. Collectively, the noncoding loci converge on a set of core pathways, permitting a classification of tumors into pathway-based subtypes. The somatic eQTL network is disrupted in 88% of tumors, suggesting widespread impact of noncoding mutations in cancer

    Speech-driven facial animation with realistic dynamics

    Full text link

    Anålisis Comparativo del Posicionamiento Preciso Utilizando el Receptor de Bajo Costo GNSS ZED-F9P en Conjunto con la Antena BEIBT300 y Diferentes Modelos de Antena de Orden Geodésico

    Get PDF
    Con el avance de la Geodesia y la mejora de las especificaciones tĂ©cnicas de los receptores de bajo costo, los GNSS abren nuevas alternativas para investigar las capacidades tĂ©cnicas y rendimiento real que proveen este tipo de receptores para diferentes propĂłsitos geodĂ©sicos. En este contexto, la precisiĂłn alcanzable fue analizada usando el receptor de bajo costo GNSS ZED-F9P en conjunto con dos antenas de orden geodĂ©sico (ASH701975.01B y LEIAS10 NONE) y una antena de bajo costo (BEIBT300 NONE). Las observaciones GNSS fueron llevadas a cabo en un periodo de dos dĂ­as para cada modelo de antena. El anĂĄlisis fue realizado en tiempos de observaciĂłn de 12, 6 y 1 h, respectivamente. Estas observaciones fueron procesadas usando el mĂ©todo relativo estĂĄtico mediante la inclusiĂłn de una estaciĂłn de referencia continua del Instituto Nacional de EstadĂ­stica y GeografĂ­a, la cual estĂĄ localizada a una distancia aproximada de 4 km. Los resultados demuestran que la mayor precisiĂłn es lograda en un periodo de 12 h, con diferencias mĂ­nimas de 3 cm para la componente Norte y 33 cm para la vertical. En este sentido, la soluciĂłn menos precisa es obtenida en el periodo de 1 h resultando diferencias de 70 cm, 46 cm y 2.3 m para la componente Norte, Este y vertical respectivamente.   With advancements in geodesy and enhancements in the technical specifications of low-cost receivers, GNSS opens up new avenues for investigating the capabilities and performance provided by these receivers for various geodetic purposes. In this context, the precision achievable using the low-cost GNSS receiver ZED-F9P in conjunction with two geodetic antennas (ASH701975.01B and LEIAS10 NONE) and a low-cost antenna (BEIBT300 NONE) was analyzed. GNSS observations were conducted over a 2-day period for each antenna model. The analysis involved observation durations of 12, 6, and 1 h. These observations were processed using the static relative method alongside a continuously operating GNSS station from the Active National Geodetic Network of the National Institute of Statistics and Geography, situated at ~4 km. The results demonstrate that the highest precision was achieved over a 12 h period, with minimal differences of 3 cm for the North component and 33 cm for the vertical component. Conversely, the least accurate solution was obtained within a 1 h observation period, resulting in differences of up to 70 cm, 46 cm, and 2.3 m for the North, East, and vertical components, respectively

    Cell Walls of Saccharomyces cerevisiae Differentially Modulated Innate Immunity and Glucose Metabolism during Late Systemic Inflammation

    Get PDF
    BACKGROUND: Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS) from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. METHODS AND PRINCIPAL FINDINGS: Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic) on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK) and liver glycolysis (ENO2), and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS) down-regulation and ATP citrate lyase (ACLY) and malic enzyme (ME) up-regulations. However, MOS host's lower energy demands were sufficiently met through TCA citrate-derived energy, as indicated by CS up-regulation. CONCLUSIONS: MOS terminated inflammation earlier than VIRG and reduced glucose mobilization, thus representing a novel biological strategy to alleviate Salmonella-induced systemic inflammation in human and animal hosts

    Evidence for widespread hydrated minerals on asteroid (101955) Bennu

    Get PDF
    Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 ”m and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 ”m) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth

    The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

    Get PDF
    The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

    Properties of Rubble-Pile Asteroid (101955) Bennu from OSIRIS-REx Imaging and Thermal Analysis

    Get PDF
    Establishing the abundance and physical properties of regolith and boulders on asteroids is crucial for understanding the formation and degradation mechanisms at work on their surfaces. Using images and thermal data from NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft, we show that asteroid (101955) Bennu's surface is globally rough, dense with boulders, and low in albedo. The number of boulders is surprising given Bennu's moderate thermal inertia, suggesting that simple models linking thermal inertia to particle size do not adequately capture the complexity relating these properties. At the same time, we find evidence for a wide range of particle sizes with distinct albedo characteristics. Our findings imply that ages of Bennu's surface particles span from the disruption of the asteroid's parent body (boulders) to recent in situ production (micrometre-scale particles)
    • 

    corecore