206 research outputs found

    Building a Resilient Coast. Climate Variability and Coastal Community Resilience: Developing and Testing a National Model of State-based Outreach

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    The Maine Sea Grant College Program, in partnership with the Oregon Sea Grant College Program, conducted a two-year NOAA-funded project: 1) to explore how climate variability and coastal hazards may be affecting our coastal regions and how these relate to coastal development in the two states; 2) to encourage and facilitate collaboration among and between decision makers and coastal property owners to determine and implement appropriate responses to climate variability on short and longer timescales; 3) to discover the barriers that targeted audiences in the states have to taking action to either prepare for or mitigate the effects of climate variability; and 4) to develop educational and informational materials and strategies concerning these issues. The ultimate goal of the project is to move behavior toward decisive action that results in coastal communities that are more resilient to climate variability at all scales. In Maine, two groups were targeted with these strategies and materials: coastal property owners (CPOs); and municipal elected and appointed officials, including local and regional planning agency personnel. For the purposes of this report, “coastal hazards” include shoreline erosion, sea-level rise, higher tides, increased storm severity, and coastal flooding. This technical report covers only the Maine component of the project

    Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide

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    Glioma stem cells (GSCs) from human glioblastomas (GBMs) are resistant to radiation and chemotherapy and may drive recurrence. Treatment efficacy may depend on GSCs, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype

    Computational Modeling for the Activation Cycle of G-proteins by G-protein-coupled Receptors

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    In this paper, we survey five different computational modeling methods. For comparison, we use the activation cycle of G-proteins that regulate cellular signaling events downstream of G-protein-coupled receptors (GPCRs) as a driving example. Starting from an existing Ordinary Differential Equations (ODEs) model, we implement the G-protein cycle in the stochastic Pi-calculus using SPiM, as Petri-nets using Cell Illustrator, in the Kappa Language using Cellucidate, and in Bio-PEPA using the Bio-PEPA eclipse plug in. We also provide a high-level notation to abstract away from communication primitives that may be unfamiliar to the average biologist, and we show how to translate high-level programs into stochastic Pi-calculus processes and chemical reactions.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

    Modeling Astrocytoma Pathogenesis <em>In Vitro</em> and <em>In Vivo</em> Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

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    Current astrocytoma models are limited in their ability to define the roles of oncogenic mutations in specific brain cell types during disease pathogenesis and their utility for preclinical drug development. In order to design a better model system for these applications, phenotypically wild-type cortical astrocytes and neural stem cells (NSC) from conditional, genetically engineered mice (GEM) that harbor various combinations of floxed oncogenic alleles were harvested and grown in culture. Genetic recombination was induced in vitro using adenoviral Cre-mediated recombination, resulting in expression of mutated oncogenes and deletion of tumor suppressor genes. The phenotypic consequences of these mutations were defined by measuring proliferation, transformation, and drug response in vitro. Orthotopic allograft models, whereby transformed cells are stereotactically injected into the brains of immune-competent, syngeneic littermates, were developed to define the role of oncogenic mutations and cell type on tumorigenesis in vivo. Unlike most established human glioblastoma cell line xenografts, injection of transformed GEM-derived cortical astrocytes into the brains of immune-competent littermates produced astrocytomas, including the most aggressive subtype, glioblastoma, that recapitulated the histopathological hallmarks of human astrocytomas, including diffuse invasion of normal brain parenchyma. Bioluminescence imaging of orthotopic allografts from transformed astrocytes engineered to express luciferase was utilized to monitor in vivo tumor growth over time. Thus, astrocytoma models using astrocytes and NSC harvested from GEM with conditional oncogenic alleles provide an integrated system to study the genetics and cell biology of astrocytoma pathogenesis in vitro and in vivo and may be useful in preclinical drug development for these devastating diseases

    Optical and Radio Properties of Extragalactic Sources Observed by the FIRST and SDSS Surveys

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    We discuss the optical and radio properties of 30,000 FIRST sources positionally associated with an SDSS source in 1230 deg2^2 of sky. The majority (83%) of the FIRST sources identified with an SDSS source brighter than r=21 are optically resolved. We estimate an upper limit of 5% for the fraction of quasars with broad-band optical colors indistinguishable from those of stars. The distribution of quasars in the radio flux -- optical flux plane supports the existence of the "quasar radio-dichotomy"; 8% of all quasars with i<18.5 are radio-loud and this fraction seems independent of redshift and optical luminosity. The radio-loud quasars have a redder median color by 0.08 mag, and a 3 times larger fraction of objects with red colors. FIRST galaxies represent 5% of all SDSS galaxies with r<17.5, and 1% for r<20, and are dominated by red galaxies. Magnitude and redshift limited samples show that radio galaxies have a different optical luminosity distribution than non-radio galaxies selected by the same criteria; when galaxies are further separated by their colors, this result remains valid for both blue and red galaxies. The distributions of radio-to-optical flux ratio are similar for blue and red galaxies in redshift-limited samples; this similarity implies that the difference in their luminosity functions, and resulting selection effects, are the dominant cause for the preponderance of red radio galaxies in flux-limited samples. We confirm that the AGN-to-starburst galaxy number ratio increases with radio flux, and find that radio emission from AGNs is more concentrated than radio emission from starburst galaxies (abridged).Comment: submitted to AJ, color gif figures, PS figures available from [email protected]

    In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

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    RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions

    Validación de un documento de Word bajo la norma NTC1486 a partir de la metadata

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    Investigación TecnológicaEn el presente documento se encuentra contemplado el fundamento teórico de los tipos de datos y de los modelos de datos que se manejan en la actualidad, así como la web semántica y aspectos de ingeniería de software requeridos para la construcción de un prototipo de software que automatice el proceso de extracción de metadatos en un documento de Word, validando que la información contenida en este cumpla con la NTC 1486 en su totalidad, siendo una herramienta que facilite el proceso de calificación y caracterización de trabajos de grado y documentos de tipo investigativo. Esta investigación tiene un impacto dentro de la comunidad investigativa en la medida en que genera un prototipo de software que facilita el proceso de revisión de documentos investigativos en construcción.Glosario RESUMEN INTRODUCCIÓN 1.JUSTIFICACIÓN 2. PLANTEAMIENTO DEL PROBLEMA 3. OBJETIVO GENERAL 4. MARCO TEÓRICO 5. MARCO CONCEPTUAL 6. ESTADO DEL ARTE 7. METODOLOGÍA 8. RESULTADOS 9. CONCLUSIONES 10. TRABAJOS FUTUROS 11. BIBLIOGRAFÍAPregradoIngeniero de Sistema

    Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis

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    Glioblastoma (GBM) genomes feature recurrent genetic alterations that dysregulate core intracellular signaling pathways, including the G1/S cell cycle checkpoint and the MAPK and PI3K effector arms of receptor tyrosine kinase (RTK) signaling. Elucidation of the phenotypic consequences of activated RTK effectors is required for the design of effective therapeutic and diagnostic strategies

    Caries risk documentation and prevention : eMeasures for dental electronic health records

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    BACKGROUND: Longitudinal patient level dataavailable in the electronic health record (EHR)allows for the development, implementation, and validations of dental quality measures (eMeasures). Objective We report the feasibility and validity of implementing two eMeasures. The eMeasures determined the proportion of patients receiving a caries risk assessment (eCRA) and corresponding appropriate risk-based preventative treatments for patients at elevated risk of caries (appropriateness of care [eAoC]) in two academic institutions and one accountable care organization, in the 2019 reporting year. METHODS: Both eMeasures define the numerator and denominator beginning at the patient level, populations’ specifications, and validated the automated queries. For eCRA, patients who completed a comprehensive or periodic oral evaluation formed the denominator, and patients of any age who received a CRA formed the numerator. The eAoC evaluated the proportion of patients at elevated caries risk who received the corresponding appropriate risk-based preventative treatments. RESULTS: EHR automated queries identified in three sites 269,536 patients who met the inclusion criteria for receiving a CRA. The overall proportion of patients who received a CRA was 94.4% (eCRA). In eAoC, patients at elevated caries risk levels (moderate, high, or extreme) received fluoride preventive treatment ranging from 56 to 93.8%. For patients at high and extreme risk, antimicrobials were prescribed more frequently site 3 (80.6%) than sites 2 (16.7%) and 1 (2.9%). CONCLUSION: Patient-level data available in the EHRs can be used to implement process-ofcare dental eCRA and AoC, eAoC measures identify gaps in clinical practice. EHR-based measures can be useful in improving delivery of evidence-based preventative treatments to reduce risk, prevent tooth decay, and improve oral health.U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research.http://www.thieme.com/books-main/clinical-informatics/product/4433-aci-applied-clinical-informaticsDental Management Science
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