567 research outputs found

    Solving the problem of the red eye

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    This software is designed to aid the clinician and the student in the differential diagnosis and treatment of a red eye. The program, consisting of three disks, was designed with HyperCard v. 1.2.5 for the Macintosh computer. Included in the program are objective and subjective findings, diagnostic tests, suggested treatment regimens and any contraindications, follow-up care and prognosis for forty-five etiologies of a red eye. One of the major features of this program allows the clinician to enter subjective and/or objective findings. Given these findings, the computer will provide a list of possible ocular conditions. From this list, the clinician can select one of the possibilities listed in which he/she feels is most appropriate for that particular patient. At this point the program will proceed to a stack of information specific for the selected condition. Once a choice has been made, the clinician always has the freedom of returning back to the list of possible ocular conditions

    Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer

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    Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer

    Experimental Everglades Virus Infection of Cotton Rats (Sigmodon hispidus)

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    We characterized Everglades virus infection of cotton rats from South Florida to validate their role as reservoir hosts in the enzootic transmission cycle

    Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism

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    © 2015, National Academy of Sciences. All rights reserved. The correlations between intramyocellular lipid (IMCL), decreased fatty acid oxidation (FAO), and insulin resistance have led to the hypothesis that impaired FAO causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling. Using a skeletal muscle-specific carnitine palmitoyltransferase-1 KO model, we show that prolonged and severe mitochondrial FAO inhibition results in increased carbohydrate utilization, along with reduced physical activity; increased circulating nonesterified fatty acids; and increased IMCLs, diacylglycerols, and ceramides. Perhaps more importantly, inhibition of mitochondrial FAO also initiates a local, adaptive response in muscle that invokes mitochondrial biogenesis, compensatory peroxisomal fat oxidation, and amino acid catabolism. Loss of its major fuel source (lipid) induces an energy deprivation response in muscle coordinated by signaling through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) to maintain energy supply for locomotion and survival. At the whole-body level, these adaptations result in resistance to obesity

    Lessons on Marine Protected Area Management in Northern Boreal Regions from the United States and Norway

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    In comparison to tropical reef systems, relatively few marine protected areas (MPA’s) exist in temperate or subarctic systems (e.g., North Pacific and North Atlantic) where species diversity is lower, abundance of individual species is often higher, and many fish species exhibit large amounts of movement during one or more of their life stages, especially as adults. A review of MPA’s in three northern areas—the Northwest Atlantic, Northeast Atlantic, and the Northeast Pacific—indicates that MPA’s can be useful management tools towards fisheries management and habitat conservation. However, achieving fishery goals, such as sustainable use of the fisheries resources, will depend on population abundance (relative to unfished conditions) and fish behavior and movement. For example, depleted populations of stationary species such as Atlantic sea scallops, Placopecten magellanicus, in the Northeast Atlantic and European lobster, Homarus grammarus, in the North Sea have responded positively to small MPA’s, whereas migratory offshore Atlantic cod, Gadus morhua, and Pacific cod, Gadus macrocephalus, apparently do not appear to benefit from closed areas because of movement into fished areas. Efficient habitat conservation requires detailed habitat mapping on relevant spatial scales. In northern boreal systems with large remote areas, this information is difficult and expensive to access. An alternative strategy of closing and protecting unexploited areas has worked well for the Aleutian Island coral closure area in Alaska. MPA’s can be effective fisheries management tools when the species to be protected have been depleted and show a small to moderate level of movement, and reproductive success is ensured. MPA’s can be effective at preserving habitat when the design is based on scientific information and takes into account the impact on the user groups.publishedVersio

    Where's the transformation? Unlocking the potential of technology-enhanced assessment

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    This study provides insight into technology-enhanced assessment (TEA) in diverse higher education contexts. The effectiveness of using technology for assessment in higher education is still equivocal, particularly in regard to evidence of improvements in student learning. This empirical research explores the affordances that technology offers to assessment for transforming student learning. A systematic literature review, guided by an analytic survey tool, was used to identify and interrogate recent scholarly articles published in 19 international journals. From a total of 1713 articles, 139 articles were identified as being focused on the use of technology for assessment. The analytic tool guided the rigorous exploration of the literature regarding the types of technology being used, the educational goal, the type of assessment, and the degree of “transformation” afforded by the technology. Results showed that, in the sample investigated, TEA is used most frequently for formative peer learning, as part of the task design and feedback stages of the assessment cycle, and that social media has been a major affordance for this. Results are discussed with a view to fostering a future culture of inquiry and scholarship around TEA in higher education

    Bringing metabolic networks to life: convenience rate law and thermodynamic constraints

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    BACKGROUND: Translating a known metabolic network into a dynamic model requires rate laws for all chemical reactions. The mathematical expressions depend on the underlying enzymatic mechanism; they can become quite involved and may contain a large number of parameters. Rate laws and enzyme parameters are still unknown for most enzymes. RESULTS: We introduce a simple and general rate law called "convenience kinetics". It can be derived from a simple random-order enzyme mechanism. Thermodynamic laws can impose dependencies on the kinetic parameters. Hence, to facilitate model fitting and parameter optimisation for large networks, we introduce thermodynamically independent system parameters: their values can be varied independently, without violating thermodynamical constraints. We achieve this by expressing the equilibrium constants either by Gibbs free energies of formation or by a set of independent equilibrium constants. The remaining system parameters are mean turnover rates, generalised Michaelis-Menten constants, and constants for inhibition and activation. All parameters correspond to molecular energies, for instance, binding energies between reactants and enzyme. CONCLUSION: Convenience kinetics can be used to translate a biochemical network – manually or automatically - into a dynamical model with plausible biological properties. It implements enzyme saturation and regulation by activators and inhibitors, covers all possible reaction stoichiometries, and can be specified by a small number of parameters. Its mathematical form makes it especially suitable for parameter estimation and optimisation. Parameter estimates can be easily computed from a least-squares fit to Michaelis-Menten values, turnover rates, equilibrium constants, and other quantities that are routinely measured in enzyme assays and stored in kinetic databases
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