233 research outputs found

    Coupling interactive fire with atmospheric composition and climate in the UK Earth System Model

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    Fire constitutes a key process in the Earth system (ES), being driven by climate as well as affecting the climate by changing atmospheric composition and impacting the terrestrial carbon cycle. However, studies on the effects of fires on atmospheric composition, radiative forcing and climate have been limited to date, as the current generation of ES models (ESMs) does not include fully atmosphere–composition–vegetation coupled fires feedbacks. The aim of this work is to develop and evaluate a fully coupled fire–composition–climate ES model. For this, the INteractive Fires and Emissions algoRithm for Natural envirOnments (INFERNO) fire model is coupled to the atmosphere-only configuration of the UK's Earth System Model (UKESM1). This fire–atmosphere interaction through atmospheric chemistry and aerosols allows for fire emissions to influence radiation, clouds and generally weather, which can consequently influence the meteorological drivers of fire. Additionally, INFERNO is updated based on recent developments in the literature to improve the representation of human and/or economic factors in the anthropogenic ignition and suppression of fire. This work presents an assessment of the effects of interactive fire coupling on atmospheric composition and climate compared to the standard UKESM1 configuration that uses prescribed fire emissions. Results show a similar performance when using the fire–atmosphere coupling (the “online” version of the model) when compared to the offline UKESM1 that uses prescribed fire. The model can reproduce observed present-day global fire emissions of carbon monoxide (CO) and aerosols, despite underestimating the global average burnt area. However, at a regional scale, there is an overestimation of fire emissions over Africa due to the misrepresentation of the underlying vegetation types and an underestimation over equatorial Asia due to a lack of representation of peat fires. Despite this, comparing model results with observations of CO column mixing ratio and aerosol optical depth (AOD) show that the fire–atmosphere coupled configuration has a similar performance when compared to UKESM1. In fact, including the interactive biomass burning emissions improves the interannual CO atmospheric column variability and consequently its seasonality over the main biomass burning regions – Africa and South America. Similarly, for aerosols, the AOD results broadly agree with the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Aerosol Robotic Network (AERONET) observations

    Anterior gradient protein 2 promotes survival, migration and invasion of papillary thyroid carcinoma cells

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    Through a transcriptome microarray analysis, we have isolated Anterior gradient protein 2 (AGR2) as a gene up-regulated in papillary thyroid carcinoma (PTC). AGR2 is a disulfide isomerase over-expressed in several human carcinomas and recently linked to endoplasmic reticulum (ER) stress. Here, we analyzed the expression of AGR2 in PTC and its functional role

    α-cell glucokinase suppresses glucose-regulated glucagon secretion

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    Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K javax.xml.bind.JAXBElement@dee6e8 channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype

    Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

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    BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

    Plantar fascia ultrasound images characterization and classification using support vector machine

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    The examination of plantar fascia (PF) ultrasound (US) images is subjective and based on the visual perceptions and manual biometric measurements carried out by medical experts. US images feature extraction, characterization and classification have been widely introduced for improving the accuracy of medical assessment, reducing its subjective nature and the time required by medical experts for PF pathology diagnosis. In this paper, we develop an automated supervised classification approach using the Support Vector Machine (Linear and Kernel) to distinguishes between symptomatic and asymptomatic PF cases. Such an approach will facilitate the characterization and the classification of the PF area for the identification of patients with inferior heel pain at risk of plantar fasciitis. Six feature sets were extracted from the segmented PF region. Additionally, features normalization, features ranking and selection analysis using an unsupervised infinity selection method were introduced for the characterization and the classification of symptomatic and asymptomatic PF subjects. The performance of the classifiers was assessed using confusion matrix attributes and some derived performance measures including recall, specificity, balanced accuracy, precision, F-score and Matthew’s correlation coefficient. Using the best selected features sets, Linear SVM and Kernel SVM achieved an F-Score of 97.06 and 98.05 respectively

    High Glucose Suppresses Human Islet Insulin Biosynthesis by Inducing miR-133a Leading to Decreased Polypyrimidine Tract Binding Protein-Expression

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    BACKGROUND: Prolonged periods of high glucose exposure results in human islet dysfunction in vitro. The underlying mechanisms behind this effect of high glucose are, however, unknown. The polypyrimidine tract binding protein (PTB) is required for stabilization of insulin mRNA and the PTB mRNA 3'-UTR contains binding sites for the microRNA molecules miR-133a, miR-124a and miR-146. The aim of this study was therefore to investigate whether high glucose increased the levels of these three miRNAs in association with lower PTB levels and lower insulin biosynthesis rates. METHODOLOGY/PRINCIPAL FINDINGS: Human islets were cultured for 24 hours in the presence of low (5.6 mM) or high glucose (20 mM). Islets were also exposed to sodium palmitate or the proinflammatory cytokines IL-1beta and IFN-gamma, since saturated free fatty acids and cytokines also cause islet dysfunction. RNA was then isolated for real-time RT-PCR analysis of miR-133a, miR-124a, miR-146, insulin mRNA and PTB mRNA contents. Insulin biosynthesis rates were determined by radioactive labeling and immunoprecipitation. Synthetic miR-133a precursor and inhibitor were delivered to dispersed islet cells by lipofection, and PTB was analyzed by immunoblotting following culture at low or high glucose. Culture in high glucose resulted in increased islet contents of miR-133a and reduced contents of miR-146. Cytokines increased the contents of miR-146. The insulin and PTB mRNA contents were unaffected by high glucose. However, both PTB protein levels and insulin biosynthesis rates were decreased in response to high glucose. The miR-133a inhibitor prevented the high glucose-induced decrease in PTB and insulin biosynthesis, and the miR-133a precursor decreased PTB levels and insulin biosynthesis similarly to high glucose. CONCLUSION: Prolonged high-glucose exposure down-regulates PTB levels and insulin biosynthesis rates in human islets by increasing miR-133a levels. We propose that this mechanism contributes to hyperglycemia-induced beta-cell dysfunction

    Pseudotumoural soft tissue lesions of the foot and ankle: a pictorial review

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    In the foot and ankle region, benign neoplasms and pseudotumoural soft tissue lesions are significantly more frequent than malignant tumours. The pseudotumoural lesions constitute a heterogeneous group, with highly varied aetiology and histopathology. This article reviews the imaging features of the most common pseudotumours of the soft tissues in the foot and ankle. Although the imaging characteristics of several of the lesions discussed are non-specific, combining them with lesion location and clinical features allows the radiologist to suggest a specific diagnosis in most cases

    Endothelial Differentiation of Human Stem Cells Seeded onto Electrospun Polyhydroxybutyrate/Polyhydroxybutyrate-Co-Hydroxyvalerate Fiber Mesh

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    Tissue engineering is based on the association of cultured cells with structural matrices and the incorporation of signaling molecules for inducing tissue regeneration. Despite its enormous potential, tissue engineering faces a major challenge concerning the maintenance of cell viability after the implantation of the constructs. The lack of a functional vasculature within the implant compromises the delivery of nutrients to and removal of metabolites from the cells, which can lead to implant failure. In this sense, our investigation aims to develop a new strategy for enhancing vascularization in tissue engineering constructs. This study's aim was to establish a culture of human adipose tissue-derived stem cells (hASCs) to evaluate the biocompatibility of electrospun fiber mesh made of polyhydroxybutyrate (PHB) and its copolymer poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-HV) and to promote the differentiation of hASCs into the endothelial lineage. Fiber mesh was produced by blending 30% PHB with 70% PHB-HV and its physical characterization was conducted using scanning electron microscopy analysis (SEM). Using electrospinning, fiber mesh was obtained with diameters ranging 300 nm to 1.3 ”m. To assess the biological performance, hASCs were extracted, cultured, characterized by flow cytometry, expanded and seeded onto electrospun PHB/PHB-HV fiber mesh. Various aspects of the cells were analyzed in vitro using SEM, MTT assay and Calcein-AM staining. The in vitro evaluation demonstrated good adhesion and a normal morphology of the hASCs. After 7, 14 and 21 days of seeding hASCs onto electrospun PHB/PHB-HV fiber mesh, the cells remained viable and proliferative. Moreover, when cultured with endothelial differentiation medium (i.e., medium containing VEGF and bFGF), the hASCs expressed endothelial markers such as VE-Cadherin and the vWF factor. Therefore, the electrospun PHB/PHB-HV fiber mesh appears to be a suitable material that can be used in combination with endothelial-differentiated cells to improve vascularization in engineered bone tissues

    Pulsatility of insulin release – a clinically important phenomenon

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    The mechanisms and clinical importance of pulsatile insulin release are presented against the background of more than half a century of companionship with the islets of Langerhans. The insulin-secreting ÎČ-cells are oscillators with intrinsic variations of cytoplasmic ATP and Ca2+. Within the islets the ÎČ-cells are mutually entrained into a common rhythm by gap junctions and diffusible factors (ATP). Synchronization of the different islets in the pancreas is supposed to be due to adjustment of the oscillations to the same phase by neural output of acetylcholine and ATP. Studies of hormone secretion from the perfused pancreas of rats and mice revealed that glucose induces pulses of glucagon anti-synchronous with pulses of insulin and somatostatin. The anti-synchrony may result from a paracrine action of somatostatin on the glucagon-producing α-cells. Purinoceptors have a key function for pulsatile release of islet hormones. It was possible to remove the glucagon and somatostatin pulses with maintenance of those of insulin with an inhibitor of the P2Y1 receptors. Knock-out of the adenosine A1 receptor prolonged the pulses of glucagon and somatostatin without affecting the duration of the insulin pulses. Studies of isolated human islets indicate similar relations between pulses of insulin, glucagon, and somatostatin as found during perfusion of the rodent pancreas. The observation of reversed cycles of insulin and glucagon adds to the understanding how the islets regulate hepatic glucose production. Current protocols for pulsatile intravenous infusion therapy (PIVIT) should be modified to mimic the anti-synchrony between insulin and glucagon normally seen in the portal blood
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