1,233 research outputs found

    Structural Optimization Using Simulated Annealing

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    Population-Monotonicity of the Nucleolus on a Class of Public Good Problems

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    Sprumont (1990) shows that the Shapley value (Shapley 1957) is population-monotonic (Thomson 1983) on the class of convex games (Shapley 1971). In this paper we study the population-monotonicity of the nucleolus (Schmeidler 1969). We show that the nucleolus is not population-monotonic on the class of convex games. Our main result is that the nucleolus is population-monotonic on a class of public good problems which is formalized in Litilechild and Owen (1973) under the name of airport games. We also provide a recursive formula for the nucleolus of the airport game

    A composite sandwich plate with a novel core design

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    © 2018 Elsevier Ltd In this study, a new core design is introduced for sandwich composite structures. Its strength and failure behavior are investigated via three-point bending tests. E-glass-fiber-reinforced epoxy resin is selected as the material for both the core and the face sheets. The core has an egg-crate shape. Acoustic emission (AE) method is used to detect the progression of damage. Signals due to elastic waves caused by activated damage mechanisms are investigated in order to identify the corresponding failure modes. A finite element model of the sandwich structure is developed to predict the failure behavior of the specimens under the loading conditions in the tests. A promising agreement between the results of the finite element model and the experiments is observed. The force-deflection-relation, the failure load as well as the region where damage initiates are accurately predicted

    Failure behavior of composite laminates under four-point bending

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    In this study, failure behavior of fiber-reinforced composites under four-point bending is investigated. First, the tests are modeled analytically using the classical lamination theory (CLT). The maximum allowable moment resultants of [ 12]Toffaxis laminate as well as balanced and symmetric angle-ply [ 3/ 3]s composite laminates as a function of fiber orientation angle, , are obtained using Tsai-Wu, maximum stress, maximum strain, Hashin, Tsai-Hill, Hoffman, quadric surfaces, modified quadric surfaces, and Norris failure criteria. Second, the same tests are simulated using the finite element method (FEM). Thermal residual stresses are calculated and accounted for in the failure analysis. An analysis is conducted for optimal positioning of the supports so as to ensure that intralaminar failure modes dominate interlaminar (delamination) failure mode. A test setup is then constructed accordingly and experiments are conducted. The correlation of the predicted failure loads and the experimental results is discussed. The quadric surfaces criterion is found to correlate better with the experimental results among the chosen failure criteria for the selected configurations

    Exogenous application of humic acid mitigates salinity stress in maize (Zea mays L.) plants by improving some key physico-biochemical attributes

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    Application of salt stress (100 mM) through root growing medium caused a considerable decrease in plant fresh and dry biomass, maximum quantum yield (Fv/Fm), chlorophyll contents, leaf water potential, and leaf Ca, K, P and N concentrations of two maize cultivars (Apex 836 and DK 5783). However, salt-induced increase was observed in leaf osmolality (LO), proline, hydrogen peroxide (H2O2), malondialdehyde (MDA), Na+ concentration and activities of enzymatic antioxidants, such as catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD). Of five humic acid (HA) levels used under non-stress and stress conditions in an initial experiment, 100 mg L−1 was chosen for subsequent studies. Exogenous application of humic acid (HA) at the rate of 100 mM as a foliar or pre-sowing seed treatment significantly increased the plant biomass, Fv/Fm, chlorophyll pigments and proline contents, while it considerably reduced the leaf water potential, H2O2 and MDA contents as well as the activities of all the afore-mentioned enzymatic antioxidants. Of both modes of exogenous treatment, foliar spray was better in improving plant biomass, chlorophyll contents, LO, leaf Na+ as well as the accumulation of all nutrients measured, however, in contrast, seed pre-treatment was more effective in altering leaf proline, H2O2 and MDA contents. Of both maize cultivars, cv. DK 5783 excelled in plant biomass, chlorophyll contents and leaf N, Ca and K concentrations as well as in the activities of all three antioxidant enzymes, whereas cv. Apex 836 was superior in leaf Na+ and P concentrations, H2O2 and MDA contents. Cv. DK 5783 was comparatively better in salt tolerance as compared to cv. Apex 836. Overall, exogenous application of HA was effective in improving salinity tolerance of maize plants which can be attributed to HA-induced increase in plant biomass, chlorophyll contents, mineral nutrients and activities of key antioxidant enzymes

    Effect of pathologic fractures on survival in multiple myeloma patients: a case control study

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    <p>Abstract</p> <p>Background</p> <p>Multiple Myeloma (MM) is a B cell neoplasm characterized by the clonal proliferation of plasma cells. Skeletal complications are found in up to 80% of myeloma patients at presentation and are major cause of morbidity.</p> <p>Methods</p> <p>49 patients were enrolled with MM admitted to Black Sea Technical University Hospital between 2002–2005. Pathologic fractures (PFs) were determined and the patients with or without PF were followed up minumum 3 years for survival analysis.</p> <p>Results</p> <p>PF was observed in 24 patients (49%) and not observed in 25 patients (51%). The risk of death was increased in the patients with PF compared with patients who had no fractures. While overall survival was 17.6 months in the patients with PFs, it was 57.3 months in the patients with no PFs.</p> <p>Conclusion</p> <p>These findings suggest that PFs may induce reduced survival and increased mortality in the MM patients, however, larger sample size is essential to draw clearer conclusions added to these data.</p

    Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events

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    Objectives. Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. Methods. We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessedand ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. Results. Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis.Conclusion. Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients

    Evolutionary Sequence Modeling for Discovery of Peptide Hormones

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    There are currently a large number of “orphan” G-protein-coupled receptors (GPCRs) whose endogenous ligands (peptide hormones) are unknown. Identification of these peptide hormones is a difficult and important problem. We describe a computational framework that models spatial structure along the genomic sequence simultaneously with the temporal evolutionary path structure across species and show how such models can be used to discover new functional molecules, in particular peptide hormones, via cross-genomic sequence comparisons. The computational framework incorporates a priori high-level knowledge of structural and evolutionary constraints into a hierarchical grammar of evolutionary probabilistic models. This computational method was used for identifying novel prohormones and the processed peptide sites by producing sequence alignments across many species at the functional-element level. Experimental results with an initial implementation of the algorithm were used to identify potential prohormones by comparing the human and non-human proteins in the Swiss-Prot database of known annotated proteins. In this proof of concept, we identified 45 out of 54 prohormones with only 44 false positives. The comparison of known and hypothetical human and mouse proteins resulted in the identification of a novel putative prohormone with at least four potential neuropeptides. Finally, in order to validate the computational methodology, we present the basic molecular biological characterization of the novel putative peptide hormone, including its identification and regional localization in the brain. This species comparison, HMM-based computational approach succeeded in identifying a previously undiscovered neuropeptide from whole genome protein sequences. This novel putative peptide hormone is found in discreet brain regions as well as other organs. The success of this approach will have a great impact on our understanding of GPCRs and associated pathways and help to identify new targets for drug development

    Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway

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    <p>Abstract</p> <p>Background</p> <p>Treatment strategies for Retinoblastoma (RB), the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K<sup>+ </sup>channels.</p> <p>Case presentation</p> <p>Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the <it>vegf-a, flt-1, kdr</it>, and <it>hif1-α </it>transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K<sup>+ </sup>channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue.</p> <p>Conclusions</p> <p>We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the <it>vegf-a</it>, <it>flt-1</it>, <it>kdr </it>and <it>hif1-α </it>transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the <it>herg1 </it>gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress the relevance of the VEGF-A pathway in RB and the correlation with hERG1, making aggressive and recurrent RB cases good candidates for antiangiogenesis therapies based on the targeting of VEGF-A.</p

    Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study

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    Background: Androgen Receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients’ prognosis. Methods: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n=420), UK (n=239), Norway (n=104), Ireland (n=222), Nigeria (n=180), and India (n=242); total n=1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. Results: AR status shows population-specific patterns of association with patients’ overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted
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