588 research outputs found
Alternative Approaches to a Calibration of Rainfall-Runoff Models for a Flood Frequency Analysis
One of the tools which are currently being used in flood frequency analysis (FFA) is rainfall-runoff (RR) modelling. Its use in FFA often confronts the problem of how to correctly calibrate RR models to extreme flows. Since FFA only deals with extreme flows, traditional calibration techniques using simple objective functions such as the Nash-Sutcliffe model’s efficiency criterion are not sufficient. In this paper we have focused on proposing alternative approaches for calibration techniques of RR models in order to enhance the description of extreme flows. We have selected the HBV type conceptual, lumped model HRON as an RR model. We have suggested two alternative calibration approaches: 1) the use of a new optimization function that compares only values higher than the 95th percentile of observed flows and 2) using two sets of parameters to separately simulate low and high flows. Each of these improvements has enhanced the simulation of extreme flows, which has been demonstrated in the empirical cumulative distribution function calculated for the simulated and observed annual maximum series of flows. The results of this paper show that improvement can be obtained by both approaches, which give good agreement between observed and simulated extreme flows, while preserving a good simulation of low and medium flows
Mast cells and mast cell growth factor: possible role in auricular thrombosis
Although mast cells have been implicated in many vascular and inflammatory reactions, the mechanisms underlying such mast cell-dependent processes have not been fully clarified. Recently we have established an association between mast cells and local thrombus formation. The most useful model for studying molecular mechanisms of mast cell-thrombosis interactions appeared to be auricular thrombosis. In the present review we summarize our findings in patients with auricular thrombosis with regard to functionally important molecules that can either be expressed and released by cardiac mast cells or interact with mast cells via distinct cell surface molecules. The potential prothrombolytic function of mast cells in atrial thrombosis is discussed.Biomedical Reviews 1995; 4: 29-34
KIT mutation analysis in mast cell neoplasms: Recommendations of the European Competence Network on Mastocytosis
PMCID: PMC4522520.-- et al.Although acquired mutations in KIT are commonly detected in various categories of mastocytosis, the methodologies applied to detect and quantify the mutant type and allele burden in various cells and tissues are poorly defined. We here propose a consensus on methodologies used to detect KIT mutations in patients with mastocytosis at diagnosis and during follow-up with sufficient precision and sensitivity in daily practice. In addition, we provide recommendations for sampling and storage of diagnostic material as well as a robust diagnostic algorithm. Using highly sensitive assays, KIT D816V can be detected in peripheral blood leukocytes from most patients with systemic mastocytosis (SM) that is a major step forward in screening and SM diagnosis. In addition, the KIT D816V allele burden can be followed quantitatively during the natural course or during therapy. Our recommendations should greatly facilitate diagnostic and follow-up investigations in SM in daily practice as well as in clinical trials. In addition, the new tools and algorithms proposed should lead to a more effective screen, early diagnosis of SM and help to avoid unnecessary referrals.M. Arock is supported by Fondation de France; P. Dubreuil is supported by La Ligue
Nationale Contre le Cancer (équipe labellisée) and INCa; A. Garcia-Montero and A. Orfao are Supported by grants from the Instituto de Salud Carlos III, Ministry of Economy and Competitivity, Madrid, Spain (grant numbers RD12/0036/0048 and PI11/02399, FEDER) and from Fundacion Ramon Areces, Madrid, Spain (grant number
CIVP16A1806); D.D. Metcalfe is supported in part by the Division of Intramural Research, NIAID; P. Valent is supported by Austrian Science Funds (FWF) Project SFB F4611 and SFB F4704-B20.Peer Reviewe
Assessment of The Uncertainties of a Conceptual Hydrologic Model By Using Artificially Generated Flows
ABSTRACTMost of the studies that assess the performance of various calibration techniques have todeal with a certain amount of uncertainty in the calibration data. In this study we testedHBV model calibration procedures in hypothetically ideal conditions under the assumptionof no errors in the measured data. This was achieved by creating an artificial time seriesof the flows created by the HBV model using the parameters obtained from calibrating themeasured flows. The artificial flows were then used to replace the original flows in thecalibration data, which was then used for testing how calibration procedures can reproduceknown model parameters. The results showed that in performing one hundred independentcalibration runs of the HBV model, we did not manage to obtain parameters that werealmost identical to those used to create the artificial flow data without a certain degree ofuncertainty. Although the calibration procedure of the model works properly froma practical point of view, it can be regarded as a demonstration of the equifinality principle,since several parameter sets were obtained which led to equally acceptable or behaviouralrepresentations of the observed flows. The study demonstrated that this concept forassessing how uncertain hydrological predictions can be applied in the further developmentof a model or the choice of calibration method using artificially generated data
Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal
Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base
Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia
Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34+/CD38─ CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4+ SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26+ LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26+ CML LSC engrafted NOD-SCID-IL-2Rγ−/− (NSG) mice with BCR/ABL1+ cells, whereas CD26─ SC from the same patients produced multilineage BCR/ABL1– engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1+ cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy
THE DEVELOPMENT OF A NEW ADSORPTION-DESORPTION DEVICE
The aim of this work was to construct a new adsorption-desorption device based on the principle of separation of volatile organic compounds, e.g., ethanol. As an adsorbent, it is possible to use granulated activated carbon (GAC) in the adsorption and desorption process. In this study, two kinds of GACs were used and marked as GAC1 and GAC2. A particle size distribution and water vapour sorption for the selected GACs were measured. An experiment with distilled water was performed as a preliminary study of the new device’s functionality. After the determination of the time necessary for the adsorption and desorption, the experiments were carried out with a model mixture (5% v/v ethanol-water mixture), which resulted in a product with the ethanol content of 39.6 %. The main advantage of this device would be the potential competition of conventional distillation
Case report of a clinically indolent but morphologically high-grade cutaneous mast cell tumor in an adult:Atypical cutaneous mastocytoma or mast cell sarcoma?
We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within 2 years, was reexcised after 4 years and did not recur >6 years after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67‐staining from the onset. No KIT mutations were identified in the tumor and bone marrow. Serum tryptase levels and a bone marrow aspirate and trephine biopsy were normal. Although the histomorphology of the skin tumor was consistent with mast cell sarcoma, the clinical behavior without systemic progression argued against this diagnosis. The tumor was finally considered as atypical mastocytoma, borderline to mast cell sarcoma. Currently, the patient is in close follow‐up and still in complete remission
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