879 resultados para model testing


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This thesis is divided in three chapters. In the first chapter we analyse the results of the world forecasting experiment run by the Collaboratory for the Study of Earthquake Predictability (CSEP). We take the opportunity of this experiment to contribute to the definition of a more robust and reliable statistical procedure to evaluate earthquake forecasting models. We first present the models and the target earthquakes to be forecast. Then we explain the consistency and comparison tests that are used in CSEP experiments to evaluate the performance of the models. Introducing a methodology to create ensemble forecasting models, we show that models, when properly combined, are almost always better performing that any single model. In the second chapter we discuss in depth one of the basic features of PSHA: the declustering of the seismicity rates. We first introduce the Cornell-McGuire method for PSHA and we present the different motivations that stand behind the need of declustering seismic catalogs. Using a theorem of the modern probability (Le Cam's theorem) we show that the declustering is not necessary to obtain a Poissonian behaviour of the exceedances that is usually considered fundamental to transform exceedance rates in exceedance probabilities in the PSHA framework. We present a method to correct PSHA for declustering, building a more realistic PSHA. In the last chapter we explore the methods that are commonly used to take into account the epistemic uncertainty in PSHA. The most widely used method is the logic tree that stands at the basis of the most advanced seismic hazard maps. We illustrate the probabilistic structure of the logic tree, and then we show that this structure is not adequate to describe the epistemic uncertainty. We then propose a new probabilistic framework based on the ensemble modelling that properly accounts for epistemic uncertainties in PSHA.

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For the improvement of current neutron capture therapy, several liposomal formulations of neutron capture agent gadolinium were developed and tested in a glioma cell model. Formulations were analyzed regarding physicochemical and biological parameters, such as size, zeta potential, uptake into cancer cells and performance under neutron irradiation. The neutron and photon dose derived from intracellular as well as extracellular Gd was calculated via Monte Carlo simulations and set in correlation with the reduction of cell survival after irradiation. To investigate the suitability of Gd as a radiosensitizer for photon radiation, cells were also irradiated with synchrotron radiation in addition to clinically used photons generated by linear accelerator.rnIrradiation with neutrons led to significantly lower survival for Gd-liposome-treated F98 and LN229 cells, compared to irradiated control cells and cells treated with non-liposomal Gd-DTPA. Correlation between Gd-content and -dose and respective cell survival displayed proportional relationship for most of the applied formulations. Photon irradiation experiments showed the proof-of-principle for the radiosensitizer approach, although the photon spectra currently used have to be optimized for higher efficiency of the radiosensitizer. In conclusion, the newly developed Gd-liposomes show great potential for the improvement of radiation treatment options for highly malignant glioblastoma.rn

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Sub-grid scale (SGS) models are required in order to model the influence of the unresolved small scales on the resolved scales in large-eddy simulations (LES), the flow at the smallest scales of turbulence. In the following work two SGS models are presented and deeply analyzed in terms of accuracy through several LESs with different spatial resolutions, i.e. grid spacings. The first part of this thesis focuses on the basic theory of turbulence, the governing equations of fluid dynamics and their adaptation to LES. Furthermore, two important SGS models are presented: one is the Dynamic eddy-viscosity model (DEVM), developed by \cite{germano1991dynamic}, while the other is the Explicit Algebraic SGS model (EASSM), by \cite{marstorp2009explicit}. In addition, some details about the implementation of the EASSM in a Pseudo-Spectral Navier-Stokes code \cite{chevalier2007simson} are presented. The performance of the two aforementioned models will be investigated in the following chapters, by means of LES of a channel flow, with friction Reynolds numbers $Re_\tau=590$ up to $Re_\tau=5200$, with relatively coarse resolutions. Data from each simulation will be compared to baseline DNS data. Results have shown that, in contrast to the DEVM, the EASSM has promising potentials for flow predictions at high friction Reynolds numbers: the higher the friction Reynolds number is the better the EASSM will behave and the worse the performances of the DEVM will be. The better performance of the EASSM is contributed to the ability to capture flow anisotropy at the small scales through a correct formulation for the SGS stresses. Moreover, a considerable reduction in the required computational resources can be achieved using the EASSM compared to DEVM. Therefore, the EASSM combines accuracy and computational efficiency, implying that it has a clear potential for industrial CFD usage.

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Despite the many proposed advantages related to nanotechnology, there are increasing concerns as to the potential adverse human health and environmental effects that the production of, and subsequent exposure to nanoparticles (NPs) might pose. In regard to human health, these concerns are founded upon the plethora of knowledge gained from research relating to the effects observed following exposure to environmental air pollution. It is known that increased exposure to environmental air pollution can cause reduced respiratory health, as well as exacerbate pre-existing conditions such as cardiovascular disease and chronic obstructive pulmonary disease. Such disease states have also been associated with exposure to the NP component contained within environmental air pollution, raising concerns as to the effects of NP exposure. It is not only exposure to accidentally produced NPs however, which should be approached with caution. Over the past decades, NPs have been specifically engineered for a wide range of consumer, industrial and technological applications. Due to the inevitable exposure of NPs to humans, owing to their use in such applications, it is therefore imperative that an understanding of how NPs interact with the human body is gained. In vivo research poses a beneficial model for gaining immediate and direct knowledge of human exposure to such xenobiotics. This research outlook however, has numerous limitations. Increased research using in vitro models has therefore been performed, as these models provide an inexpensive and high-throughput alternative to in vivo research strategies. Despite such advantages, there are also various restrictions in regard to in vitro research. Therefore, the aim of this review, in addition to providing a short perspective upon the field of nanotoxicology, is to discuss (1) the advantages and disadvantages of in vitro research and (2) how in vitro research may provide essential information pertaining to the human health risks posed by NP exposure.

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Naive T cells are migratory cells that continuously recirculate between blood and lymphoid tissues. Antigen-specific stimulation of T cells within the lymph nodes reprograms the trafficking properties of T cells by inducing a specific set of adhesion molecules and chemokine receptors on their surface which allow these activated and effector T cells to effectively and specifically home to extralymphoid organs. The observations of organ-specific homing of T cells initiated the development of therapeutic strategies targeting adhesion receptors for organ-specific inhibition of chronic inflammation. As most adhesion receptors have additional immune functions besides mediating leukocyte trafficking, these drugs may have additional immunomodulatory effects. Therapeutic targeting of T-cell trafficking to the central nervous system is the underlying concept of a novel treatment of relapsing remitting multiple sclerosis with the humanized anti-alpha-4-integrin antibody natalizumab. In this chapter, we describe a possible preclinical in vivo approach to directly visualize the therapeutic efficacy of a given drug in inhibiting T-cell homing to a certain organ at the example of the potential of natalizumab to inhibit the trafficking of human T cells to the inflamed central nervous system in an animal model of multiple sclerosis.

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Modifications and upgrades to the hydraulic flume facility in the Environmental Fluid Mechanics and Hydraulics Laboratory (EFM&H) at Bucknell University are described. These changes enable small-scale testing of model marine hydrokinetic(MHK) devices. The design of the experimental platform provides a controlled environment for testing of model MHK devices to determine their effect on localsubstrate. Specifically, the effects being studied are scour and erosion around a cylindrical support structure and deposition of sediment downstream from the device.

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A new liquid-fuel injector was designed for use in the atmospheric-pressure, model gas turbine combustor in Bucknell University’s Combustion Research Laboratory during alternative fuel testing. The current liquid-fuel injector requires a higher-than-desired pressure drop and volumetric flow rate to provide proper atomization of liquid fuels. An air-blast atomizer type of fuel injector was chosen and an experiment utilizing water as the working fluid was performed on a variable-geometry prototype. Visualization of the spray pattern was achieved through photography and the pressure drop was measured as a function of the required operating parameters. Experimental correlations were used to estimate droplet sizes over flow conditions similar to that which would be experienced in the actual combustor. The results of this experiment were used to select the desired geometric parameters for the proposed final injector design and a CAD model was generated. Eventually, the new injector will be fabricated and tested to provide final validation of the design prior to use in the combustion test apparatus.

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Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis.

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Intracoronary administration of glycosaminoglycan analogs, including the complement inhibitor dextran sulfate, attenuates myocardial ischemia/reperfusion injury (I/R injury). However, dextran sulfate has a distinct anticoagulatory effect, possibly limiting its use in specific situations in vivo. We therefore developed multimeric tyrosine sulfate (sTyr-PAA), a novel, minimally anticoagulatory, fully synthetic non-carbohydrate-containing polyacrylamide conjugate, for in vivo testing in an acute closed-chest porcine model of acute myocardial infarction.

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Background The reduction in the amount of food available for European avian scavengers as a consequence of restrictive public health policies is a concern for managers and conservationists. Since 2002, the application of several sanitary regulations has limited the availability of feeding resources provided by domestic carcasses, but theoretical studies assessing whether the availability of food resources provided by wild ungulates are enough to cover energetic requirements are lacking. Methodology/Findings We assessed food provided by a wild ungulate population in two areas of NE Spain inhabited by three vulture species and developed a P System computational model to assess the effects of the carrion resources provided on their population dynamics. We compared the real population trend with to a hypothetical scenario in which only food provided by wild ungulates was available. Simulation testing of the model suggests that wild ungulates constitute an important food resource in the Pyrenees and the vulture population inhabiting this area could grow if only the food provided by wild ungulates would be available. On the contrary, in the Pre-Pyrenees there is insufficient food to cover the energy requirements of avian scavenger guilds, declining sharply if biomass from domestic animals would not be available. Conclusions/Significance Our results suggest that public health legislation can modify scavenger population trends if a large number of domestic ungulate carcasses disappear from the mountains. In this case, food provided by wild ungulates could be not enough and supplementary feeding could be necessary if other alternative food resources are not available (i.e. the reintroduction of wild ungulates), preferably in European Mediterranean scenarios sharing similar and socio-economic conditions where there are low densities of wild ungulates. Managers should anticipate the conservation actions required by assessing food availability and the possible scenarios in order to make the most suitable decisions.

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Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis (AS) and a high operative risk. Risk stratification plays a decisive role in the optimal selection of therapeutic strategies for AS patients. The accuracy of contemporary surgical risk algorithms for AS patients has spurred considerable debate especially in the higher risk patient population. Future trials will explore TAVI in patients at intermediate operative risk. During the design of the SURgical replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial, a novel concept of risk stratification was proposed based upon age in combination with a fixed number of predefined risk factors, which are relatively prevalent, easy to capture and with a reasonable impact on operative mortality. Retrospective application of this algorithm to a contemporary academic practice dealing with clinically significant AS patients allocates about one-fourth of these patients as being at intermediate operative risk. Further testing is required for validation of this new paradigm in risk stratification. Finally, the Heart Team, consisting of at least an interventional cardiologist and cardiothoracic surgeon, should have the decisive role in determining whether a patient could be treated with TAVI or SAVR.

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The aim of the study was to evaluate bovine synoviocyte culture as an in vitro model to test new intra-articular drugs. The inflammatory reaction pattern of synoviocytes as compared to fibroblasts was studied over nine passages. Expression of pro-inflammatory cytokines was assessed after stimulation with lipopolysaccharide. Immunohistochemical markers were used to identify synoviocyte populations. Primary synoviocytes expressed markedly higher amounts of interleukin-1beta mRNA and tumour necrosis factor-alpha mRNA than fibroblasts after stimulation. This difference was lost over two passages. CD68-positive macrophage-like synoviocytes diminished over three passages, which may explain the reduced pro-inflammatory cytokine response. Primary bovine synoviocytes appear to be an appropriate and optimised model for testing novel drugs for cattle, because their response may more closely reflect in vivo tissue responses compared to cultured cell lines.

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The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects of meloxicam were investigated in a placebo controlled study in 2-week-old piglets. Inflammation was induced by a subcutaneous injection of kaolin in the left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered intramuscularly. The absorption half-life was relatively short (0.19 h) and the elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was used to evaluate the analgesic effect, but no significant effect of the meloxicam treatment was found. The skin temperature of the inflamed area increased after the kaolin injection, but no significant decrease in temperature was found after administration of meloxicam. Only limited pyresis was observed after the kaolin injection, and no significant antipyretic effect of meloxicam was found. The results indicated that this dose of meloxicam had very limited anti-inflammatory and analgesic effects in piglets.

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As lightweight and slender structural elements are more frequently used in the design, large scale structures become more flexible and susceptible to excessive vibrations. To ensure the functionality of the structure, dynamic properties of the occupied structure need to be estimated during the design phase. Traditional analysis method models occupants simply as an additional mass; however, research has shown that human occupants could be better modeled as an additional degree-of- freedom. In the United Kingdom, active and passive crowd models are proposed by the Joint Working Group as a result of a series of analytical and experimental research. It is expected that the crowd models would yield a more accurate estimation to the dynamic response of the occupied structure. However, experimental testing recently conducted through a graduate student project at Bucknell University indicated that the proposed passive crowd model might be inaccurate in representing the impact on the structure from the occupants. The objective of this study is to provide an assessment of the validity of the crowd models proposed by JWG through comparing the dynamic properties obtained from experimental testing data and analytical modeling results. The experimental data used in this study was collected by Firman in 2010. The analytical results were obtained by performing a time-history analysis on a finite element model of the occupied structure. The crowd models were created based on the recommendations from the JWG combined with the physical properties of the occupants during the experimental study. During this study, SAP2000 was used to create the finite element models and to implement the analysis; Matlab and ME¿scope were used to obtain the dynamic properties of the structure through processing the time-history analysis results from SAP2000. The result of this study indicates that the active crowd model could quite accurately represent the impact on the structure from occupants standing with bent knees while the passive crowd model could not properly simulate the dynamic response of the structure when occupants were standing straight or sitting on the structure. Future work related to this study involves improving the passive crowd model and evaluating the crowd models with full-scale structure models and operating data.