Search results for " Simulation"
showing 10 items of 4034 documents
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and ov…
2016
Orally administered drugs are subject to a number of barriers impacting bioavailability (Foral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp®, and GastroPlus™) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters.Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exer…
Oral biopharmaceutics tools – Time for a new initiative – An introduction to the IMI project OrBiTo
2013
OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharm…
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysin…
2016
Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp® Simulator, and GastroPlus™) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded “bottom-up” anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (Foral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foral was also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on pe…
Left Ventricle Biomechanics of Low-Flow, Low-Gradient Aortic Stenosis: A Patient-Specific Computational Model
2022
This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated …
Guided ultrasonic waves in long bones: modelling, experiment and in vivo application.
2002
Existing ultrasound devices for assessing the human tibia are based on detecting the first arriving signal, corresponding to a wave propagating at, or close to, the bulk longitudinal velocity in bone. However, human long bones are effectively irregular hollow tubes and should theoretically support the propagation of more complex guided modes similar to Lamb waves in plates. Guided waves are attractive because they propagate throughout the bone thickness and can potentially yield more information on bone material properties and architecture. In this study, Lamb wave theory and numerical simulations of wave propagation were used to gain insights into the expected behaviour of guided waves in …
Metodología para la mejora acústica de recintos de culto. Aplicación en la Catedral de Valencia
2021
[ES] Los recintos de culto son espacios patrimoniales de gran valor cultural, artístico y arquitectónico. Asimismo, en ellos tienen lugar eventos, integrantes de su patrimonio cultural inmaterial, donde la transmisión del sonido es un factor preferente. Por todo ello, resulta relevante garantizar un adecuado acondicionamiento acústico de los recintos de culto para sus dos usos fundamentales, la música religiosa y la palabra. Para ello, se ha establecido una metodología compuesta por las fases de medición acústica, estudio del comportamiento acústico del recinto, levantamiento y calibración del modelo acústico y simulaciones acústicas. Al tratarse de edificios protegidos, las propuestas de i…
Destination Governance at Stake: Fostering Policy Coordination Among Decision-Makers of a Small Town
2018
This research aims to foster small-town decision-makers’ awareness of policy coordination as a central issue in either implementing collaborative governance and designing tourism development policies. To this end, a System Dynamics-based Interactive Learning Environment (ILE) has been designed with the intent of challenging decision-makers to increase tourism in the small town, while managing trade-offs among individualistic vs. collaborative behaviour. The action research took place in Castelbuono, a small tourism destination in Sicily (Italy). Three major decision-makers were involved: the mayor of the town, the museum’s director, and a restaurant owner. The use of the ILE has enabled dec…
Investigating particle acceleration dynamics in interpenetrating magnetized collisionless super-critical shocks
2023
Colliding collisionless shocks appear in a great variety of astrophysical phenomena and are thought to be possible sources of particle acceleration in the Universe. We have previously investigated particle acceleration induced by single super-critical shocks (whose magnetosonic Mach number is higher than the critical value of 2.7) (Yao et al., Nat. Phys., vol. 17, issue 10, 2021, pp. 1177–1182; Yao et al., Matter Radiat. Extrem., vol. 7, issue 1, 2022, 014402), as well as the collision of two sub-critical shocks (Fazzini et al., Astron. Astrophys., vol. 665, 2022, A87). Here, we propose to make measurements of accelerated particles from interpenetrating super-critical shocks to observe the …
The Internal Dynamics of Fibrinogen and Its Implications for Coagulation and Adsorption
2015
Fibrinogen is a serum multi-chain protein which, when activated, aggregates to form fibrin, one of the main components of a blood clot. Fibrinolysis controls blood clot dissolution through the action of the enzyme plasmin, which cleaves fibrin at specific locations. Although the main biochemical factors involved in fibrin formation and lysis have been identified, a clear mechanistic picture of how these processes take place is not available yet. This picture would be instrumental, for example, for the design of improved thrombolytic or anti-haemorrhagic strategies, as well as, materials with improved biocompatibility. Here, we present extensive molecular dynamics simulations of fibrinogen w…
Finite Element Studies On Friction Stir Welding Processes of Tailored Blanks
2008
Although friction stir welding (FSW) has been successfully used to join materials that are difficult-to-weld or unweldable by fusion welding methods, it is still in its early development stage and, therefore, its potential has not been fully exploited yet. FSW appears to be a very promising process for tailor-welded blanks to overcome the difficulties encountered in traditional fusion welding processes for obtaining a sound welding with good nugget integrity. In this paper the friction stir welding process for tailored blanks of aluminum alloy is investigated through a FEM developed by the authors. In particular FSW for sheets with different thicknesses is studied. For each setup a differen…