An advanced modeling technique for rolling element bearings in elastohydrodynamic field

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Shortage of Albendazole and Its Consequences for Patients with Cystic Echinococcosis Treated at a Referral Center in Italy

Albendazole (ABZ) is the best drug available to treat cystic echinococcosis (CE), a neglected tropical disease. Cystic echinococcosis patients often receive a continuous course of the drug for 6-12 months. In Italy, ABZ shortages occur almost on a yearly basis. We searched clinical records at the World Health Organization Collaborating Center for the Clinical Management of CE in Pavia, Italy, to estimate the amount of ABZ prescribed to patients between January 2012 and February 2017. The cost of ABZ was estimated at €2.25 per tablet based on the current market price in Italy. Patients to whom ABZ had been prescribed were contacted to determine if they had experienced difficulties in purchasing the drug and to assess how such problems affected their treatment. Of 348 identified CE patients, 127 (36.5%) were treated with ABZ for a total of 20,576 days. This led to an estimated cost of €92,592. Seventy-five patients were available for follow-up, 42 (56%) reported difficulties in obtaining ABZ. Of these patients, four (9.5%) had to search out of their region and 10 (23.8%) had to go out of the country. A total of 27 patients (64%) had to visit more than five pharmacies to locate the drug and 10 patients (23.8%) interrupted treatment because of ABZ nonavailability. Shortages in ABZ distribution can disrupt CE treatment schedules and jeopardize patient health

Pros and cons of different therapeutic antibody formats for recombinant antivenom development.

Antibody technologies are being increasingly applied in the field of toxinology. Fuelled by the many advances in immunology, synthetic biology, and antibody research, different approaches and antibody formats are being investigated for the ability to neutralize animal toxins. These different molecular formats each have their own therapeutic characteristics. In this review, we provide an overview of the advances made in the development of toxin-targeting antibodies, and discuss the benefits and drawbacks of different antibody formats in relation to their ability to neutralize toxins, pharmacokinetic features, propensity to cause adverse reactions, formulation, and expression for research and development (R&D) purposes and large-scale manufacturing. A research trend seems to be emerging towards the use of human antibody formats as well as camelid heavy-domain antibody fragments due to their compatibility with the human immune system, beneficial therapeutic properties, and the ability to manufacture these molecules cost-effectively

MLCP_DAE formulation for 2D Contact Rigid

This document is meant to be a detailed description of how my MLCP-gen alpha solver evolved, what are its features, implementation issues, results, etc. There will also be a detailed comparison with VL to check how accurate it is and what it can and cannot do. This document is in preparation of a Journal article and in preparation of the LMS RTD meeting.status: accepte

Efficient Numerical Simulation Strategies for Flexible Multibody Systems with Variable Topology (Efficiënte numerieke simulatiestrategieën voor flexibele meerlichamensystemen met variabele topologie)

In recent years, the design of modern mechanical and mechatronic system is becoming an increasingly complex task. This trend is due to the continuously increasing functional requirements and to the vast amount of different designs that have to reach the market within tight schedules. For these reasons it becomes infeasible to perform extensive testing on each new prototype. Simulation tools offer a faster and cost-effective alternative to physical testing provided that complex systems can be simulated accurately and within reasonable time frames. In order to match these requirements novel simulation methodologies and tools are needed and are subject of constant research effort. Flexible multibody dynamics is one of these approaches, developed in recent years, to deal with complex systems including high performance and light-weight machines. Within this approach the single components of a mechanism can be modeled to include the effect of deformation on the global system motion. Despite the constant research effort in this field, flexible multibody simulation of complex machines remains computationally very demanding, especially if accurate prediction of local quantities such as dynamic stresses and strains is of relevance. So-called component and system-level model order reduction strategies have been developed over the years to reduce the computational burden to an acceptable level. Nonetheless some key issues remain unsolved. If the flexible components of a mechanism present a large number of connections with other components or experience loading in multiple locations, standard model order reduction schemes fail to give an appropriate solution due to the large number of degrees of freedom required unless accuracy is largely sacrificed.In many industrial applications though, a component can be loaded at many different locations in time but only a few of those are actually loaded at a given time instant. A typical example is a pair of gears, meshing with each other in which all the teeth can be loaded during a full revolution but only a limited amount is in contact at a certain moment in time. Other examples are e.g. bearings and sliders. The topological variation of these components makes it challenging to perform reliable and efficient simulations within a flexible multibody framework.The main focus of this dissertation is on providing solutions that allow to simulate flexible multibody systems with variable topology efficiently with minimal losses in accuracy. Component-level model order reduction strategies should be adapted to reach this goal. This dissertation proposes two alternative solutions to the problem. At first a methodology named static modes switching is developed and further extended. The core idea behind this strategy is to discontinuously adapt the reduction space used to model the displacement field of the flexible components on-line during simulation. In this way, all the degrees of freedom that show a negligible contribution to the system response can bediscarded to improve efficiency. Several application examples of increasing complexity are used to analyze this strategy both from a performance and an accuracy point of view. A second method named static modes sliding, is also proposed and validated. This method is developed to mitigate a few limits of static modes switching related to its discontinuous character. In this approach, the reduction space is continuously adapted by interpolating a pre-computed set of shape vectors during simulation. The influence of the time variability of the reduction space is retained in the equations of motion so that the scheme remains energy consistent.Both methods developed are solutions to the complex problem of flexible mechanisms with variable topology and lead to an efficient and accurate description of global and local dynamic phenomena. The research performed in this PhD project has also paved the way for improvements and further developments that are suggested as future research tracks.nrpages: 234status: publishe

Theory of STATIC MODES SLIDING

This document is meant to be a detailed description of the idea of the static modes sliding, how it works, what are the problems, possible causes of inconsistency and purposes. The motivation for the static modes sliding comes from a necessity due to some problems related to the STATIC MODES SWITCHING. Namely the fact that if you switch modes on and off, during the switching phase, the systems is subject to an impulse of small amplitude due to the fact that the static modes are dynamically loaded and coupled to the constraints.status: accepte

Parameterized nonlinear model reduction for multibody simulation with uncertain parameters

status: publishe

A system level model reduction approach for flexible multibody systems with parametric uncertainties

© 2015 The Authors. Published by Elsevier B.V. Stochastic analysis of flexible multibody system for uncertain parameters typically requires a large number of simulation runs for example for Monte-Carlo simulation. However, as the computational load of a regular flexible multibody model is typically rather high, this is often infeasible. A solution to this high computational load is model reduction, but regular model reduction approaches for flexible multibody simulation do not maintain the parameter dependency. This leads to a new model reduction for each parameter which also leads to high computational costs. The current work presents a novel system level model reduction technique for parameterized flexible multibody simulation. The proposed approach is a parameterized version of the Global Modal Parameterization method. In this approach a system level model reduction of the flexible mechanism is performed in which a configuration dependent projection space is used. For the parameterized approach, affine parameter dependence is assumed. In this case the parameter dependency can be externalized and is exactly preserved through the model reduction. The accuracy of the proposed approach is demonstrated through a numerical validation. The model is used for a Monte-Carlo simulation of mechanism with uncertain parameters and delivers accurate probabilistic distributions for the motion of the mechanisms at a highly reduced cost compared to the original model. The proposed approach is shown to provide reliable results with a computational load which is reduced from days to hours.publisher: Elsevier articletitle: A System Level Model Reduction Approach for Flexible Multibody Systems with Parametric Uncertainties. journaltitle: Procedia IUTAM articlelink: http://dx.doi.org/10.1016/j.piutam.2015.01.002 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier B.V.status: publishe

Static modes switching for more efficient flexible multibody simulation

Body flexibility is of ever-increasing importance in multibody simulation. The current state-of-the-art simulation techniques typically have difficulties with systems in which flexible bodies can be loaded in many degrees of freedom (DOFs). However, in many applications, loading is possible in many DOFs but only few are loaded simultaneously at any given moment, such that at any moment only a low-dimensional part of the reduced body flexibility description contributes to the solution. Modal Base Switching, the methodology proposed in this paper, exploits this by judiciously choosing the body flexibility mode set and at any moment only including those modes that contribute to the solution. Modal Base Switching does not improve simulation accuracy, however it can significantly reduce simulation times. In a numerical experiment, results using Modal Base Switching match results for a conventional model using the same mode set. The approximation errors are negligible compared the accuracy loss encountered when using a mode set without compensation for the quasi-static response of the high-frequency dynamics, while both simulation results are obtained at a comparable computational cost. Modal Base Switching numerically introduces discontinuities when removing a mode from the mode set. This is overcome by time integration schemes exhibiting high-frequency numerical damping.status: publishe

Analysis of Static and Dynamic Meshing Behaviour of Lightweight Gears

Dottorato di Ricerca in Ingegneria Civile ed Industriale. Ciclo XXXIIn questo lavoro di tesi si è analizzato il comportamento dinamico di ruote dentate alleggerite. Tale tipologia di ingranaggi prevede l’utilizzo di corpi ruota dalla topologia ottimizzata al fine di ridurre la massa complessiva. Le modalità con cui è ottenuta la riduzione di peso hanno un grosso impatto sulla risposta dinamica dell’intera trasmissione. In applicazioni dove le performances in termini di NVH sono rilevanti, quali ad esempio quelle in ambito automotive, è fondamentale prevedere tale comportamento già nella fase di design iniziale, attarverso tecniche di simulazione numerica. Da parte dell’industria vi è quindi la richiesta di strumenti di calcolo sufficientemente dettagliati da poter replicare gli effetti dovuti agli alleggerimenti del corpo ruota. Al tempo stesso la richiesta è per strumenti di simulazione che siano il più efficienti possibile, in modo da poter essere utilizzati in simulazioni a livello di sistema. In questo lavoro di tesi due differenti approcci sono stati considerati. Un primo approccio prevede l’utilizzo di formulazioni analitiche, dove la rigidezza di contatto degli ingranaggi è stata calcolata in una fase di pre-processing attraverso l’uso di codici agli elementi finiti. Tale approcccio ha dimostrato di riuscire a modellare gli effetti dovuti alla variazione di rigidezza introdotta dai fori di alleggerimento nel corpo ruota, riuscendo altresì a mantenere un ottimo livello di efficienza computazionale. Il secondo approccio considerato in questo lavoro di tesi è basato su un codice MB commerciale, oppurtunamente esteso per considerare gli effetti dovuti agli alleggerimenti. Tale metodologia è stata validata sperimentalmente in termini di errore di trasmissione e di deformazione al piede del dente. Tale approccio, seppur più oneroso dal punto di vista computazionale, garantisce un ottimo livello di accuratezza. La formuazione ibrida MB-FEM consente di analizzare eventi in time-domain a livello di sistema, come mostrato nel caso di studio esaminato nell’ultimo capitolo di questa dissertazione, dove sono state confrontate le performances acustiche di due differenti layout. In tal modo si è potuto apprezzare come la topologia del corpo ruota abbia un effetto non trascurabile sull’emissione sonora della trasmissione. Entrambe le formulazioni sono state analizzate nel dettaglio, riportando altresì i punti di forza e di debolezzaUniversità della Calabri