<p>Highland Group AB was helping a customer of theirs to create an All-Terrain Vehicle (ATV), a project Highland has never been involved with before. For the wishbone arms of the wheel suspension, traditional manufacturing methods and tubes with cylindrical or square shaped cross section was preferred. We performed a simulation where the ATV was driving on a bumpy road too see the forces involved. With the results we proceeded to calculate the strength of the concepts to find out which is best suited for the tough environment in which the ATV is used. The concept that turned out to be the best was a wishbone made of circular cross section, which had good structural strength and did fulfill the demands that we required for the construction. The company where interested in the project and could see themselves proceeding with the work in the future. We helped the company to find interest for computer aided simulation in collaboration with structural strength analysis, which they would like to engage in. The project has given us a larger knowledge in the choices of construction and structural strength analysis as well as experience working with computer aided construction tools.</p>

In this work, gadolinium-based carbon nanocapsules are developed as a novel nanotechnology that addresses the shortcomings of current diagnostic and therapeutic methods of stem cell-based cardiomyoplasty. With cardiovascular disease (CVD) responsible for approximately 30% of deaths worldwide, the growing need for improved cardiomyoplasty has spurred efforts in nanomedicine to develop innovative techniques to enhance the therapeutic retention and diagnostic tracking of transplanted cells. Having previously been demonstrated as a high-performance T1-weighted magnetic resonance imaging (MRI) contrast agent, Gadonanotubes (GNTs) are shown for the first time to intracellularly label pig bone marrow-derived mesenchymal stem cells (MSCs). Without the use of a transfection agent, micromolar concentrations of GNTs deliver up to 10^9 Gd(III) ions per cell, allowing for MSCs to be visualized in a 1.5 T clinical MRI scanner. The cellular response to the intracellular incorporation of GNTs is also assessed, revealing that GNTs do not compromise the viability, differentiation potential, or phenotype characteristics of the MSCs. However, it is also found that GNT-labeled MSCs exhibit a decreased response to select cell adhesion proteins and experience a non-apoptotic, non-proliferative cell cycle arrest, from which the cells recover 48 h after GNT internalization. In tandem with developing GNTs as a new stem cell diagnostic agent, this current work also explores for the first time the therapeutic application of the magnetically-active GNTs as a magnetic facilitator to increase the retention of transplanted stem cells during cardiomyoplasty. In vitro flow chamber assays, ex vivo perfusion experiments, and in vivo porcine injection procedures all demonstrate the increased magnetic-assisted retention of GNT-labeled MSCs in the presence of an external magnetic field. These studies prove that GNTs are a powerful ‘theranostic’ agent that provides a novel platform to simultaneously monitor and improve the therapeutic nature of stem cells for the treatment of CVD. It is expected that this new nanotechnology will further catalyze the development of cellular cardiomyoplasty and other stem cell-based therapies for the prevention, detection, and treatment of human diseases.

Generating a single order statistic without generating the full sample can be an important task for simulations. If the density and the CDF of the distribution are given it is no problem to compute the density of the order statistic. In the main theorem it is shown that the concavity properties of that density depend directly on the distribution itself. Especially for log-concave distributions all order statistics have log-concave distributions themselves. So recently suggested automatic transformed density rejection algorithms can be used to generate single order statistics. This idea leads to very fast generators. For example for the normal and gamma distribution the suggested new algorithms are between 10 and 60 times faster than the algorithms suggested in the literature. (author's abstract) / Series: Preprint Series / Department of Applied Statistics and Data Processing

Up to now all known efficient portable implementations of linear congruential random number generators with modulus 2^(31)-1 are working only with multipliers which are small compared with the modulus. We show that for non-uniform distributions, the rejection method may generate random numbers of bad quality if combined with a linear congruential generator with small multiplier. Therefore a method is described that works for any multiplier smaller than 2^(30). It uses the decomposition of multiplier and seed in high order and low order bits to compute the upper and the lower half of the product. The sum of the two halfs gives the product of multiplier and seed modulo 2^(31)-1. Coded in ANSI-C and FORTRAN77 the method results in a portable implementation of the linear congruential generator that is as fast or faster than other portable methods. (author's abstract) / Series: Preprint Series / Department of Applied Statistics and Data Processing

There arise two problems when the expectation of some function with respect to a nonuniform multivariate distribution has to be computed by (quasi-) Monte Carlo integration: the integrand can have singularities when the domain of the distribution is unbounded and it can be very expensive or even impossible to sample points from a general multivariate distribution. We show that importance sampling is a simple method to overcome both problems. (author's abstract) / Series: Preprint Series / Department of Applied Statistics and Data Processing

From the viewpoint of the adaptive solution of partial differential equations a finit e element method on hierarchical triangular meshes is developed permitting hanging nodes arising from nonuniform hierarchical refinement. Construction, extension and restriction of the nonuniform hierarchical basis and the accompanying mesh are described by graphs. The corresponding FE basis is generated by hierarchical transformation. The characteristic feature of the generalizable concept is the combination of the conforming hierarchical basis for easily defining and changing the FE space with an accompanying nonconforming FE basis for the easy assembly of a FE equations system. For an elliptic model the conforming FEM problem is solved by an iterative method applied to this nonconforming FEM equations system and modified by projection into the subspace of conforming basis functions. The iterative method used is the Yserentant- or BPX-preconditioned conjugate gradient algorithm. On a MIMD computer system the parallelization by domain decomposition is easy and efficient to organize both for the generation and solution of the equations system and for the change of basis and mesh.

In this paper we present some variants of transformed density rejection (TDR) that provide more flexibility (including the possibility to halve the expected number of uniform random numbers) at the expense of slightly higher memory requirements. Using a synchronized first stream of uniform variates and a second auxiliary stream (as suggested by Schmeiser and Kachitvichyanukul (1990)) TDR is well suited for correlation induction. Thus high positive and negative correlation between two streams of random variates with same or different distributions can be induced. The software can be downloaded from the UNURAN project page. (author's abstract) / Series: Preprint Series / Department of Applied Statistics and Data Processing

Highland Group AB was helping a customer of theirs to create an All-Terrain Vehicle (ATV), a project Highland has never been involved with before. For the wishbone arms of the wheel suspension, traditional manufacturing methods and tubes with cylindrical or square shaped cross section was preferred. We performed a simulation where the ATV was driving on a bumpy road too see the forces involved. With the results we proceeded to calculate the strength of the concepts to find out which is best suited for the tough environment in which the ATV is used. The concept that turned out to be the best was a wishbone made of circular cross section, which had good structural strength and did fulfill the demands that we required for the construction. The company where interested in the project and could see themselves proceeding with the work in the future. We helped the company to find interest for computer aided simulation in collaboration with structural strength analysis, which they would like to engage in. The project has given us a larger knowledge in the choices of construction and structural strength analysis as well as experience working with computer aided construction tools.

Contexte: La cardiopathie ischémique (IHD) reste une cause majeure de mortalité en Amérique du Nord. La thérapie cellulaire cardiaque (CCT) a émergé comme une thérapie prometteuse pour aider à guérir certaines malades cardiaques. Parmi les cellulaires avec propriétés pluripotentes, les cellules stromales mésenchymateuses (MSC) sont prometteuses. Cependant, plusieurs questions demeurent non résolues et certaines défis empêchent l'application clinique de la CCT se dans l'IHD, tels que le faible taux de rétention cellulaire in situ, le suivi des cellules in vivo post-implantation et post-acheminements et l`apoptose. Ici, le traitement préliminaire des MSC avec des facteurs de croissance et leur couplage avec des nanoparticules (NP) seront étudiés comme des méthodes pour optimiser MSC. Méthodes: Des MSCs provenant du rat (rMSC) et du cochon (pMSC) ont été isolés à partir de moelle osseuse. Les rMSC ont été préconditionnées avec SDF-1a, TSG-6 et PDGF-BB, et ensuite soumises à une hypoxie, une privation de sérum et a un stress oxydatif. Des études de cicatrisation ont également été effectués avec rMSCs préconditionnées. En parallèle, de nouvelles NP ferromagnétiques liées aux silicones ont été synthétisées. Les NPs ont été couplées aux pMSCs suivant leur fonctionnalisation avec l`anticorps, CD44, un antigène de surface du MSC bien connu. Par la suite, les études de biocompatibilité ont été réalisées sur pMSC-NP et en incluant des tests des processus cellulaires tels que la migration, l'adhésion, la prolifération et les propriétés de la différenciation. Résultats: Parmi toutes les cytokines testées, PDGF-BB a démontré la plus grande capacité à améliorer la survie de MSC dans des conditions d'hypoxie, de privation de sérum et en reponse au stress oxydatif. La conjugaison de NP a atténué la migration et la prolifération des pMSCs, mais n`a pas changé leur capacité de différenciation. Enfin, la complexe du MSC-NP est détectable par IRM. Conclusion: Nos données suggèrent que de nouvelles stratégies, telles que traitement préliminaire de PDGF-BB et le couplage des nanoparticules ferromagnétiques, peuvent être considérés comme des avenues prometteuse pour optimiser les MSCs pour la CCT. / Background: Ischemic heart disease (IHD) remains a leading cause of mortality in North America. Cardiac cell therapy (CCT) has emerged as a promising therapy to help heal the damaged heart. Among the various candidates for stem-progenitor cells, Mesenchymal Multipotential Stromal/Stem Cells (MSC) is of great promise. However, there remain unresolved issues and challenges that prevent clinical application of MSC-based CCT in IHD. Among the latter, low cellular retention rate, in vivo cell tracking and post-delivery apoptosis. Here in, growth factor preconditioning and MSC coupling to nanoparticles are investigated as methods to optimize MSC. Methods：Lewis Rat MSC (rMSC) and pig MSC (pMSC) were isolated from bone marrow. Rat MSCs were preconditioned with SDF-1a, TSG-6 and PDGF-BB, and then subjected to hypoxia, serum deprivation and oxidative stress. Wound healing assays were also done with preconditioned rat MSCs. In parallel, novel ferromagnetic silicone core-shell nanoparticles (NP) were synthesized. Pig MSCs were coupled to NPs following functionalization of the NPs with an antibody to a well-recognized MSC surface antigen, CD44. Subsequently, biocompatibility studies were performed on the pMSC-NP complex and included testing of key cellular processes such as migration, adhesion, proliferation and differentiation properties. Results: Of all cytokines used, PDGF-BB showed greatest capacity to improve MSC survival under conditions of hypoxia, serum deprivation and oxidative stress. NP conjugation has mitigated effect on the migration and proliferation of pig MSC, but do not change the differentiation capacity of MSC. Finally, the MSC-NP complex was detectable by MRI. Conclusion: Our data suggest that novel strategies, such as PDGF-BB preconditioning and ferromagnetic nanoparticle coupling, can be considered as promising avenues to optimize MSCs for CCT.

For discrete distributions a variant of rejection from a continuous hat function is presented. The main advantage of the new method, called rejection-inversion, is that no extra uniform random number to decide between acceptance and rejection is required which means that the expected number of uniform variates required is halved. Using rejection-inversion and a squeeze, a simple universal method for a large class of monotone discrete distributions is developed. It can be used to generate variates from the tails of most standard discrete distributions. Rejection-inversion applied to the Zipf (or zeta) distribution results in algorithms that are short and simple and at least twice as fast as the fastest methods suggested in the literature. (author's abstract) / Series: Preprint Series / Department of Applied Statistics and Data Processing