Instances of mixed buckling and post-buckling of steel RHS beams

Simply supported steel beams with rectangular hollow section (RHS) are investigated, taking into account large twist and cross-sections distortions. A closed-form expression for the critical value of the external couple inducing lateral torsional buckling is found; homotopy perturbation method (HPM) is used to investigate the post-buckling non-linear path. The linear and non-linear paths given by HPM are compared to those of: i) a Newton–Raphson algorithm with arc length; and ii) the commercial FEM code Abaqus. Some numerical examples are presented

A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

An evaluation of load balancing algorithms for distributed systems

Distributed systems are gradually being accepted as the dominant computing paradigm of the future. However, due to the diversity and multiplicity of resources, and the need for transparency to users, global resource management raises many questions. On the performance level the potential benefits of the load balancing in resolving the occasional congestion experienced by some nodes while others are idle or lightly loaded are commonly accepted. It is also acknowledged that no single load balancing algorithm deals satisfactorily with the changing system characteristics and dynamic workload environment. In modelling distributed systems for load balancing, optimistic assumptions of system characteristics are commonly made, with no evaluation of alternative system design options such as communications protocols. When realistic assumptions are made on system attributes such as communication bandwidth, load balancing overheads, and workload model, doubts are cast on the capability of load balancing to improve the performance of distributed systems significantly. A taxonomy is developed for the components as well as the attributes aspects of load balancing algorithms to provide a common terminology and a comprehensive view to load balancing in distributed systems. For adaptive algorithms the taxonomy is extended to identify the issues involved and the ways of adding adaptability along different dimensions. A design methodology is also outlined. A review of related work is used to identify the most promising load balancing strategies and the modelling assumptions made in previous load balancing studies. Subsequently the research problems addressed in this thesis and the design of new algorithms are detailed. A simulated system developed to allow an experimentation with various load balancing algorithms under different workload models and system attributes is described. Based on the nature of the file system structure and the classes of nodes processing speed involved, different models of loosely-coupled distributed systems can be defined. Four models are developed: disk-based homogeneous nodes, diskless homogeneous nodes, diskless heterogeneous nodes, and disk-based heterogeneous nodes. The nodes are connected through a broadcast transfer device. A set of representative load balancing algorithms covering a range of strategies are evaluated and compared for the four models of distributed systems. The algorithms developed include a new algorithm called Diffuse based on explicit adaptability for the homogeneous systems. In the case of heterogeneous systems, novel modifications are made to a number of algorithms to take into account the heterogeneity of nodes speed. The evaluation on homogeneous systems is two-fold: an assessment of the effect of system attributes on the performance of the distributed system subject to these algorithms, and a comparison of the relative merits of the algorithms using different performance metrics, and in particular a classification of the performance of the Diffuse algorithm with regard to others in the literature. For the heterogeneous systems the performance of the adapted algorithms is compared to that of the standard versions and to the no load balancing case. As a result of this evaluation, for a set of combinations of performance objectives, distributed system attributes, and workload environment, we identify the most . appropriate load balancing algorithm and optimal values for adjustable parameters of the algorithm

un système multi-agents pour calculer les indicateurs d'activités d'apprentissage humain à partir d'une ingénierie diririgée par les modèles

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