Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.</p> <p>Methods</p> <p>Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.</p> <p>Results</p> <p>The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both <it>in vitro </it>and <it>in vivo </it>after transplantation into regenerating muscle of immunodeficient mice.</p> <p>Conclusions</p> <p>Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess <it>in vivo </it>the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.</p

Designing Multi-Leader-Based Allgather Algorithms for Multi-Core Clusters

The increasing demand for computational cycles is being met by the use of multi-core processors. Having large number of cores per node necessitates multi-core aware designs to extract the best performance. The Message Passing Interface (MPI) is the dominant parallel programming model on modern high performance computing clusters. The MPI collective operations take a significant portion of the communication time for an application. The existing optimizations for collectives exploit shared memory for intranode communication to improve performance. However, it still would not scale well as the number of cores per node increase. In this work, we propose a novel and scalable multileader-based hierarchical Allgather design. This design allows better cache sharing for Non-Uniform Memory Access (NUMA) machines and makes better use of the network speed available with high performance interconnects such as InfiniBand. The new multi-leader-based scheme achieves a performance improvement of up to 58 % for small messages and 70 % for medium sized messages

Evaluating the networking characteristics of the Cray XC-40 Intel Knights Landing-based Cori supercomputer at NERSC

There are many potential issues associated with deploying the Intel Xeon PhiTM (code named Knights Landing [KNL]) manycore processor in a large-scale supercomputer. One in particular is the ability to fully utilize the high-speed communications network, given that the serial performance of a Xeon PhiTM core is a fraction of a Xeon®core. In this paper, we take a look at the trade-offs associated with allocating enough cores to fully utilize the Aries high-speed network versus cores dedicated to computation, eg, the trade-off between MPI and OpenMP. In addition, we evaluate new features of Cray MPI in support of KNL, such as internode optimizations. We also evaluate one-sided programming models such as Unified Parallel C. We quantify the impact of the above trade-offs and features using a suite of National Energy Research Scientific Computing Center applications

Evaluating the networking characteristics of the Cray XC-40 Intel Knights Landing-based Cori supercomputer at NERSC

There are many potential issues associated with deploying the Intel Xeon PhiTM (code named Knights Landing [KNL]) manycore processor in a large-scale supercomputer. One in particular is the ability to fully utilize the high-speed communications network, given that the serial performance of a Xeon PhiTM core is a fraction of a Xeon®core. In this paper, we take a look at the trade-offs associated with allocating enough cores to fully utilize the Aries high-speed network versus cores dedicated to computation, eg, the trade-off between MPI and OpenMP. In addition, we evaluate new features of Cray MPI in support of KNL, such as internode optimizations. We also evaluate one-sided programming models such as Unified Parallel C. We quantify the impact of the above trade-offs and features using a suite of National Energy Research Scientific Computing Center applications