Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune‐mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose‐derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti‐fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710–1722
As voltages decrease, soft errors are expected to become an increasing problem in maintaining program correctness. Unfortunately, previous mechanisms to improve processor reliability protect all processor instructions equally, causing such approaches to suffer from significant performance degradation and/or substantial hardware overhead. However, recent research has shown that in multimedia applications such as photography, video, and audio, not all instructions are created equal: many operations prove to be far more tolerant to faults than others [1].This observation can be leveraged to limit the cost of reliable computing by protecting only those instructions that are critical to correct execution. We propose a mechanism to protect against soft errors through selective instruction replication. We begin with a dynamic instruction replication framework that replicates every instruction and checks them upon commit, rolling back for any inconsistent results. Instead of replicating the entire program, instructions that the compiler identifies as tolerant to error would remain unprotected. While full replication requires 40% to 100% overhead, our mechanism requires only 30% to 75% overhead, reducing the overhead by 15-33% with minimal hardware overhead. We suffer only 0.5 -1% fidelity degradation with this approach.
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