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Shi Y.,Northern California Institute for Research and Education | Meeker W.Q.,Iowa State University
IEEE Transactions on Reliability | Year: 2012

Accelerated Destructive Degradation Tests (ADDTs) provide timely product reliability information in practical applications. This paper describes Bayesian methods for ADDT planning under a class of nonlinear degradation models with one accelerating variable. We use a Bayesian criterion based on the estimation precision of a specified failure-time distribution quantile at use conditions to find optimum test plans. A large-sample approximation for the posterior distribution provides a useful simplification to the planning criterion. The general equivalence theorem (GET) is used to verify the global optimality of the numerically optimized test plans. Optimum plans usually provide insight for constructing compromise plans which tend to be more robust, and practically useful. We present a numerical example with a log-location-scale distribution to illustrate the Bayesian test planning methods, and to investigate the effects of the prior distribution and sample size on test planning results. © 2006 IEEE. Source

Nix L.M.,University of California at San Francisco | Nix L.M.,Northern California Institute for Research and Education | Tien P.C.,University of California at San Francisco
Current HIV/AIDS Reports | Year: 2014

HIV infection and its treatment have been associated with adipose tissue changes and disorders of glucose and lipid metabolism. The proportion of HIV-infected adults over the age of 50 is also growing placing HIV-infected adults at particular risk for metabolic perturbations and cardiovascular disease. The metabolic syndrome in HIV-infected adults has been increasingly studied but whether HIV is associated with greater risk remains unclear, likely because of the interplay of host, viral and antiretroviral factors that are associated with the components of the metabolic syndrome. The relationship between HIV and diabetes mellitus (DM) risk has also been debated. While the Framingham Risk Score is a well-accepted measure of 10-year cardiovascular risk in the general population, it may not accurately predict risk in the HIV setting due to HIV-related factors such as inflammation that are not accounted for. We summarize the recent literature on metabolic syndrome, DM, and cardiovascular risk in HIV-infected adults. © 2014 Springer Science+Business Media New York. Source

Chang T.T.,University of California at San Francisco | Hughes-Fulford M.,University of California at San Francisco | Hughes-Fulford M.,Northern California Institute for Research and Education
Biomaterials | Year: 2014

Three-dimensional (3D) culture of hepatocytes leads to improved and prolonged synthetic and metabolic functions, but the underlying molecular mechanisms are unknown. In order to investigate the role of 3D cell-cell interactions in maintaining hepatocyte differentiated functions exvivo, primary mouse hepatocytes were cultured either as monolayers on tissue culture dishes (TCD) or as 3D aggregates in rotating wall vessel (RWV) bioreactors. Global gene expression analyses revealed that genes upregulated in 3D culture were distinct from those upregulated during liver development and liver regeneration. Instead, they represented a diverse array of hepatocyte-specific functional genes with significant over-representation of hepatocyte nuclear factor 4α (Hnf4a) binding sites in their promoters. Expression of Hnf4a and many of its downstream target genes were significantly increased in RWV cultures as compared to TCD. Conversely, there was concomitant suppression of mesenchymal and cytoskeletal genes in RWV cultures that were induced in TCDs. These findings illustrate the importance of 3D cell-cell interactions in maintaining fundamental molecular pathways of hepatocyte function and serve as a basis for rational design of biomaterials that aim to optimize hepatocyte functions exvivo for biomedical applications. © 2013 Elsevier Ltd. Source

Frank J.A.,University of California at San Francisco | Frank J.A.,Northern California Institute for Research and Education
Annals of the New York Academy of Sciences | Year: 2012

The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lung injury and idiopathic pulmonary fibrosis. Although relatively little is known about the function and regulation of claudin tight junction proteins in the lung, new evidence suggests that environmental stimuli can influence claudin expression and alveolar barrier function in human disease. This review considers recent advances in the understanding of the role of claudins in the breakdown of the alveolar epithelial barrier in disease and in epithelial repair. © 2012 New York Academy of Sciences. Source

Yaffe K.,University of California at San Francisco | Falvey C.M.,University of California at San Francisco | Hoang T.,Northern California Institute for Research and Education
The Lancet Neurology | Year: 2014

Sleep disturbances and cognitive impairment are common in older adults. Mounting evidence points to a potential connection between sleep and cognitive function. Findings from observational studies support a role for sleep disturbances (particularly for sleep duration, sleep fragmentation, and sleep-disordered breathing) in the development of cognitive impairment. Less consistent evidence exists for associations of insomnia and circadian rhythm dysfunction with cognition. These findings suggest that the sleep-wake cycle plays a crucial part in brain ageing, pointing to a potential avenue for improvement of cognitive outcomes in people at risk of cognitive decline and dementia. Several biological mechanisms might underlie the association between sleep and cognition, but these pathways are not completely understood. Future studies that aim to clarify the association between sleep and cognition might help to identify people at risk of cognitive disorders and to facilitate the development of novel therapies to treat and potentially prevent both sleep disturbances and cognitive impairment. © 2014 Elsevier Ltd. Source

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