PubMed Health⌕ Search

Biomedical subjects

S Sundararajan

Publications and source records attributed to S Sundararajan.

5 recordsLinked to original sources

Predictive approaches for choosing hyperparameters in gaussian processes.

Gaussian processes are powerful regression models specified by parameterized mean and covariance functions. Standard approaches to choose these parameters (known by the name hyperparameters) are maximum likelihood and maximum a posteriori. In this article, we propose and investigate predictive approaches based on Geisser's predictive sample reuse (PSR) methodology and the related Stone's cross-validation (CV) methodology. More specifically, we derive results for Geisser's surrogate predictive probability (GPP), Geisser's predictive mean square error (GPE), and the standard CV error and make a comparative study. Within an approximation we arrive at the generalized cross-validation (GCV) and establish its relationship with the GPP and GPE approaches. These approaches are tested on a number of problems. Experimental results show that these approaches are strongly competitive with the existing approaches.

Likelihood Functions↗

Exposure of developing oligodendrocytes to cadmium causes HSP72 induction, free radical generation, reduction in glutathione levels, and cell death.

Primary cultures of oligodendrocytes were used to study the toxic effects of cadmium chloride. Cell viability was evaluated by the mitochondrial dehydrogenase activity and confirmed by propidium iodide (PI) fluorescence staining. The expression of the 72 kDa stress protein, HSP72, was assayed by Western blot analysis. The results showed that Cd(2+)-induced toxicity was dependent on the time and dose of exposure, as well as on the developmental stage of the cultures. Oligodendrocyte progenitors were more vulnerable to Cd(2+) toxicity than were mature oligodendrocytes. Mature oligodendrocytes accumulated relatively higher levels of Cd(2+) than did progenitors, as determined by (109)CdCl(2) uptake; treatment with the metal ion caused a more pronounced reduction in intracellular glutathione levels and significantly higher free radical accumulation in progenitors. The latter could explain the observed differences in Cd(2+) susceptibility. HSP72 protein expression was increased both in progenitors and in mature cells exposed to Cd(2+). Pretreatment with N-acetylcysteine, a thiocompound with antioxidant activity and a precursor of glutathione, prevented Cd(2+)-induced (i) reduction in glutathione levels and (ii) induction of HSP72 and diminished (i) Cd(2+) uptake and (ii) Cd(2+)-evoked cell death. In contrast, buthionine sulfoximine, an inhibitor of gamma-glutamyl-cysteine synthetase, depleted glutathione, and potentiated the toxic effect of Cd(2+). These results strongly suggest that Cd(2+)-induced cytotoxicity in oligodendrocytes is mediated by reactive oxygen species and is modulated by glutathione levels.

Acetylcysteine↗

Thrombolysis for acute stroke: is it for everyone?

To date, there is only one US Food and Drug Administration-approved treatment for stroke. Many patients have benefited after receiving rt-PA within 3 hours of acute stroke. Although the risk of hemorrhagic conversion is real, the patients at high risk for this complication are often the same patients most at risk for poor outcome secondary to their ischemic events. In this article, we review the data supporting the use of thrombolytics, both intravenously and intra-arterially, as well as patient selection criteria. Furthermore, we provide a framework for administering rt-PA and discuss the future of thrombolytic therapy.

Fibrinolytic Agents↗