Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Dynamic Algorithm for Linear Quadratic Gaussian Predictive Control

In this paper, the optimal control law is derived for a multi-variable state-space Linear Quadratic Gaussian Predictive Controller (LQGPC). A dynamic performance index is utilized resulting in an optimal steady-state controller. Knowledge of future reference values is incorporated into the controller design and the solution is derived using the method of Lagrange multipliers. It is shown how the well-known GPC controller can be obtained as a special case of the LQGPC controller design. The important advantage of using the LQGPC framework for designing predictive controllers is that, based on stabilizing properties of LQG control, it enables a systematic approach to selection of the design parameters to yield a stable closed-loop system. The system model considered in this paper can be further extended toalso include direct feed-through and knowledge about future external inputs