A unified approach to controller design for achieving ISS and related properties

A unified approach to the design of controllers achieving various specified input-to-state stability (ISS) like properties is presented. Both full state and measurement feedback cases are considered. Synthesis procedures based on dynamic programming are given using the recently developed results on controller synthesis to achieve uniform l∞ bound. Our results provide a link between the ISS literature and the nonlinear H∞ design literature. © 2005 IEEE

Measurement feedback controller design to achieve input to state stability

An approach for design of measurement feedback controllers achieving input-to-state (ISS) stability properties is presented. A synthesis procedure based on dynamic programming is given. We make use of recently developed results on controller synthesis to achieve uniform l∞ bound [6]. Our results make an important connection between the ISS literature and nonlinear H∞ design methods

Vasoconstrictor prostanoids

In cardiovascular diseases and during aging, endothelial dysfunction is due in part to the release of endothelium-derived contracting factors that counteract the vasodilator effect of the nitric oxide. Endotheliumdependent contractions involve the activation of endothelial cyclooxygenases and the release of various prostanoids, which activate thromboxane prostanoid (TP) receptors of the underlying vascular smooth muscle. The stimulation of TP receptors elicits not only the contraction and the proliferation of vascular smooth muscle cells but also diverse physiological/pathophysiological reactions, including platelet aggregation and activation of endothelial inflammatory responses. TP receptor antagonists curtail endothelial dysfunction in diseases such as hypertension and diabetes, are potent antithrombotic agents, and prevent vascular inflammation. © Springer-Verlag 2009.postprin

Analysis of input-to-state stability for discrete time nonlinear systems via dynamic programming

The input-to-state stability (ISS) property for systems with disturbances has received considerable attention over the past decade or so, with many applications and characterizations reported in the literature. The main purpose of this paper is to present analysis results for ISS that utilize dynamic programming techniques to characterize minimal ISS gains and transient bounds. These characterizations naturally lead to computable necessary and sufficient conditions for ISS. Our results make a connection between ISS and optimization problems in nonlinear dissipative systems theory (including L2-gain analysis and nonlinear H∞ theory). As such, the results presented address an obvious gap in the literature. © 2005 Elsevier Ltd. All rights reserved

Skeletal muscle as a regulator of the longevity protein, Klotho

Klotho is a powerful longevity protein that has been linked to the prevention of muscle atrophy, osteopenia, and cardiovascular disease. Similar anti-aging effects have also been ascribed to exercise and physical activity. While an association between muscle function and Klotho expression has been previously suggested from longitudinal cohort studies, a direct relationship between circulating Klotho and skeletal muscle has not been investigated. In this paper, we present a review of the literature and preliminary evidence that, together, suggests Klotho expression may be modulated by skeletal muscle activity. Our pilot clinical findings performed in young and aged individuals suggest that circulating Klotho levels are upregulated in response to an acute exercise bout, but that the response may be dependent on fitness level. A similar upregulation of circulating Klotho is also observed in response to an acute exercise in young and old mice, suggesting that this may be a good model for mechanistically probing the role of physical activity on Klotho expression. Finally, we highlight overlapping signaling pathways that are modulated by both Klotho and skeletal muscle and propose potential mechanisms for cross-talk between the two. It is hoped that this review will stimulate further consideration of the relationship between skeletal muscle activity and Klotho expression, potentially leading to important insights into the well-documented systemic anti-aging effects of exercise. © 2014 Avin, Coen, Huang, Stolz, Sowa, Dubé, Goodpaster, O'Doherty and Ambrosio

Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive rats

Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.published_or_final_versio

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Does Gender Influence Colour Choice in the Treatment of Visual Stress?

Purpose Visual Stress (VS) is a condition in which words appear blurred, in motion, or otherwise distorted when reading. Some people diagnosed with VS find that viewing black text on white paper through coloured overlays or precision tinted lenses (PTLs) reduces symptoms attributed to VS. The aim of the present study is to determine whether the choice of colour of overlays or PTLs is influenced by a patient’s gender. Methods Records of all patients attending a VS assessment in two optometry practices between 2009 and 2014 were reviewed retrospectively. Patients who reported a significant and consistent reduction in symptoms with either overlay and or PTL were included in the analysis. Overlays and PTLs were categorized as stereotypical male, female or neutral colours based on gender preferences as described in the literature. Chi-square analysis was carried out to determine whether gender (across all ages or within age groups) was associated with overlay or PTL colour choice. Results 279 patients (133 males and 146 females, mean age 17 years) consistently showed a reduction in symptoms with an overlay and were included. Chi-square analysis revealed no significant association between the colour of overlay chosen and male or female gender (Chi-square 0.788, p = 0.674). 244 patients (120 males and 124 females, mean age 24.5 years) consistently showed a reduction in symptoms with PTLs and were included. Chi-square analysis revealed a significant association between stereotypical male/female/neutral colours of PTLs chosen and male/female gender (Chi-square 6.46, p = 0.040). More males preferred stereotypical male colour PTLs including blue and green while more females preferred stereotypical female colour PTLs including pink and purple. Conclusions For some VS patients, the choice of PTL colour is influenced not only by the alleviation of symptoms but also by other non-visual factors such as gender