Infinite-dimensional LMI approach to analysis and synthesis for linear time-delay systems

summary:This paper considers an analysis and synthesis problem of controllers for linear time-delay systems in the form of delay-dependent memory state feedback, and develops an Linear Matrix Inequality (LMI) approach. First, we present an existence condition and an explicit formula of controllers, which guarantee a prescribed level of $L^2$ gain of closed loop systems, in terms of infinite-dimensional LMIs. This result is rather general in the sense that it covers, as special cases, some known results for the cases of delay- independent/dependent and memoryless/memory controllers, while the infinity dimensionality of the LMIs makes the result difficult to apply. Second, we introduce a technique to reduce the infinite-dimensional LMIs to a finite number of LMIs, and present a feasible algorithm for synthesis of controllers based on the finite-dimensional LMIs

Mechanical Stimulation-Induced Calcium Signaling by Piezo1 Channel Activation in Human Odontoblast Reduces Dentin Mineralization

Odontoblasts play critical roles in dentin formation and sensory transduction following stimuli on the dentin surface. Exogenous stimuli to the dentin surface elicit dentinal sensitivity through the movement of fluids in dentinal tubules, resulting in cellular deformation. Recently, Piezo1 channels have been implicated in mechanosensitive processes, as well as Ca(2+) signals in odontoblasts. However, in human odontoblasts, the cellular responses induced by mechanical stimulation, Piezo1 channel expression, and its pharmacological properties remain unclear. In the present study, we examined functional expression of the Piezo1 channel by recording direct mechanical stimulation-induced Ca(2+) signaling in dentin matrix protein 1 (DMP-1)-, nestin-, and dentin sialophosphoprotein (DSPP)-immunopositive human odontoblasts. Mechanical stimulation of human odontoblasts transiently increased intracellular free calcium concentration ([Ca(2+)](i)). Application of repeated mechanical stimulation to human odontoblasts resulted in repeated transient [Ca(2+)](i) increases, but did not show any desensitizing effects on [Ca(2+)](i) increases. We also observed a transient [Ca(2+)](i) increase in the neighboring odontoblasts to the stimulated cells during mechanical stimulation, showing a decrease in [Ca(2+)](i) with an increasing distance from the mechanically stimulated cells. Application of Yoda1 transiently increased [Ca(2+)](i). This increase was inhibited by application of Gd(3+) and Dooku1, respectively. Mechanical stimulation-induced [Ca(2+)](i) increase was also inhibited by application of Gd(3+) or Dooku1. When Piezo1 channels in human odontoblasts were knocked down by gene silencing with short hairpin RNA (shRNA), mechanical stimulation-induced [Ca(2+)](i) responses were almost completely abolished. Piezo1 channel knockdown attenuated the number of Piezo1-immunopositive cells in the immunofluorescence analysis, while no effects were observed in Piezo2-immunopositive cells. Alizarin red staining distinctly showed that pharmacological activation of Piezo1 channels by Yoda1 significantly suppressed mineralization, and shRNA-mediated knockdown of Piezo1 also significantly enhanced mineralization. These results suggest that mechanical stimulation predominantly activates intracellular Ca(2+) signaling via Piezo1 channel opening, rather than Piezo2 channels, and the Ca(2+) signal establishes intercellular odontoblast-odontoblast communication. In addition, Piezo1 channel activation participates in the reduction of dentinogenesis. Thus, the intracellular Ca(2+) signaling pathway mediated by Piezo1 channels could contribute to cellular function in human odontoblasts in two ways: (1) generating dentinal sensitivity and (2) suppressing physiological/reactional dentinogenesis, following cellular deformation induced by hydrodynamic forces inside dentinal tubules

酵母の細胞分裂に対する理論システム生物学の構築に関する研究

宇都宮大学 / 金沢大学理工研究域平成18年度における研究補助金を受けて,酵母の細胞分裂におけるCdc25タンパク質及びWee1タンパク質の機能を,システム理論を用いることによって,理論的に示すことが可能となった.まず,Active MPFに基づく酵母の細胞分裂の基本タンパク質ネットワークモデルを,質量方程式手法及びミカエレス・メンテン法の2種類の方法を用いて,非線形方程式として記述した.次に,非線形方程式に対して周期感度を定義し,それぞれの非線形方程式に対して適用した.そして,この周期感度に基づいて酵母の細胞分裂のロバスト性を検証したところ,Cdc25タンパク質及びWee1タンパク質を考慮することで,酵母の細胞分裂のロバスト性が飛躍的に向上することが示された.特に,質量方程式手法及びミカエレス・メンテン法のどちらの場合においても,Cdc25タンパク質及びWee1タンパク質を考慮することでロバスト性の飛躍的な向上が見られ,表現方法によらずロバスト性向上の結果が得られたことは従来の実験ベースの酵母の細胞分裂研究では得られていないものである.以上の研究成果を考慮すると,本研究の結果として,酵母の細胞分裂に対する理論システム生物学に対するロバスト性を検証するための一つの方法を確立することが出来た.しかし,酵母の細胞分裂に関連するタンパク質はすでに数百個見つかっており,その遺伝子-タンパク質ネットワーク構造を考慮すると,状態が1千次元程度のロバスト性解析手法の確立が必要となる.また,ロバスト性解析以外に,細胞分裂を停止させるための制御手法を確立するなどの課題が残されている.研究課題/領域番号:17760347, 研究期間(年度):2005 – 2006出典：「酵母の細胞分裂に対する理論システム生物学の構築に関する研究」研究成果報告書　課題番号17760347（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-17760347/)を加工して作