Stochastic Asymptotic Stabilizers for Deterministic Input-Affine Systems based on Stochastic Control Lyapunov Functions

In this paper, a stochastic asymptotic stabilization method is proposed for deterministic input-affine control systems, which are randomized by including Gaussian white noises in control inputs. The sufficient condition is derived for the diffucion coefficients so that there exist stochastic control Lyapunov functions for the systems. To illustrate the usefulness of the sufficient condition, the authors propose the stochastic continuous feedback law, which makes the origin of the Brockett integrator become globally asymptotically stable in probability.Comment: A preliminary version of this paper appeared in the Proceedings of the 48th Annual IEEE Conference on Decision and Control [14

Sirtuins in Neuroendocrine Regulation and Neurological Diseases

Silent information regulator 1 (SIRT1) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Sirtuin was originally studied as the lifespan-extending gene, silent information regulator 2 (SIRT2) in budding yeast. There are seven mammalian homologs of sirtuin (SIRT1–7), and SIRT1 is the closest homolog to SIRT2. SIRT1 modulates various key targets via deacetylation. In addition to histones, these targets include transcription factors, such as forkhead box O (FOXO), Ku70, p53, NF-κB, PPAR-gamma co-activator 1-alpha (PGC-1α), and peroxisome proliferator-activated receptor γ (PPARγ). SIRT1 has many biological functions, including aging, cell survival, differentiation, and metabolism. Genetic and physiological analyses in animal models have shown beneficial roles for SIRT1 in the brain during both development and adulthood. Evidence from in vivo and in vitro studies have revealed that SIRT1 regulates the cellular fate of neural progenitors, axon elongation, dendritic branching, synaptic plasticity, and endocrine function. In addition to its importance in physiological processes, SIRT1 has also been implicated in protection of neurons from degeneration in models of neurological diseases, such as traumatic brain injury and Alzheimer’s disease. In this review, we focus on the role of SIRT1 in the neuroendocrine system and neurodegenerative diseases. We also discuss the potential therapeutic implications of targeting the sirtuin pathway

グルコースセンサーヘノオウヨウヘムケタチョクセツデンシイドウノウヲユウスルグルコースダツスイソコウソノキシツトクイセイノカイゼントデンシデンタツケイロノカイメイ

博士（工学）東京農工大

Monotonicity for Multiobjective Accelerated Proximal Gradient Methods

Accelerated proximal gradient methods, which are also called fast iterative shrinkage-thresholding algorithms (FISTA) are known to be efficient for many applications. Recently, Tanabe et al. proposed an extension of FISTA for multiobjective optimization problems. However, similarly to the single-objective minimization case, the objective functions values may increase in some iterations, and inexact computations of subproblems can also lead to divergence. Motivated by this, here we propose a variant of the FISTA for multiobjective optimization, that imposes some monotonicity of the objective functions values. In the single-objective case, we retrieve the so-called MFISTA, proposed by Beck and Teboulle. We also prove that our method has global convergence with rate $O(1/k^2)$, where $k$ is the number of iterations, and show some numerical advantages in requiring monotonicity.Comment: - Added new numerical experiment

Interference of CLN6 mutants

CLN6 (Ceroid Lipofuscinosis, Neuronal, 6) is a 311-amino acid protein spanning the endoplasmic reticulum membrane. Mutations in CLN6 are linked to CLN6 disease, a hereditary neurodegenerative disorder categorized into the neuronal ceroid lipofuscinoses. CLN6 disease is an autosomal recessive disorder and individuals affected with this disease have two identical (homozygous) or two distinct (compound heterozygous) CLN6 mutant alleles. Little has been known about CLN6’s physiological roles and the disease mechanism. We recently found that CLN6 prevents protein aggregate formation, pointing to impaired CLN6’s anti-aggregate activity as a cause for the disease. To comprehensively understand the pathomechanism, overall anti-aggregate activity derived from two different CLN6 mutants needs to be investigated, considering patients compound heterozygous for CLN6 alleles. We focused on mutant combinations involving the S132CfsX18 (132fsX) prematurely terminated protein, produced from the most frequent mutation in CLN6. The 132fsX mutant nullified anti-aggregate activity of the P299L CLN6 missense mutant but not of wild-type CLN6. Wild-type CLN6’s resistance to the 132fsX mutant was abolished by replacement of amino acids 297–301, including Pro297 and Pro299, with five alanine residues. Given that removal of CLN6’s C-terminal fifteen amino acids 297–311 (luminal tail) did not affect the resistance, we suggested that CLN6’s luminal tail, when unleashed from Pro297/299-mediated conformational constraints, is improperly positioned by the 132fsX mutant, thereby blocking the induction of anti- aggregate activity. We here reveal a novel mechanism for dissipating CLN6 mutants’ residual functions, providing an explanation for the compound heterozygosity-driven pathogenesis

Zyxin is a novel interacting partner for SIRT1

<p>Abstract</p> <p>Background</p> <p>SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development.</p> <p>Results</p> <p>To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation.</p> <p>Conclusion</p> <p>Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.</p

High-voltage scanning transmission electron microscopy: A tool for structural characterization of micrometer-thick specimens

Herein, the advantages of high-voltage scanning transmission electron microscopy (STEM) as a tool for structural characterization of micrometer-thick specimens are reported. Dislocations introduced in a wedge-shaped Si crystal were clearly observed by bright-field STEM operating at 1 MV. Many of the dislocations were straight and parallel to the 〈110〉, 〈112〉 or 〈113〉 directions. The widths of the dislocations in the STEM images were almost constant at 13–16 nm (i.e., 4–5 pixels) in the thickness range between 1 and 7.5 µm. The latest high-voltage STEM instrumentation is thus useful for imaging crystal defects in micrometer-thick materials, and enables multi-scale fields of view from a few nanometers squared to over 100 µm2