多言語の認知症に対する影響

Tohoku University谷内　一彦論

Computation-Performance Optimization of Convolutional Neural Networks with Redundant Kernel Removal

Deep Convolutional Neural Networks (CNNs) are widely employed in modern computer vision algorithms, where the input image is convolved iteratively by many kernels to extract the knowledge behind it. However, with the depth of convolutional layers getting deeper and deeper in recent years, the enormous computational complexity makes it difficult to be deployed on embedded systems with limited hardware resources. In this paper, we propose two computation-performance optimization methods to reduce the redundant convolution kernels of a CNN with performance and architecture constraints, and apply it to a network for super resolution (SR). Using PSNR drop compared to the original network as the performance criterion, our method can get the optimal PSNR under a certain computation budget constraint. On the other hand, our method is also capable of minimizing the computation required under a given PSNR drop.Comment: This paper was accepted by 2018 The International Symposium on Circuits and Systems (ISCAS

Enzymatic Cross-Linking of Dynamic Thiol-Norbornene Click Hydrogels

Enzyme-mediated in situ forming hydrogels are attractive for many biomedical applications because gelation afforded by enzymatic reactions can be readily controlled not only by tuning macromer compositions, but also by adjusting enzyme kinetics. For example, horseradish peroxidase (HRP) has been used extensively for in situ cross-linking of macromers containing hydroxyl-phenol groups. The use of HRP to initiate thiol-allylether polymerization has also been reported, yet no prior study has demonstrated enzymatic initiation of thiol-norbornene gelation. In this study, we discovered that HRP can generate the thiyl radicals needed for initiating thiol-norbornene hydrogelation, which has only been demonstrated previously using photopolymerization. Enzymatic thiol-norbornene gelation not only overcomes light attenuation issue commonly observed in photopolymerized hydrogels, but also preserves modularity of the cross-linking. In particular, we prepared modular hydrogels from two sets of norbornene-modified macromers, 8-arm poly(ethylene glycol)-norbornene (PEG8NB) and gelatin-norbornene (GelNB). Bis-cysteine-containing peptides or PEG-tetra-thiol (PEG4SH) was used as a cross-linker for forming enzymatically and orthogonally polymerized hydrogel. For HRP-initiated PEG-peptide hydrogel cross-linking, gelation efficiency was significantly improved via adding tyrosine residues on the peptide cross-linkers. Interestingly, these additional tyrosine residues did not form permanent dityrosine cross-links following HRP-induced gelation. As a result, they remained available for tyrosinase-mediated secondary cross-linking, which dynamically increased hydrogel stiffness. In addition to material characterizations, we also found that both PEG- and gelatin-based hydrogels exhibited excellent cytocompatibility for dynamic 3D cell culture. The enzymatic thiol-norbornene gelation scheme presented here offers a new cross-linking mechanism for preparing modularly and dynamically cross-linked hydrogels

Improving gelation efficiency and cytocompatibility of visible light polymerized thiol-norbornene hydrogels via addition of soluble tyrosine

Hydrogels immobilized with biomimetic peptides have been used widely for tissue engineering and drug delivery applications. Photopolymerization has been among the most commonly used techniques to fabricate peptide-immobilized hydrogels as it offers rapid and robust peptide immobilization within a crosslinked hydrogel network. Both chain-growth and step-growth photopolymerizations can be used to immobilize peptides within covalently crosslinked hydrogels. A previously developed visible light mediated step-growth thiol-norbornene gelation scheme has demonstrated efficient crosslinking of hydrogels composed of an inert poly(ethylene glycol)-norbornene (PEGNB) macromer and a small molecular weight bis-thiol linker, such as dithiothreitol (DTT). Compared with conventional visible light mediated chain-polymerizations where multiple initiator components are required, step-growth photopolymerized thiol-norbornene hydrogels are more cytocompatible for the in situ encapsulation of radical sensitive cells (e.g., pancreatic β-cells). This contribution explored visible light based crosslinking of various bis-cysteine containing peptides with macromer 8-arm PEGNB to form biomimetic hydrogels suitable for in situ cell encapsulation. It was found that the addition of soluble tyrosine during polymerization not only significantly accelerated gelation, but also improved the crosslinking efficiency of PEG-peptide hydrogels as evidenced by a decreased gel point and enhanced gel modulus. In addition, soluble tyrosine drastically enhanced the cytocompatibility of the resulting PEG-peptide hydrogels, as demonstrated by in situ encapsulation and culture of pancreatic MIN6 β-cells. This visible light based thiol-norbornene crosslinking mechanism provides an attractive gelation method for preparing cytocompatible PEG-peptide hydrogels for tissue engineering applications

Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix interactions in pancreatic ductal adenocarcinoma

The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT)

Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age.

We hypothesize that altered intensities of a few morphogenic pathways account for most/all the phenotypes of aging. Investigating this has revealed a novel approach to rejuvenate multiple mammalian tissues by defined pharmacology. Specifically, we pursued the simultaneous youthful in vivo calibration of two determinants: TGF-beta which activates ALK5/pSmad 2,3 and goes up with age, and oxytocin (OT) which activates MAPK and diminishes with age. The dose of Alk5 inhibitor (Alk5i) was reduced by 10-fold and the duration of treatment was shortened (to minimize overt skewing of cell-signaling pathways), yet the positive outcomes were broadened, as compared with our previous studies. Alk5i plus OT quickly and robustly enhanced neurogenesis, reduced neuro-inflammation, improved cognitive performance, and rejuvenated livers and muscle in old mice. Interestingly, the combination also diminished the numbers of cells that express the CDK inhibitor and marker of senescence p16 in vivo. Summarily, simultaneously re-normalizing two pathways that change with age in opposite ways (up vs. down) synergistically reverses multiple symptoms of aging

Manganese-Catalyzed Cross-Coupling of Thiols with Aryl Iodides

Here we report the manganesecatalyzedcoupling reaction of thiols witharyl iodides, giving the aryl thioethers ingood to excellent yields; the system showsgood functional group tolerance and enablesthe sterically demanding aryl iodides tocouple with thiols

The Effect of Culture on Trust in Automation: Reliability and Workload

Trust in automation has become a topic of intensive study over the past two decades. While the earliest trust experiments involved human interventions to correct failures/errors in automated control systems a majority of subsequent studies have investigated information acquisition and analysis decision aiding tasks such as target detection for which automation reliability is more easily manipulated. Despite the high level of international dependence on automation in industry and transport almost all current studies have employed Western samples primarily from the US. The present study addresses these gaps by running a large sample experiment in three (US, Taiwan and Turkey) diverse cultures using a ‘trust sensitive task’ consisting of both automated control and target detection subtasks. This paper presents results for the target detection subtask for which reliability and task load were manipulated. The current experiments allow us to determine whether reported effects are universal or specific to Western culture, vary in baseline or magnitude, or differ across cultures. Results generally confirm consistent effects of manipulations across the three cultures as well as cultural differences in initial trust and variation in effects of manipulations consistent with 10 cultural hypotheses based on Hofstede’s Cultural Dimensions and Leung and Cohen’s theory of Cultural Syndromes. These results provide critical implications and insights for enhancing human trust in intelligent automation systems across cultures. Our paper presents the following contributions: First, to the best of our knowledge, this is the first set of studies that deal with cultural factors across all the cultural syndromes identified in the literature by comparing trust in the Honor, Face, Dignity cultures. Second, this is the first set of studies that uses a validated cross-cultural trust measure for measuring trust in automation. Third, our experiments are the first to study the dynamics of trust across cultures