建設会社のオフィスにおけるナレッジワーカーの滞在行動と会話行動の研究 : 固定席、自由席ワークプレイス、大規模オープンプラン形式のワークプレイスでのケーススタディ

京都大学0048新制・課程博士博士(工学)甲第16279号工博第3440号新制||工||1520(附属図書館)28888京都大学大学院工学研究科建築学専攻(主査)教授 鉾井 修一, 教授 髙田 光雄, 教授 加藤 直樹, 准教授 吉田 哲学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDFA

Optimal Mixed-ADC arrangement for DOA Estimation via CRB using ULA

We consider a mixed analog-to-digital converter (ADC) based architecture for direction of arrival (DOA) estimation using a uniform linear array (ULA). We derive the Cram{\'e}r-Rao bound (CRB) of the DOA under the optimal time-varying threshold, and find that the asymptotic CRB is related to the arrangement of high-precision and one-bit ADCs for a fixed number of ADCs. Then, a new concept called ``mixed-precision arrangement" is proposed. It is proven that better performance for DOA estimation is achieved when high-precision ADCs are distributed evenly around the edges of the ULA. This result can be extended to a more general case where the ULA is equipped with various precision ADCs. Simulation results show the validity of the asymptotic CRB and better performance under the optimal mixed-precision arrangement.Comment: 5 pages, 3 figures, accepted by ICASSP202

Mannose-modified erythrocyte membrane-encapsulated chitovanic nanoparticles as a DNA vaccine carrier against reticuloendothelial tissue hyperplasia virus

IntroductionThe erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs).MethodsIn this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo.ResultsCS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge.ConclusionOverall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects

Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine (4, AChE: IC50 = 0.223 μM) with pyrimidone compound 5 (GSK-3β: IC50 = 3 μM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3β (GSK-3β). The optimal compound 18a possessed potent dual AChE/GSK-3β inhibition (AChE: IC50 = 0.047 ± 0.002 μM, GSK-3β: IC50 = 0.930 ± 0.080 μM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 μM. Collectively, this work explored the structure–activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD