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Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/m TOR inhibitor

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World Journal of Gastroenterology 2017年第42期23卷 7551-7562页

作者： Winn Aung Atsushi B Tsuji Hitomi Sudo Aya Sugyo yoshinori ukai Katsushi Kouda Yoshikazu Kurosawa Takako Furukawa Tsuneo Saga Tatsuya Higashi Department of Molecular Imaging and Theranostics National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and Technology(QST-NIRS) Perseus Proteomics Inc. Innovation Center for Advanced Medicine Fujita Health University Department of Radiological and Medical Laboratory Sciences Nagoya University Graduate School of Medicine Department of Diagnostic Radiology Kyoto University Hospital

AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer *** Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm *** We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, dec

关键词： Radioimmunotherapy Pancreatic cancer Anti-integrin α6β4 antibody Yttrium-90 NVP-BEZ235

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Experimental study on boundary lubricity of superficial area of articular cartilage and synovial fluid

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Friction 2024年第5期12卷 981-996页

作者： Wenxiao LI Takehiro MORITA yoshinori SAWAE Departure of Mechanical Engineering Kyushu UniversityFukuoka8190395Japan International Institute for Carton-Neutral Energy Research Kyushu UniversityFukuoka8190395Japan Advanced Research Center for Biomechanics Kyushu UniversityFukuoka8190395Japan

The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in *** this study,to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid(SF),cartilage specimens were processed with four different treatments:gentle and severe washing with detergent,incubation in NaCl solution,and trypsin digestion to selectively remove certain constituents from the cartilage ***,the frictional characteristics were examined in phosphate-buffered saline(PBS)and SF against *** reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage ***,the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion *** coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in ***,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited *** the low COF group of specimens,all four treatments increased the COF in PBS to different extents,and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by *** means that the intact cartilage surface had lubricating constituents to maintain low friction,and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage *** variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage *** lubricating effect of SF could be confirmed even after degenerative treatment.

关键词： articular cartilage synovial fluid the uppermost superficial layer boundary lubrication

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Regeneration mechanisms and therapeutic strategies for neuromuscular junctions in aging and diseases

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Neural Regeneration Research 2025年第1期20卷 193-194页

作者： Masashi Fujitani Abu Md Mamun Tarif yoshinori Otani Department of Anatomy and Neuroscience Faculty of MedicineShimane UniversityShimaneJapan

The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ structure is classically described as having a“pretzel-like”shape in mice(Figure 1),whereas human NMJs have a smaller,fragmented structure throughout *** NMJs exhibit smaller or fragmented endplates,partial denervation,reduced numbers of synaptic vesicles,abnormal presynaptic mitochondria,and dysfunctional perisynaptic Schwann cells(Alhindi et al.,2022).

关键词： aging structure Figure

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Development of a scintillating-fiber-based beam monitor for the coherent muon-to-electron transition experiment

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Nuclear Science and Techniques 2024年第4期35卷 156-164页

作者： Yu Xu Yun-Song Ning Zhi-Zhen Qin Yao Teng Chang-Qing Feng Jian Tang Yu Chen yoshinori Fukao Satoshi Mihara Kou Oishi School of Physics Sun Yat-sen UniversityGuangzhou 510275China State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China High Energy Accelerator Research Organization(KEK) Ibaraki 305‑0801Japan Department of Physics Imperial College LondonLondon SW72AZUK

The coherent muon-to-electron transition(COMET)experiment is a leading experiment for the coherent conversion of μ^(-)N→e^(-)N using a high-intensity pulsed muon beamline,produced using innovative slow-extraction ***,it is critical to measure the muon beam *** set up a muon beam monitor(MBM),where scintillating fibers woven in a cross shape were coupled to silicon photomultipliers to measure the spatial profile and timing structure of the extracted muon beam for the *** MBM detector was tested successfully with a proton beamline at the China Spallation Neutron Source and took data with good performance in the commissioning *** development of the MBM,including its mechanical structure,electronic readout,and beam measurement results,are discussed.

关键词： Beam instrumentation Profile monitor Scintillating fiber Silicon photomultipliers

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Ssu72磷酸酶缺失导致减数第二次分裂过程中纺锤体交叉

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遗传 2024年第6期46卷 502-508页

作者：闫静亮马玲玲渡边嘉典江南大学未来食品科学中心无锡214122 江南大学生物工程学院无锡214122

Ssu72磷酸酶是酵母裂解/多聚腺苷化因子(cleavage/polyadenylation factor,CPF)复合物的组成成分,可以催化RNA聚合酶II的C末端结构域(C-terminal domain,CTD)S5-P、S7-P的去磷酸化。后又有研究指出Ssu72磷酸酶参与有丝分裂过程中染色体... 详细信息

Ssu72磷酸酶是酵母裂解/多聚腺苷化因子(cleavage/polyadenylation factor,CPF)复合物的组成成分,可以催化RNA聚合酶II的C末端结构域(C-terminal domain,CTD)S5-P、S7-P的去磷酸化。后又有研究指出Ssu72磷酸酶参与有丝分裂过程中染色体凝聚力的调控。为进一步明确Ssu72磷酸酶是否会影响裂殖酵母减数分裂过程中染色体的分离,本研究利用绿色荧光蛋白(green fluorescent protein,GFP)标记着丝粒、红色荧光蛋白标记微管蛋白Atb2,并在荧光显微镜下实时观察ssu72Δ细胞的整个减数分裂染色体分离过程。结果表明,ssu72Δ细胞在减数第二次分裂中后期发生纺锤体交叉,并且这种纺锤体的交叉产生了一种新型的孢子排布缺陷模式。本研究为高等生物中磷酸酶Ssu72的研究提供重要的借鉴意义。

关键词：裂殖酵母减数分裂 Ssu72 纺锤体交叉

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Recovery of rare-earth metal neodymium from aqueous solutions by poly-γ-glutamic acid and its sodium salt as biosorbents:Effects of solution pH on neodymium recovery mechanisms

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Journal of Rare Earths 2018年第5期36卷 528-536页

作者： Misaki Hisada yoshinori Kawase Research Center for Biochemical and Environmental Engineering Department of Applied Chemistry Toyo University 2100 Kujirai kawagoe Saitama 350-8585 Japan

For recovery of metals from low-concentration sources, biosorption is one of promising technologies and poly-γ-glutamic acid（γ-PGA） has been known as a potential biosorbent for recovery of heavy metals from aqueous solutions. Effects of solution pH on recovery of rare-earth metal Nd are systematically examined to clarify mechanisms of Nd recovery by y-PGA and its sodium salt（y-PGANa）. The recovery efficiency of Nd by y-PGA increases from 2.4 to 19.6% as pH increases from 2 to 4. Subsequently the Nd recovery efficiencies for y-PGA and y-PGANa remain almost constant in the range of pH from 4 to 7. For pH 〉 7 the increase in Nd recovery is significant and 100% recovery of Nd is achieved at pH 9. The pH dependency on Nd recovery by y-PGANa is similar to that by y-PGA. Contributions of adsorption and precipitation/coagulation to Nd recovery process are quantified. Whereas the adsorption dominates Nd recovery at lower pH（〈～4）, the precipitation/coagulation controls Nd recovery process for pH 〉 7. At higher pH, purple gel precipitates are observed. The maximum adsorption capacities for γ-PGA and yPGANa are 215 mg-Nd/（g-γ-PGA） at pH 4 and 305 mg-Nd/（g-y-PGANa） at pH 3, respectively. From the spectra of FT-IR and XPS, the biosorption of Nd onto y-PGA and y-PGANa via electrostatic interaction with carboxylate anions at pH 3 is verified. The Nd complexation with amide and carboxylate anion groups on γ-PGA and γ-PGANa may also contribute to the Nd recovery. The biosorption isotherms for Nd recovery by γ-PGA and γ-PGANa can be satisfactorily fitted by the Langmuir model. The thermodynamic studies suggest that the biosorptions of Nd by γ-PGA and γ-PGANa are endothermic. The utilization of γ-PGA and γ-PGANa as potential and eco-friendly biosorbents for the highly effective recovery of Nd from aqueous solution is confirmed.

关键词： Rare-earth metal Nd recovery Poly-y-glutamic acid Biosorption Precipitation Coexisting cations

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Estimating camera parameters from starry night photographs

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Computational Visual Media 2020年第4期6卷 445-454页

作者： Naoto Ishikawa yoshinori Dobashi Graduate School of Information Science and Technology Hokkaido UniversitySapporoJapan

We propose an efficient, specific method for estimating camera parameters from a single starry night image. Such an image consists of a collection of disks representing stars, so traditional estimation methods for common pictures do not work. Our method uses a database, a star catalog, that stores the positions of stars on the celestial sphere. Our method computes magnitudes(i.e., brightnesses) of stars in the input image and uses them to find the corresponding stars in the star catalog. Camera parameters can then be estimated by a simple geometric calculation. Our method is over ten times faster and more accurate than a previous method.

关键词： astrophotography constellation star identification pattern matching

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着丝粒蛋白Fta2磷酸化对减数分裂的影响

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遗传 2024年第7期46卷 552-559页

作者：倪子涵闵羽马玲玲渡边嘉典江南大学未来食品科学中心无锡214122 江南大学生物工程学院无锡214122

在减数分裂过程中,黏连蛋白(cohesin)在着丝粒区域定位出现缺陷时会导致一系列疾病的产生。黏连蛋白的正确定位离不开装载复合体Mis4-Ssl3的参与,现已知黏连蛋白在装载复合体的帮助下完成装载过程,但是其如何在着丝粒区域定位仍不清楚... 详细信息

在减数分裂过程中,黏连蛋白(cohesin)在着丝粒区域定位出现缺陷时会导致一系列疾病的产生。黏连蛋白的正确定位离不开装载复合体Mis4-Ssl3的参与,现已知黏连蛋白在装载复合体的帮助下完成装载过程,但是其如何在着丝粒区域定位仍不清楚。基于已有研究报道黏连蛋白在着丝粒的定位由着丝粒蛋白的磷酸化介导,本研究从Sim4着丝粒蛋白复合体组分Fta2蛋白着手,通过生物信息学手段寻找潜在的磷酸化位点,在裂殖酵母(Schizosaccharomyces pombe)中构建了fta2-9A和fta2-9D突变体,并通过噻苯咪唑(thiabendazole,TBZ)敏感度测试和荧光显微定位对其表型进行检测。结果显示,Fta2蛋白的磷酸化对有丝分裂没有影响,但对减数分裂染色体分离存在影响。本研究表明Fta2的磷酸化对减数分裂非常重要,很可能与减数分裂特有的黏连蛋白定位有关。

关键词：减数分裂黏连蛋白 Fta2 磷酸化装载复合体

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Study on multimers and their structures in molecular association mixture

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Science China Chemistry 2007年第1期50卷 23-31页

作者： YAMAGUCHI yoshinori OZAKI Yukihiro Consolidated Research Institute for Advanced Science and Medical Care Waseda UniversityJapan Department of Chemistry School of Science and TechnologyKwansei-Gakuin UniversitySandaHyogo 669-1337Japan

Self-association system of(R)-1,3-butanediol in dilute carbon tetrachloride(CCl4)solution is studied as a model of molecular association *** methods including FSMWEFA(fixed-size moving window evolving factor analysis)combined with PCA(principal component analysis),SIMPLISMA (simple-to-use interactive self-modeling mixture analysis),and ITTFA(iterative target transformation factor analysis)are adopted to resolve infrared spectra of(R)-1,3-butanediol *** number and equilibrium constant are computed.(R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium *** investigation of trimer structures is carried out with DFT(density functional theory),and structural factors are analyzed.

关键词： (R)-1 3-butanediol multimer chemometrics density functional theory

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Moa1与CENP-C和Rec8的相互作用及其在裂殖酵母减数分裂中的功能

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遗传 2024年第8期46卷 649-660页

作者：闵羽倪子涵马玲玲渡边嘉典江南大学未来食品科学中心无锡214122 江南大学生物工程学院无锡214122

减数分裂特异性调控分子Moa1定位到着丝粒受到动粒蛋白CENP-C的调控,同时Moa1参与黏连蛋白Rec8介导的着丝粒区域姐妹染色单体的黏连。为了研究这些蛋白质之间的相互作用,本研究利用酵母双杂交实验(yeast two-hybrid assay)测定分析了Moa... 详细信息

减数分裂特异性调控分子Moa1定位到着丝粒受到动粒蛋白CENP-C的调控,同时Moa1参与黏连蛋白Rec8介导的着丝粒区域姐妹染色单体的黏连。为了研究这些蛋白质之间的相互作用,本研究利用酵母双杂交实验(yeast two-hybrid assay)测定分析了Moa1和CENP-C、Rec8之间的相互作用,并通过在Moa1中定点突变鉴定了与CENP-C和Rec8相互作用所需的一些氨基酸残基。实验结果表明,Moa1和CENP-C的相互作用对于Moa1参与调节姐妹动粒的单极附着很重要。然而,双杂交实验中与Rec8相互作用所需的Moa1的S143和T150突变没有显示出Moa1或Rec8功能的显著缺陷。这表明氨基酸残基的突变可能不足以干扰体内Moa1和Rec8之间的相互作用,需要进一步的研究来确定Moa1和Rec8的相互作用域。本研究揭示了影响减数分裂同源染色体分离的Moa1氨基酸位点,为减数分裂的染色体分离机制提供更深入的理解。

关键词：减数分裂黏连蛋白动粒单取向

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