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    Large-Deformation Behavior and Failure Process of Steel Moment-Resisting Frames Examined by a Shake-Table Test

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    Steel moment-resisting frames are popular structural systems in seismic areas. However, seismic excitations produce large deformations that eventually lead to member damage, degradation of strength and stiffness, and collapse. The structural damage changes the vibration properties and therefore the response structural response. Very few studies have been conducted in the past to examine the behavior of steel moment-resisting frames to very large deformations, i.e., story drift ratios greater than 0.10 rad. Furthermore, ductile moment-resisting beam-to-column connections are important to achieve good performance against earthquakes. This research studies the behavior of steel moment-resisting frames through cyclic static tests on beam-to column moment connection subassemblages (component-level response) and dynamic shake-table tests of a scaled moment-resisting frame (system-level response). The beam-to-column connections of the subassemblages and shake-table tests use the current detailing of the Japanese construction practice. Six beam-to-column moment connections that used an I-section column were tested under cyclic loading. I-section columns were chosen instead of the typical square box-section columns to examine the effect of the current Japanese welding details and fabrication in moment connections to the flange and to the web of the column. The T-configuration of the specimen represented an external beam-to-column subassembly of two to four-story steel moment frame buildings in Japan. The specimens to cyclic loading according to the protocol specified in Section K2 of AISC Seismic Provisions. Three specimens were for moment connection to the column flange and three for moment connection to the column web. Complete Joint Penetration (CJP) groove welds were used to connect the beam flanges to the column. In all cases, the CJP welds were completed with no weld access holes. The tests showed that beam-tocolumn web connections were prone to fracture of continuity plates initiating at the corner between the beam flange and the continuity plate. This failure mode was promoted by yielding in the continuity plates. The shop-welded, no-access-hole detail for beam-to-column moment-resisting connections, which is commonly adopted in Japan, is a detail not included in the ANSI/AISC 358 but met ductility requirements for the highly ductile Special Moment Frames per the AISC Seismic Provisions. Furthermore, the quality of the welding process, in combination with having the beam web directly welded to the column web and the use of a stronger continuity plate were important factors in achieving a good seismic performance of the minor-axis moment connections even when continuity plates flush to the column flanges were used. The same no-weld access hole detail was used in the shake-table test specimen, but with the connection to square-HSS columns. Shake-table tests of a steel moment-resisting frame were conducted to obtain detailed data on the occurrence and propagation of damage leading to the collapse of steel structures. A 2/5-scale, 4-story, 2-bay, planar specimen was subjected to in-plane, unidirectional ground motions. The specimen was intended to sustain large deformations, or story drift ratio greater than 0.10 rad, and avoid a first-story collapse mechanism. The specimen comprised I-section beams and square-HSS columns. The CJP groove welds between the beam flanges and column diaphragm plates were completed with no weldaccess-hole. The ground motions included the JMA Kobe NS record scaled from 10 to 100%, and white noise excitations to trace the change in vibration properties between primary excitations. The 100%- scale record was repeated four times to produce as much deformation and damage as possible. The frame deformation response, change in internal load distribution, and acceleration were measured with a combination of displacement transducers, strain gages and accelerometers, respectively. Each of the 100% motions induced significant yielding of the beams, columns, and some column panels, which resulted in story drift of +0.08 and -0.02 rad, and added a residual story drift of +0.02 rad. As expected by design, a sidesway mechanism involving the first three stories formed during the first 100% excitation. Beam fracture occurred at two locations on the second floor, and the maximum story drift reached +0.15 rad during the last 100% excitation. The fundamental period remained constant until beam fracture occurred. Despite the widespread damage and fracture of the second-floor beams, the specimen did not collapse due to the high strength of the columns, which had 1.8 times the nominal strength. Three supplementary cyclic-loading tests were conducted on beam-column subassemblages constructed from the same materials and fabrication process as the shake-table specimen. The subassemblages represented one interior and two exterior connections of the shake-table test specimen. The loading protocol followed the AISC loading protocol for beam-to-column moment connections up to 0.05-rad story drift, but it was changed to a ratchetting protocol up to 0.125 rad afterward to emulate the observed beam-to-column large deformation response in the shake-table tests. However, the subassemblages exhibited more rapid development of local buckling deformation and associated strength degradation. Comparison of the shake-table and component test results showed good agreement in strength capacity at the beam-to-column connection level but differed in terms of degradation. The difference was attributed to axial deformation restraint in the shake-table test beams, evidenced by smaller beam contractions than in the component test beams. Additionally, the inertia forces imposed on the beams of the shake-table test specimen axial loads that were not present in the component tests. The axial loads synchronized with the bending moments to increase the demands in the beam bottom flange. For this reason, fracture occurred in the bottom flange of the shake-table test beams. The subassemblage test beams, which were subject to axial-free bending moment, fractured at either the top or bottom flange. The size effect of the shake-table test was examined by comparing the subassemblage test beam response with full-scale beam-to-column connection tests that followed a similar fabrication practice and load protocol. The weld detail and fabrication used in this study was found to not affect the test outcome. The larger length-to-depth ratio of the scaled specimen, however, reduced the maximum bending strength of the beam with respect to full-scale specimens. The major contributions of this research are: first, the obtention of seismic response data of a steel moment-resisting frame that experienced deformations up to 0.15-rad, without premature collapse. The data can be used to develop analysis schemes for large-deformation behavior prediction. Second, the comparison with subassemblage tests showed that in order to predict the global behavior with component tests, the axial restraint and moment redistribution present in the steel moment frame must be addressed. Third, even though small cracks are likely to happen, the current Japanese fabrication of welded beam-to-column moment connections ensures ductile behavior in either beam-and-column subassemblages or complete moment-resisting frames

    Genetic analysis of the human hereditary thrombocythemia and thrombocythemia in mice

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    A study on the increased CD44 expression in primary meningioma

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    【背景と⽬的】髄膜腫は原発性脳腫瘍のうち約30%を占める最も⼀般的な腫瘍である。髄膜腫の⼤部分は世界保健機関 (World Health Organization: 以下 WHO)グレード 1 の良性腫瘍であり、外科的切除によって治癒が可能であるが、ときに腫瘍周囲脳浮腫(peritumoral brain edema; 以下 PTBE)を伴い、重篤な場合には神経脱落症状を呈したり、てんかん発作の原因となったりすることで治療に難渋することがある。CD44 はヒアルロン酸や他の多くの細胞外マトリックス成分に対する細胞表⾯レセプターである。ほとんど全てのヒト細胞に発現しており、細胞接着、細胞移動、⾎管新⽣、増殖、炎症等に関与し、近年は特にがん幹細胞マーカーとみなされている。CD44とヒアルロン酸の相互作⽤により、様々な癌において腫瘍の浸潤と移動を促進することが報告されている。髄膜腫における CD44 発現を調べた研究はわずかであり、主に CD44 発現と増殖能または予後との関連にのみ焦点が当てられていた。しかし CD44 の発現は細胞増殖以外に細胞移動や炎症に関与しているため、その他の臨床因⼦にも影響を与えていることが考えられた。そこで本研究では、初発髄膜腫の凍結保存検体を⽤いて、初発髄膜腫における CD44 発現と臨床因⼦との相関について明らかにすることを⽬的に検証を⾏った。 【対象と⽅法】2003 年から 2022 年までに北海道⼤学病院脳神経外科で摘出術を受けた初発髄膜腫患者 106 症例を後⽅視的に評価した。保存腫瘍凍結標本より total RNAを抽出し、SYBR green 法による定量的逆転写 PCR 法を⽤いて CD44 mRNA 発現量を定量した。また免疫化学染⾊法を⽤いて、CD44 タンパクの発現と、炎症性マーカーである IL-6 の発現についての検証を⾏った。これらのデータと、年齢、性別、腫瘍の部位、腫瘍の⼤きさ、病理組織学的悪性度(WHO グレード)、組織学的サブタイプ、予後、および PTBE を含む画像所⾒といった臨床因⼦との関係を解析した。PTBE はSteinhoff classification(0, I, II, III の 4 段階; 以下 SC)を⽤いた半定量的⽅法と、EdemaIndex を⽤いた定量的⽅法で評価した。【結果】WHOグレード2および3の悪性髄膜腫におけるCD44遺伝⼦発現は、グレード1の良性髄膜腫における発現よりも有意に⾼かった (p = 0.0044)。さらに注⽬すべきは、PTBEの重症度に応じてCD44発現が増加したことで、SC-IIおよびSC-IIIのPTBEを伴う髄膜腫を伴う髄膜腫のCD44発現値は、PTBEのない(SC-0)髄膜腫と⽐較してそれぞれ有意に⾼かった(それぞれp = 0.0037およびp = 0.021)。PTBEを定量的に評価したEdema indexに対しても、CD44の発現レベルは有意に相関していた(r = 0.413,p = 0.000011)。⼀⽅で、年齢、腫瘍の⼤きさ、腫瘍の部位、予後に関してはCD44発現の程度で有意差は認められなかった。3 またWHO分類によるグレード別、および腫瘍の⼤きさ別に、CD44発現とPTBEの関係について分析した。その結果WHOグレード1の髄膜腫においてSC-IIおよびSC-IIIのPTBEを伴う髄膜腫のCD44発現はPTBEを伴わない (SC-0)髄膜腫のそれよりもそれぞれ有意に⾼く(それぞれ p = 0.040、p = 0.022)、43mm未満の⼩型腫瘍においては、SC-II/III群のCD44発現は、SC-0群のそれよりも有意に⾼かった (p = 0.0034)。加えて組織学的サブタイプによる検証において、PTBEを⾼頻度に伴う⾎管腫型、微⼩嚢胞型、および分泌型髄膜腫の要素を含む症例では、これらを含まない症例よりもCD44の発現が有意に⾼かった (p = 0.018)。さらに初発髄膜腫の PTBE における CD44 発現に他の臨床因⼦が影響するかどうかを評価するため多変量ロジスティック回帰分析を⾏ったところ,CD44 の発現値は初発髄膜腫における重度 PTBE(SC-II/III)発症の独⽴したリスク因⼦であることが明らかになった (OR 1.63, p = 0.0050)。CD44 は炎症との関連性が知られていることから、PTBE が炎症と関連していると考えた。CD44 発現と炎症との相関を評価するため、⾼ PTBE(SC-II/III)4検体と低 PTBE(SC-0/I)6検体で、代表的炎症性マーカーである IL-6 の免疫染⾊を⾏った。⾼ PTBE群では CD44 および IL-6 の発現は陽性となる傾向を⽰し、対照的に、低 PTBE 群ではCD44 および IL-6 の染⾊は陰性の傾向を⽰した。 【考察】今回われわれの研究では、腫瘍の活動性・侵攻性に加えて、髄膜腫におけるCD44 発現の程度と PTBE との間に正の相関があることを新たに⾒出した。髄膜腫における PTBE の発⽣機序は完全には解明されておらず、腫瘍による脳実質や脳静脈洞の圧迫や腫瘍の悪性度では説明のつかない PTBE を経験することがある。本研究では、WHO グレード 1 の良性腫瘍や⼩型腫瘍において、より CD44 発現と PTBE の間に関連が⾒られたことから、CD44 発現が髄膜腫における PTBE の発症を促進する分⼦因⼦である可能性が⽰された。この機序として、CD44 の発現によって引き起こされる炎症反応により PTBE が引き起こされていることが考えられ、われわれの IHC の結果はこの可能性を⽀持するものであった。PTBEは、髄膜腫における周術期てんかん発症の因⼦の1つであり、これによって患者のQOLに悪影響を与えたり、認知機能低下をもたらしたりする。髄膜腫のPTBE発⽣におけるCD44の役割がさらに解明され、CD44の過剰発現が髄膜腫におけるPTBEの治療標的となりうれば、髄膜腫関連合併症の管理に役⽴つ可能性がある。 【結論】髄膜腫における CD44 の発現は、PTBE の発⽣と関連していた。分⼦機序についてはさらなる研究によって明らかにする必要があるが、CD44 は髄膜腫におけるPTBE の治療標的となる可能性がある

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