MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Numerical Analysis of Aerodynamic Characteristics of the HALE Diamond Joined-Wing Configuration UAV

The investigation on the aerodynamic characteristics of the high-attitude long-endurance (HALE) Diamond Joined-Wing configuration unmanned aerial vehicle ( UAV) was carried out by the theoretical analysis method and numerical simulation. Research indicates that as the wing of the UAV is composed of the front wing and the after wing, the after wing has the ability to transmit the front wing's boundary layer to the after wing root which can inhibit the front wing's flow separation. Although the front wing was affected by the retardation of the after wing, the aerodynamic performance of the front wing was better than that of alone front wing in most cases. The after wing was also affected by the wake and downwash of the front wing, and its aerodynamic performance was greatly decreased. The characteristic curve of the pitching moment of the UAV had nonlinear characteristics. The flow field structure of the after wing changed by the front wing wake direct sweep and flow separation at the after wing root were the main reasons that non-linear ′rise′phenomenon occurred in two segments ( α = 0° and α = 8° ) of the characteristic curve of pitching moment. Moreover, coupling of the flow separation characteristic of the front wing and the after wing resulted in the pitching moment ′pitchup′ phenomenon. The lateral-directional static stability of the flat layout was weak. The HALE Diamond Joined-Wing configuration UAV ' s aerodynamic performance can be improved and the problems in engineering applications can be effectively alleviated by adjusting the overall layout parameters.

Effect of hydrogen fluoride and magnesium oxide on AZ31 Mg alloy/carbon fiber-reinforced plastic composite by thermal laser joining technique

Although hydrofluoric acid(HF)surface treatment is known to enhance the joining of metals with polymers,there is limited information on its effect on the joining of AZ31 alloy and carbon-fiber-reinforced plastics(CFRPs)through laser-assisted metal and plastic direct joining(LAMP).This study uses the LAMP technique to produce AZ31-CFRP joints.The joining process involves as-received AZ31,HFpretreated AZ31,and thermally oxidized HF-pretreated AZ31 alloy sheets.Furthermore,the bonding strength of joints prepared with thermally oxidized AZ31 alloy sheets is examined to ascertain the combined effect of HF treatment and thermal oxidation on bonding strength.The microstructures,surface chemical interactions,and mechanical performances of joints are investigated under tensile shear loading.Various factors,such as bubble formation,CFRP resin decomposition,and mechanical interlocking considerably affect joint strength.Additionally,surface chemical interactions between the active species on metal parts and the polar amide along with carbonyl groups of polymer play a significant role in improving joint strength.Joints prepared with surface-pretreated AZ31 alloy sheets show significant improvements in bonding strength.

AN URGENT JOINT CAUSE

COP29-the 29th session of the Conference of the Parties to the United Nations Framework Convention on Climate Change-has accentuated the urgency of jointly addressing climate change,our common global threat,by pushing for a fair and ambitious new climate financing target.It has also brought into the global spotlight China’s progress in green transition and carbon emission reduction and its commitment to international cooperation.

Study on Key Joining Technology and Test Method of Steel/Al Hybrid Structure Body-in-White

Green and low carbon promote the application and development of light-weight materials in body-in-white. Large-scale die-casting Al alloy (DCAA) and high-strength thermo-formed steel sheet (TFSS) have put forward higher requirements for the application of joining technology of high-strength steel/Al dissimilar materials. Taking the new die-casting Al alloy body as an example, this paper systematically studies the progress of the latest joining methods of steel/Al dissimilar material with combination of two-layer plate and three-layer plate. By analyzing the joining technologies such as FSPR, RES, FDS and SPR, the technology and process characteristics of steel/Al dissimilar material joining are studied, and the joining technical feasibility and realization means of different material combination of the body are analyzed. The conditions of material combination, material thickness, material strength, flange height, preformed holes and joint spacing for achieving high-quality joining are given. The FSPR joining technology is developed and tested in order to meet with the joining of parts with DCAA and TFSS, especially for the joining of three-layer plates with them. It finds the method and technical basis for the realization of high quality joining of dissimilar materials, provides the early conditions for the application of large DCAA and TFSS parts in body-in-white, and meets the design requirements of new energy body. .

Conceptual Design and Aerodynamic Study of Joined-Wing Business Jet Aircraft

The concept of joined-wing aircraft with nonplanar wings as conceived and patented by Wolkovitch is attractive due to various advantages such as light weight, high stiffness, low induced drag, high trimmed CLmax, reduced wetted area and parasite drag and good stability and control, which have been supported by independent analyses, design studies and wind tunnel tests. With such foreseen advantages, the present work is carried out to design joined-wing business-jet aircraft and study and investigate its advantages and benefits as compared to the current available conventional business jet of similar size, passenger and payload capacity. In particular, the work searches for a conceptual design of joined-wing configured business-jet aircraft that possesses more superior characteristics and better aerodynamic performance in terms of increased lift and reduced drag, and lighter than the conventional business jet of similar size. Another significant objective of this work is to prove that the added rigidity possessed by the joined wing configuration can contribute to weight reduction.

Fabrication and Life Prediction of SSiC Ceramic Joint Joined with Silicon Resin YR3370

Joints between sintered silicon carbide （SSiC） were produced using a polysiloxane silicon resin YR3370 （GE Toshiba Silicones） as joining material. Samples were heat treated in a 99.99% nitrogen flux at temperatures ranging from 1 100 ℃ to 1 300 ℃. Three point bending strength of the joint reached the maximum of 179 MPa as joined at 1 200℃. The joining layer is continuous, homogeneous and densified and has a thickness of 2 μm -5μm. The joining mechanism is that the amorphous silicon oxycarbide （SixOyCz） ceramic pyrolyzed from silicon resin YR3370 acts as an inorganic adhesive to SSiC substrate, which means the formation of the continuous Si-C bond structure between SixOyCz structure and SSiC substrate. Life prediction of the ceramic joint can be realized through the measurement of the critical time of the joint after the cyclic loading test.

Study of galvanic corrosion and mechanical joint properties of AZ31B and carbon-fiber–reinforced polymer joined by friction self-piercing riveting

A new testing methodology was developed to quantitively study galvanic corrosion of AZ31B and thermoset carbon-fiber–reinforced polymer spot-joined by a friction self-piercing riveting process.Pre-defined areas of AZ31B in the joint were exposed in 0.1 M NaCl solution over time.Massive galvanic corrosion of AZ31B was observed as exposure time increased.The measured volume loss was converted into corrosion current that was at least 48 times greater than the corrosion current of AZ31B without galvanic coupling.Ninety percent of the mechanical joint integrity was retained for corroded F-SPR joints to 200 h and then decreased because of the massive volume loss of AZ31B。

TiC Particle Reinforced Silicon Nitride Composite Joined With Y_2O_3-Al_2O_3-SiO_2 Mixture

Silicon nitride composite is joined to itself by heating interlayer of Y2 O3 -AL2O3 -SiO2 mixtures above their liquidus temperatures in flowing nitrogen. The joined specimens are tested in four point flexure from room temperature to 1373 K. The interface microstruclure and fractured surfaces after testing are observed and analyzed by SEM, EPMA and XRD respectively. The results show that F2 O3 -A12 O3 -SiO2 glass reacts with Si3 N4 at interface, forming the Si3 N4/Si2 N2 O( Y-AlrSi-O-N glass/ Y-Al- Si-O glass gradient interface. With the increase of bonding temperature and holding time, the joint strength first increases, reaching a peak, and then decreases . According to interfacial analyses , the bonding strength depends on joint thickness .

Quantum search of many vertices on the joined complete graph

The quantum search on the graph is a very important topic.In this work,we develop a theoretic method on searching of single vertex on the graph[Phys.Rev.Lett.114110503(2015)],and systematically study the search of many vertices on one low-connectivity graph,the joined complete graph.Our results reveal that,with the optimal jumping rate obtained from the theoretical method,we can find such target vertices at the time O(√N),where N is the number of total vertices.Therefore,the search of many vertices on the joined complete graph possessing quantum advantage has been achieved.

CNOOC Joined Hands with WorleyParsons

On Aug. 25, China National Offshore Oil Corporation （CNOOC） and WorleyParsons, a world famous project construction company, signed an agreement for jointly setting up Huizhou Refinery Project Construction Team in Beijing KEMPINSKI Hotel. Zheng Changbo, assistant president of CNOOC, Dong Xiaoli, general manager of Huizhou Refinery Project Team, and Lynn C. Fister, deputy general manager of WorleyParsons attended the signing ceremony.

基于Fork/Join的事务日志伴随模式挖掘方法

信息系统产生的大量事务日志数据蕴含着潜在的伴随模式,伴随模式是指在时空上频繁共现的一组对象.由于传统的滑动窗口算法和FP-Growth算法只能调用单一线程进行计算,随着数据规模的扩张,会导致挖掘伴随模式的时间急剧增加.为此本文提出了一种基于Fork/Join并行技术的伴随模式挖掘框架,其能够实现从单线程到多线程的迁移,充分利用多核配置的加速性能.该框架由划定伴随数据集、频繁项集挖掘和关联规则挖掘三部分组成.首先,提出了基于Fork/Join的多核并行滑动窗口算法,以缩短从事务日志中划定伴随数据集的时间;然后,提出基于Fork/Join的多核并行FP-Growth算法,以并行地挖掘伴随数据集中的频繁项集;最后,引入支持度、置信度和提升度3个参数,对伴随模式中各对象间的关联规则进行挖掘.基于门禁刷卡数据的实验结果表明,相比传统算法,本文所提出的框架能够挖掘出更多的伴随模式,同时挖掘效率较高.

铋酸盐封接玻璃的研究及其连接应用现状

无铅低温封接玻璃由于具有绿色安全、成本低、封接温度低等优势,被广泛应用于航空航天、电真空、集成电路等领域。在磷酸盐、钒酸盐、硼酸盐和铋酸盐等多种封接玻璃体系中,因铋与铅具有相似的性质特点,使得铋酸盐玻璃成为最有可能替代铅酸盐玻璃的绿色玻璃钎料。综述了铋酸盐玻璃的成分和性能调控、网络结构的研究现状,介绍了目前使用铋酸盐封接玻璃进行金属、陶瓷同质/异质材料连接的研究进展,最后对未来的发展趋势进行了展望。

旋转锻造连接工艺研究

为了解决焊接性能差的材料间的连接问题,提出了一种利用旋转锻造工艺进行管材-管材、管材-棒料连接的新方法,并进行了旋转锻造连接过程的有限元分析和试验研究,揭示了旋转锻造连接过程的材料流动规律,得到了影响连接头强度的工艺参数。试验设备为自主研发的基于能量控制的小型旋转锻造设备,材料为T2铜管、6061铝管及塑料棒。对旋转锻造连接成形过程进行了有限元分析,得到了材料流动情况和连接工艺参数。结果表明:旋转锻造连接工艺可以形成稳定连接头;连接长度越小,连接头越容易被拉脱;径缩量是影响连接头强度的主要因素,在一定范围内随着径缩量的增加,连接强度不断增加;径缩量过大时,内管将在旋转锻造过程中发生破裂,无法形成连接头;试验结果表明,径缩量为0.8 mm时,铜管-铝管连接头强度达到铝管强度的62%,铜管-铜管连接头强度达到内铜管强度的68%,铜管-塑料棒连接头强度达到塑料棒强度的63%。

一种联合指导嵌入的实体对齐方法

实体对齐是知识图谱完善过程中必不可少的环节,当前实体对齐工作中利用了许多实体属性的信息,忽略了实体和本体之间的联系.针对实体对齐问题中缺少本体概念知识信息的问题,提出一种由实体属性和本体自下而上共同指导及联合嵌入的实体对齐方法.该方法首先对本体信息、实体信息、实体属性信息进行嵌入,之后通过本体类别信息和种子词进行本体类冲突构建、再经过本体和实体属性进行嵌入指导,最终将得到的实体对加入到种子词中并通过全连接网络进行迭代的训练.在公共数据集上进行了大量实验,使用Hits@1,Hits@5,MRR值作为模型的评价指标,并通过对比实验和消融实验验证了该模型的有效性.

基于微分方程曲面求交跟踪法的包容式节点相贯区域建模研究

包容式节点是一种新型管状相贯式节点,其形态是一种典型的薄壁自由曲面结构。在进行曲面造型过程中会涉及曲面求交的问题,而曲面求交是计算机辅助几何设计(CAGD)领域中的关键技术之一。本文构建了包容式节点非均匀有理B样条(NURBS)曲面模型,将求包容式节点中的相贯线问题转化为NURBS曲面的求交问题。基于微分方程的跟踪算法原理,在分割法求得初始交点的基础上,采用微分方程追踪法求出所有交点,最后将所求得交点进行曲线拟合,交线包围区域即为包容式节点与腹杆相贯焊接区域。

飞秒激光表面织构化对CFRP/2060铝锂合金高速激光连接接头剪切性能的影响

激光表面织构化作为提高异质结构接头剪切性能的有效手段,已广泛应用于碳纤维增强复合材料(CFRP)与金属材料激光连接领域中。采用波长515 nm的飞秒激光在2060铝锂合金表面制备微结构,采用能量密度分布均匀的矩形光斑实现CFRP和2060铝锂合金异质接头的高速光纤激光连接,探讨飞秒激光刻蚀深度、扫描线间距对异质结构接头剪切强度的影响规律。结果表明,通过飞秒激光织构化处理,异质接头剪切强度得到了大幅提升,接头破坏形式均为界面断裂和基体断裂的混合断裂模式。在激光功率5 kW、焊接速度高达3.6 m/min条件下,接头平均剪切强度可达35.7 MPa,是未经飞秒激光织构化接头的2.3倍。

碳纤维层合板胶接接头在湿热环境下的性能演变

为了研究碳纤维复合材料(CFRP)胶接接头对汽车涂装过程中的高温高湿环境的适应性,对单搭接CFRP胶接接头进行了烘烤和加速吸湿实验,对经历不同湿热环境的胶接接头进行了剪切拉伸和正向拉伸试验,对连接强度改变及接头的失效模式演变进行了讨论,对环氧树脂与聚氨酯两种胶粘剂连接的接头对烘烤的适应性进行了比较,并研究了在搭接区域边缘增加胶瘤对提高连接强度的效果。研究结果表明:单搭接CFRP胶接接头的剪切拉伸强度远高于正向拉伸强度。烘烤处理后CFRP层合板及CFRP胶接接头的强度不但没有下降,反而有所提高。DP420环氧树脂胶比DP6330聚氨酯胶具有更好的耐烘烤性。吸湿后,CFRP胶接接头的强度、刚度以及最大断裂位移出现了减小。接头的失效模式从胶层内聚失效逐渐演变为与CFRP层合板的层间失效。在搭接区域边缘增加胶瘤能有效提高CFRP胶接接头的剪切拉伸强度。

赣南采茶歌舞剧《八子参军》的张力美

赣南采茶歌舞剧《八子参军》屡屡获得国家级大奖和资助,其宝贵的创作经验既有助于推动赣南采茶戏的传承与发展,也为地方戏剧的转型升级指明了一条可资借鉴的路。从美学上来说,该戏通过张弛有度的情节叙事、对立统一的剧本立意、形神兼备的舞台表演和虚实相生的舞美设计,生成了丰富而充盈的审美张力,展现出摇曳生姿的动态美,极富艺术魅力。