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.

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. .

Kinematics Analysis and Optimization of the Fast Shearing-extrusion Joining Mechanism for Solid-state Metal

Dynamical Joining of the solid-state metal is the key technology to realize endless hot rolling. The heating and laser welding method both require long joining time. Based on super deformation method, a 7-bar and 2-slider mechanism was developed in Japan, and the joining time is less than 0.5 s, however the length of each bar are not reported and this mechanism is complex. A relatively simple 6-bar and 1-slider mechanism is put forward, which can realize the shearing and extrusion motion of the top and bottom blades with a speed approximately equal to the speed of the metal plates. In order to study the kinematics property of the double blades, based on complex vector method, the multi-rigid-body model is built, and the displacement and speed functions of the double blades, the joining time and joining thickness are deduced, the kinematics analysis shows that the initial parameters can＇t satisfy the joining process. Hence, optimization of this mechanism is employed using genetic algorithm（GA） and the optimization parameters of this mechanism are obtained, the kinematics analysis show that the joining time is less than 0.1 s, the joining thickness is more than 80% of the thickness of the solid-state metal, and the horizontal speeds of the blades are improved. A new mechanism is provided for the joining of the solid-state metal and a foundation is laid for the design of the device.

Joining Performance and Microstructure of the 2024/7075 Aluminium Alloys Welded Joints by Vaporizing Foil Actuator Welding

Vaporizing foil actuator welding(VFAW) was used for joining 2024-T3 and 7075-T6 aluminum alloy sheets, and the resulting joint microstructure was analyzed. 2024/7075 aluminum alloy pairs with suitable processing parameters can be prepared by using VFAW. Dynamic preform addresses the poor formability problem of target material and advantage of VFAW on dissimilar materials in some conditions. But with standoff sheet inserting in the flyer and target, 2024/7075 welded pairs gets the better weld strength, compared with flyer preformed method. The microstructure of the circular weld area of the welded joint showed a wave interface, in which a thin melt layer formed at the center and edge parts. The crystal grains near the bonding interface were remarkably elongated and refined. Therefore, the joining of the 2024/7075 pairs was facilitated through plastic forming and melting.

Climatological Characteristics of the Moisture Budget and Their Anomalies over the Joining Area of Asia and the Indian-Pacific Ocean

The climatological characteristics of the moisture budget over the joining area of Asia and the IndianPacific Ocean （AIPO） and its adjacent regions as well as their anomalies have been estimated in this study. The main results are as follows. In the winter, the northeasterly moisture transport covers the extensive areas at the lower latitudes of the AIPO. The westerly and northerly moisture transport is the major source and the South Indian Ocean （SIO） is the moisture sink. In the summer, influenced by the southwesterly monsoonal wind, the crossequatorial southwesterly moisture transport across Somali originating from the SIO is transported through the Arabian Sea （AS）, the Bay of Bengal （BOB）, and the South China Sea （SCS） to eastern China. The AIPO is controlled by the southwesterly moisture transport. The net moisture influx over the AIPO has obvious interannual and interdecadal variations. From the mid- or late 1970s, the influxes over the SIO, the AS, the northern part of the western North Pacific （NWNP）, and North China （NC） as well as South China （SC） begin to decrease abruptly, while those over Northeast China （NEC） and the Yangtze River-Huaihe River basins （YHRB） have increased remarkably. As a whole, the net moisture influxes over the BOB and the southern part of the western North Pacific （SWNP） in the recent 50 years take on a linear increasing trend. However, the transition timing for these two regions is different with the former being at the mid- or late 1980s and the latter occurring earlier, approximately at the early stage of the 1970s. The anomalous moisture source associated with the precipitation anomalies is different from the normal conditions of the summer precipitation. For the drought or flood years or the years of E1 Nifio and its following years, the anomalous moisture transport originating from the western North Pacific （WNP） is the vital source of the anomalous precipitation over eastern China, which is greatly related with the variation of the subtropical Pacific high.

Thermal fatigue behaviors of SiC power module by Ag sinter joining under harsh thermal shock test

The excellent properties of SiC bring new challenges for the device packaging.In this study,the bonding strength,fracture behaviors and microstructural evolution of micron-porous Ag joint were elevated during thermal cycling(–50 ℃–250 ℃) in SiC/DBC(direct bonding copper) die attachment structure for different time.During harsh thermal shock test,the strength of sintered joint deceased gradually with the increase of cycling number,and the value just was half of the value of as-sintered after 1 000 cycles.Coarsening of Ag grains was observed in micron-porous joint with the structure inhomogeneity and defects increasing,which were the reasons of the strength decease.In addition,it was also found that the fracture behavior of sintered joints was changed from ductile deformation of Ag grain to brittle fracture of crack propagation after 1 000 cycles.This study will add the understanding in the mechanical properties of Ag sinter joining and its applications at high temperature.

Interface structure and mechanical property of the brazed joint of graphite and copper

A kind of self-made AgCuTiSn braze alloy powder was used to join graphite and copper. The whole brazing process was performed under vacuum circumstances at different temperatures （ 1 033 - 1 193 K） for several holding time （300 - 1 800 s ）. According to scanning electron microscope （SEM）, energy dispersive spectrometer （EDS） and electron probe X-ray microanalysis （ EPMA ） results, the reaction products of the interface are TiC, Ti3Sn, Cu（s. s）, Ag（s. s） and Cu-Sn compound. As the brazing parameters increase, the quantity of Ag（ s. s） in the braze alloy and C fibers on graphite/AgCuTiSn interface reduce, while that of Cu （ s. s） in the braze alloy improves. When the brazing temperature /s 1 093 K and holding time is 900 s, the joint can obtain the maximum room temperature shear strength 24 MPa.

Joining of SiC Ceramics by the Flash-Bonding Technique

Because Silicon carbide (SiC) ceramics have various excellent properties, the demand for larger and complicated shapes has been increasing. This paper introduces an innovative method that would not require a large furnace, and further, would minimize the production cost and the thermal history, namely the “flash-bonding” technique. The borosilicate glass with low thermal expansion coefficient, Pyrex glass, was selected as the brazing material. In this work, as-is or surface-oxidized SiC plates were joined using Pyrex glass as brazing material, and the reaction and wetting of Pyrex glass on as-is or surface-oxidized SiC plate were investigated. It was found that the protective film of the surface-oxidized SiC lowered the oxygen partial pressure, and hence, generated many pores in the interface.

Effect of Applied Pressure on the Joining of Combustion Synthesized Ni_3Al Intermetallics with Al Alloy

We focused on the surface reinforcement of ligth weight casting alloys with Ni-AI intermetallic compounds by in-situ combustion reaction to improve the surface properties of non-ferrous casting components.In our previous works,green compact of elemental Ni and Al powders were reacted to form Ni-3Al intermetallic compound by SHS （Self-propagating high temperature synthesis） reaction with the heat of molten Al alloy and simultaneously bonded with Al casting alloy.But some defects such as tiny cracks and porosities were remained in the reacted compact.So we applied pressure to prevent thermal cracks and fill up the pores with liquid Al alloy by squeeze casting process.The compressed Al alloy bonded with the Ni-3Al intermetallic compound was sectioned and observed by optical microscopy and scanning electron microscopy （SEM）.The stoichiometric compositions of the intermetallics formed around the bonded interface and in the reacted compact were identified by energy dispersive spectroscopy （EDS） and electron probe micro analysis （EPMA）. Si rich layer was formed on the Al alloy side near the bonded interface by the sequential solidification of Al alloy.The porosities observed in the reacted Ni-3Al compact were filled up with the liquid AI alloy.The Si particles from the molten Al alloy were detected in the pores of reacted Ni-3Al intermetallic compact.The Al casting alloy and Ni-3Al intermetallic compound were joined very soundly by applying pressure to the liquid Al alloy.

Microstructure of TiAl/TiC cermet joint bonded by combustion synthesis

TiAl alloys were joined to TiC cermets using combustion synthesis method. The Ti-C-Ni metallic powder compact acted as a joining interlayer in the joining process. The identification and mechanisms of the reaction at the interface and interlayer were investigated. From the analysis of the microstructure of TiAl/TiC cermet joint, it is noted that TiC and TiNi compounds are main reaction products and unreacted Ni is observed in the interlayer. The reaction products consist of a large volume of voids or unreacted regions. It is confirmed that Al addition as well as joining pressure are effective to decrease the voids. It is considered that high flowability of liquid Al enhances the SHS reaction and the densification of reaction products. There is a continuous Ni-rich layer observed at the interface between the interlayer and TiC cermets substrate. Ti3Al, TiC and TiNi compounds are observed in the reaction products.

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.

The effect of zinc coating during joining aluminium to zinc-coated steel by welding-brazing process

An optical sensing system was constructed to study the coating when joining ahtminium alloy to zinc-coated steel by MIG welding-brazing process. The results showed that the coating fused to form a liquid zinc film on surface during process. The Al-Si filler metal reacted with the liquid zinc film to improve the spreadability of filler metal and thus a new method was established to join aluminium alloy and uncoated steel by depositing a mixed layer on steel surface.

<i>L</i>(2,1)-Labeling Number of the Product and the Join Graph on Two Fans

L(2,1)-labeling number of the product and the join graph on two fans are discussed in this paper, we proved that L(2,1)-labeling number of the product graph on two fans is?λ(G) ≤ Δ+3 , L(2,1)-labeling number of the join graph on two fans is?λ(G) ≤ 2Δ+3.

JOINING OF Ni_3Al BY PRESSURIZED COMBUSTION SYNTHESIS USING GLEEBLE 1500 TEST SIMULATOR

In this investigation, the Gleeble 1500 test simulator was used for carrying out experiments of joining by the pressurized combustion synthesis (PCS). The intermetallic compound Ni3Al was bonded by us- ing the exothermic synthesis reaction of a mixture of element Ni and Al poweders pre - compacted as the interlayer material.Effects of the key process parameters, such as the heating rate and joining tem- perature as well as the hold time, on the joint formation and microstructural homogeneity were studied. The feasibility of the addition of Al2O3 particles in the joint interlayer for producing intermetallic -ma- trix composite joints are also explored. Results show that the microstructrual homogeneity in the synthe- sized joint interlayer was significantly influenced by the joining process paramenters.The fully synthesized Ni2Al joints exhibited an average tensile strength of 486MPa at R. T. With the addition of Al2O3 ce- ramic particles in the reactants, joints with reighrced Ni3Al - matrix composite interlayer were ob- tained.

“Join the Spirit”可持续新能源研究全国科技竞赛结果揭晓

2013年9月25日．空中客车及其母公司欧洲字航防务集团在第十五届北京国际航空展览会上宣布与其中国合作伙伴共同发起的“JointheSpirit”可持续新能源研究全国科技竞赛比赛结果并举行颁奖仪式。来自于全国各大学及研究机构的研究团队参加竞赛。

The Equitable Total Chromatic Number of Some Join graphs

A proper total-coloring of graph G is said to be?equitable if the number of elements (vertices and edges) in any?two color classes differ by at most one, which the required?minimum number of colors is called the equitable total chromatic?number. In this paper, we prove some theorems on equitable?total coloring and derive the equitable total chromatic numbers?of Pm V?Sn, Pm V?Fn and Pm V Wn.

Strengthen Exchanges and Mutual Learning among Civilizations,Join Hands to Create a Better Future:Keynote speech of H.E.Ji Bingxuan on the Dialogue on Exchanges and Mutual Learning among Civilizations

On November 28,the First Dialogue on Exchanges and Mutual Learning among Civilizations organized by the Chinese Association for International Understanding was staged in the Forbidden City.Some 100 participants from all over the world were present at the Dialogue.Participants made discussions themed on"building a world featuring mutual learning and harmonious coexistence among different civilizations".Ji Bingxuan,Vice Chairman of Standing Committee of the National People’s Congress and President of the Chinese Association for International Understanding attended the opening ceremony and delivered a keynote speech.

Please join us for the 3rd New Horizons in Cancer Research Conference

On behalf of the American Association for Cancer Research(AACR),we have the great pleasure to invite you to attend the New Horizons in Cancer Research Conference:Delivering Cures Through Cancer Science,which will be held from November 2-5,2016,in Shanghai,China.This third conference in this series has,once again,been designed to highlight some of the very

An Effective Thermal Splicing Method to Join Fluoride and Silica Fibers for a High Power Regime

A repeatable and simple thermal splicing method for low loss splice between fluoride and silica fibers is presented. The minimum splicing loss of 0.58 dB is achieved experimentally with this approach, Meanwhile, the power capacity of this splicing joint is also tested with a high power fiber laser. The maximum input power is up to 15 W, only limited by the available power of the laser source. To the best of our knowledge, this is the first report on thermal splicing between fluoride and silica fibers operating in a high power regime without any complicated ion-assisted deposition process.

An Expansion of Boundary Theory and the Application of Joint Condition

The manuscript reviews the history and quo of the theory of Timoshenko’s method in stability analysis of compressive levers first, taking an example to explain the m-simulation method and putting forward the 3rd-7th boundary conditions demonstrating their superiorities in improving the precision through examples, followed by proposing and applying the join conditions in the stability analysis of combined axial force compressive levers gaining success. Through a brief example showing the effect of some related theories in a simple structural stability analysis, its application prospect is discussed.