Upon growth factor stimulation, the scaffold protein, Gabl, is tyrosine phosphorylated and subsequently the adaptor protein, Crk, transmits signals from Gabl. We have previously shown that Crk overexpression, which is...Upon growth factor stimulation, the scaffold protein, Gabl, is tyrosine phosphorylated and subsequently the adaptor protein, Crk, transmits signals from Gabl. We have previously shown that Crk overexpression, which is detectable in various human cancers, induces tyrosine phosphorylation of Gabl without extracellular stimuli. In the present study, the underlying mechanisms were further investigated. Mutational analyses of CrkII demonstrated that the SH2 domain, but not the SH3(N) or the regulatory Y221 residue of CrkII, is critical for the induction of Gabl- Y307 phosphorylation. SH2 mutation of CrkII also decreased the interaction with Gabl. In GST pull-down assay, Crk-SH2 bound to wild-type Gahl, whereas Crk-SH3(N) interacted with the Gabl mutant, which lacks the clus- tered tyrosine region (residues 242-410). Tyrosine phosphorylation of Gabl was induced by all Crk family proteins, but not other SH2-containing signalling adaptors. Src-family kinase inhibitor, PP2, abrogates Crk-induced tyrosine phosphorylations of Gabl. Y307 phosphorylation was undetectable in fibroblasts lacking Src, Yes, and Fyn, even upon overexpression of Crk, whereas cells lacking only Yes and Fyn still contained Gabl with phosphorylated Y307. Furthermore, Crk induced the phosphorylation of Src-Y416; accordingly the interaction between Crk and Csk was increased. The Gabl-Y307F mutant failed to localize near the plasma membrane even upon HGF stimulation and decreased cell migration. Moreover, Gabl-Y307F disturbed the localization of Crk, FAK, and paxillin, which are the typical components of focal adhesions. Taken together, these results indicate that Crk facilitates tyrosine phosphory- lation of Gabl-Y307 through Src, contributing to the organization of focal adhesions and enhanced cell migration, thereby possibly promoting human cancer development.展开更多
In many circumstances,dissimilar metals have to be bonded together and the resulting joint interfaces must typically sustain mechanical and/or electrical forces without failure,which is not possible by fusion welding ...In many circumstances,dissimilar metals have to be bonded together and the resulting joint interfaces must typically sustain mechanical and/or electrical forces without failure,which is not possible by fusion welding processes.The melting points of magnesium(Mg)and copper(Cu)have a significant difference(nearly 400℃)and this may lead to a large difference in the microstructure and joint performance of Mg-Cu joints.However,diffusion bonding can be used to join these alloys without much difficulty.This work analyses the effect of parameters on diffusion layer thickness,hardness and strength of magnesium-copper dissimilar joints.The experiments were conducted using three-factor,five-level,central composite rotatable design matrix.Empirical relationships were developed to predict diffusion layer thickness,hardness and strength using response surface methodology.It is found that bonding temperature has predominant effect on bond characteristics.Joints fabricated at a bonding temperature of 450℃, bonding pressure of 12 MPa and bonding time of 30 min exhibited maximum shear strength and bonding strength of 66 and 81 MPa, respectively.展开更多
Abstract: In a test-fixture that the authors were using, steel tabs adhesively bonded to an aluminum panel debonded before the design load on the real test panel was fully applied. Therefore, studying behavior of adh...Abstract: In a test-fixture that the authors were using, steel tabs adhesively bonded to an aluminum panel debonded before the design load on the real test panel was fully applied. Therefore, studying behavior of adhesive joints for joining dissimilar materials was deemed to be necessary. To determine the failure load responsible for debonding of adhesive joints of two dissimilar materials, stress distributions in adhesive joints as obtained by a nonlinear finite element model of the test-fixture were studied under a gradually increasing compression-shear load. It was observed that in-plane stresses were responsible for the debonding of the steel tabs. To achieve a better understanding of adhesive joints of dissimilar materials, finite element models of adhesive lap joints and ADCB (asymmetric double cantilever beam) were studied, under loadings similar to the loading faced by the test-fixture. The analysis was performed using ABAQUS, a commercially available software, and the cohesive zone modeling was used to study the debonding growth.展开更多
This series of study focused on analysing and assessing the changes of the physical and chemical characteristics of the surfaces of the masonrystones and bricks during the sandblasting cleaning process by conducting v...This series of study focused on analysing and assessing the changes of the physical and chemical characteristics of the surfaces of the masonrystones and bricks during the sandblasting cleaning process by conducting various physical and chemical tests. Seven masonry stones and bricks were adopted, including yellow sandstone, red sandstone, limestone, marble, granite, white clay brick and yellow clay brick. The physical testing included evaluating the cleaning degree, determining the Vickers hardness, and detecting the water absorption. Using a digital imaging analysis method, the greyscale and cleanness were introduced to quantitatively assess the effectiveness of masonry building cleaning and confirmed to be useful and appropriate. The cleanness analysis, together with the hardness and water absorption tests showed that a masonry stone or a brick with a higher cleaning degree corresponded to a brighter and harder stone surface. In general, the physical properties were found to vary largely during the building cleaning.展开更多
A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hos...A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.展开更多
In this review paper,the challenges and some recent developments of adhesive bonding technology in composite aircraft structures are discussed.The durability of bonded joints is defined and presented for parameters th...In this review paper,the challenges and some recent developments of adhesive bonding technology in composite aircraft structures are discussed.The durability of bonded joints is defined and presented for parameters that may influence bonding quality.Presented is also,a numerical design approach for composite joining profiles used to realize adhesive bonding.It is shown that environmental ageing and pre-bond contamination of bonding surfaces may degrade significantly fracture toughness of bonded joints.Moreover,it is obvious that additional research is needed in order to design joining profiles that will enable load transfer through shearing of the bondline.These findings,together with the limited capabilities of existing non-destructive testing techniques,can partially explain the confined use of adhesive bonding in primary composite aircraft structural parts.展开更多
Silver nanofluids with three different volume fractions are prepared by a one-step chemical reduction method(Ultra-sound-assisted Membrane Reaction(UAMR)).The convective heat transfer and friction characteristics of s...Silver nanofluids with three different volume fractions are prepared by a one-step chemical reduction method(Ultra-sound-assisted Membrane Reaction(UAMR)).The convective heat transfer and friction characteristics of silver nanofluid in micro-pin fin heat sink are investigated experimentally.The results indicate that the pressure drops of nanofluids with different volume fractions have little difference.Compared to the base fluid(polyvinylpyrrolidone(PVP) solution),the pressure drop of nanofluids increases slightly at the same volume flow rate.When the flow rate is small,the increment is not obvious.The in-troduction of surfactant increases the fluid viscosity,so the pressure drops of nanofluids are larger than those of pure water,under the same flow rate.However,the maximum difference is no more than 10%.The volume fraction of silver nanoparticles significantly affects the convection heat transfer coefficient of micro-pin fin heat sink.The presence of nanoparticles improves significantly the heat transfer performance.However,high viscosity of the nanofluids hinders the heat transfer strengthening effect of nanofluids.In the present work,when the volume fraction of silver particles reaches to 0.012%,the thermal resistance of nanofluid gradually becomes lower than that of deionized water,which indicates the integrated heat transfer enhancement of nanofluids.展开更多
The shear modulus of the adhesive layer and the failure mode of adhesive structure on single lap joint specimens under tensile tests are investigated in this paper.The aluminum-aluminum adherends are bonded by two dif...The shear modulus of the adhesive layer and the failure mode of adhesive structure on single lap joint specimens under tensile tests are investigated in this paper.The aluminum-aluminum adherends are bonded by two different adhesives:polydimethylsiloxane (PDMS) and epoxy.The full deformation fields are measured using the digital image correlation (DIC) method with the images on the middle part of the adhesive layer recorded by a high resolution microscope.Then,the shear modulus values of the two adhesives are calculated with a simple pure shear strain model.A numerical model is proposed to simulate the single lap joint structure under tensile load in comparison with the experimental results.The results show that this method can successfully estimate the shear modulus of the adhesive layer.The failure behavior of epoxy adhesive/adherend interface is also analyzed and discussed.展开更多
基金Acknowledgments We thank M Hamaguchi (Nagoya Univ., Japan) and T Iwahara (Osaka Bioscience Institute, Japan) forJak null MEFs, and N Gotoh (Tokyo Univ., Japan), H Higashi (Hokkaido Univ., Japan), N Mochizuki (National Cardiovascular Cent. Res. Inst., Japan), H Hanafusa (Prof. emeritus, The Rockefeller Univ., USA and Direc- tor em., OBI, Japan), SK Hanks (Vanderbilt Univ., USA), and M Matsuda (Kyoto Univ., Japan) for plasmids. We also thank K Sasai (Hokkaido Univ., Japan) and Y Ohba (Hokkaido Univ., Japan) for valuable discussion. This work was supported in part by grants-in- aid from the Ministry of Education, Science, Culture, and Sports, and the Ministry of Health, Labor, and Welfare, Japan, as well as Suhara Memorial Foundation (Sapporo, Japan), and the Mochida Medical Science Foundation (Tokyo, Japan). The work of SF and TK is supported by grants from Cancer Research UK and the Brit- ish Cancer Charity "Heads Up". We dedicate this work to our great mentor Hidesaburo Hana- fusa, professor emeritus of the Rockefeller University, who passed away on March 15, 2009 at the age of 79. He devoted his life to science and in particular to creating the oncogene research field, to teaching and to providing profound affection to his students and postdocs. All of the alumni of Saburo's laboratory pride them- selves in having been his apprentices and we would like to hereby express our deeply felt gratitude to Saburo.
文摘Upon growth factor stimulation, the scaffold protein, Gabl, is tyrosine phosphorylated and subsequently the adaptor protein, Crk, transmits signals from Gabl. We have previously shown that Crk overexpression, which is detectable in various human cancers, induces tyrosine phosphorylation of Gabl without extracellular stimuli. In the present study, the underlying mechanisms were further investigated. Mutational analyses of CrkII demonstrated that the SH2 domain, but not the SH3(N) or the regulatory Y221 residue of CrkII, is critical for the induction of Gabl- Y307 phosphorylation. SH2 mutation of CrkII also decreased the interaction with Gabl. In GST pull-down assay, Crk-SH2 bound to wild-type Gahl, whereas Crk-SH3(N) interacted with the Gabl mutant, which lacks the clus- tered tyrosine region (residues 242-410). Tyrosine phosphorylation of Gabl was induced by all Crk family proteins, but not other SH2-containing signalling adaptors. Src-family kinase inhibitor, PP2, abrogates Crk-induced tyrosine phosphorylations of Gabl. Y307 phosphorylation was undetectable in fibroblasts lacking Src, Yes, and Fyn, even upon overexpression of Crk, whereas cells lacking only Yes and Fyn still contained Gabl with phosphorylated Y307. Furthermore, Crk induced the phosphorylation of Src-Y416; accordingly the interaction between Crk and Csk was increased. The Gabl-Y307F mutant failed to localize near the plasma membrane even upon HGF stimulation and decreased cell migration. Moreover, Gabl-Y307F disturbed the localization of Crk, FAK, and paxillin, which are the typical components of focal adhesions. Taken together, these results indicate that Crk facilitates tyrosine phosphory- lation of Gabl-Y307 through Src, contributing to the organization of focal adhesions and enhanced cell migration, thereby possibly promoting human cancer development.
基金support rendered through a Major Research Project No. F-31-51/2005(SR)
文摘In many circumstances,dissimilar metals have to be bonded together and the resulting joint interfaces must typically sustain mechanical and/or electrical forces without failure,which is not possible by fusion welding processes.The melting points of magnesium(Mg)and copper(Cu)have a significant difference(nearly 400℃)and this may lead to a large difference in the microstructure and joint performance of Mg-Cu joints.However,diffusion bonding can be used to join these alloys without much difficulty.This work analyses the effect of parameters on diffusion layer thickness,hardness and strength of magnesium-copper dissimilar joints.The experiments were conducted using three-factor,five-level,central composite rotatable design matrix.Empirical relationships were developed to predict diffusion layer thickness,hardness and strength using response surface methodology.It is found that bonding temperature has predominant effect on bond characteristics.Joints fabricated at a bonding temperature of 450℃, bonding pressure of 12 MPa and bonding time of 30 min exhibited maximum shear strength and bonding strength of 66 and 81 MPa, respectively.
文摘Abstract: In a test-fixture that the authors were using, steel tabs adhesively bonded to an aluminum panel debonded before the design load on the real test panel was fully applied. Therefore, studying behavior of adhesive joints for joining dissimilar materials was deemed to be necessary. To determine the failure load responsible for debonding of adhesive joints of two dissimilar materials, stress distributions in adhesive joints as obtained by a nonlinear finite element model of the test-fixture were studied under a gradually increasing compression-shear load. It was observed that in-plane stresses were responsible for the debonding of the steel tabs. To achieve a better understanding of adhesive joints of dissimilar materials, finite element models of adhesive lap joints and ADCB (asymmetric double cantilever beam) were studied, under loadings similar to the loading faced by the test-fixture. The analysis was performed using ABAQUS, a commercially available software, and the cohesive zone modeling was used to study the debonding growth.
文摘This series of study focused on analysing and assessing the changes of the physical and chemical characteristics of the surfaces of the masonrystones and bricks during the sandblasting cleaning process by conducting various physical and chemical tests. Seven masonry stones and bricks were adopted, including yellow sandstone, red sandstone, limestone, marble, granite, white clay brick and yellow clay brick. The physical testing included evaluating the cleaning degree, determining the Vickers hardness, and detecting the water absorption. Using a digital imaging analysis method, the greyscale and cleanness were introduced to quantitatively assess the effectiveness of masonry building cleaning and confirmed to be useful and appropriate. The cleanness analysis, together with the hardness and water absorption tests showed that a masonry stone or a brick with a higher cleaning degree corresponded to a brighter and harder stone surface. In general, the physical properties were found to vary largely during the building cleaning.
文摘A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.
文摘In this review paper,the challenges and some recent developments of adhesive bonding technology in composite aircraft structures are discussed.The durability of bonded joints is defined and presented for parameters that may influence bonding quality.Presented is also,a numerical design approach for composite joining profiles used to realize adhesive bonding.It is shown that environmental ageing and pre-bond contamination of bonding surfaces may degrade significantly fracture toughness of bonded joints.Moreover,it is obvious that additional research is needed in order to design joining profiles that will enable load transfer through shearing of the bondline.These findings,together with the limited capabilities of existing non-destructive testing techniques,can partially explain the confined use of adhesive bonding in primary composite aircraft structural parts.
基金supported by the National Natural Science Foundation of China (Grant No. 51176002)National Basic Research Program of China (Grant No. 2011CB710704)funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality (Grant No. PHR200906104)
文摘Silver nanofluids with three different volume fractions are prepared by a one-step chemical reduction method(Ultra-sound-assisted Membrane Reaction(UAMR)).The convective heat transfer and friction characteristics of silver nanofluid in micro-pin fin heat sink are investigated experimentally.The results indicate that the pressure drops of nanofluids with different volume fractions have little difference.Compared to the base fluid(polyvinylpyrrolidone(PVP) solution),the pressure drop of nanofluids increases slightly at the same volume flow rate.When the flow rate is small,the increment is not obvious.The in-troduction of surfactant increases the fluid viscosity,so the pressure drops of nanofluids are larger than those of pure water,under the same flow rate.However,the maximum difference is no more than 10%.The volume fraction of silver nanoparticles significantly affects the convection heat transfer coefficient of micro-pin fin heat sink.The presence of nanoparticles improves significantly the heat transfer performance.However,high viscosity of the nanofluids hinders the heat transfer strengthening effect of nanofluids.In the present work,when the volume fraction of silver particles reaches to 0.012%,the thermal resistance of nanofluid gradually becomes lower than that of deionized water,which indicates the integrated heat transfer enhancement of nanofluids.
基金support by the National Basic Research Program of China(Grant Nos. 2010CB631005 and 2011CB606105)the National Natural Science Foundation of China(Grant Nos. 10625209,10732080 and 90916010)+2 种基金China Postdoctoral Science Foundation(Grant No. 20090460335)Specialized Research Fund for the Doctoral Program of Higher Education(Grant No. 20090002110048)the opening funds from the State Key Laboratory of Explosion Science and Technology(Grant No. KFJJ10-18Y)
文摘The shear modulus of the adhesive layer and the failure mode of adhesive structure on single lap joint specimens under tensile tests are investigated in this paper.The aluminum-aluminum adherends are bonded by two different adhesives:polydimethylsiloxane (PDMS) and epoxy.The full deformation fields are measured using the digital image correlation (DIC) method with the images on the middle part of the adhesive layer recorded by a high resolution microscope.Then,the shear modulus values of the two adhesives are calculated with a simple pure shear strain model.A numerical model is proposed to simulate the single lap joint structure under tensile load in comparison with the experimental results.The results show that this method can successfully estimate the shear modulus of the adhesive layer.The failure behavior of epoxy adhesive/adherend interface is also analyzed and discussed.