The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Bjorn Birgisson - One of the best experts on this subject based on the ideXlab platform.
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calibration of load and resistance factor design resistance factors for drilled shaft design
Transportation Research Record, 2002Co-Authors: Ching L Kuo, Michael Mcvay, Bjorn BirgissonAbstract:The AASHTO load and resistance factor design specification was approved for use in 1994 with phi factors determined from fitting allowable stress design (ASD). Unfortunately, the latter did not provide resistance factors for shafts founded in sand, gravel, and rock or identify the influence of construction (dry, wet, and cased). Using a database of 273 shafts, of which 185 failed (settlement equal to 5% of the diameter) and have sufficient soil information, the resistance factors were determined for a number of different AASHTO design Methods based on probability of failure. Effects of skin friction, combined skin and end bearing, and Method of construction were investigated for different soils/rock. It was found that all the Methods had resistance factors between 0.3 and 0.6, which correspond to a factor of safety of 2.5 to 4.5 in ASD. Current FHWA design Methods gave the highest resistance factors in soils with the cased Method of construction. In the case of rock, the dry Hole Method of construction an...
Cory A. Ocasio - One of the best experts on this subject based on the ideXlab platform.
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Type II Kinase Inhibitors Targeting Cys-Gatekeeper Kinases Display Orthogonality with Wild Type and Ala/Gly-Gatekeeper Kinases
2018Co-Authors: Cory A. Ocasio, Alexander A. Warkentin, Patrick J. Mcintyre, Krister J. Barkovich, Clare Vesely, John Spencer, Kevan M. Shokat, Richard BaylissAbstract:Analogue-sensitive (AS) kinases contain large to small mutations in the gatekeeper position rendering them susceptible to inhibition with bulky analogues of pyrazolopyrimidine-based Src kinase inhibitors (e.g., PP1). This “bump-Hole” Method has been utilized for at least 85 of ∼520 kinases, but many kinases are intolerant to this approach. To expand the scope of AS kinase technology, we designed type II kinase inhibitors, ASDO2/6 (analogue-sensitive “DFG-out” kinase inhibitors 2 and 6), that target the “DFG-out” conformation of Cys-gatekeeper kinases with submicromolar potency. We validated this system in vitro against Greatwall kinase (GWL), Aurora-A kinase, and cyclin-dependent kinase-1 and in cells using M110C-GWL-expressing mouse embryonic fibroblasts. These Cys-gatekeeper kinases were sensitive to ASDO2/6 inhibition but not AS kinase inhibitor 3MB-PP1 and vice versa. These compounds, with AS kinase inhibitors, have the potential to inhibit multiple AS kinases independently with applications in systems level and translational kinase research as well as the rational design of type II kinase inhibitors targeting endogenous kinases
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Type II Kinase Inhibitors Targeting Cys-Gatekeeper Kinases Display Orthogonality with Wild Type and Ala/Gly-Gatekeeper Kinases
'American Chemical Society (ACS)', 2018Co-Authors: Cory A. Ocasio, Kevan M. Shokat, Aa Warkentin, Pj Mcintyre, Kj Barkovich, Vesely C, Spencer J, Bayliss RAbstract:Analogue-sensitive (AS) kinases contain large to small mutations in the gatekeeper position rendering them susceptible to inhibition with bulky analogues of pyrazolopyrimidine-based Src kinase inhibitors (e.g., PP1). This “bump-Hole” Method has been utilized for at least 85 of ∼520 kinases, but many kinases are intolerant to this approach. To expand the scope of AS kinase technology, we designed type II kinase inhibitors, ASDO2/6 (analogue-sensitive “DFG-out” kinase inhibitors 2 and 6), that target the “DFG-out” conformation of Cys-gatekeeper kinases with submicromolar potency. We validated this system in vitro against Greatwall kinase (GWL), Aurora-A kinase, and cyclin-dependent kinase-1 and in cells using M110C-GWL-expressing mouse embryonic fibroblasts. These Cys-gatekeeper kinases were sensitive to ASDO2/6 inhibition but not AS kinase inhibitor 3MB-PP1 and vice versa. These compounds, with AS kinase inhibitors, have the potential to inhibit multiple AS kinases independently with applications in systems level and translational kinase research as well as the rational design of type II kinase inhibitors targeting endogenous kinases
Ching L Kuo - One of the best experts on this subject based on the ideXlab platform.
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calibration of load and resistance factor design resistance factors for drilled shaft design
Transportation Research Record, 2002Co-Authors: Ching L Kuo, Michael Mcvay, Bjorn BirgissonAbstract:The AASHTO load and resistance factor design specification was approved for use in 1994 with phi factors determined from fitting allowable stress design (ASD). Unfortunately, the latter did not provide resistance factors for shafts founded in sand, gravel, and rock or identify the influence of construction (dry, wet, and cased). Using a database of 273 shafts, of which 185 failed (settlement equal to 5% of the diameter) and have sufficient soil information, the resistance factors were determined for a number of different AASHTO design Methods based on probability of failure. Effects of skin friction, combined skin and end bearing, and Method of construction were investigated for different soils/rock. It was found that all the Methods had resistance factors between 0.3 and 0.6, which correspond to a factor of safety of 2.5 to 4.5 in ASD. Current FHWA design Methods gave the highest resistance factors in soils with the cased Method of construction. In the case of rock, the dry Hole Method of construction an...
M Awad - One of the best experts on this subject based on the ideXlab platform.
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new crack stop Hole shape using structural optimizing technique
Ain Shams Engineering Journal, 2015Co-Authors: Mohamed Fanni, Noha Fouda, M A N Shabara, M AwadAbstract:Abstract In the present study, the stop-Hole Method was investigated with creating a noncircular Hole. The aim of the present work was to obtain an optimum stop Hole shape that gives maximum fatigue crack initiation life by using finite element program. It was found that the fatigue life obtained by using the optimum Hole shape ranges from 2 to 9 times the fatigue life obtained by using the circular Holes. It was found that the optimum Hole shape increased the initial fatigue life for all specimens used. Opposite to the traditional stress concentration factor minimization problem where the nominal area remains constant during optimization, here it is allowed to vary nominal area using design variables resulting in decreasing of the nominal stress in addition to decreasing of the stress concentration factor. This leads to higher fatigue life compared to previous studies.
Fanwei Meng - One of the best experts on this subject based on the ideXlab platform.
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safety control and mechanical response of existing tunnels induced by excavation of new shallow tunnel in beijing
DEStech Transactions on Materials Science and Engineering, 2017Co-Authors: Jianchen Wang, Dingli Zhang, Sulei Zhang, Nanxin Du, Fanwei MengAbstract:In crossing engineering, new tunnels’ section and construction Methods are numerous, geological conditions are complex, and existing tunnels’ structure forms are various. New tunnels, geological conditions, and existing tunnels have a complex composition relationship which is no corresponding research. 18 sets of measured data from 13 projects in Beijing were found to summarize the construction Methods of the new tunnels, analyses the existing tunnel’s deformation law and study the existing tunnels’ mechanical response by the two stage Method. Research shows: (1) the new tunnels have three types of municipal pipelines, subway stations and metro tunnel. The new tunnel construction Method have guiding Hole Method, bench Method, cavern-pile Method and center drift Method. The corresponding relationship between the construction Method and excavation area is clear. (2) The probability distribution of the existing tunnels’ maximum settlement accorded with normal distribution. The mathematical expectation is 4.89, and the variance is 16.4. The existing tunnels’ average maximum settlements are 2.56mm, 3.82mm and 11.07mm, which caused by excavation of municipal Pipeline, metro tunnel and subway stations. The research results can provide reference for similar engineering of new subway tunnels excavated beneath adjacent existing underground structures in urban areas.