23 research outputs found

    Boundary friction characterisation of a used cylinder liner subject to fired engine conditions and surface deposition

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    In cylinder friction contributes as a primary source of parasitic dissipations in IC engines. For future engines to become more efficient, with enhanced fuel economy and increased power output, accurate prediction of new designs is required over the full lifetime of an engine. The work carried out presents use of a local pressure coefficient of boundary shear strength of asperities value, taking into account the localised effects of surface texture, coating and surface deposition. XPS spectra analysis was also carried out to identify the surface depositions as a result of combustion, not previously taken into account during piston ring pack simulation. Friction was shown by simulation to drop by up to 30% between the compression and combustion stroke as a result of using a carriable coefficient of boundary shear strength of asperities. It was found that piston varnish on the liner corresponded to higher values of the pressure coefficient of boundary shear strength of asperities, therefore showing the importance of using real system components run under representative operating conditions or numerical analyses

    Employers' Feedback on the Competencies of MBA Graduates based on Curriculum and Student Outcomes

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    Abstract: This study aims to determine the feedback of the immediate superiors or employers of the Master in Business Administration (MBA

    The talon cusp – an uncommon anomaly

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    Talon cusps are an uncommon dental anomaly of odontogenic origin. Talon cusps can also present with other dental anomalies, however these have been infrequently reported in the literature.The following is a report of two cases in which talon cusps were detected in combination with two distinct dental anomalies: an ectopic canine and transposition.</p

    Identification of Small Molecule Inhibitors and Ligand Directed Degraders of Calcium/Calmodulin Dependent Protein Kinase Kinase 1 and 2 (CaMKK1/2)

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    CaMKK2 signals through AMPK-dependent and AMPK-independent pathways to trigger cellular outputs including proliferation, differentiation, and migration, resulting in changes to metabolism, bone mass accrual, neuronal function, hematopoiesis, and immunity. CAMKK2 is upregulated in tumors including hepatocellular carcinoma, prostate, breast, and gastric cancer, and genetic deletion in myeloid cells results in increased antitumor immunity in several syngeneic models. Validation of the biological roles of CaMKK2 has relied on genetic deletion or small molecule inhibitors with activity against several biological targets. We sought to generate selective inhibitors and degraders to understand the biological impact of inhibiting catalytic activity and scaffolding and the potential therapeutic benefits of targeting CaMKK2. We report herein selective, ligand-efficient inhibitors and ligand-directed degraders of CaMKK2 that were used to probe immune and tumor intrinsic biology. These molecules provide two distinct strategies for ablating CaMKK2 signaling in vitro and in vivo

    Identification of Small Molecule Inhibitors and Ligand Directed Degraders of Calcium/Calmodulin Dependent Protein Kinase Kinase 1 and 2 (CaMKK1/2)

    No full text
    CaMKK2 signals through AMPK-dependent and AMPK-independent pathways to trigger cellular outputs including proliferation, differentiation, and migration, resulting in changes to metabolism, bone mass accrual, neuronal function, hematopoiesis, and immunity. CAMKK2 is upregulated in tumors including hepatocellular carcinoma, prostate, breast, and gastric cancer, and genetic deletion in myeloid cells results in increased antitumor immunity in several syngeneic models. Validation of the biological roles of CaMKK2 has relied on genetic deletion or small molecule inhibitors with activity against several biological targets. We sought to generate selective inhibitors and degraders to understand the biological impact of inhibiting catalytic activity and scaffolding and the potential therapeutic benefits of targeting CaMKK2. We report herein selective, ligand-efficient inhibitors and ligand-directed degraders of CaMKK2 that were used to probe immune and tumor intrinsic biology. These molecules provide two distinct strategies for ablating CaMKK2 signaling in vitro and in vivo
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