The restoration of constraints in nonholonomic problems

Restoration of constraints in nonholonomic equation

The restoration of constraints in nonholonomic problems - Numerical examples

Numerical examples for restoration of constraints in nonholonomic problem

P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils

ABSTRACT G-protein-coupled receptors (GPCRs) regulate the organisation of the actin cytoskeleton by activating the Rac subfamily of small GTPases. The guanine-nucleotide-exchange factor (GEF) P-Rex1 is engaged downstream of GPCRs and phosphoinositide 3-kinase (PI3K) in many cell types, and promotes tumorigenic signalling and metastasis in breast cancer and melanoma, respectively. Although P-Rex1-dependent functions have been attributed to its GEF activity towards Rac1, we show that P-Rex1 also acts as a GEF for the Rac-related GTPase RhoG, both in vitro and in GPCR-stimulated primary mouse neutrophils. Furthermore, loss of either P-Rex1 or RhoG caused equivalent reductions in GPCR-driven Rac activation and Rac-dependent NADPH oxidase activity, suggesting they both function upstream of Rac in this system. Loss of RhoG also impaired GPCR-driven recruitment of the Rac GEF DOCK2, and F-actin, to the leading edge of migrating neutrophils. Taken together, our results reveal a new signalling hierarchy in which P-Rex1, acting as a GEF for RhoG, regulates Rac-dependent functions indirectly through RhoG-dependent recruitment of DOCK2. These findings thus have broad implications for our understanding of GPCR signalling to Rho GTPases and the actin cytoskeleton

SCFAs Induce Mouse Neutrophil Chemotaxis through the GPR43 Receptor

Short chain fatty acids (SCFAs) have recently attracted attention as potential mediators of the effects of gut microbiota on intestinal inflammation. Some of these effects have been suggested to occur through the direct actions of SCFAs on the GPR43 receptor in neutrophils, though the precise role of this receptor in neutrophil activation is still unclear. We show that mouse bone marrow derived neutrophils (BMNs) can chemotax effectively through polycarbonate filters towards a source of acetate, propionate or butyrate. Moreover, we show that BMNs move with good speed and directionality towards a source of propionate in an EZ-Taxiscan chamber coated with fibrinogen. These effects of SCFAs were mimicked by low concentrations of the synthetic GPR43 agonist phenylacetamide-1 and were abolished in GPR43−/− BMNs. SCFAs and phenylacetamide-1 also elicited GPR43-dependent activation of PKB, p38 and ERK and these responses were sensitive to pertussis toxin, indicating a role for Gi proteins. Phenylacetamide-1 also elicited rapid and transient activation of Rac1/2 GTPases and phosphorylation of ribosomal protein S6. Genetic and pharmacological intervention identified important roles for PI3Kγ, Rac2, p38 and ERK, but not mTOR, in GPR43-dependent chemotaxis. These results identify GPR43 as a bona fide chemotactic receptor for neutrophils in vitro and start to define important elements in its signal transduction pathways

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Surface Engineering in Heat-Transfer Applications

The purpose of this dissertation is to show the effectiveness of surface engineering (wettability patterning) in thermal management applications. The study is centered on redesigning an existing thermal-management system, the vapor chamber, using an innovative concept to improve its performance. The study was inspired by the tremendous potential of surface-energy patterning to provide a platform for harnessing surface-tension forces to transport fluids in a pumpless and rapid manner, which resulted in the development of a pattern combination that improves the condensation heat transfer of a metallic surface. The following steps were taken to accomplish this goal; initially, the conventional vapor-chamber heat-spreader was modified by replacing a portion of the totally wick-lined system (condenser) with a wickless and wettability patterned one, resulting in a hybrid vapor chamber. Furthermore, the hybrid vapor-chamber's capacity to serve as a passive thermal diode was demonstrated. Moreover, an attempt was made to completely reap the benefits of the wettability-patterning process by fabricating a quite effective wick-free vapor chamber. This system constitutes the first completely wick-free thermal-management apparatus. Additionally, femtosecond laser processing technology was applied on the wick-free system to develop a wickless and laser-fabricated vapor-chamber thermal diode, which takes advantage of the extreme limits of wettability. Finally, in order to further investigate the condensation phenomena that occur on the novel vapor-chamber's wickless and wettability-patterned condenser, a unique experimental setup was developed that focuses solely on steam dropwise condensation on metallic surfaces in an environment similar to the vapor chamber’s interior