Study of industrially relevant boundary layer and axisymmetric flows, including swirl and turbulence

Micropolar and RNG-based modelling of industrially relevant boundary layer and recirculating swirling flows is described. Both models contain a number of adjustable parameters and auxiliary conditions that must be either modelled or experimentally determined, and the effects of varying these on the resulting flow solutions is quantified. To these ends, the behaviour of the micropolar model for self-similar flow over a surface that is both stretching and transpiring is explored in depth. The simplified governing equations permit both analytic and numerical approaches to be adopted, and a number of closed form solutions (both exact and approximate) are obtained using perturbation and order of magnitude analyses. Results are compared with the corresponding Newtonian flow solution in order to highlight the differences between the micropolar and classical models, and significant new insights into the behaviour of the micropolar model are revealed for this flow. The behaviour of the RNG-bas based models for swirling flow with vortex breakdown zones is explored in depth via computational modelling of two experimental data sets and an idealised breakdown flow configuration. Meticulous modeling of upstream auxillary conditions is required to correctly assess the behavior of the models studied in this work. The novel concept of using the results to infer the role of turbulence in the onset and topology of the breakdown zone is employed.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.

Including airport duty-free shopping in arriving passenger simulation and the opportunities this presents

Simulating passenger flows within airports is very important as it can provide an indication of queue lengths, bottlenecks, system capacity and overall level of service. To date, visual simulation tools such as agent based models have focused on processing formalities such as check-in, and not incorporate discretionary activities such as duty-free shopping. As airport retail contributes greatly to airport revenue generation, but also has potentially detrimental effects on facilitation efficiency benchmarks, this study developed a simplistic simulation model which captures common duty-free purchasing opportunities, as well as high-level behaviours of passengers. It is argued that such a model enables more realistic simulation of passenger facilitation, and provides a platform for simulating real-time revenue generation as well as more complex passenger behaviours within the airport. Simulations are conducted to verify the suitability of the model for inclusion in the international arrivals process for assessing passenger flow and infrastructure utilization.

Enhanced photoconduction of free-standing ZnO nanowire films by L-lysine treatment

Flexible paper-like ZnO nanowire films are fabricated and the effect of L-lysine passivation of the nanowire surfaces on improving the UV photoresponse is studied. We prepare three types of nanowires with different defect contents, and find that the L-lysine treatment can suppress the oxygen-vacancy-related photoluminescence as well as enhance the UV photoconduction. The nanowires with fewer defects gain larger enhancement of UV photoconduction after L-lysine treatment. Reproducible UV photoresponse of the devices in humid air is obtained due to L-lysine surface passivation, ruling out the influence of water molecules in degrading the UV photocurrent.

Bending and bundling of metal-free vertically aligned ZnO nanowires due to electrostatic interaction

Bending and bundling was observed from vertically aligned arrays of ZnO nanowires with flat (0001) top surfaces, which were synthesized using a vapor-phase method without metal catalysts. Sufficient evidence was found to exclude electron-beam bombardment during scanning electron microscopy as a cause for bending and bundling. We attribute the bending and bundling to electrostatic interactions due to charged (0001) polar surfaces, and also discussed the threshold surface charge densities for the bending and bundling based on a simple cantilever-bending model. Some growth features were indicative of the operation of electrostatic interactions during the growth.

Free convection in a triangular enclosure with fluid-saturated porous medium and internal heat generation

Unsteady natural convection inside a triangular cavity has been studied in this study. The cavity is filled with a saturated porous medium with non-isothermal left inclined wall while the bottom surface is isothermally heated and the right inclined surface is isothermally cold. An internal heat generation is also considered which is dependent of the fluid temperature. The governing equations are solved numerically by finite element method. The Prandtl number of the fluid is considered as 0.7 (air) while the aspect ratio and the Rayleigh number are considered as 0.5 and 105 respectively. The effect of the porosity of the medium and heat generation on the fluid flow and heat transfer have been presented as a form of streamlines and isotherms. The rate of heat transfer through three surfaces of the enclosure is also presented.

Core-shell microspheres with surface grafted poly(vinyl alcohol) as drug carriers for the treatment of hepatocellular carcinoma

Core(polyvinyl neodecanoate-ethylene glycol dimethacrylate)-shell(polyvinyl alcohol) (core (P(VND-EGDMA))-shell(PVA)) microspheres were developed by seeded polymerization with the use of conventional free radical and RAFT/MADIX mediated polymerization. Poly(vinyl pivalate) PVPi was grafted onto microspheres prepared via suspension polymerization of vinylneodecanoate and ethylene glycol dimethacrylate. The amount of grafted polymer was found to be independent from the technique used with conventional free radical polymerization and MADIX polymerization resulting into similar shell thicknesses. Both systems—grafting via free radical polymerization or the MADIX process—were found to follow slightly different kinetics. While the free radical polymerization resulted in a weight gain linear with the monomer consumption in solution the growth in the MADIX controlled system experienced a delay. The core-shell microspheres were obtained by hydrolysis of the poly(vinyl pivalate) surface grafted brushes to form poly(vinyl alcohol). During hydrolysis the microspheres lost a significant amount of weight, consistent with the hydrolysis of 40–70% of all VPi units. Drug loading was found to be independent of the shell layer thickness, suggesting that the drug loading is governed by the amount of bulk material. The shell layer does not appear to represent an obstacle to the drug ingress. Cell testing using colorectal cancer cell lines HT 29 confirm the biocompatibility of the empty microspheres whereas the clofazimine loaded particles lead to 50% cell death, confirming the release of the drug.

Free convection in a triangular enclosure with fluid-saturated porous medium and internal heat generation

Unsteady natural convection inside a triangular cavity has been studied in this study. The cavity is filled with a saturated porous medium with non-isothermal left inclined wall while the bottom surface is isothermally heated and the right inclined surface is isothermally cooled. An internal heat generation is also considered which is dependent on the fluid temperature. The governing equations are solved numerically by finite volume method. The Prandtl number, Pr of the fluid is considered as 0.7 (air) while the aspect ratio and the Rayleigh number, Ra are considered as 0.5 and 105 respectively. The effect of heat generation on the fluid flow and heat transfer have been presented as a form of streamlines and isotherms. The rate of heat transfer through three surfaces of the enclosure is also presented.

Double diffusive magneto-convection fluid flow in a strong cross magnetic field with uniform surface heat and mass flux

In this study, magnetohydrodynamic natural convection boundary layer flow of an electrically conducting and viscous incompressible fluid along a heated vertical flat plate with uniform heat and mass flux in the presence of strong cross magnetic field has been investigated. For smooth integrations the boundary layer equations are transformed in to a convenient dimensionless form by using stream function formulation as well as the free variable formulation. The nonsimilar parabolic partial differential equations are integrated numerically for Pr ≪1 that is appropriate for liquid metals against the local Hartmann parameter ξ . Further, asymptotic solutions are obtained near the leading edge using regular perturbation method for smaller values of ξ . Solutions for values of ξ ≫ 1 are also obtained by employing the matched asymptotic technique. The results obtained for small, large and all ξ regimes are examined in terms of shear stress, τw, rate of heat transfer, qw, and rate of mass transfer, mw, for important physical parameter. Attention has been given to the influence of Schmidt number, Sc, buoyancy ratio parameter, N and local Hartmann parameter, ξ on velocity, temperature and concentration distributions and noted that velocity and temperature of the fluid achieve their asymptotic profiles for Sc ≥ 10:0.

Surface plasmon hybridization and exciton coupling

We derive a semianalytical model to describe the interaction of a single photon emitter and a collection of arbitrarily shaped metal nanoparticles. The theory treats the metal nanoparticles classically within the electrostatic eigenmode method, wherein the surface plasmon resonances of collections of nanoparticles are represented by the hybridization of the plasmon modes of the noninteracting particles. The single photon emitter is represented by a quantum mechanical two-level system that exhibits line broadening due to a finite spontaneous decay rate. Plasmon-emitter coupling is described by solving the resulting Bloch equations. We illustrate the theory by studying model systems consisting of a single emitter coupled to one, two, and three nanoparticles, and we also compare the predictions of our model to published experimental data. ©2012 American Physical Society.

Near-Wall Turbulent Pressure Diffusion Modeling and Influence in Three-Dimensional Secondary Flows

The purpose of this paper is to develop a second-moment closure with a near-wall turbulent pressure diffusion model for three-dimensional complex flows, and to evaluate the influence of the turbulent diffusion term on the prediction of detached and secondary flows. A complete turbulent diffusion model including a near-wall turbulent pressure diffusion closure for the slow part was developed based on the tensorial form of Lumley and included in a re-calibrated wall-normal-free Reynolds-stress model developed by Gerolymos and Vallet. The proposed model was validated against several one-, two, and three-dimensional complex flows.

Accurate stratospheric particle-size distributions from a flat-plate collection surface

The first representative chemical, structural, and morphological analysis of the solid particles from a single collection surface has been performed. This collection surface sampled the stratosphere between 17 and 19km in altitude in the summer of 1981, and therefore before the 1982 eruptions of El Chichón. A particle collection surface was washed free of all particles with rinses of Freon and hexane, and the resulting wash was directed through a series of vertically stacked Nucleopore filters. The size cutoff for the solid particle collection process in the stratosphere is found to be considerably less than 1 μm. The total stratospheric number density of solid particles larger than 1μm in diameter at the collection time is calculated to be about 2.7×10−1 particles per cubic meter, of which approximately 95% are smaller than 5μm in diameter. Previous classification schemes are expanded to explicitly recognize low atomic number material. With the single exception of the calcium-aluminum-silicate (CAS) spheres all solid particle types show a logarithmic increase in number concentration with decreasing diameter. The aluminum-rich particles are unique in showing bimodal size distributions. In addition, spheres constitute only a minor fraction of the aluminum-rich material. About 2/3 of the particles examined were found to be shards of rhyolitic glass. This abundant volcanic material could not be correlated with any eruption plume known to have vented directly to the stratosphere. The micrometeorite number density calculated from this data set is 5×10−2 micrometeorites per cubic meter of air, an order of magnitude greater than the best previous estimate. At the collection altitude, the maximum collision frequency of solid particles >5μm in average diameter is calculated to be 6.91×10−16 collisions per second, which indicates negligible contamination of extraterrestrial particles in the stratosphere by solid anthropogenic particles.

Assessing eco-environmental performance of agricultural production in OECD countries : combination of soil surface, soil system and farm gate methods of nutrient auditing

Nitrogen balance is increasingly used as an indicator of the environmental performance of agricultural sector in national, international, and global contexts. There are three main methods of accounting the national nitrogen balance: farm gate, soil surface, and soil system. OECD (2008) recently reported the nitrogen and phosphorus balances for member countries for the 1985 - 2004 period using the soil surface method. The farm gate and soil system methods were also used in some international projects. Some studies have provided the comparison among these methods and the conclusion is mixed. The motivation of this present paper was to combine these three methods to provide a more detailed auditing of the nitrogen balance and flows for national agricultural production. In addition, the present paper also provided a new strategy of using reliable international and national data sources to calculate nitrogen balance using the farm gate method. The empirical study focused on the nitrogen balance of OECD countries for the period from 1985 to 2003. The N surplus sent to the total environment of OECD surged dramatically in early 1980s, gradually decreased during 1990s but exhibited an increasing trends in early 2000s. The overall N efficiency however fluctuated without a clear increasing trend. The eco-environmental ranking shows that Australia and Ireland were the worst while Korea and Greece were the best.