Stratum basale keratinocyte expression of the cell surface glycoprotein CDCP1 during epidermogenesis and its role in keratinocyte migration

Background: Epidermogenesis and epidermal wound healing are tightly regulated processes during which keratinocytes must migrate, proliferate and differentiate. Cell to cell adhesion is crucial to the initiation and regulation of these processes. CUB domain containing protein 1 (CDCP1) is a transmembrane glycoprotein that is differentially tyrosine phosphorylated during changes in cell adhesion and survival signalling and is expressed by keratinocytes in native human skin, as well as in primary cultures. Objectives: To investigate the expression of CDCP1 during epidermogenesis and its role in keratinocyte migration. Methods: We examined both human skin tissue and an in vitro three-dimensional human skin equivalent model to examine the expression of CDCP1 during epidermogenesis. To examine the role of CDCP1 in keratinocyte migration we used a function blocking anti-CDCP1 antibody and a real-time Transwell™ cell migration assay. Results: Immunohistochemical analysis indicated that in native human skin CDCP1 is expressed in the stratum basale and stratum spinosum. In contrast, during epidermogenesis in a 3-dimensional human skin equivalent model CDCP1 was expressed only in the stratum basale, with localization restricted to the cell-cell membrane. No expression was detected in basal keratinocytes that were in contact with the basement membrane. Further, an anti-CDCP1 function blocking antibody was shown to disrupt keratinocyte chemotactic migration in vitro. Conclusions: These findings delineate the expression of CDCP1 in human epidermal keratinocytes during epidermogenesis and demonstrate that CDCP1 is involved in keratinocyte migration.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Evaluation of the Suchey-Brooks Method of age estimation in an Australian subpopulation using computed tomography of the pubic symphyseal surface

Despite the prominent use of the Suchey-Brooks (S-B) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential inter-population error rates between geographical locations. This study assessed the accuracy of the S-B method to a contemporary adult population in Queensland, Australia and provides robust age parameters calibrated for our population. Three-dimensional surface reconstructions were generated from computed tomography scans of the pubic symphysis of male and female Caucasian individuals aged 15–70 years (n = 195) in Amira® and Rapidform®. Error was analyzed on the basis of bias, inaccuracy and percentage correct classification for left and right symphyseal surfaces. Application of transition analysis and Chi-square statistics demonstrated 63.9% and 69.7% correct age classification associated with the left symphyseal surface of Australian males and females, respectively, using the S-B method. Using Bayesian statistics, probability density distributions for each S-B phase were calculated, providing refined age parameters for our population. Mean inaccuracies of 6.77 (±2.76) and 8.28 (±4.41) years were reported for the left surfaces of males and females, respectively; with positive biases for younger individuals (<55 years) and negative biases in older individuals. Significant sexual dimorphism in the application of the S-B method was observed; and asymmetry in phase classification of the pubic symphysis was a frequent phenomenon. These results recommend that the S-B method should be applied with caution in medico-legal death investigations of Queensland skeletal remains and warrant further investigation of reliable age estimation techniques.

Mixed convection over a horizontal plate with streamwise non-uniform surface temperature distribution

Numerical investigation on mixed convection of a two-dimensional incompressible laminar flow over a horizontal flat plate with streamwise sinusoidal distribution of surface temperature has been performed for different values of Rayleigh number, Reynolds number and frequency of periodic temperature for constant Prandtl number and amplitude of periodic temperature. Finite element method adapted to rectangular non-uniform mesh elements by a non-linear parametric solution algorithm basis numerical scheme has been employed. The investigating parameters are the Rayleigh number, the Reynolds number and frequency of periodic temperature. The effect of variation of individual investigating parameters on mixed convection flow characteristics has been studied to observe the hydrodynamic and thermal behavior for while keeping the other parameters constant. The fluid considered in this study is air with Prandtl number 0.72. The results are obtained for the Rayleigh number range of 102 to 104, Reynolds number ranging from 1 to 100 and the frequency of periodic temperature from 1 to 5. Isotherms, streamlines, average and local Nusselt numbers are presented to show the effect of the different values of aforementioned investigating parameters on fluid flow and heat transfer.

Natural convection flow with surface radiation along a vertical wavy surface

In this study, natural convection boundary layer flow of thermally radiating fluid along a heated vertical wavy surface is analyzed. Here, the radiative component of heat flux emulates the surface temperature. Governing equations are reduced to dimensionless form, subject to the appropriate transformation. Resulting dimensionless equations are transformed to a set of parabolic partial differential equations by using primitive variable formulation, which are then integrated numerically via iterative finite difference scheme. Emphasis has been given to low Prandtl number fluid. The numerical results obtained for the physical parameters, such as, surface radiation parameter, R, and radiative length parameter, ξ, are discussed in terms of local skin friction and Nusselt number coefficients. Comprehensive interpretation of velocity distribution is also given in the form of streamlines.

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.

Predicting the localized surface plasmon resonances of spherical nanoparticles on substrate : electrostatic eigenmode method

We present experimental results that demonstrate that the wavelength of the fundamental localised surface plasmon resonance for spherical gold nanoparticles on glass can be predicted using a simple, one line analytical formula derived from the electrostatic eigenmode method. This allows the role of the substrate in lifting mode degeneracies to be determined, and the role of local environment refractive indices on the plasmon resonance to be investigated. The effect of adding silica to the casting solution in minimizing nanopaticle agglomeration is also discussed.

Exponential asymptotics of free surface flow due to a line source

The steady problem of free surface flow due to a submerged line source is revisited for the case in which the fluid depth is finite and there is a stagnation point on the free surface directly above the source. Both the strength of the source and the fluid speed in the far field are measured by a dimensionless parameter, the Froude number. By applying techniques in exponential asymptotics, it is shown that there is a train of periodic waves on the surface of the fluid with an amplitude which is exponentially small in the limit that the Froude number vanishes. This study clarifies that periodic waves do form for flows due to a source, contrary to a suggestion by Chapman & Vanden-Broeck (2006, J. Fluid Mech., 567, 299--326). The exponentially small nature of the waves means they appear beyond all orders of the original power series expansion; this result explains why attempts at describing these flows using a finite number of terms in an algebraic power series incorrectly predict a flat free surface in the far field.

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.

Free-surface flow past arbitrary topography and an inverse approach for wave-free solutions

An efficient numerical method to compute nonlinear solutions for two-dimensional steady free-surface flow over an arbitrary channel bottom topography is presented. The approach is based on a boundary integral equation technique which is similar to that of Vanden-Broeck's (1996, J. Fluid Mech., 330, 339-347). The typical approach for this problem is to prescribe the shape of the channel bottom topography, with the free-surface being provided as part of the solution. Here we take an inverse approach and prescribe the shape of the free-surface a priori while solving for the corresponding bottom topography. We show how this inverse approach is particularly useful when studying topographies that give rise to wave-free solutions, allowing us to easily classify eleven basic flow types. Finally, the inverse approach is also adapted to calculate a distribution of pressure on the free-surface, given the free-surface shape itself.

In situ SANS study of the surface and pore filling adsorption of subcritical and supercritical CO2 in porous silica as a function of pore size

We applied small-angle neutron scattering (SANS) and ultra small-angle neutron scattering (USANS) to monitor evolution of the CO2 adsorption in porous silica as a function of CO2 pressure and temperature in pores of different sizes. The range of pressures (0 < P < 345 bar) and temperatures (T=18 OC, 35 OC and 60 OC) corresponded to subcritical, near critical and supercritical conditions of bulk fluid. We observed that the adsorption behavior of CO2 is fundamentally different in large and small pores with the sizes D > 100 Å and D < 30 Å, respectively. Scattering data from large pores indicate formation of a dense adsorbed film of CO2 on pore walls with the liquid-like density (ρCO2)ads≈0.8 g/cm3. The adsorbed film coexists with unadsorbed fluid in the inner pore volume. The density of unadsorbed fluid in large pores is temperature and pressure dependent: it is initially lower than (ρCO2)ads and gradually approaches it with pressure. In small pores compressed CO2 gas completely fills the pore volume. At the lowest pressures of the order of 10 bar and T=18 OC, the fluid density in smallest pores available in the matrix with D ~ 10 Å exceeds bulk fluid density by a factor of ~ 8. As pressure increases, progressively larger pores become filled with the condensed CO2. Fluid densification is only observed in pores with sizes less than ~ 25 – 30 Å. As the density of the invading fluid reaches (ρCO2)bulk~ 0.8 g/cm3, pores of all sizes become uniformly filled with CO2 and the confinement effects disappear. At higher densities the fluid in small pores appears to follow the equation of state of bulk CO2 although there is an indication that the fluid density in the inner volume of large pores may exceed the density of the adsorbed layer. The equivalent internal pressure (Pint) in the smallest pores exceeds the external pressure (Pext) by a factor of ~ 5 for both sub- and supercritical CO2. Pint gradually approaches Pext as D → 25 – 30 Å and is independent of temperature in the studied range of 18 OC ≤ T ≤ 60 OC. The obtained results demonstrate certain similarity as well as differences between adsorption of subcritical and supercritical CO2 in disordered porous silica. High pressure small angle scattering experiments open new opportunities for in situ studies of the fluid adsorption in porous media of interest to CO2 sequestration, energy storage, and heterogeneous catalysis.

Effect of rehydration on structure and surface properties of thermally treated palygorskite

Palygorskite has a fibrous like morphology with a distinctive layered appearance. The simplified formula of palygorskite (Mg5Si8O20(OH)2(OH2)4 nH2O) indicates that two different types of water are present. The dehydration and rehydration of palygorskite have been studied using thermogravimetry and H2O-tem- perature programmed desorption. X-ray diffractograms, NH3 adsorption profiles, and NH3 desorption profiles were obtained for thermally treated palygorskite as a function of temperature. The results proved water molecules were mainly derived from Si–OH units. In addition, five kinds of acid sites were found for palygorskite. The number of acid sites of external surfaces was larger than that of the internal sur- faces. Bonding on the internal surface acid sites was stronger than the bonding of the external surfaces. Rehydration restored the folded structure of palygorskite when thermal treatment temperature was lower than 300 oC.

Hydrogen spillover mechanism on a pd-doped mg surface as revealed by ab initio density functional calculation

The hydrogenation kinetics of Mg is slow, impeding its application for mobile hydrogen storage. We demonstrate by ab initio density functional theory (DFT) calculations that the reaction path can be greatly modified by adding transition metal catalysts. Contrasting with Ti doping, a Pd dopant will result in a very small activation barrier for both dissociation of molecular hydrogen and diffusion of atomic H on the Mg surface. This new computational finding supports for the first time by ab initio simulationthe proposed hydrogen spillover mechanism for rationalizing experimentally observed fast hydrogenation kinetics for Pd-capped Mg materials.

Bubble extinction in Hele-Shaw flow with surface tension and kinetic undercooling regularisation

We perform an analytic and numerical study of an inviscid contracting bubble in a two-dimensional Hele-Shaw cell, where the effects of both surface tension and kinetic undercooling on the moving bubble boundary are not neglected. In contrast to expanding bubbles, in which both boundary effects regularise the ill-posedness arising from the viscous (Saffman-Taylor) instability, we show that in contracting bubbles the two boundary effects are in competition, with surface tension stabilising the boundary, and kinetic undercooling destabilising it. This competition leads to interesting bifurcation behaviour in the asymptotic shape of the bubble in the limit it approaches extinction. In this limit, the boundary may tend to become either circular, or approach a line or "slit" of zero thickness, depending on the initial condition and the value of a nondimensional surface tension parameter. We show that over a critical range of surface tension values, both these asymptotic shapes are stable. In this regime there exists a third, unstable branch of limiting self-similar bubble shapes, with an asymptotic aspect ratio (dependent on the surface tension) between zero and one. We support our asymptotic analysis with a numerical scheme that utilises the applicability of complex variable theory to Hele-Shaw flow.