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Biomedical subjects

P J King

Publications and source records attributed to P J King.

At least 19 recordsLinked to original sources
PubMed2007

Instabilities in vertically vibrated fluid-grain systems.

When a bed of fluid-immersed fine grains is exposed to vertical vibration a wealth of phenomena may be observed. At low frequencies a horizontal bed geometry is generally unstable and the bed breaks spatial symmetry, acquiring a tilt. At the same time it undergoes asymmetric granular convection. Fine binary mixtures may separate completely into layers or patterns of stripes. The separated regions may exhibit instabilities in which they undergo wave-like motion or exhibit quasi-periodic oscillations. We briefly review these and a number of related behaviours, identifying the physical mechanisms behind each. Finally, we discuss the magneto-vibratory separation of binary mixtures which results from exposing each component to a different effective gravity and describe the influence of a background fluid on this process.

Journal Article↗
PubMed2005

Traveling waves in a water-immersed binary granular system vibrated within an annular cell.

It has been known since the time of Faraday that vertically vibrated fine grains may spontaneously form piles through their interaction with a fluid. More recently, it has been observed that a fine binary mixture may separate under vertical vibration through the differential influence of the fluid on the two granular components. Here, we report a detailed study of a system of water-immersed bronze and glass grains held between two coaxial cylinders. Under vertical vibration, the bronze separates to form a layer above the glass, which itself breaks symmetry to form a pile. Symmetry is broken a second time by the bronze forming layers of different thicknesses upon the two slopes of the glass pile. The pile then travels as a wave with the thicker bronze layer upon its leading surface. We examine the conditions for these traveling waves and determine how their speed varies with particle size, frequency, and amplitude of vibration. A model is developed which provides a semiquantitative account of the wave motion.

Journal Article↗
PubMed2005

Separation of binary granular mixtures under vibration and differential magnetic levitation force.

The application of both a strong magnetic field and a magnetic field gradient to a diamagnetic or paramagnetic material can produce a vertical force that acts in concert with the force of gravity. We consider a binary granular mixture in which the two components have different magnetic susceptibilities and therefore experience different effective forces of gravity when subjected to an inhomogeneous magnetic field. Under vertical vibration, such a mixture may rapidly separate into regions almost pure in the two components. We investigate the conditions for this behavior, studying the speed and completeness of separation as a function of differential effective gravity and the frequency and amplitude of vibration. The influence of the cohesive magnetic dipole-dipole interactions on the separation process is also investigated. In our studies insight is gained through the use of a molecular dynamics simulation model.

Journal Article↗
PubMed2005

Faraday tilting of water-immersed granular beds.

Under low-frequency vertical vibration, a system of fine grains within a fluid is observed to tilt or to form piles, an effect studied by Faraday for grains in air. Here, we investigate the physical mechanisms behind Faraday tilting in a bed of vertically vibrated bronze spheres fully immersed in water. Experimental observations of surface tilting and bulk convection are compared with the results of molecular dynamics simulations in which the water is treated as an incompressible fluid. Our simulations reproduce the main features observed experimentally. Most tilt construction is shown to be due to horizontal fluid flow within the bed, principally occurring when the gap between the bed and the supporting platform is close to a maximum. Tilt destruction occurs by granular surface flow and in the bulk of the bed at times during each vibratory cycle close to and just later than bed impact. Destruction becomes more important for higher values of frequency and vibration amplitude, leading to lower tilt angles, partial tilting, or the symmetric domed geometry of Muchowski flow.

Journal Article↗
PubMed2005

Method for locating the vapor-liquid critical point of multicomponent fluid mixtures using a shear mode piezoelectric sensor.

A new approach to locating the critical point of fluid mixtures is reported, utilizing a shear mode piezoelectric sensor. This technique employs a single piece of quartz crystal that is installed at the bottom of a strongly stirred high-pressure vessel. The sensor response indicates whether liquid or gas is in contact with its surfaces. Thus, the sensor is able to identify vapor-liquid phase separation by registering a discontinuity in the impedance minimum of the sensor as a function of pressure. Two systems (methanol + CO2 and H2 + CO2) have been investigated using this method. The critical point data of the methanol + CO2 system were chosen to validate the approach against a wealth of literature data, and good agreement was obtained. The sensor behavior in the two-phase region, as well as the effect of stirring, is discussed. The method is general and can be used with other sensors.

Biosensing Techniques↗
PubMed2004

Are Brazil nuts attractive?

We present event-driven simulation results for single and multiple intruders in a vertically vibrated granular bed. Under our vibratory conditions, the mean vertical position of a single intruder is governed primarily by a buoyancylike effect. Multiple intruders also exhibit buoyancy governed behavior; however, multiple neutrally buoyant intruders cluster spontaneously and undergo horizontal segregation. These effects can be understood by considering the dynamics of two neutrally buoyant intruders. We have measured an attractive force between such intruders which has a range of five intruder diameters, and we provide a mechanistic explanation for the origins of this force.

Journal Article↗
PubMed2004

Stripe formation in granular mixtures due to the differential influence of drag.

We describe an investigation of fluid-immersed granular mixtures subjected to horizontal vibration. For sufficiently large amplitudes of vibration, a mixture of equal-sized glass and bronze particles in water is found to separate into a striped pattern. Numerical simulations based on soft-sphere molecular dynamics coupled to the interstitial fluid are able to capture many of the features observed experimentally. We propose a general pattern-formation mechanism based on the differential influence of drag on the components of the mixture. An expression for the number of stripes as a function of the system parameters is derived and shown to be in good agreement with experiments.

Journal Article↗
PubMed2003

Numerical simulations of air-driven granular separation.

Recently it has been shown that binary mixtures of equal-sized fine granular materials exhibit spontaneous separation under vertical vibration in the presence of air [Science 295, 1877 (2002)]. Here we describe a model of this behavior based on soft-sphere molecular dynamics coupled to the motion of the surrounding air. It exhibits many of the features observed experimentally including almost complete separation of the components into well defined regions with extremely sharp boundaries. The basic separation mechanism is robust and insensitive to many of the model parameters. Our results show that the forced flow of air through the bed, induced by vibration of the container, is responsible for this form of separation.

Journal Article↗
PubMed2003

Surface instabilities on liquid oxygen in an inhomogeneous magnetic field.

Liquid oxygen exhibits surface instabilities when subjected to a sufficiently strong magnetic field. A vertically oriented magnetic field gradient both increases the magnetic field value at which the pattern forms and shrinks the length scale of the surface patterning. We show that these effects of the field gradient may be described in terms of an "effective gravity," which in our experiments may be varied from 1 g to 360 g.

Journal Article↗
PubMed2003

Air-driven Brazil nut effect.

A large heavy object may rise to the top of a bed of smaller particles under the influence of vertical vibration, the "Brazil nut effect." Recently it has been noted that interstitial air can influence the Brazil nut rise time. Here we report that the air movement induced by vertical vibration produces a very strong Brazil nut effect for fine granular beds. We use a porous-bottomed box to investigate the mechanism responsible for this effect and to demonstrate that it is related to the piling of fine beds, first reported by Chladni and studied by Faraday. Both effects are due to the strong interaction of the fine particles with the air, as it is forced through the bed by the vibration.

Air↗
PubMed2002

Spontaneous air-driven separation in vertically vibrated fine granular mixtures.

We report the observation of the spontaneous separation of vertically vibrated mixtures of fine bronze and glass spheres of similar diameters. At low frequencies and at sufficient vibrational amplitudes, a sharp boundary forms between a lower region of glass and an upper region of the heavier bronze. The boundary undergoes various oscillations, including periodic tilting motion, but remains extremely sharp. At higher frequencies, the bronze separates as a mid-height layer between upper and lower glass regions, and the oscillations are largely absent. The mechanism responsible for the separation can be traced to the effect of air on the granular motion.

Journal Article↗
PubMed2002

Agonist activated adrenocorticotropin receptor internalizes via a clathrin-mediated G protein receptor kinase dependent mechanism.

The physiological effects of the pituitary hormone, adrenocorticotropic hormone (ACTH) on the adrenal are mediated by the melanocortin 2 receptor (MC2R), a G protein coupled receptor (GPCR) that signals via adenylate cyclase to elevate intracellular cyclic AMP (cAMP) levels. The function and expression of the receptor is likely to be a major determinant of the response to ACTH. Following repeated stimulation, the cAMP signal is diminished or desensitized. Prolonged desensitization may involve internalization of the receptor. Internalization may occur by at least two mechanisms--receptor mediated endocytosis via clathrin-coated pits and by caveolae mediated internalization. The mode of internalization for the endogenous MC2R in Y1 cells was determined using radiolabelled ACTH. Treatment of Y1 cells with hypertonic sucrose or with concanavalin A, which inhibit clathrin-mediated endocytosis, blocked internalization. Filipin and nystatin, which inhibit caveolae formation, did not influence internalization. A dominant negative GRK2 inhibited internalization whilst the protein kinase A (PKA) consensus site mutant MC2R (S208A) internalized normally. However, dominant negative V53D beta-arrestin-1 did not inhibit ACTH internalization in Y1 cells. In conclusion, it appears that the MC2R in Y1 cells internalizes by a G protein coupled receptor kinase (GRK) dependent clathrin-coated pit mechanism.

Animals↗
PubMed2002

Tumour-derived human adrenocortical cells express beta-adrenergic receptors: steroidogenic effects of beta-adrenergic input.

It is well established that catecholamines have potent actions on adrenocortical function and steroidogenesis in different species. The effect of these substances on steroid production of the human adrenal cell line H295R is the subject of this study. H295R cells were cultured in the presence of the synthetic catecholamine, isoproterenol for four hours. Aldosterone, cortisol, and DHEA secretion was measured using direct radioimmunoassays. Administration of 10(-11)-10(-7) mol/L isoproterenol produced a dose-dependent increase in secretion of aldosterone, cortisol, and DHEA by H295R cells resulting in 3-fold, 2.5-fold, and 2-fold stimulation respectively, relative to basal values. Analysis of mRNA using nested PCR revealed the presence of all three types of beta-adrenergic receptors namely beta1, beta2, and beta3 in H295R cells. Isoproterenol had no effect on the proliferation rate of H295R cells as determined by 3H-incorporation assay and the colorimetric WST-1 cell proliferation assay.

Adrenal Cortex↗
PubMed2002

Failed export of the adrenocorticotrophin receptor from the endoplasmic reticulum in non-adrenal cells: evidence in support of a requirement for a specific adrenal accessory factor.

Difficulty in expressing the adrenocorticotrophin (ACTH) receptor (melanocortin 2 receptor; MC2R) after transfection of various MC2R expression vectors has been experienced by many researchers. Reproducible evidence for expression has been obtained only in the Y6/OS3 corticoadrenal cell lines or in cells expressing endogenous melanocortin receptors. In order to determine the cause of this failure of expression we have undertaken the following studies. An MC2R expression plasmid was constructed in which the green fluorescent protein (GFP) coding region had been added to the C-terminus of the mature protein. Transfection of this plasmid into Y6 cells with a cAMP-responsive reporter plasmid demonstrated normal function of this receptor. Imaging of CHO cells expressing MC2R-GFP revealed perinuclear expression, although a cholecystokinin receptor (CCKR)-GFP construct was efficiently expressed at the cell surface. Y6 cells, in contrast, showed cell surface fluorescence after transfection with MC2R-GFP. Several other cell types showed a similar pattern of GFP distribution characteristic of retention in the endoplasmic reticulum. Counterstaining with an anti-KDEL antibody confirmed this location. Co-expression of the MC2R and the CCKR-GFP did not impair CCKR trafficking to the cell surface, implying a receptor-specific impairment to trafficking in the CHO cell which was absent in the Y6 cell.

Adrenocorticotropic Hormone↗
PubMed2001

Desensitization of the Y1 cell adrenocorticotropin receptor: evidence for a restricted heterologous mechanism implying a role for receptor-effector complexes.

Receptor desensitization provides a potential mechanism for the regulation of adrenocortical adrenocorticotropin (ACTH) responsiveness. Using the mouse adrenocortical Y1 cell line we demonstrate that ACTH effectively desensitizes the cAMP response of its own receptor, the melanocortin 2 receptor (MC2R), in these cells with a maximal effect between 30 and 60 min. Neither forskolin nor isoproterenol (in Y1 cells stably transfected with the beta(2)-adrenergic receptor) desensitize this ACTH response. ACTH desensitizes its receptor at concentrations at which only a fraction of receptors are occupied, implying that this mechanism acts on agonist-unoccupied receptors. Y1 cells express G protein-coupled receptor kinase (GRK) 2 and 5, but stable expression of a dominant negative GRK2 (K220W) only marginally reduces the desensitization by ACTH. The protein kinase A (PKA) inhibitor, H89, extinguishes almost the entire desensitization response over the initial 30-min period at all concentrations of ACTH. A mutant MC2R in which the single consensus PKA phosphorylation site has been mutated (S208A) when expressed in MC2R-negative Y6 cells is also unable to desensitize. These data imply a heterologous, PKA-dependent, mode of desensitization, which is restricted to agonist-occupied and -unoccupied MC2R, possibly as a consequence of receptor/effector complexes that functionally compartmentalize this receptor.

Adrenocorticotropic Hormone↗
PubMed2001

Experimental confirmation of the predicted shallow donor hydrogen state in zinc oxide.

We confirm the recent prediction that interstitial protium may act as a shallow donor in zinc oxide, by direct spectroscopic observation of its muonium counterpart. On implantation into ZnO, positive muons--chemically analogous to protons in this context--form paramagnetic centers below about 40 K. The muon-electron contact hyperfine interaction, as well as the temperature and activation energy for ionization, imply a shallow level. Similar results for the cadmium chalcogenides suggest that such shallow donor states are generic to the II-VI compounds. The donor level depths should serve as a guide for the electrical activity of interstitial hydrogen.

Journal Article↗