Kinetics of propranolol uptake in muscle, skin, and fat of the isolated perfused rat hindlimb

The tissue distribution kinetics of a highly bound solute, propranolol, was investigated in a heterogeneous organ, the isolated perfused limb, using the impulse-response technique and destructive sampling. The propranolol concentration in muscle, skin, and fat as well as in outflow perfusate was measured up to 30 min after injection. The resulting data were analysed assuming (1) vascular, muscle, skin and fat compartments as well mixed (compartmental model) and (2) using a distributed-in-space model which accounts for the noninstantaneous intravascular mixing and tissue distribution processes but consists only of a vascular and extravascular phase (two-phase model). The compartmental model adequately described propranolol concentration-time data in the three tissue compartments and the outflow concentration-time curve (except of the early mixing phase). In contrast, the two-phase model better described the outflow concentration-time curve but is limited in accounting only for the distribution kinetics in the dominant tissue, the muscle. The two-phase model well described the time course of propranolol concentration in muscle tissue, with parameter estimates similar to those obtained with the compartmental model. The results suggest, first that the uptake kinetics of propranolol into skin and fat cannot be analysed on the basis of outflow data alone and, second that the assumption of well-mixed compartments is a valid approximation from a practical point of view las, e.g., in physiological based pharmacokinetic modelling). The steady-state distribution volumes of skin and fat were only 16 and 4%, respectively, of that of muscle tissue (16.7 ml), with higher partition coefficient in fat (6.36) than in skin (2.64) and muscle (2.79. (C) 2000 Elsevier Science B.V. All rights reserved.

Robust Mixture Modelling Using the t Distribution

Normal mixture models are being increasingly used to model the distributions of a wide variety of random phenomena and to cluster sets of continuous multivariate data. However, for a set of data containing a group or groups of observations with longer than normal tails or atypical observations, the use of normal components may unduly affect the fit of the mixture model. In this paper, we consider a more robust approach by modelling the data by a mixture of t distributions. The use of the ECM algorithm to fit this t mixture model is described and examples of its use are given in the context of clustering multivariate data in the presence of atypical observations in the form of background noise.

Heterogeneous distribution of isoactins in cultured vascular smooth muscle cells does not reflect segregation of contractile and cytoskeletal domains

We have previously demonstrated that or-smooth muscle (alpha -SM) actin is predominantly distributed in the central region and beta -non-muscle (beta -NM) actin in the periphery of cultured rabbit aortic smooth muscle cells (SMCs). To determine whether this reflects a special form of segregation of contractile and cytoskeletal components in SMCs, this study systematically investigated the distribution relationship of structural proteins using high-resolution confocal laser scanning fluorescent microscopy. Not only isoactins but also smooth muscle myosin heavy chain, alpha -actinin, vinculin, and vimentin were heterogeneously distributed in the cultured SMCs. The predominant distribution of beta -NM actin in the cell periphery was associated with densely distributed vinculin plaques and disrupted or striated myosin and ol-actinin aggregates, which may reflect a process of stress fiber assembly during cell spreading and focal adhesion formation. The high-level labeling of alpha -SM actin in the central portion of stress fibers was related to continuous myosin and punctate alpha -actinin distribution, which may represent the maturation of the fibrillar structures. The findings also suggest that the stress fibers, in which actin and myosin filaments organize into sar-comere-like units with alpha -actinin-rich dense bodies analogous to Z-lines, are the contractile vimentin structures of cultured SMCs that link to the network of vimentin-containing intermediate alpha -actinin filaments through the dense bodies and dense plaques.

Commentary: Using the convection-dispersion model and transit time density functions in the analysis of organ distribution kinetics

The convection-dispersion model and its extended form have been used to describe solute disposition in organs and to predict hepatic availabilities. A range of empirical transit-time density functions has also been used for a similar purpose. The use of the dispersion model with mixed boundary conditions and transit-time density functions has been queried recently by Hisaka and Sugiyanaa in this journal. We suggest that, consistent with soil science and chemical engineering literature, the mixed boundary conditions are appropriate providing concentrations are defined in terms of flux to ensure continuity at the boundaries and mass balance. It is suggested that the use of the inverse Gaussian or other functions as empirical transit-time densities is independent of any boundary condition consideration. The mixed boundary condition solutions of the convection-dispersion model are the easiest to use when linear kinetics applies. In contrast, the closed conditions are easier to apply in a numerical analysis of nonlinear disposition of solutes in organs. We therefore argue that the use of hepatic elimination models should be based on pragmatic considerations, giving emphasis to using the simplest or easiest solution that will give a sufficiently accurate prediction of hepatic pharmacokinetics for a particular application. (C) 2000 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 89:1579-1586, 2000.

Heat flow for Yang-Mills-Higgs fields, part I

The Yang-Mills-Higgs field generalizes the Yang-Mills field. The authors establish the local existence and uniqueness of the weak solution to the heat flow for the Yang-Mills-Higgs field in a vector bundle over a compact Riemannian 4-manifold, and show that the weak solution is gauge-equivalent to a smooth solution and there are at most finite singularities at the maximum existing time.

Increasingly inequitable distribution of general practitioners in Australia, 1986-96

Objective: To document trends in the distribution of general practitioners (GPs) in Australia between 1986 and 1996, adjusted for community need. Methods: Data on the location of GPs, population size and crude mortality in statistical divisions (SD) were obtained from the Australian Bureau of Statistics Census of Population and Housing in 1986 and 1996. From these data, we calculated measures of distribution equality (number of people sharing each GP in each SD) and distribution equity (number of people sharing each GP divided by the crude mortality rate; the Robin Hood Index), and analysed temporal changes in the distribution of GPs. Results: Nationally the number of people sharing each GP fell 11% from 1,038 in 1986 to 921 in 1996. However, in 41 of 57 SDs (72%, p=0.01) the number of people sharing a GP actually increased over this time, and the average Robin Hood Index across SDs fell from 0.943 to 0.783 (p=0.004), indicating increasingly inequitable distribution. Comparing the Robin Hood index values of all SDs ranked in pairs, the value fell in 53 of 57 (93%, p<0.001) paired SDs over the decade. These patterns demonstrate increasing inequity over the decade. The number of people sharing each GP was consistently and substantially lower in the capital city SDs and the Robin Hood Index values were consistently and substantially higher (overserved) compared with country SDs. Conclusions: Despite there being more GPs per capita in Australia, their distribution became increasingly unequal and inequitable between 1986 and 1996, such that rural and remote areas became increasingly poorly served.

Residence time distributions of gas flowing through rotating drum bioreactors

Residence time distribution studies of gas through a rotating drum bioreactor for solid-state fermentation were performed using carbon monoxide as a tracer gas. The exit concentration as a function of time differed considerably from profiles expected for plug flow, plug flow with axial dispersion, and continuous stirred tank reactor (CSTR) models. The data were then fitted by least-squares analysis to mathematical models describing a central plug flow region surrounded by either one dead region (a three-parameter model) or two dead regions (a five-parameter model). Model parameters were the dispersion coefficient in the central plug flow region, the volumes of the dead regions, and the exchange rates between the different regions. The superficial velocity of the gas through the reactor has a large effect on parameter values. Increased superficial velocity tends to decrease dead region volumes, interregion transfer rates, and axial dispersion. The significant deviation from CSTR, plug flow, and plug flow with axial dispersion of the residence time distribution of gas within small-scale reactors can lead to underestimation of the calculation of mass and heat transfer coefficients and hence has implications for reactor design and scaleup. (C) 2001 John Wiley & Sons, Inc.

Heat flow for the Yang-Mills-Higgs field and the Hermitian Yang-Mills-Higgs metric

For a parameter lambda > 0, we study a type of vortex equations, which generalize the well-known Hermitian-Einstein equation, for a connection A and a section phi of a holomorphic vector bundle E over a Kahler manifold X. We establish a global existence of smooth solutions to heat flow for a self-dual Yang-Mills-Higgs field on E. Assuming the lambda -stability of (E, phi), we prove the existence of the Hermitian Yang-Mills-Higgs metric on the holomorphic bundle E by studying the limiting behaviour of the gauge flow.

Similitude applied to centrifugal scaling of unsaturated flow

Centrifuge experiments modeling single-phase flow in prototype porous media typically use the same porous medium and permeant. Then, well-known scaling laws are used to transfer the results to the prototype. More general scaling laws that relax these restrictions are presented. For permeants that are immiscible with an accompanying gas phase, model-prototype (i.e., centrifuge model experiment-target system) scaling is demonstrated. Scaling is shown to be feasible for Miller-similar (or geometrically similar) media. Scalings are presented for a more, general class, Lisle-similar media, based on the equivalence mapping of Richards' equation onto itself. Whereas model-prototype scaling of Miller-similar media can be realized easily for arbitrary boundary conditions, Lisle-similarity in a finite length medium generally, but not always, involves a mapping to a moving boundary problem. An exception occurs for redistribution in Lisle-similar porous media, which is shown to map to spatially fixed boundary conditions. Complete model-prototype scalings for this example are derived.

Finite element modelling of heat transfer through permeable cracks in hydrothermal systems with upward throughflow

We use the finite element method to model the heat transfer phenomenon through permeable cracks in hydrothermal systems with upward throughflow. Since the finite element method is an approximate numerical method, the method must be validated before it is used to soh,e any new, kind of problem. However, the analytical solution, which can be used to validate the finite element method and other numerical methods, is rather limited in the literature, especially, for the problem considered here. Keeping this in mind, we have derived analytical solutions for the temperature distribution along the vertical axis of a crack in a fluid-saturated porous layer. After the finite element method is validated by comparing the numerical solution with the analytical solution for the same benchmark problem, it is used to investigate the pore-fluid flow and heat transfer in layered hydrothermal systems with vertical permeable cracks. The related analytical and numerical results have demonstrated that vertical cracks are effective and efficient members to transfer heat energy from the bottom section to the top section in hydrothermal systems with upward throughflow.

Analytical solution to the zero-inertia problem for surge flow phenomena in nonprismatic channels

Surge flow phenomena. e.g.. as a consequence of a dam failure or a flash flood, represent free boundary problems. ne extending computational domain together with the discontinuities involved renders their numerical solution a cumbersome procedure. This contribution proposes an analytical solution to the problem, It is based on the slightly modified zero-inertia (ZI) differential equations for nonprismatic channels and uses exclusively physical parameters. Employing the concept of a momentum-representative cross section of the moving water body together with a specific relationship for describing the cross sectional geometry leads, after considerable mathematical calculus. to the analytical solution. The hydrodynamic analytical model is free of numerical troubles, easy to run, computationally efficient. and fully satisfies the law of volume conservation. In a first test series, the hydrodynamic analytical ZI model compares very favorably with a full hydrodynamic numerical model in respect to published results of surge flow simulations in different types of prismatic channels. In order to extend these considerations to natural rivers, the accuracy of the analytical model in describing an irregular cross section is investigated and tested successfully. A sensitivity and error analysis reveals the important impact of the hydraulic radius on the velocity of the surge, and this underlines the importance of an adequate description of the topography, The new approach is finally applied to simulate a surge propagating down the irregularly shaped Isar Valley in the Bavarian Alps after a hypothetical dam failure. The straightforward and fully stable computation of the flood hydrograph along the Isar Valley clearly reflects the impact of the strongly varying topographic characteristics on the How phenomenon. Apart from treating surge flow phenomena as a whole, the analytical solution also offers a rigorous alternative to both (a) the approximate Whitham solution, for generating initial values, and (b) the rough volume balance techniques used to model the wave tip in numerical surge flow computations.

New status, species, distribution records and phylogeny for Australian mandibulate Chironomidae (Diptera)

All life-history stages of the Australian Podonominae (Chironomidae) genus Archaeochlus Brundin are revised, providing evidence for recognition of a separate clade, named here as Austrochlus Cranston. Based on molecular and morphological evidence, the clade contains two additional species: Austrochlus parabrundini Cranston, Edward and Cook sp. n. is described from Western Australia where its granite outcrop seepage habitat and geographical range is almost identical to that of the type species Austrochlus brundini Cranston, Edward and Colless (n. comb); Austrochlus centralaustralis Cranston, Edward and Cook sp. n. is described from ephemeral seepage/flows in the MacDonnell and James Ranges of central Australia. Molecular studies reported here confirm species distinctions, relationships to African taxa, and basal relationships within the Chironomidae. Modelled distributions provide evidence for range restriction by seasonal rainfall patterns.