Vesicles in a Poiseuille flow

Vesicle dynamics in unbounded Poiseuille flow is analyzed using a small-deformation theory. Our analytical results quantitatively describe vesicle migration and provide new physical insights. At low ratio between the inner and outer viscosity $\lambda$ (i.e. in the tank-treading regime), the vesicle always migrates towards the flow centerline, unlike other soft particles such as drops. Above a critical $\lambda$, vesicle tumbles and cross-stream migration vanishes. A novel feature is predicted, namely the coexistence of two types of nonequilibrium configurations at the centreline, a bullet-like and a parachute-like shapes.Comment: 4 pages and 5 figure

Bistability in a simple fluid network due to viscosity contrast

We study the existence of multiple equilibrium states in a simple fluid network using Newtonian fluids and laminar flow. We demonstrate theoretically the presence of hysteresis and bistability, and we confirm these predictions in an experiment using two miscible fluids of different viscosity--sucrose solution and water. Possible applications include bloodflow, microfluidics, and other network flows governed by similar principles

A multiple scale model for tumor growth

We present a physiologically structured lattice model for vascular tumor growth which accounts for blood flow and structural adaptation of the vasculature, transport of oxygen, interaction between cancerous and normal tissue, cell division, apoptosis, vascular endothelial growth factor release, and the coupling between these processes. Simulations of the model are used to investigate the effects of nutrient heterogeneity, growth and invasion of cancerous tissue, and emergent growth laws

BMW – Mastering the Crises with “New Efficiency?”

Purpose Make a contribution on company business models and typical reactions to economic crises. Design/methodology/approach Media-analysis-based case study. Findings Crisis is handled through drawing on a strategy deriving from the typical features of the company; through the crisis these features are even intensified. Research limitations/implications Multinational companies are complex and only transparent to a small degree; the empirical data therefore rests on a database with articles. Social implications Social implications can be seen at the BMW as a functioning example for social partnership as a form of economic embeddedness at the societal level

A simplified particulate model for coarse-grained hemodynamics simulations

Human blood flow is a multi-scale problem: in first approximation, blood is a dense suspension of plasma and deformable red cells. Physiological vessel diameters range from about one to thousands of cell radii. Current computational models either involve a homogeneous fluid and cannot track particulate effects or describe a relatively small number of cells with high resolution, but are incapable to reach relevant time and length scales. Our approach is to simplify much further than existing particulate models. We combine well established methods from other areas of physics in order to find the essential ingredients for a minimalist description that still recovers hemorheology. These ingredients are a lattice Boltzmann method describing rigid particle suspensions to account for hydrodynamic long range interactions and---in order to describe the more complex short-range behavior of cells---anisotropic model potentials known from molecular dynamics simulations. Paying detailedness, we achieve an efficient and scalable implementation which is crucial for our ultimate goal: establishing a link between the collective behavior of millions of cells and the macroscopic properties of blood in realistic flow situations. In this paper we present our model and demonstrate its applicability to conditions typical for the microvasculature.Comment: 12 pages, 11 figure

The integral monodromy of hyperelliptic and trielliptic curves

We compute the \integ/\ell and \integ_\ell monodromy of every irreducible component of the moduli spaces of hyperelliptic and trielliptic curves. In particular, we provide a proof that the \integ/\ell monodromy of the moduli space of hyperelliptic curves of genus $g$ is the symplectic group \sp_{2g}(\integ/\ell). We prove that the \integ/\ell monodromy of the moduli space of trielliptic curves with signature $(r,s)$ is the special unitary group \su_{(r,s)}(\integ/\ell\tensor\integ[\zeta_3])

Semiflexible polymer conformation, distribution and migration in microcapillary flows

The flow behavior of a semiflexible polymer in microchannels is studied using Multiparticle Collision Dynamics (MPC), a particle-based hydrodynamic simulation technique. Conformations, distributions, and radial cross-streamline migration are investigated for various bending rigidities, with persistence lengths Lp in the range 0.5 < Lp/Lr < 30. The flow behavior is governed by the competition between a hydrodynamic lift force and steric wall-repulsion, which lead to migration away from the wall, and a locally varying flow-induced orientation, which drives polymer away from the channel center and towards the wall. The different dependencies of these effects on the polymer bending rigidity and the flow velocity results in a complex dynamical behavior. However, a generic effect is the appearance of a maximum in the monomer and the center-of-mass distributions, which occurs in the channel center for small flow velocities, but moves off-center at higher velocities.Comment: in press at J. Phys. Condens. Matte

Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase: Effects on Stability, Kinetics, and Structure

Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other α/β-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.

Model-based inference from microvascular measurements: Combining experimental measurements and model predictions using a Bayesian probabilistic approach

Objective: In vivo imaging of the microcirculation and network-oriented modeling have emerged as powerful means of studying microvascular function and understanding its physiological significance. Network-oriented modeling may provide the means of summarizing vast amounts of data produced by high-throughput imaging techniques in terms of key, physiological indices. To estimate such indices with sufficient certainty, however, network-oriented analysis must be robust to the inevitable presence of uncertainty due to measurement errors as well as model errors. Methods: We propose the Bayesian probabilistic data analysis framework as a means of integrating experimental measurements and network model simulations into a combined and statistically coherent analysis. The framework naturally handles noisy measurements and provides posterior distributions of model parameters as well as physiological indices associated with uncertainty. Results: We applied the analysis framework to experimental data from three rat mesentery networks and one mouse brain cortex network. We inferred distributions for more than 500 unknown pressure and hematocrit boundary conditions. Model predictions were consistent with previous analyses, and remained robust when measurements were omitted from model calibration. Conclusion: Our Bayesian probabilistic approach may be suitable for optimizing data acquisition and for analyzing and reporting large data sets acquired as part of microvascular imaging studies

Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks

Relative to normal tissues, tumor microcirculation exhibits high structural and functional heterogeneity leading to hypoxic regions and impairing treatment efficacy. Here, computational simulations of blood vessel structural adaptation are used to explore the hypothesis that abnormal adaptive responses to local hemodynamic and metabolic stimuli contribute to aberrant morphological and hemodynamic characteristics of tumor microcirculation. Topology, vascular diameter, length, and red blood cell velocity of normal mesenteric and tumor vascular networks were recorded by intravital microscopy. Computational models were used to estimate hemodynamics and oxygen distribution and to simulate vascular diameter adaptation in response to hemodynamic, metabolic and conducted stimuli. The assumed sensitivity to hemodynamic and conducted signals, the vascular growth tendency, and the random variability of vascular responses were altered to simulate ‘normal’ and ‘tumor’ adaptation modes. The heterogeneous properties of vascular networks were characterized by diameter mismatch at vascular branch points (d3var) and deficit of oxygen delivery relative to demand (O2def). In the tumor, d3var and O2def were higher (0.404 and 0.182) than in normal networks (0.278 and 0.099). Simulated remodeling of the tumor network with ‘normal’ parameters gave low values (0.288 and 0.099). Conversely, normal networks attained tumor-like characteristics (0.41 and 0.179) upon adaptation with ‘tumor’ parameters, including low conducted sensitivity, increased growth tendency, and elevated random biological variability. It is concluded that the deviant properties of tumor microcirculation may result largely from defective structural adaptation, including strongly reduced responses to conducted stimuli