Hysteretic and chaotic dynamics of viscous drops in creeping flows with rotation

It has been shown in our previous publication (Blawzdziewicz,Cristini,Loewenberg,2003) that high-viscosity drops in two dimensional linear creeping flows with a nonzero vorticity component may have two stable stationary states. One state corresponds to a nearly spherical, compact drop stabilized primarily by rotation, and the other to an elongated drop stabilized primarily by capillary forces. Here we explore consequences of the drop bistability for the dynamics of highly viscous drops. Using both boundary-integral simulations and small-deformation theory we show that a quasi-static change of the flow vorticity gives rise to a hysteretic response of the drop shape, with rapid changes between the compact and elongated solutions at critical values of the vorticity. In flows with sinusoidal temporal variation of the vorticity we find chaotic drop dynamics in response to the periodic forcing. A cascade of period-doubling bifurcations is found to be directly responsible for the transition to chaos. In random flows we obtain a bimodal drop-length distribution. Some analogies with the dynamics of macromolecules and vesicles are pointed out.Comment: 22 pages, 13 figures. submitted to Journal of Fluid Mechanic

On a Cahn--Hilliard--Darcy system for tumour growth with solution dependent source terms

We study the existence of weak solutions to a mixture model for tumour growth that consists of a Cahn--Hilliard--Darcy system coupled with an elliptic reaction-diffusion equation. The Darcy law gives rise to an elliptic equation for the pressure that is coupled to the convective Cahn--Hilliard equation through convective and source terms. Both Dirichlet and Robin boundary conditions are considered for the pressure variable, which allows for the source terms to be dependent on the solution variables.Comment: 18 pages, changed proof from fixed point argument to Galerkin approximatio

Programming as a soft skill for project managers: How to have a computer take over some of your work

Large part of the project manager's work can be described in terms of retrieving, processing, analysing and synthesizing various types of data from different sources. The types of information become more and more diverse (including participants, task and financial details, and dates) and data volumes continue to increase, especially for large international collaborations. In this paper we explore the possibility of using the python programming language as a tool for retrieving and processing data for some project management tasks. python is a general-purpose programming language with a very rich set of libraries. In recent years python experienced explosive growth leading to development of several libraries that help to efficiently solve many data related tasks without very deep knowledge of programming in general and python in particular. In this paper we present some of the core python libraries that can be used to solve some typical project management tasks and demonstrate several real-world applications using a HORIZON 2020 type European project and as example.</p

On a diffuse interface model for tumour growth with non-local interactions and degenerate mobilities

We study a non-local variant of a diffuse interface model proposed by Hawkins--Darrud et al. (2012) for tumour growth in the presence of a chemical species acting as nutrient. The system consists of a Cahn--Hilliard equation coupled to a reaction-diffusion equation. For non-degenerate mobilities and smooth potentials, we derive well-posedness results, which are the non-local analogue of those obtained in Frigeri et al. (European J. Appl. Math. 2015). Furthermore, we establish existence of weak solutions for the case of degenerate mobilities and singular potentials, which serves to confine the order parameter to its physically relevant interval. Due to the non-local nature of the equations, under additional assumptions continuous dependence on initial data can also be shown.Comment: 28 page

The standardisation of vernacular architecture: Wine buildings in Andalusia

Production buildings constitute a specific section of vernacular architecture, with distinct characteristics. In Andalusia, within this group, the architecture of wine, acquires an important relevancne, the wine cellars. They are a large number of buildings, which were built in the 18th, and 19th centuries. This happened when traditional Andalusian wine production was transformed into a modern wine industry. An industrial development generated a vast architectural ensemble of unique characteristics. This has been studied especially in the Sherry wine region, but it is also present in other regions such as MontillaMoriles or El Condado de Huelva. The architectural, and industrial wine development in the 19th century was fundamentally based on the repetition of a specific model: the basilica cellar. A simplified formal, and constructive system that comes from the standardisation of the vernacular cellar, and that establishes early points of convergence with the industrial building. A model that continues the tradition in terms of construction, and structure, but conceptually modern in its modular, and repeatable condition. Its reiteration, and extreme simplification made possible the construction of large industrial complexes, and the city transformation. The industrial importance achieved by the wine agro-industry, and the vernacular quality of its architecture introduce different references in Spanish industrial historiograph

Intratumoral injection of hydrogel-embedded nanoparticles enhances retention in glioblastoma

Intratumoral drug delivery is a promising approach for the treatment of glioblastoma multiforme (GBM). However, drug washout remains a major challenge in GBM therapy. Our strategy, aimed at reducing drug clearance and enhancing site-specific residence time, involves the local administration of a multi-component system comprised of nanoparticles (NPs) embedded within a thermosensitive hydrogel (HG). Herein, our objective was to examine the distribution of NPs and their cargo following intratumoral administration of this system in GBM. We hypothesized that the HG matrix, which undergoes rapid gelation upon increases in temperature, would contribute towards heightened site-specific retention and permanence of NPs in tumors. BODIPY-containing, infrared dye-labeled polymeric NPs embedded in a thermosensitive HG (HG-NPs) were fabricated and characterized. Retention and distribution dynamics were subsequently examined over time in orthotopic GBM-bearing mice. Results demonstrate that the HG-NPs system significantly improved site-specific, long-term retention of both NPs and BODIPY, with co-localization analyses showing that HG-NPs covered larger areas of the tumor and the peri-tumor region at later time points. Moreover, NPs released from the HG were shown to undergo uptake by surrounding GBM cells. Findings suggest that intratumoral delivery with HG-NPs has immense potential for GBM treatment, as well as other strategies where site-specific, long-term retention of therapeutic agents is warranted. This journal i

A new ghost cell/level set method for moving boundary problems:application to tumor growth

In this paper, we present a ghost cell/level set method for the evolution of interfaces whose normal velocity depend upon the solutions of linear and nonlinear quasi-steady reaction-diffusion equations with curvature-dependent boundary conditions. Our technique includes a ghost cell method that accurately discretizes normal derivative jump boundary conditions without smearing jumps in the tangential derivative; a new iterative method for solving linear and nonlinear quasi-steady reaction-diffusion equations; an adaptive discretization to compute the curvature and normal vectors; and a new discrete approximation to the Heaviside function. We present numerical examples that demonstrate better than 1.5-order convergence for problems where traditional ghost cell methods either fail to converge or attain at best sub-linear accuracy. We apply our techniques to a model of tumor growth in complex, heterogeneous tissues that consists of a nonlinear nutrient equation and a pressure equation with geometry-dependent jump boundary conditions. We simulate the growth of glioblastoma (an aggressive brain tumor) into a large, 1 cm square of brain tissue that includes heterogeneous nutrient delivery and varied biomechanical characteristics (white matter, gray matter, cerebrospinal fluid, and bone), and we observe growth morphologies that are highly dependent upon the variations of the tissue characteristics—an effect observed in real tumor growth

Predicting drug pharmacokinetics and effect in vascularized tumors using computer simulation

In this paper, we investigate the pharmacokinetics and effect of doxorubicin and cisplatin in vascularized tumors through two-dimensional simulations. We take into account especially vascular and morphological heterogeneity as well as cellular and lesion-level pharmacokinetic determinants like P-glycoprotein (Pgp) efflux and cell density. To do this we construct a multi-compartment PKPD model calibrated from published experimental data and simulate 2-h bolus administrations followed by 18-h drug washout. Our results show that lesion-scale drug and nutrient distribution may significantly impact therapeutic efficacy and should be considered as carefully as genetic determinants modulating, for example, the production of multidrug-resistance protein or topoisomerase II. We visualize and rigorously quantify distributions of nutrient, drug, and resulting cell inhibition. A main result is the existence of significant heterogeneity in all three, yielding poor inhibition in a large fraction of the lesion, and commensurately increased serum drug concentration necessary for an average 50% inhibition throughout the lesion (the IC50 concentration). For doxorubicin the effect of hypoxia and hypoglycemia (“nutrient effect”) is isolated and shown to further increase cell inhibition heterogeneity and double the IC50, both undesirable. We also show how the therapeutic effectiveness of doxorubicin penetration therapy depends upon other determinants affecting drug distribution, such as cellular efflux and density, offering some insight into the conditions under which otherwise promising therapies may fail and, more importantly, when they will succeed. Cisplatin is used as a contrast to doxorubicin since both published experimental data and our simulations indicate its lesion distribution is more uniform than that of doxorubicin. Because of this some of the complexity in predicting its therapeutic efficacy is mitigated. Using this advantage, we show results suggesting that in vitro monolayer assays using this drug may more accurately predict in vivo performance than for drugs like doxorubicin. The nonlinear interaction among various determinants representing cell and lesion phenotype as well as therapeutic strategies is a unifying theme of our results. Throughout it can be appreciated that macroscopic environmental conditions, notably drug and nutrient distributions, give rise to considerable variation in lesion response, hence clinical resistance. Moreover, the synergy or antagonism of combined therapeutic strategies depends heavily upon this environment