Hybrid Multiscale Finite Volume method for two-phase flow in porous media

We present a novel hybrid (or multiphysics) algorithm, which couples pore-scale and Darcy descriptions of two-phase flow in porous media. The flow at the pore-scale is described by the Navier?Stokes equations, and the Volume of Fluid (VOF) method is used to model the evolution of the fluid?fluid interface. An extension of the Multiscale Finite Volume (MsFV) method is employed to construct the Darcy-scale problem. First, a set of local interpolators for pressure and velocity is constructed by solving the Navier?Stokes equations; then, a coarse mass-conservation problem is constructed by averaging the pore-scale velocity over the cells of a coarse grid, which act as control volumes; finally, a conservative pore-scale velocity field is reconstructed and used to advect the fluid?fluid interface. The method relies on the localization assumptions used to compute the interpolators (which are quite straightforward extensions of the standard MsFV) and on the postulate that the coarse-scale fluxes are proportional to the coarse-pressure differences. By numerical simulations of two-phase problems, we demonstrate that these assumptions provide hybrid solutions that are in good agreement with reference pore-scale solutions and are able to model the transition from stable to unstable flow regimes. Our hybrid method can naturally take advantage of several adaptive strategies and allows considering pore-scale fluxes only in some regions, while Darcy fluxes are used in the rest of the domain. Moreover, since the method relies on the assumption that the relationship between coarse-scale fluxes and pressure differences is local, it can be used as a numerical tool to investigate the limits of validity of Darcy's law and to understand the link between pore-scale quantities and their corresponding Darcy-scale variables.

Error estimate and control in the MSFV method for multiphase flow in porous media

n this paper the iterative MSFV method is extended to include the sequential implicit simulation of time dependent problems involving the solution of a system of pressure-saturation equations. To control numerical errors in simulation results, an error estimate, based on the residual of the MSFV approximate pressure field, is introduced. In the initial time steps in simulation iterations are employed until a specified accuracy in pressure is achieved. This initial solution is then used to improve the localization assumption at later time steps. Additional iterations in pressure solution are employed only when the pressure residual becomes larger than a specified threshold value. Efficiency of the strategy and the error control criteria are numerically investigated. This paper also shows that it is possible to derive an a-priori estimate and control based on the allowed pressure-equation residual to guarantee the desired accuracy in saturation calculation.

Increased flow of fatty acids toward beta-oxidation in developing seeds of Arabidopsis deficient in diacylglycerol acyltransferase activity or synthesizing medium-chain-length fatty acids.

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid beta-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0. 06 mg g(-1) dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward beta-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via beta-oxidation and that a considerable flow toward beta-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids.

Low relatedness among cooperatively breeding workers of the greenhead ant Rhytidoponera metallica

The greenhead ant Rhytidoponera metallica has long been recognized as posing a potential challenge to kin selection theory because it has large queenless colonies where apparently many of the morphological workers are mated and reproducing. However this species has never been studied genetically and important elements of its breeding system and kin structure remain uncertain. We used microsatellite markers to measure the relatedness among nestmates unravel the fine-scale population genetic structure and infer the breeding system of R. metallica. The genetic relatedness among worker nestmates is very low but significantly greater than zero (r = 0.082 +/- 0.015) which demonstrates that nests contain many distantly related breeders. The inbreeding coefficient is very close to and not significantly different from zero indicating random mating and lack of microgeographic genetic differentiation. On average. closely located nests are not more similar genetically than distant nests which is surprising as new colonies form by budding and female dispersal is restricted. Lack of inbreeding and absence of population viscosity indicates high gene flow mediated by males. Overall the genetic pattern detected in R. metallica suggests that a high number of moderately related workers mate with unrelated males from distant nests. This breeding system results in the lowest relatedness among nestmates reported for social insect species where breeders and helpers are not morphologically differentiated. [References: 69]

Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation.

Lymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction.

Intracellular pattern-recognition receptors

The last ten years of research in the field of innate immunity have been incredibly fertile: the transmembrane Toll-like receptors (TLRs) were discovered as guardians protecting the host against microbial attacks and the emerging pathways characterized in detail. More recently, cytoplasmic sensors were identified, which are capable of detecting not only microbial, but also self molecules. Importantly, while such receptors trigger crucial host responses to microbial insult, over-activity of some of them has been linked to autoinflammatory disorders, hence demonstrating the importance of tightly regulating their actions over time and space. Here, we provide an overview of recent findings covering this area of innate and inflammatory responses that originate from the cytoplasm

Fine-scale spatial genetic structure and gene dispersal in Silene latifolia.

Plants are sessile organisms, often characterized by limited dispersal. Seeds and pollen are the critical stages for gene flow. Here we investigate spatial genetic structure, gene dispersal and the relative contribution of pollen vs seed in the movement of genes in a stable metapopulation of the white campion Silene latifolia within its native range. This short-lived perennial plant is dioecious, has gravity-dispersed seeds and moth-mediated pollination. Direct measures of pollen dispersal suggested that large populations receive more pollen than small isolated populations and that most gene flow occurs within tens of meters. However, these studies were performed in the newly colonized range (North America) where the specialist pollinator is absent. In the native range (Europe), gene dispersal could fall on a different spatial scale. We genotyped 258 individuals from large and small (15) subpopulations along a 60 km, elongated metapopulation in Europe using six highly variable microsatellite markers, two X-linked and four autosomal. We found substantial genetic differentiation among subpopulations (global F(ST)=0.11) and a general pattern of isolation by distance over the whole sampled area. Spatial autocorrelation revealed high relatedness among neighboring individuals over hundreds of meters. Estimates of gene dispersal revealed gene flow at the scale of tens of meters (5-30 m), similar to the newly colonized range. Contrary to expectations, estimates of dispersal based on X and autosomal markers showed very similar ranges, suggesting similar levels of pollen and seed dispersal. This may be explained by stochastic events of extensive seed dispersal in this area and limited pollen dispersal.

Oligoclonal expansions in the CD8(+)CD28(-) T cells largely explain the shorter telomeres detected in this subset: analysis by flow FISH.

We have previously reported that CD8(+)CD28(-) T cells have relatively shorter telomeres compared with CD8(+)CD28(+) T cells. Oligoclonal expansion is a common feature of CD8(+) T cells in human peripheral blood, and these expansions predominantly occur in the CD57(+)/CD28(-) population. We studied the telomere length in subsets of CD8(+) T cells using quantitative fluorescence in situ hybridization and flow cytometry (flow FISH). Our results confirm that CD8(+)CD28(-) T cells have shorter telomeres as compared with their CD28(+) counterpart cells. In addition, the oligoclonally expanded cells within the CD8(+)CD28(-) T cell subset generally have even shorter telomeres than the CD28(-) subset as a whole. We conclude that the presence of clonal expansions in the CD8(+)CD28(-) T cell population largely explain the shorter telomeres in this subset. These clonally expanded CD8(+)CD28(-) T cells generally have characteristics of terminally differentiated effector cells. Nevertheless, there is considerable individual variation in the degree of telomere shortening in these cells, which may reflect host genetic factors as well as the type and timing of the antigenic exposure.

The pattern and Loci of training-induced brain changes in healthy older adults are predicted by the nature of the intervention.

There is enormous interest in designing training methods for reducing cognitive decline in healthy older adults. Because it is impaired with aging, multitasking has often been targeted and has been shown to be malleable with appropriate training. Investigating the effects of cognitive training on functional brain activation might provide critical indication regarding the mechanisms that underlie those positive effects, as well as provide models for selecting appropriate training methods. The few studies that have looked at brain correlates of cognitive training indicate a variable pattern and location of brain changes - a result that might relate to differences in training formats. The goal of this study was to measure the neural substrates as a function of whether divided attentional training programs induced the use of alternative processes or whether it relied on repeated practice. Forty-eight older adults were randomly allocated to one of three training programs. In the SINGLE REPEATED training, participants practiced an alphanumeric equation and a visual detection task, each under focused attention. In the DIVIDED FIXED training, participants practiced combining verification and detection by divided attention, with equal attention allocated to both tasks. In the DIVIDED VARIABLE training, participants completed the task by divided attention, but were taught to vary the attentional priority allocated to each task. Brain activation was measured with fMRI pre- and post-training while completing each task individually and the two tasks combined. The three training programs resulted in markedly different brain changes. Practice on individual tasks in the SINGLE REPEATED training resulted in reduced brain activation whereas DIVIDED VARIABLE training resulted in a larger recruitment of the right superior and middle frontal gyrus, a region that has been involved in multitasking. The type of training is a critical factor in determining the pattern of brain activation.

IEF pattern classification-derived criteria for the identification of epoetin-delta in urine.

Epoetin-delta (Dynepo Shire Pharmaceuticals, Basing stoke, UK) is a synthetic form of erythropoietin (EPO) whose resemblance with endogenous EPO makes it hard to identify using the classical identification criteria. Urine samples collected from six healthy volunteers treated with epoetin-delta injections and from a control population were immuno-purified and analyzed with the usual IEF method. On the basis of the EPO profiles integration, a linear multivariate model was computed for discriminant analysis. For each sample, a pattern classification algorithm returned a bands distribution and intensity score (bands intensity score) saying how representative this sample is of one of the two classes, positive or negative. Effort profiles were also integrated in the model. The method yielded a good sensitivity versus specificity relation and was used to determine the detection window of the molecule following multiple injections. The bands intensity score, which can be generalized to epoetin-alpha and epoetin-beta, is proposed as an alternative criterion and a supplementary evidence for the identification of EPO abuse.

Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment.

In the paracortex of the lymph node (LN), T zone fibroblastic reticular cells (TRCs) orchestrate an immune response by guiding lymphocyte migration both physically, by creating three-dimensional (3D) cell networks, and chemically, by secreting the chemokines CCL19 and CCL21 that direct interactions between CCR7-expressing cells, including mature dendritic cells and naive T cells. TRCs also enwrap matrix-based conduits that transport fluid from the subcapsular sinus to high endothelial venules, and fluid flow through the draining LN rapidly increases upon tissue injury or inflammation. To determine whether fluid flow affects TRC organization or function within a 3D network, we regenerated the 3D LN T zone stromal network by culturing murine TRC clones within a macroporous polyurethane scaffold containing type I collagen and Matrigel and applying slow interstitial flow (1-23 microm/min). We show that the 3D environment and slow interstitial flow are important regulators of TRC morphology, organization, and CCL21 secretion. Without flow, CCL21 expression could not be detected. Furthermore, when flow through the LN was blocked in mice in vivo, CCL21 gene expression was down-regulated within 2 h. These results highlight the importance of lymph flow as a homeostatic regulator of constitutive TRC activity and introduce the concept that increased lymph flow may act as an early inflammatory cue to enhance CCL21 expression by TRCs, thereby ensuring efficient immune cell trafficking, lymph sampling, and immune response induction.

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Debris flow hazard modelling on medium scale: Valtellina di Tirano, Italy

Debris flow hazard modelling at medium (regional) scale has been subject of various studies in recent years. In this study, hazard zonation was carried out, incorporating information about debris flow initiation probability (spatial and temporal), and the delimitation of the potential runout areas. Debris flow hazard zonation was carried out in the area of the Consortium of Mountain Municipalities of Valtellina di Tirano (Central Alps, Italy). The complexity of the phenomenon, the scale of the study, the variability of local conditioning factors, and the lacking data limited the use of process-based models for the runout zone delimitation. Firstly, a map of hazard initiation probabilities was prepared for the study area, based on the available susceptibility zoning information, and the analysis of two sets of aerial photographs for the temporal probability estimation. Afterwards, the hazard initiation map was used as one of the inputs for an empirical GIS-based model (Flow-R), developed at the University of Lausanne (Switzerland). An estimation of the debris flow magnitude was neglected as the main aim of the analysis was to prepare a debris flow hazard map at medium scale. A digital elevation model, with a 10 m resolution, was used together with landuse, geology and debris flow hazard initiation maps as inputs of the Flow-R model to restrict potential areas within each hazard initiation probability class to locations where debris flows are most likely to initiate. Afterwards, runout areas were calculated using multiple flow direction and energy based algorithms. Maximum probable runout zones were calibrated using documented past events and aerial photographs. Finally, two debris flow hazard maps were prepared. The first simply delimits five hazard zones, while the second incorporates the information about debris flow spreading direction probabilities, showing areas more likely to be affected by future debris flows. Limitations of the modelling arise mainly from the models applied and analysis scale, which are neglecting local controlling factors of debris flow hazard. The presented approach of debris flow hazard analysis, associating automatic detection of the source areas and a simple assessment of the debris flow spreading, provided results for consequent hazard and risk studies. However, for the validation and transferability of the parameters and results to other study areas, more testing is needed.