Anomalous Diffusion of Deformable Particles in a Honeycomb Network.

Transport of deformable particles in a honeycomb network is studied numerically. It is shown that the particle deformability has a strong impact on their distribution in the network. For sufficiently soft particles, we observe a short memory behavior from one bifurcation to the next, and the overall behavior consists in a random partition of particles, exhibiting a diffusionlike transport. On the contrary, stiff enough particles undergo a biased distribution whereby they follow a deterministic partition at bifurcations, due to long memory. This leads to a lateral ballistic drift in the network at small concentration and anomalous superdiffusion at larger concentration, even though the network is ordered. A further increase of concentration enhances particle-particle interactions which shorten the memory effect, turning the particle anomalous diffusion into a classical diffusion. We expect the drifting and diffusive regime transition to be generic for deformable particles.

From whole-organ imaging to in-silico blood flow modeling: A new multi-scale network analysis for revisiting tissue functional anatomy.

We present a multi-disciplinary image-based blood flow perfusion modeling of a whole organ vascular network for analyzing both its structural and functional properties. We show how the use of Light-Sheet Fluorescence Microscopy (LSFM) permits whole-organ micro-vascular imaging, analysis and modelling. By using adapted image post-treatment workflow, we could segment, vectorize and reconstruct the entire micro-vascular network composed of 1.7 million vessels, from the tissue-scale, inside a ∼ 25 × 5 × 1 = 125mm3 volume of the mouse fat pad, hundreds of times larger than previous studies, down to the cellular scale at micron resolution, with the entire blood perfusion modeled. Adapted network analysis revealed the structural and functional organization of meso-scale tissue as strongly connected communities of vessels. These communities share a distinct heterogeneous core region and a more homogeneous peripheral region, consistently with known biological functions of fat tissue. Graph clustering analysis also revealed two distinct robust meso-scale typical sizes (from 10 to several hundred times the cellular size), revealing, for the first time, strongly connected functional vascular communities. These community networks support heterogeneous micro-environments. This work provides the proof of concept that in-silico all-tissue perfusion modeling can reveal new structural and functional exchanges between micro-regions in tissues, found from community clusters in the vascular graph.

Numerical modelling of long flexible fibers in homogeneous isotropic turbulence.

We numerically investigated the transport, deformation and buckling events of an isolated elastic fiber in Taylor-Green vortices and studied the dynamics of long filaments in homogeneous isotropic turbulence. The fiber is modelled by an assembly of spherical beads. The contact between beads enforces the inextensibility of the filament while bending is accounted for by the Gears Bead Model (GBM) proposed by Delmotte et al. (2015). In the cellular Taylor-Green flow, the buckling probability is a function of a dimensionless number, called Sperm number, which is a balance between the compression rate of the flow and the elastic response of the filament. The shapes of the filament and its ability to buckle have been successfully validated through comparisons with experiments from the work by Quennouz et al. (2015). The deformation statistics of long flexible fibers in sustained homogeneous isotropic turbulence were analyzed for various flow and fiber material conditions. Two regimes have been identified depending on the ratio of fiber length to persistence length which is a measure of turbulent forcing to flexibility. The numerical results are in good agreement with existing experimental data (C. Brouzet et al., Phys. Rev. Lett. 112, 074501 (2014)) validating the assumptions of our model for the configurations we investigated.

3D analysis of the whole subcutaneous adipose tissue reveals a complex spatial network of interconnected lobules with heterogeneous browning ability.

Adipose tissue, as the main energy storage organ and through its endocrine activity, is interconnected with all physiological functions. It plays a fundamental role in energy homeostasis and in the development of metabolic disorders. Up to now, this tissue has been analysed as a pool of different cell types with very little attention paid to the organization and putative partitioning of cells. Considering the absence of a complete picture of the intimate architecture of this large soft tissue, we developed a method that combines tissue clearing, acquisition of autofluorescence or lectin signals by confocal microscopy, segmentation procedures based on contrast enhancement, and a new semi-automatic image analysis process, allowing accurate and quantitative characterization of the whole 3D fat pad organization. This approach revealed the unexpected anatomic complexity of the murine subcutaneous fat pad. Although the classical picture of adipose tissue corresponds to a superposition of simple and small ellipsoidal lobules of adipose cells separated by mesenchymal spans, our results show that segmented lobules display complex 3D poly-lobular shapes. Despite differences in shape and size, the number of these poly-lobular subunits is similar from one fat pad to another. Finally, investigation of the relationships of these subunits between each other revealed a never-described organization in two clusters with distinct molecular signatures and specific vascular and sympathetic nerve densities correlating with different browning abilities. This innovative procedure reveals that subcutaneous adipose tissue exhibits a subtle functional heterogeneity with partitioned areas, and opens new perspectives towards understanding its functioning and plasticity.

Toward quantitative three-dimensional microvascular networks segmentation with multiview light-sheet fluorescence microscopy.

Three-dimensional (3-D) large-scale imaging of microvascular networks is of interest in various areas of biology and medicine related to structural, functional, developmental, and pathological issues. Light-sheet fluorescence microscopy (LSFM) techniques are rapidly spreading and are now on the way to offer operational solutions for large-scale tissue imaging. This contribution describes how reliable vessel segmentation can be handled from LSFM data in very large tissue volumes using a suitable image analysis workflow. Since capillaries are tubular objects of a few microns scale radius, they represent challenging structures to reliably reconstruct without distortion and artifacts. We provide a systematic analysis of multiview deconvolution image processing workflow to control and evaluate the accuracy of the reconstructed vascular network using various low to high level, metrics. We show that even if low-level structural metrics are sensitive to isotropic imaging enhancement provided by a larger number of views, functional high-level metrics, including perfusion permeability, are less sensitive. Hence, combining deconvolution and registration onto a few number of views appears sufficient for a reliable quantitative 3-D vessel segmentation for their possible use for perfusion modeling.

Analysis of vascular homogeneity and anisotropy on high-resolution primate brain imaging.

Using a systematic investigation of brain blood volume, in high-resolution synchrotron 3D images of microvascular structures within cortical regions of a primate brain, we challenge several basic questions regarding possible vascular bias in high-resolution functional neuroimaging. We present a bilateral comparison of cortical regions, where we analyze relative vascular volume in voxels from 150 to 1000 µm side lengths in the white and grey matter. We show that, if voxel size reaches a scale smaller than 300 µm, the vascular volume can no longer be considered homogeneous, either within one hemisphere or in bilateral comparison between samples. We demonstrate that voxel size influences the comparison between vessel-relative volume distributions depending on the scale considered (i.e., hemisphere, lobe, or sample). Furthermore, we also investigate how voxel anisotropy and orientation can affect the apparent vascular volume, in accordance with actual fMRI voxel sizes. These findings are discussed from the various perspectives of high-resolution brain functional imaging. Hum Brain Mapp 38:5756-5777, 2017. © 2017 Wiley Periodicals, Inc.

Identification of internal properties of fibres and micro-swimmers.

In this paper, we address the identifiability of constitutive parameters of passive or active micro-swimmers. We first present a general framework for describing fibres or micro-swimmers using a bead-model description. Using a kinematic constraint formulation to describe fibres, flagellum or cilia, we find explicit linear relationship between elastic constitutive parameters and generalized velocities from computing contact forces. This linear formulation then permits one to address explicitly identifiability conditions and solve for parameter identification. We show that both active forcing and passive parameters are both identifiable independently but not simultaneously. We also provide unbiased estimators for generalized elastic parameters in the presence of Langevin-like forcing with Gaussian noise using a Bayesian approach. These theoretical results are illustrated in various configurations showing the efficiency of the proposed approach for direct parameter identification. The convergence of the proposed estimators is successfully tested numerically.

Symmetry-breaking phase transitions in highly concentrated semen.

New experimental evidence of self-motion of a confined active suspension is presented. Depositing fresh semen sample in an annular shaped microfluidic chip leads to a spontaneous vortex state of the fluid at sufficiently large sperm concentration. The rotation occurs unpredictably clockwise or counterclockwise and is robust and stable. Furthermore, for highly active and concentrated semen, richer dynamics can occur such as self-sustained or damped rotation oscillations. Experimental results obtained with systematic dilution provide a clear evidence of a phase transition towards collective motion associated with local alignment of spermatozoa akin to the Vicsek model. A macroscopic theory based on previously derived self-organized hydrodynamics models is adapted to this context and provides predictions consistent with the observed stationary motion.

Regionalization of browning revealed by whole subcutaneous adipose tissue imaging.

OBJECTIVE: White and brown adipose tissues play a major role in the regulation of metabolic functions. With the explosion of obesity and metabolic disorders, the interest in adipocyte biology is growing constantly. While several studies have demonstrated functional differences between adipose fat pads, especially in their involvement in metabolic diseases, there are no data available on possible heterogeneity within an adipose depot. METHODS: This study investigated the three-dimensional (3-D) organization of the inguinal fat pad in adult mice by combining adipose tissue clearing and autofluorescence signal acquisition by confocal microscopy. In addition, the study analyzed the expression of genes involved in adipocyte biology and browning at the mARN and protein levels in distinct areas of the inguinal adipose tissue, in control conditions and after cold exposure. RESULTS: Semiautomated 3-D image analysis revealed an organization of the fat depot showing two regions: the core was structured into segmented lobules, whereas the periphery appeared unsegmented. Perilipin immunostaining showed that most of the adipocytes located in the core region had smaller lipid droplets, suggesting a brown-like phenotype. qPCR analysis showed a higher expression of the browning markers Ucp1, Prdm16, Ppargc1a, and Cidea in the core region than at the periphery. Finally, cold exposure induced upregulation of thermogenic gene expression associated with an increase of UCP1 protein, specifically in the core region of the inguinal fat depot. CONCLUSIONS: Altogether, these data demonstrate a structural and functional heterogeneity of the inguinal fat pad, with an anatomically restricted browning process in the core area.

Turbulence of swarming sperm.

Collective motion of self-sustained swarming flows has recently provided examples of small-scale turbulence arising where viscous effects are dominant. We report the first observation of universal enstrophy cascade in concentrated swarming sperm consistent with a body of evidence built from various independent measurements. We found a well-defined k^{-3} power-law decay of a velocity field power spectrum and relative dispersion of small beads consistent with theoretical predictions in 2D turbulence. Concentrated living sperm displays long-range, correlated whirlpool structures of a size that provides an integral scale of turbulence. We propose a consistent explanation for this quasi-2D turbulence based on self-structured laminated flow forced by steric interactions and alignment, a state of active matter that we call "swarming liquid crystal." We develop scaling arguments consistent with this interpretation.

Broadband converging plasmon resonance at a conical nanotip.

We propose an analytical theory which predicts that Converging Plasmon Resonance (CPR) at conical nanotips exhibits a red-shifted and continuous band of resonant frequencies and suggests potential application of conical nanotips in various fields, such as plasmonic solar cells, photothermal therapy, tip-enhanced Raman and other spectroscopies. The CPR modes exhibit superior confinement and ten times broader scattering bandwidth over the entire solar spectrum than smooth nano-structures. The theory also explicitly connects the optimal angles and resonant optical frequencies to the material permittivities, with a specific optimum half angle that depends only on the real permittivity for high-permittivity and low-loss materials.

On the normalization of cerebral blood flow.

Cerebral blood flow (CBF) is the most common parameter for the quantification of brain's function. Literature data indicate a widespread dispersion of values that might be related to some differences in the measurement conditions that are not properly taken into account in CBF evaluation. Using recent high-resolution imaging of the complete cortical microvasculature of primate brain, we perform extensive numerical evaluation of the cerebral perfusion. We show that blood perfusion associated with intravascular tracers should be normalized by the surface of the voxel rather than by its volume and we consistently test this result on the available literature data.

Simple patient-based transmantle pressure and shear estimate from cine phase-contrast MRI in cerebral aqueduct.

From measurements of the oscillating flux of the cerebrospinal fluid (CSF) in the aqueduct of Sylvius, we elaborate a patient-based methodology for transmantle pressure (TRP) and shear evaluation. High-resolution anatomical magnetic resonance imaging first permits a precise 3-D anatomical digitalized reconstruction of the Sylvius's aqueduct shape. From this, a very fast approximate numerical flow computation, nevertheless consistent with analytical predictions, is developed. Our approach includes the main contributions of inertial effects coming from the pulsatile flow and curvature effects associated with the aqueduct bending. Integrating the pressure along the aqueduct longitudinal centerline enables the total dynamic hydraulic admittances of the aqueduct to be evaluated, which is the pre-eminent contribution to the CSF pressure difference between the lateral ventricles and the subarachnoidal spaces also called the TRP. The application of the method to 20 healthy human patients validates the hypothesis of the proposed approach and provides a first database for normal aqueduct CSF flow. Finally, the implications of our results for modeling and evaluating intracranial cerebral pressure are discussed.

Coupling and robustness of intra-cortical vascular territories.

Vascular domains have been described as being coupled to neuronal functional units enabling dynamic blood supply to the cerebral cyto-architecture. Recent experiments have shown that penetrating arterioles of the grey matter are the building blocks for such units. Nevertheless, vascular territories are still poorly known, as the collection and analysis of large three-dimensional micro-vascular networks are difficult. By using an exhaustive reconstruction of the micro-vascular network in an 18 mm(3) volume of marmoset cerebral cortex, we numerically computed the blood flow in each blood vessel. We thus defined arterial and venular territories and examined their overlap. A large part of the intracortical vascular network was found to be supplied by several arteries and drained by several venules. We quantified this multiple potential to compensate for deficiencies by introducing a new robustness parameter. Robustness proved to be positively correlated with cortical depth and a systematic investigation of coupling maps indicated local patterns of overlap between neighbouring arteries and neighbouring venules. However, arterio-venular coupling did not have a spatial pattern of overlap but showed locally preferential functional coupling, especially of one artery with two venules, supporting the notion of vascular units. We concluded that intra-cortical perfusion in the primate was characterised by both very narrow functional beds and a large capacity for compensatory redistribution, far beyond the nearest neighbour collaterals.

Electrolyte stability in a nanochannel with charge regulation.

The stability of an electrolyte confined in one dimension between two solid surfaces is analyzed theoretically in the case where overlapping double layers produce nontrivial interactions. Within the Poisson-Boltzmann-Nernst-Planck description of the electrostatic interaction and transport of electrical charges, the presence of Stern layers can enrich the set of possible solutions. Our analytical and numerical study of the stability properties of the trivial state of this system identified an instability to a new antisymmetric state. This state is stable for a range of gap widths that depends on the Debye and Stern lengths, but for smaller gap widths, where the Stern layers overlap, a second transition takes place and the stable nontrivial solution diverges. The origin of this divergence is explained and its properties analyzed using asymptotic techniques which are in good agreement with numerical results. The relevance of our results to confined electrolytes at nanometer scales is discussed in the context of energy storage in nanometric systems.

Cerebral blood flow modeling in primate cortex.

We report new results on blood flow modeling over large volumes of cortical gray matter of primate brain. We propose a network method for computing the blood flow, which handles realistic boundary conditions, complex vessel shapes, and complex nonlinear blood rheology. From a detailed comparison of the available models for the blood flow rheology and the phase separation effect, we are able to derive important new results on the impact of network structure on blood pressure, hematocrit, and flow distributions. Our findings show that the network geometry (vessel shapes and diameters), the boundary conditions associated with the arterial inputs and venous outputs, and the effective viscosity of the blood are essential components in the flow distribution. In contrast, we show that the phase separation effect has a minor function in the global microvascular hemodynamic behavior. The behavior of the pressure, hematocrit, and blood flow distributions within the network are described through the depth of the primate cerebral cortex and are discussed.

Attraction between two similar particles in an electrolyte: effects of Stern layer absorption.

When Debye length is comparable or larger than the distance between two identical particles, the overlapping among the particles double-layers can play an important role in their interactions. This paper presents a theoretical analysis of the interaction among two identical particles with overlapped double-layers. We particularly focus on the effect of a Stern electro static condition from linearization of the adsorption isotherm near the isoelectric (neutrality) point in order to capture how polyvalent ion condensation affect sand reverses the surface charge. The stationary potential problem is solved within the framework of an asymptotic lubrication approach for a mean-field Poisson-Boltzmann model. Both spherical and cylindrical particles are analyzed. The results are finally discussed in the context of Debye-Hückel (D-H) limit and beyond it.

Attraction between two similar particles in an electrolyte: effects of Stern layer absorption

When Debye length is comparable or larger than the distance between two identical particles, the overlapping among the particles double-layers can play an important role in their interactions. This paper presents a theoretical analysis of the interaction among two identical particles with overlapped double-layers. We particularly focus on the effect of a Stern electro static condition from linearization of the adsorption isotherm near the isoelectric (neutrality) point in order to capture how polyvalent ion condensation affect sand reverses the surface charge. The stationary potential problem is solved within the framework of an asymptotic lubrication approach for a mean-field Poisson-Boltzmann model. Both spherical and cylindrical particles are analyzed. The results are finally discussed in the context of Debye-Hückel (D-H) limit and beyond it.

Quando o comprimento de Debye é comparável ou maior do que as distâncias entre duas partículas idênticas, a interseção entre as duplas camadas pode desempenhar papel importante na interação entre elas. Este artigo apresenta uma análise teórica da interação entre duas partículas idênticas as quais apresentam interseção entre as camadas duplas. Nós particularmente focamos a análise sobre o efeito da condição eletrostática de Stern a partir da linearização da isoterma de adsorção perto do ponto isoelétrico para capturar como a condensação do íon polivalente afeta e reverte a densidade de carga superficial. O problema que governa o potencial estacionário é resolvido no contexto de uma teoria assintótica de lubrificação para o modelo de Poisson-Boltzmann. O modelo é analisado para partículas cilíndricas e esféricas. Os resultados são finalmente discutidos no contexto do limite de Debye-Hückel e além dele.

A 3D-investigation shows that angiogenesis in primate cerebral cortex mainly occurs at capillary level.

This paper describes the use of a new 3D high-resolution imaging technique dedicated to functional vessels for a systematic quantitative study of angiogenesis in the primate cortex. We present a new method which permits, using synchrotron X-ray micro-tomography imaging, the identification of micro-vascular components as well as their automatic numerical digitalization and extraction from very large 3D image analysis and post-treatments. This method is used to analyze various levels of micro-vascular organization and their postnatal modifications. Comparing newborn- and adult marmosets, we found an increase in vascular volume (270%), exchange surface (260%) and vessel length (290%) associated to a decrease in distances between vessel and tissue (32%). The increase in relative vascular volumes between the two ages, examined through the whole cortical depth, has been found to be mainly sustained by events occurring at the capillary level, and only marginally at the perforating vessel level. This work shows that the postnatal cortical maturation classically described in terms of synaptogenesis, gliogenesis and connectivity plasticity is accompanied by an intensive remodeling of micro-vascular patterns.