A multiscale analysis of flow and transport in the human placenta

The human placenta is characterised by a unique circulatory arrangement, with numerous villous trees containing fetal vessels immersed in maternal blood. Placental tissue therefore manifests a multiscale structure balancing microscopic delivery of nutrients and macroscopic flow. The aims of this study are to examine the interaction between these scales and to understand the influence of placental organisation on the effectiveness of nutrient uptake, which can be compromised in pathologies like pre-eclampsia and diabetes. We first systematically analyse solute transport by a unidirectional flow past an array of microscopic sinks, taking up a dissolved nutrient or gas, for both regular and random sink distributions. We classify distinct asymptotic transport regimes, each characterised by the dominance of advective, diffusive or uptake effects at the macroscale, and analyse a set of simplified model problems to assess the accuracy of homogenization approximations as a function of governing parameters (Peclet and Damkohler numbers) and the statistical properties of the sink distribution. The difference between the leading-order homogenization approximation and the exact solute distribution is determined by large spatial gradients at the scale of individual villi (depending on transport parameter values) and substantial fluctuations that can be correlated over lcngthscales comparable to the whole domain. In addition, we consider the nonlinear advective effects of solute-carriers, such as red blood cells carrying oxygen. Homogenization of the solute-carrier-facilitated transport introduces an effective Peclet number that depends on the slowly varying leading-order concentration, so that an asymptotic transport regime can be changed within the domain. At large Peclet and Damkohler numbers (typical for oxygen transport in the human placenta), nonlinear advection due to solute-carriers leads to a more uniform solute distribution than for a linear carrier-free transport, suggesting a "homogenizing" effect of red blood cells on placental oxygen transport. We then use image analysis and homogenization concepts to extract the effective transport properties (diffusivity and hydraulic resistance) from the microscopic images of histological sections of the normal human placenta. The resulting two-dimensional tensor quantities allow us to assess the anisotropy of placental tissue for solute transport. We also show how the pattern of villous centres of mass can be characterised using an integral correlation measure, and identify the minimum spatial scale over which the distribution of villous branches appears statistically homogeneous. Finally, we propose a mathematical model for maternal blood flow in a placental functional unit (a placentone), describing flow of maternal blood via Darcy's law and steady advective transport of a dissolved nutrient. An analytical method of images and computational integration along streamlines are employed to find flow and solute concentration distributions, which are illustrated for a range of governing system parameters. Predictions of the model agree with experimental radioangiographic studies of tracer dynamics in the intervillous space. The model supports the hypothesis that basal veins are located on the periphery of the placentone in order to optimise delivery of nutrients. We also explain the importance of dilatation of maternal spiral arteries and suggest the existence of an optimal volume fraction of villous tissue, which can both be involved in the placental dysfunction. Theoretical studies of this thesis thus constitute a step towards modelling-based diagnostics and treatment of placental disorders

Quantifying the impact of tissue metabolism on solute transport in feto-placental microvascular networks

The primary exchange units in the human placenta are terminal villi, in which fetal capillary networks are surrounded by a thin layer of villous tissue, separating fetal from maternal blood. To understand how the complex spatial structure of villi influences their function, we use an image-based theoretical model to study the effect of tissue metabolism on the transport of solutes from maternal blood into the fetal circulation. For solute that is taken up under first-order kinetics, we show that the transition between flow-limited and diffusion-limited transport depends on two new dimensionless parameters defined in terms of key geometric quantities, with strong solute uptake promoting flow-limited transport conditions. We present a simple algebraic approximation for solute uptake rate as a function of flow conditions, metabolic rate and villous geometry. For oxygen, accounting for nonlinear kinetics using physiological parameter values, our model predicts that villous metabolism does not significantly impact oxygen transfer to fetal blood, although the partitioning of fluxes between the villous tissue and the capillary network depends strongly on the flow regim

2019 IEEE 9th International Conference Nanomaterials: Applications & Properties (NAP-2019)

This is a post-peer-review, pre-copyedit version of an article published in 2019 IEEE 9th International Conference Nanomaterials: Applications & Properties (NAP). The final authenticated version is available online at: https://doi.org/10.1109/NAP47236.2019.216967Ministry of Education and Science of Ukraine [project # 2106]This study reports the structural evolution of multi-component AlNiCoFeCrTi high-entropy alloy from elemental materials to nanocrystalline metastable solid solution during mechanical alloying (MA), and further, to equilibrium phases during subsequent thermal annealing. It was justified experimentally that shot-time mechanical milling of Al-Ni-Co-Fe-Cr-Ti powder mixture during 3 hours resulted in a single-phase nanocrystalline high-entropy alloy (HEA) with a structure of bcc solid solution. During thermal annealing of the bcc solid solution phase transformation take place, and grain growth of equilibrium phases occur. The phase composition of as-MA alloy transforms to fcc and bcc solid solutions with TiC precipitations’ when the MA powder was annealed at 1200 °C for 1 h. X-ray diffraction and electron microscopy data show that the nanocrystalline powder microstructure is retained in the alloy with no grain growth. The AlNiCoFeCrTi HEA exhibit 7.1 GPa and 9.2±0.3 GPa in Vickers hardness after mechanical alloying and after thermal annealing, respectively

Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD) is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2—the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC) and immunocytes—can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFNγ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγR in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD

Magmatic and geotectonic significance of Santa Elena Peninsula, Costa Rica

We present a new integrated interpretation of the geochemistry and geotectonic significance of the Santa Elena Peninsula, which is divided in three units: 1) an overthrust allocthonous unit of ultramafic and mafic rocks, the Santa Elena Nappe; 2) an autochthonous basaltic sedimentary suite, resting immediately below the overthrust, the Santa Rosa Accretionary Complex; and 3) Islas Murciélago pillow and massive basaltic flows. In the Santa Elena Nappe three petrological affinities have been recognized: 1) the ultramafic complex, that corresponds to depleted (MORB-like) mantle serpentinizated peridotites, with very low TiO2 and high Ni and Cr; 2) the pegmatitic gabbros, layered gabbros and plagiogranites and basaltic dikes with low TiO2 (0.89%). These mafic associations have geochemical signatures that suggest an island arc origin and petrographic evidences of low grade metamorphism and hydrothermal alteration. The Santa Rosa Accretionary Complex includes pelagic and volcanoclastic sediments, tuffs and alkaline magmatic rocks, originated by low degree melting of enrichment OIB mantle source, and probably related with seamount portions incorporated into the accretionary prism. Islas Murciélago pillow and massive basalts show no clear structural relationship with the rest of the units, but are geochemically similar to the dolerites of the Santa Elena Nappe. Sr, Nd, and Pb isotopic ratios of the Santa Elena Nappe and the Santa Elena Accretionary Complex samples do not correspond to the Galapagos Mantle array, and have different mantle reservoirs and geochemical characteristics than the Nicoya Complex

Placenta Imaging Workshop 2018 report:Multiscale and multimodal approaches

The Centre for Medical Image Computing (CMIC) at University College London (UCL) hosted a two-day workshop on placenta imaging on April 12th and 13th 2018. The workshop consisted of 10 invited talks, 3 contributed talks, a poster session, a public interaction session and a panel discussion about the future direction of placental imaging. With approximately 50 placental researchers in attendance, the workshop was a platform for engineers, clinicians and medical experts in the field to network and exchange ideas. Attendees had the chance to explore over 20 posters with subjects ranging from the movement of blood within the placenta to the efficient segmentation of fetal MRI using deep learning tools. UCL public engagement specialists also presented a poster, encouraging attendees to learn more about how to engage patients and the public with their research, creating spaces for mutual learning and dialogue