Shear induced diffusion of platelets revisited

The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory

Personalized pathology test for Cardio-vascular disease : approximate Bayesian computation with discriminative summary statistics learning

Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment

STEPS 4.0: Fast and memory-efficient molecular simulations of neurons at the nanoscale

Recent advances in computational neuroscience have demonstrated the usefulness and importance of stochastic, spatial reaction-diffusion simulations. However, ever increasing model complexity renders traditional serial solvers, as well as naive parallel implementations, inadequate. This paper introduces a new generation of the STochastic Engine for Pathway Simulation (STEPS) project (http://steps.sourceforge.net/), denominated STEPS 4.0, and its core components which have been designed for improved scalability, performance, and memory efficiency. STEPS 4.0 aims to enable novel scientific studies of macroscopic systems such as whole cells while capturing their nanoscale details. This class of models is out of reach for serial solvers due to the vast quantity of computation in such detailed models, and also out of reach for naive parallel solvers due to the large memory footprint. Based on a distributed mesh solution, we introduce a new parallel stochastic reaction-diffusion solver and a deterministic membrane potential solver in STEPS 4.0. The distributed mesh, together with improved data layout and algorithm designs, significantly reduces the memory footprint of parallel simulations in STEPS 4.0. This enables massively parallel simulations on modern HPC clusters and overcomes the limitations of the previous parallel STEPS implementation. Current and future improvements to the solver are not sustainable without following proper software engineering principles. For this reason, we also give an overview of how the STEPS codebase and the development environment have been updated to follow modern software development practices. We benchmark performance improvement and memory footprint on three published models with different complexities, from a simple spatial stochastic reaction-diffusion model, to a more complex one that is coupled to a deterministic membrane potential solver to simulate the calcium burst activity of a Purkinje neuron. Simulation results of these models suggest that the new solution dramatically reduces the per-core memory consumption by more than a factor of 30, while maintaining similar or better performance and scalability

Digital Blood

This thesis aims at building high-fidelity models for the simulation of blood at both the microscopic and the macroscopic scales. Our work focuses on creating a digital replica of human blood through various tools of multi-scale/multi-physics nature, and on contributing novel pieces towards the realisation of a digital lab. We then use these tools for investigating cases that span from fundamental research to problems of clinical relevance. Focal point has been the understanding of the underlying mechanisms of platelet transport. For this, we followed a bottom-up approach, i.e. started from fully resolved blood flow simulations (microscopic scale) and moved towards calibrated stochastic models (macroscopic scale). Our results help clarify platelet transport physics, leading to more accurate modelling and design of PLT function tests (e.g. Impact-R device). Given the limited prognostic capacity of these tests, we believe that our models could lead in next generation tests with higher clinical relevance/readiness

Experimental investigation of Double-Diffusive Convection

196 σ.Στην παρούσα διπλωματική εργασία εξετάζεται πειραματικά το φαινόμενο της διπλής διάχυσης και της επακόλουθης συναγωγής (Double-Diffusive Convection). Αναλυτικότερα, η ύπαρξη δύο παραγόντων που επηρεάζουν την πυκνότητα συστήματος υγρών σε συνδυασμό με την διαφορετική ταχύτητα μοριακής διάχυσης αυτών, δύναται να προκαλέσει ροές σε βαρυτικά ευσταθές σύστημα. Η αστάθεια αυτή εκδηλώνεται με δομές που ομοιάζουν με δάκτυλα τα αποκαλούμενα στην διεθνή βιβλιογραφία ως Salt Fingers ή Fingers. Εν προκειμένω, εξετάσθηκε το φαινόμενο χρησιμοποιώντας συνδυασμούς διαλυμάτων αλατόνερου και ζαχαρόνερου. Η οπτικοποίηση του φαινομένου έγινε με την εφαρμογή της τεχνικής LIF (Laser-Induced Fluorescence) και με χρήση ροδαμίνης 6G (R6G). Με σκοπό την διεξοδική ανάλυση του φαινομένου εκτελέσθηκαν τρείς τύποι πειραμάτων και συνολικά 30 μετρήσιμα πειράματα. Στον πρώτο τύπο πειραμάτων το φαινόμενο εξελίσσεται σε σύστημα δύο στρώσεων (‘’The Two Layer System’’). Η άνω και ελαφρύτερη στρώση είναι διάλυμα ζαχαρόνερου και η κάτω στρώση διάλυμα αλατόνερου. Τα πάχη (L) των Salt Fingers κυμάνθηκαν περί το 1 mm και η περιοχή ανάπτυξης του φαινομένου περί την διαχωριστική επιφάνεια (h) των δύο στρώσεων κυμάνθηκε από 5 έως 35 mm για χρόνους παρακολούθησης του φαινομένου στα 180 min. Επίσης, παρατηρήθηκε ότι οι ανοδικές και καθοδικές ροές σε αυτό το διάστημα εξελίσσονται ασύμμετρα. Στο δεύτερο τύπο πειραμάτων το φαινόμενο εξελίσσεται με την διάχυση συστατικού σε γραμμική πυκνομετρική στρωμάτωση άλλου συστατικού διαφορετικής ταχύτητας μοριακής διάχυσης. Πρακτικά, στην πειραματική δεξαμενή δημιουργείται γραμμική πυκνομετρική στρωμάτωση εφαρμόζοντας την τεχνική των Oster & Yamamoto (1963) και ακολούθως εγχέεται ρευστό από επάνω υπό μορφή τυρβώδους ανωστικής φλέβας. Μετρήθηκαν τα πάχη των Fingers (L) και τα μήκη τους (λ) για εξέλιξη του φαινομένου σε 180 min. Οι τιμές του L κυμαίνονται στο διάστημα 1 έως 2.5 mm και το λ στο διάστημα 0 έως 9 mm. Ο μηχανισμός των Fingers φαίνεται να ομογενοποιεί το πεδίο αποβλήτων και ως αποτέλεσμα να αποτελεί έναν επικουρικό μηχανισμό αραίωσης. Στον τρίτο τύπο πειραμάτων δημιουργείται γραμμική πυκνομετρική στρωμάτωση με ρευστό που προκύπτει από την ανάμειξη ζαχαρόνερου και αλατόνερου (‘’The Double Gradient System’’). Η συγκέντρωση ζαχαρόνερου μειώνεται γραμμικά από την επιφάνεια προς τον πυθμένα, ενώ η συγκέντρωση αλατόνερου αυξάνεται γραμμικά από την επιφάνεια προς τον πυθμένα. Μετρήθηκαν τα πάχη των Fingers στο υπό εξέταση στρώμα και αυτά κυμάνθηκαν από 1 έως 2.5 mm. Παρατηρήθηκε ότι στις μικρές πυκνομετρικές κλίσεις το φαινόμενο εξελίσσεται ταχύτατα και το μελετώμενο στρώμα 25 cm ομογενοποιείται σε χρόνους περί των 100 min. Από την άλλη, στις περιπτώσεις μεγάλων πυκνομετρικών κλίσεων το φαινόμενο εξελίσσεται πολύ αργά και οι αντίστοιχοι χρόνοι ομογενοποίησης αγγίζουν τα 300 min. Η συνύπαρξη των άνω υγρών, σε όλα τα παραπάνω συστήματα, εκκινεί το φαινόμενο της διπλής διάχυσης και εμφανίζονται ροές σε φαινομενικά ευσταθή συστήματα. Η παρούσα πειραματική εργασία εστιάζει στα γεωμετρικά χαρακτηριστικά της δομής των Fingers και της ευρύτερης γεωμετρίας του αναπτυσσόμενου φαινομένου συναρτήσει του χρόνου εξέλιξής του.In the present diploma thesis the double-diffusive convection phenomenon is investigated experimentally. More precisely, the existence of two density affecting components in a system of fluids with different molecular diffusion coefficients is able to cause instabilities in a gravitationally stable system. The aforementioned instabilities appear with thread-like streams which are called Salt Fingers or (simply) Fingers. In this work, the phenomenon was examined by using combinations of salt and sugar solutions. The visualization of Salt Fingers was accomplished by the implementation of LIF technique (Laser-Induced Fluorescence) and with rhodamine 6G (R6G). In order to understand double-diffusive convection we performed three different types of experiments and totally 30 measurable experiments. In the first type of experiments, Salt Fingers were developed in a two layer system. The upper and lighter layer is sugar solution and the down layer is salt solution. The width of Salt Fingers (L) in this experiment is around 1 mm and the length of interface thickness (h) ranges from 5 to 35 mm for 180 min of observation. Additionally, we observed that the ascending and descending flows developed asymmetrically. In the second type of experiments, the phenomenon is developed through the diffusion of a component inside a linearly stratified ambient with a component with different velocity of molecular diffusion. Practically, inside the experimental tank a linear stratification is created by using the two tank method of Oster & Yamamoto (1963) and after this, a turbulent buoyant jet is injected from above in the tank. The width (L) and the length (λ) of Fingers were measured for 180 min of observation. L ranges from 1 to 2.5 mm and λ from 0 to 9 mm. The Salt Fingers mechanism seems to homogenize the waste field and as a result to be an additional mechanism of dilution. In the third type of experiments, a linear stratification is created by a complex fluid which is a combination of salt and sugar solution (‘’The Double Gradient System’’). Particularly, sugar concentration is decreased from the surface of the experimental tank to the bottom, while salt concentration is increased from the free surface to the bottom (Oster & Yamamoto). We measured the width of Salt Fingers which ranges from 1 to 2.5 mm. Also, it is observed that in experiments with small gradient of density stratification Salt Fingers are developed quickly enough and the stratified layer (25 cm) is homogenized in approximately 100 min. On the other hand, in experiments with large gradient of density stratification, the phenomenon is developed slowly and the time for the homogenization of the stratified layer (25 cm) is approximately 300 min. The coexistence of these solutions, in all the above mentioned systems, starts the double-diffusive convection phenomenon in an apparent stable system. The present thesis focuses on the geometrical characteristics of Fingers structure and generally on the geometry of the Finger phenomenon as a function of time.Χρήστος Ε. Κότσαλο

Bridging the computational gap between mesoscopic and continuum modeling of red blood cells for fully resolved blood flow

We present a computational framework for the simulation of blood flow with fully resolved red blood cells (RBCs) using a modular approach that consists of a lattice Boltzmann solver for the blood plasma, a novel finite element based solver for the deformable bodies and an immersed boundary method for the fluid-solid interaction. For the RBCs, we propose a nodal projective FEM (npFEM) solver which has theoretical advantages over the more commonly used mass-spring systems (mesoscopic modeling), such as an unconditional stability, versatile material expressivity, and one set of parameters to fully describe the behavior of the body at any mesh resolution. At the same time, the method is substantially faster than other FEM solvers proposed in this field, and has an efficiency that is comparable to the one of mesoscopic models. At its core, the solver uses specially defined potential energies, and builds upon them a fast iterative procedure based on quasi-Newton techniques. For a known material, our solver has only one free parameter that demands tuning, related to the body viscoelasticity. In contrast, state-of-the-art solvers for deformable bodies have more free parameters, and the calibration of the models demands special assumptions regarding the mesh topology, which restrict their generality and mesh independence. We propose as well a modification to the potential energy proposed by Skalak et al. 1973 for the red blood cell membrane, which enhances the strain hardening behavior at higher deformations. Our viscoelastic model for the red blood cell, while simple enough and applicable to any kind of solver as a post-convergence step, can capture accurately the characteristic recovery time and tank-treading frequencies. The framework is validated using experimental data, and it proves to be scalable for multiple deformable bodies