scholarly journals Towards the virtual artery: a multiscale model for vascular physiology at the physics–chemistry–biology interface

2016 ◽  
Vol 374 (2080) ◽  
pp. 20160146 ◽  
Author(s):  
Alfons G. Hoekstra ◽  
Saad Alowayyed ◽  
Eric Lorenz ◽  
Natalia Melnikova ◽  
Lampros Mountrakis ◽  
...  
Keyword(s):  
Multiscale Model ◽  
Cellular Level ◽  
Multiscale Modelling ◽  
Multiscale Models ◽  
Discussion Paper ◽  
Vascular Physiology ◽  
Health And Disease ◽  
Mesoscopic Level ◽  
Coupling Cell

This discussion paper introduces the concept of the Virtual Artery as a multiscale model for arterial physiology and pathologies at the physics–chemistry–biology (PCB) interface. The cellular level is identified as the mesoscopic level, and we argue that by coupling cell-based models with other relevant models on the macro- and microscale, a versatile model of arterial health and disease can be composed. We review the necessary ingredients, both models of arteries at many different scales, as well as generic methods to compose multiscale models. Next, we discuss how this can be combined into the virtual artery. Finally, we argue that the concept of models at the PCB interface could or perhaps should become a powerful paradigm, not only as in our case for studying physiology, but also for many other systems that have such PCB interfaces. This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’.

scholarly journals An Embedded Multiscale Modelling to Guide Control and Elimination of Paratuberculosis in Ruminants

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Rendani Netshikweta ◽  
Winston Garira
Keyword(s):  
Infectious Disease ◽  
Multiscale Model ◽  
Multiscale Modelling ◽  
Disease Dynamics ◽  
Multiscale Models ◽  
Efficacy Data ◽  
Infectious Episode ◽  
Repeated Infection ◽  
To Receive ◽  
Modelling Approach

In recent years, multiscale modelling approach has begun to receive an overwhelming appreciation as an appropriate technique to characterize the complexity of infectious disease systems. In this study, we develop an embedded multiscale model of paratuberculosis in ruminants at host level that integrates the within-host scale and the between-host. A key feature of embedded multiscale models developed at host level of organization of an infectious disease system is that the within-host scale and the between-host scale influence each other in a reciprocal (i.e., both) way through superinfection, that is, through repeated infection before the host recovers from the initial infectious episode. This key feature is demonstrated in this study through a multiscale model of paratuberculosis in ruminants. The results of this study, through numerical analysis of the multiscale model, show that superinfection influences the dynamics of paratuberculosis only at the start of the infection, while the MAP bacteria replication continuously influences paratuberculosis dynamics throughout the infection until the host recovers from the initial infectious episode. This is largely because the replication of MAP bacteria at the within-host scale sustains the dynamics of paratuberculosis at this scale domain. We further use the embedded multiscale model developed in this study to evaluate the comparative effectiveness of paratuberculosis health interventions that influence the disease dynamics at different scales from efficacy data.

Regulation of renin processing and secretion: chemiosmotic control and novel secretory pathway

1993 ◽  
Vol 265 (2) ◽  
pp. C305-C320 ◽  
Author(s):  
J. A. King ◽  
D. J. Lush ◽  
J. C. Fray
Keyword(s):  
Secretory Pathway ◽  
Secretory Granules ◽  
Surface Membrane ◽  
Water Flux ◽  
Cellular Level ◽  
Macula Densa ◽  
Secretory Proteins ◽  
Juxtaglomerular Cells ◽  
Cl Channels ◽  
Health And Disease

The renin-angiotensin-aldosterone system (RAAS) plays an important role in cardiovascular and electrolyte regulation in health and disease. Juxtaglomerular cells in the kidney regulate endocrine RAAS by physiologically controlling conversion of prorenin and secretion of renin. The classical baroceptor, neurogenic, and macula densa mechanisms regulate renin expression at the cellular level by Ca2+, adenosine 3',5'-cyclic monophosphate (cAMP), and chemiosmotic forces (K+, Cl-, and water flux coupled to H+ movement). The baroceptor mechanism (through Ca2+) activates K+ and Cl- channels in the surface membrane and deactivates a KCl-H+ exchange chemiosmotic transporter in the secretory granular membrane. The neurogenic mechanism (through cAMP) promotes prorenin processing to renin. The macula densa mechanism (through K+ and Cl-) involves the processing of prorenin to renin. Ca2+, by inhibiting the KCl-H+ exchange transporter, prevents secretory granules from engaging in chemiosmotically mediated exocytosis. cAMP, on the other hand, by stimulating H+ influx, provides the acidic granular environment for prorenin processing to renin. It is concluded that, in the presence of a favorable chemiosmotic environment, prorenin is processed to renin, which may then be secreted by regulative degranulation or divergence translocation, a novel secretory pathway used by several secretory proteins, including renin.

scholarly journals Multiscale computing for science and engineering in the era of exascale performance

2019 ◽  
Vol 377 (2142) ◽  
pp. 20180144 ◽  
Author(s):  
Alfons G. Hoekstra ◽  
Bastien Chopard ◽  
David Coster ◽  
Simon Portegies Zwart ◽  
Peter V. Coveney
Keyword(s):  
Multiscale Model ◽  
Multiscale Simulation ◽  
Multiscale Models ◽  
Theme Issue ◽  
Science And Engineering ◽  
High Performing ◽  
The Face ◽  
Strong Scaling ◽  
Computing Environments ◽  
Modelling Simulation

In this position paper, we discuss two relevant topics: (i) generic multiscale computing on emerging exascale high-performing computing environments, and (ii) the scaling of such applications towards the exascale. We will introduce the different phases when developing a multiscale model and simulating it on available computing infrastructure, and argue that we could rely on it both on the conceptual modelling level and also when actually executing the multiscale simulation, and maybe should further develop generic frameworks and software tools to facilitate multiscale computing. Next, we focus on simulating multiscale models on high-end computing resources in the face of emerging exascale performance levels. We will argue that although applications could scale to exascale performance relying on weak scaling and maybe even on strong scaling, there are also clear arguments that such scaling may no longer apply for many applications on these emerging exascale machines and that we need to resort to what we would call multi-scaling . This article is part of the theme issue ‘Multiscale modelling, simulation and computing: from the desktop to the exascale’.

Probabilistic Multiscale Models for Fracture Analysis of Functionally Graded Composites

2008 ◽  
Author(s):  
Arindam Chakraborty ◽  
Sharif Rahman
Keyword(s):  
Driving Forces ◽  
Multiscale Model ◽  
Fracture Analysis ◽  
Computational Effort ◽  
Functionally Graded ◽  
Stochastic Methods ◽  
Multiscale Models ◽  
Particle Volume ◽  
Two Phase ◽  
Microscale Model

This paper reports three multiscale models, including sequential, invasive, and concurrent models, for fracture analysis of a crack in a two-phase, functionally graded composite. The models involve stochastic description of the particle volume fractions, particle locations, and constituent material properties; a two-scale algorithm including microscale and macroscale analyses for determining crack-driving forces; and two stochastic methods for fracture reliability analysis. Numerical results indicate that the sequential and invasive multiscale models are the most computationally inexpensive models available, but they may not produce acceptable probabilistic characteristics of stress-intensity factors or accurate probability of fracture initiation. The concurrent multiscale model is sufficiently accurate, gives probabilistic solutions very close to those generated from the microscale model, and can reduce the computational effort of the latter model by more than a factor of two. In addition, the concurrent multiscale model predicts crack trajectory as accurately as the microscale model.

Multiscale Modelling of Softening Materials

2007 ◽  
Vol 348-349 ◽  
pp. 1-4
Author(s):  
I.M. Gitman ◽  
H. Askes ◽  
L.J. Sluys
Keyword(s):  
Cell Size ◽  
Size Dependence ◽  
Multiscale Model ◽  
Multiscale Modelling ◽  
Macro Level ◽  
Length Scales ◽  
Meso Level ◽  
Hierarchical Multiscale

A hierarchical multiscale procedure for softening materials is proposed in this paper. A standard multiscale model has been analysed with respect to macro-level mesh dependence and meso-level cell size dependence. In order to eliminate spurious macro-level mesh dependence and meso-level cell size dependence a coupled-volume approach has been proposed. A discussion on the various interacting length scales in the model is included.

The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery

2008 ◽  
Vol 366 (1879) ◽  
pp. 3343-3360 ◽  
Author(s):  
D.J.W Evans ◽  
P.V Lawford ◽  
J Gunn ◽  
D Walker ◽  
D.R Hose ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Spatial Scales ◽  
Multiscale Model ◽  
Multiscale Modelling ◽  
Agent Based ◽  
Stent Restenosis ◽  
Biomedical Systems ◽  
Single Scale ◽  
Wide Range ◽  
Generic Description

The inherent complexity of biomedical systems is well recognized; they are multiscale, multiscience systems, bridging a wide range of temporal and spatial scales. While the importance of multiscale modelling in this context is increasingly recognized, there is little underpinning literature on the methodology and generic description of the process. The COAST (complex autonoma simulation technique) project aims to address this by developing a multiscale, multiscience framework, coined complex autonoma (CxA), based on a hierarchical aggregation of coupled cellular automata (CA) and agent-based models (ABMs). The key tenet of COAST is that a multiscale system can be decomposed into N single-scale CA or ABMs that mutually interact across the scales. Decomposition is facilitated by building a scale separation map on which each single-scale system is represented according to its spatial and temporal characteristics. Processes having well-separated scales are thus easily identified as the components of the multiscale model. This paper focuses on methodology, introduces the concept of the CxA and demonstrates its use in the generation of a multiscale model of the physical and biological processes implicated in a challenging and clinically relevant problem, namely coronary artery in-stent restenosis.

scholarly journals An Overview of Iron Metabolism in Health and Disease

2021 ◽  
pp. 70-78
Author(s):  
Nabiyev Abdusamat Utkurovich
Keyword(s):  
Cell Death ◽  
Iron Metabolism ◽  
Growth And Development ◽  
Biochemical Parameters ◽  
Cellular Level ◽  
The Body ◽  
Viral Diseases ◽  
Correct Interpretation ◽  
Working Capacity ◽  
Health And Disease

Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically important part of many aspects of human health and disease. Iron deficiency states are the reason for a decrease in working capacity, an increase in susceptibility to viral diseases, especially in children and cause growth and development retardation. Iron overload and poisoning lead to the activation of processes that can cause cell death. Timely diagnosis of disorders of iron metabolism and subsequent monitoring of treatment require knowledge of not only pathophysiological mechanisms, but also methodological capabilities and correct interpretation of clinical and biochemical parameters of iron metabolism.

Seeing the fetus from a DOHaD perspective: discussion paper from the advanced imaging techniques of DOHaD applications workshop held at the 2019 DOHaD World Congress

2020 ◽  
pp. 1-15
Author(s):  
Janna L. Morrison ◽  
Oyekoya T. Ayonrinde ◽  
Alison S. Care ◽  
Geoffrey D. Clarke ◽  
Jack R.T. Darby ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Research Capacity ◽  
Adult Health ◽  
Advanced Imaging ◽  
World Congress ◽  
Discussion Paper ◽  
Future Health ◽  
Health And Disease ◽  
Hyperpolarized Mri ◽  
Novel Applications

Abstract Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

scholarly journals mTOR: A Cellular Regulator Interface in Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 18 ◽  
Author(s):  
Fahd Boutouja ◽  
Christian M. Stiehm ◽  
Harald W. Platta
Keyword(s):  
Protein Composition ◽  
Mtor Inhibitors ◽  
Cellular Level ◽  
Serine Threonine Kinase ◽  
Central Function ◽  
Extend Life Span ◽  
Dependent Inhibition ◽  
Physiologic Function ◽  
Health And Disease

The mechanistic target of Rapamycin (mTOR) is a ubiquitously-conserved serine/threonine kinase, which has a central function in integrating growth signals and orchestrating their physiologic effects on cellular level. mTOR is the core component of differently composed signaling complexes that differ in protein composition and molecular targets. Newly identified classes of mTOR inhibitors are being developed to block autoimmune diseases and transplant rejections but also to treat obesity, diabetes, and different types of cancer. Therefore, the selective and context-dependent inhibition of mTOR activity itself might come into the focus as molecular target to prevent severe diseases and possibly to extend life span. This review provides a general introduction to the molecular composition and physiologic function of mTOR complexes as part of the Special Issue “2018 Select Papers by Cells’ Editorial Board Members”.

scholarly journals Cardiovascular deconditioning during long-term spaceflight through multiscale modeling

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Caterina Gallo ◽  
Luca Ridolfi ◽  
Stefania Scarsoglio
Keyword(s):  
Cardiovascular Response ◽  
Accelerated Aging ◽  
Multiscale Model ◽  
Cellular Level ◽  
Physical Capability ◽  
Cardiovascular Deconditioning ◽  
Partial Gravity ◽  
Volume Shift ◽  
Blood Volume Shift

Abstract Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes—from blood volume shift and reduction to altered cardiac function—induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts’ safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D–0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary–venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.

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