scholarly journals Gradual loading ameliorates maladaptation in computational simulations of vein graft growth and remodelling

2017 ◽  
Vol 14 (130) ◽  
pp. 20160995 ◽  
Author(s):  
Abhay B. Ramachandra ◽  
Jay D. Humphrey ◽  
Alison L. Marsden
Keyword(s):  
Vein Graft ◽  
Computational Models ◽  
Constitutive Relations ◽  
Mixture Theory ◽  
Initial Step ◽  
Gradual Change ◽  
Beneficial Effects ◽  
Parameter Estimations ◽  
Constrained Mixture Theory ◽  
Starting Point

Vein graft failure is a prevalent problem in vascular surgeries, including bypass grafting and arteriovenous fistula procedures in which veins are subjected to severe changes in pressure and flow. Animal and clinical studies provide significant insight, but understanding the complex underlying coupled mechanisms can be advanced using computational models. Towards this end, we propose a new model of venous growth and remodelling (G&R) based on a constrained mixture theory. First, we identify constitutive relations and parameters that enable venous adaptations to moderate perturbations in haemodynamics. We then fix these relations and parameters, and subject the vein to a range of combined loads (pressure and flow), from moderate to severe, and identify plausible mechanisms of adaptation versus maladaptation. We also explore the beneficial effects of gradual increases in load on adaptation. A gradual change in flow over 3 days plus an initial step change in pressure results in fewer maladaptations compared with step changes in both flow and pressure, or even a gradual change in pressure and flow over 3 days. A gradual change in flow and pressure over 8 days also enabled a successful venous adaptation for loads as severe as the arterial loads. Optimization is used to accelerate parameter estimation and the proposed framework is general enough to provide a good starting point for parameter estimations in G&R simulations.

scholarly journals VASCULAR MECHANICS, MECHANOBIOLOGY, AND REMODELING

2009 ◽  
Vol 09 (02) ◽  
pp. 243-257 ◽  
Author(s):  
J. D. HUMPHREY
Keyword(s):  
Constitutive Relations ◽  
Mixture Theory ◽  
Clinical Treatment ◽  
Vascular Mechanics ◽  
Growth And Remodeling ◽  
Theoretical Frameworks ◽  
Future Directions ◽  
Constrained Mixture Theory ◽  
Constrained Mixture ◽  
Recent Developments

Arteries exhibit a remarkable ability to adapt in response to sustained alterations in hemodynamic loading as well as to disease, injury, and clinical treatment. A better understanding of such adaptations will be aided greatly by formulating, testing, and refining appropriate theoretical frameworks for modeling the biomechanics and associated mechanobiology. The goal of this brief review is to highlight some recent developments in the use of a constrained mixture theory of arterial growth and remodeling, with particular attention to the requisite constitutive relations, and to highlight future directions of needed research.

scholarly journals How Perspectives of a System Change Based on Exposure to Positive or Negative Evidence

Systems ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 23
Author(s):  
Philippe J. Giabbanelli ◽  
Andrew A. Tawfik
Keyword(s):  
Initial Step ◽  
Thinking Skills ◽  
Professional Lives ◽  
Negative Evidence ◽  
Problem Space ◽  
Root Cause ◽  
Starting Point ◽  
Direction Of Causation ◽  
Case Libraries ◽  
Support Students

The system that shapes a problem can be represented using a map, in which relevant constructs are listed as nodes, and salient interrelationships are provided as directed edges which track the direction of causation. Such representations are particularly useful to address complex problems which are multi-factorial and may involve structures such as loops, in contrast with simple problems which may have a clear root cause and a short chain of causes-and-effects. Although students are often evaluated based on either simple problems or simplified situations (e.g., true/false, multiple choice), they need systems thinking skills to eventually deal with complex, open-ended problems in their professional lives. A starting point is thus to construct a representation of the problem space, such as a causal map, and then to identify and contrast solutions by navigating this map. The initial step of abstracting a system into a map is challenging for students: unlike seasoned experts, they lack a detailed understanding of the application domain, and hence struggle in capturing its key concepts and interrelationships. Case libraries can remedy this disadvantage, as they can transfer the knowledge of experts to novices. However, the content of the cases can impact the perspectives of students. For example, their understanding of a system (as reflected in a map) may differ when they are exposed to case studies depicting successful or failed interventions in a system. Previous studies have abundantly documented that cases can support students, using a variety of metrics such as test scores. In the present study, we examine the ways in which the representation of a system (captured as a causal map) changes as a function of exposure to certain types of evidence. Our experiments across three cohorts at two institutions show that providing students with cases tends to broaden their coverage of the problem space, but the knowledge afforded by the cases is integrated in the students’ maps differently depending on the type of case, as well as the cohort of students.

scholarly journals The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core Release 2

2019 ◽  
Vol 16 (2) ◽  
Author(s):  
Michael Hucka ◽  
Frank T. Bergmann ◽  
Claudine Chaouiya ◽  
Andreas Dräger ◽  
Stefan Hoops ◽  
...  
Keyword(s):  
Computational Models ◽  
Software Systems ◽  
Markup Language ◽  
Starting Point ◽  
Extensible Markup ◽  
Systems Biology Markup Language ◽  
Level 3 ◽  
Translation Errors ◽  
Language Specification ◽  
Cell Signaling Pathways

AbstractComputational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Release 2 of Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. Release 2 corrects some errors and clarifies some ambiguities discovered in Release 1. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project website at http://sbml.org/.

scholarly journals Naturally Occurring PCSK9 Inhibitors

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1440
Author(s):  
Maria Pia Adorni ◽  
Francesca Zimetti ◽  
Maria Giovanna Lupo ◽  
Massimiliano Ruscica ◽  
Nicola Ferri
Keyword(s):  
Ldl Cholesterol ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Pcsk9 Inhibitors ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Starting Point

Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.

scholarly journals Enskog kinetic theory for monodisperse gas–solid flows

2012 ◽  
Vol 712 ◽  
pp. 129-168 ◽  
Author(s):  
V. Garzó ◽  
S. Tenneti ◽  
S. Subramaniam ◽  
C. M. Hrenya
Keyword(s):  
Reynolds Number ◽  
Kinetic Theory ◽  
Gas Phase ◽  
Parameter Space ◽  
Shear Viscosity ◽  
Solid Phase ◽  
Constitutive Relations ◽  
Solid Particles ◽  
Analytical Treatment ◽  
Starting Point

AbstractThe Enskog kinetic theory is used as a starting point to model a suspension of solid particles in a viscous gas. Unlike previous efforts for similar suspensions, the gas-phase contribution to the instantaneous particle acceleration appearing in the Enskog equation is modelled using a Langevin equation, which can be applied to a wide parameter space (e.g. high Reynolds number). Attention here is limited to low Reynolds number flow, however, in order to assess the influence of the gas phase on the constitutive relations, which was assumed to be negligible in a previous analytical treatment. The Chapman–Enskog method is used to derive the constitutive relations needed for the conservation of mass, momentum and granular energy. The results indicate that the Langevin model for instantaneous gas–solid force matches the form of the previous analytical treatment, indicating the promise of this method for regions of the parameter space outside of those attainable by analytical methods (e.g. higher Reynolds number). The results also indicate that the effect of the gas phase on the constitutive relations for the solid-phase shear viscosity and Dufour coefficient is non-negligible, particularly in relatively dilute systems. Moreover, unlike their granular (no gas phase) counterparts, the shear viscosity in gas–solid systems is found to be zero in the dilute limit and the Dufour coefficient is found to be non-zero in the elastic limit.

Control of the Microstructure of Al Metallization by Graphoepitaxy

1995 ◽  
Vol 391 ◽  
Author(s):  
Marc J.C. Van Den Homberg ◽  
P.F.A. Alkemade ◽  
J.L. Hurd ◽  
G.J. Leusink ◽  
S. Radelaar
Keyword(s):  
Substrate Material ◽  
Model Systems ◽  
Grain Structure ◽  
Gradual Change ◽  
X Ray Diffraction ◽  
Rapid Thermal Anneal ◽  
Single Crystalline ◽  
Additional Control ◽  
Starting Point ◽  
Al Metallization

AbstractMicrostructure is an important factor determining the lifetime of Al metallization lines. Deposition conditions, substrate material, alloying elements, and anneal treatments are the key parameters that influence microstructure. In this work we explore the use of graphoepitaxy as a tool for additional control over the grain structure of metallization lines. Onto a submicrometer topography in SiO2 (viz., a large number of parallel grooves), a pure Al film is grown by dc magnetron sputtering, followed by an in situ rapid thermal anneal. The topography of the annealed Al is investigated by cross section SEM. It is observed that if it is heated up to its melting point, Al fills the grooves and leaves the ridges between the grooves uncovered. X-Ray Diffraction, TEM, and Backscatter Kikuchi Diffraction are used to determine the global as well as the local crystallographic orientation of the grains in the quenched aluminum. The analyses are performed for various anneal and cool down treatments. Depending on the treatment, the Al lines in the grooves are either polycrystalline with an almost perfect (111) texture, or single crystalline but with a gradual change of 0.067°/μm in orientation. In the latter case, there is no preferred orientation. The single crystalline Al lines will be used as a starting point for the fabrication of model systems for fundamental electromigration studies.

SELECTION AND ASSESSMENT OF PHENOMENOLOGICAL MODELS OF TUMOR GROWTH

2013 ◽  
Vol 23 (07) ◽  
pp. 1309-1338 ◽  
Author(s):  
J. TINSLEY ODEN ◽  
ERNESTO E. PRUDENCIO ◽  
ANDREA HAWKINS-DAARUD
Keyword(s):  
Tumor Growth ◽  
High Performance ◽  
Computational Models ◽  
Synthetic Data ◽  
Mixture Theory ◽  
Mass Conservation ◽  
Diffuse Interface ◽  
Maximum Information ◽  
Monte Carlo Algorithms ◽  
Maximum Information Entropy

We address general approaches to the rational selection and validation of mathematical and computational models of tumor growth using methods of Bayesian inference. The model classes are derived from a general diffuse-interface, continuum mixture theory and focus on mass conservation of mixtures with up to four species. Synthetic data are generated using higher-order base models. We discuss general approaches to model calibration, validation, plausibility, and selection based on Bayesian-based methods, information theory, and maximum information entropy. We also address computational issues and provide numerical experiments based on Markov chain Monte Carlo algorithms and high performance computing implementations.

scholarly journals Vertical flow of a multiphase mixture in a channel

2001 ◽  
Vol 6 (6) ◽  
pp. 505-526 ◽  
Author(s):  
Mehrdad Massoudi ◽  
C. Lakshmana Rao
Keyword(s):  
Volume Fraction ◽  
Constitutive Relations ◽  
Mixture Theory ◽  
Interaction Force ◽  
Solid Particles ◽  
Vertical Flow ◽  
Dimensionless Numbers ◽  
Dimensionless Velocity ◽  
Multiphase Mixture ◽  
Linear Boundary Value Problem

The flow of a multiphase mixture consisting of a viscous fluid and solid particles between two vertical plates is studied. The theory of interacting continua or mixture theory is used. Constitutive relations for the stress tensor of the granular materials and the interaction force are presented and discussed. The flow of interest is an ideal one where we assume the flow to be steady and fully developed; the mixture is flowing between two long vertical plates. The non-linear boundary value problem is solved numerically, and the results are presented for the dimensionless velocity profiles and the volume fraction as functions of various dimensionless numbers.

scholarly journals The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Michael Hucka ◽  
Frank T. Bergmann ◽  
Andreas Dräger ◽  
Stefan Hoops ◽  
Sarah M. Keating ◽  
...  
Keyword(s):  
Systems Biology ◽  
Computational Models ◽  
Software Systems ◽  
Markup Language ◽  
Starting Point ◽  
Extensible Markup ◽  
Systems Biology Markup Language ◽  
Level 3 ◽  
Translation Errors ◽  
Language Specification

AbstractComputational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language), validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

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