Modeling mitochondrial function

2006 ◽  
Vol 291 (6) ◽  
pp. C1107-C1113 ◽  
Author(s):  
Robert S. Balaban
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Mitochondrial Function ◽  
Metabolic Networks ◽  
Complex Biological System ◽  
Regulatory Data ◽  
The Matrix ◽  
Definition Of ◽  
The Individual

The mitochondrion represents a unique opportunity to apply mathematical modeling to a complex biological system. Understanding mitochondrial function and control is important since this organelle is critical in energy metabolism as well as playing key roles in biochemical synthesis, redox control/signaling, and apoptosis. A mathematical model, or hypothesis, provides several useful insights including a rigorous test of the consensus view of the operation of a biological process as well as providing methods of testing and creating new hypotheses. The advantages of the mitochondrial system for applying a mathematical model include the relative simplicity and understanding of the matrix reactions, the ability to study the mitochondria as a independent contained organelle, and, most importantly, one can dynamically measure many of the internal reaction intermediates, on line. The developing ability to internally monitor events within the metabolic network, rather than just the inflow and outflow, is extremely useful in creating critical bounds on complex mathematical models using the individual reaction mechanisms available. However, many serious problems remain in creating a working model of mitochondrial function including the incomplete definition of metabolic pathways, the uncertainty of using in vitro enzyme kinetics, as well as regulatory data in the intact system and the unknown chemical activities of relevant molecules in the matrix. Despite these formidable limitations, the advantages of the mitochondrial system make it one of the best defined mammalian metabolic networks that can be used as a model system for understanding the application and use of mathematical models to study biological systems.

Synthesis of Calcium Carbonate Biological Materials: How Many Proteins are Needed?

2014 ◽  
Vol 614 ◽  
pp. 52-61 ◽  
Author(s):  
Frédéric Marin ◽  
Nathalie Le Roy ◽  
Benjamin Marie ◽  
Paula Ramos-Silva ◽  
Stephan Wolf ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Low Complexity ◽  
Mean Value ◽  
Test Tube ◽  
Future Research ◽  
Biological Origin ◽  
Biomimetic Materials ◽  
The Matrix ◽  
The Individual

In Nature, calcium carbonate biomineralizations are the most abundant mineralized structures of biological origin. Because many exhibit remarkable characteristics, several attempts have been made to use them as substitution materials for bone reconstruction or as models for generating biomimetic composites that exhibit tailored properties. CaCO3biomineralizations contain small amounts of amalgamate of proteins and polysaccharides that are secreted during the calcification process. They contribute to control the morphology of the crystallites and to spatially organize them in well-defined microstructures. These macromolecules, collectively defined as the skeletal matrix, have been the focus of a large number of studies aiming at synthesizingin vitrobiomimetic materials, according to a bottom-up approach. However, recent proteomic investigations performed on the organic matrices associated to mollusc shells or to coral skeletons have quashed our hopes to generate, with only few macromolecular ingredients, biomimetic materials with properties approaching to those of natural biominerals. As a mean value, each matrix comprises a minimum of few tens of different proteins that seem to be strictly associated to calcium carbonate biominerals. Among the proteins that are currently detected, one finds RLCDs-containing proteins (Repetitive-Low-Complexity Domains), enzymes, proteins with protease inhibitors domains and at last, proteins that contains typical ECM (ExtraCellular Matrix) domains. Today, we still do not understand how the skeletal matrix works, and unveiling its complex functioning is one of the challenges for the coming decade, both from fundamental and applied viewpoints. Is it realistic to attempt generating abiotically, in a test tube at room temperature, biomimetic composites that mimic natural biomineralizations in their properties? If so, and by supposing that we know the individual functions of all the components of the matrix, is there a minimal number of proteins required for producingin vitrocalcium carbonate biomaterials that approximate natural biominerals? These issues are of importance for the future research directions in biomaterials science.

scholarly journals Time Lapse Observation Based Modeling and Identification of Cell Behaviors in Angiogenic Sprout Development

2010 ◽  
Author(s):  
Levi B. Wood ◽  
Roger D. Kamm ◽  
H. Harry Asada
Keyword(s):  
Blood Vessel ◽  
Real Time ◽  
Time Lapse ◽  
Model Parameters ◽  
Cell Behaviors ◽  
The Matrix ◽  
The Individual ◽  
Sprout Formation ◽  
Cell Motion

This paper presents a method for deriving dynamic equations for Endothelial Cell (EC) motion and estimating parameters based on time lapse imagery of angiogenic sprout development. Angiogenesis is the process whereby a collection of endothelial cells sprout out from an existing blood vessel, degrade the surrounding scaffold and form a new blood vessel. Sprout formation requires that a collection of ECs all work together and coordinate their movements and behaviors. The process is initiated and guided by a collection of external growth factors. In addition, the individual cells communicate and respond to each other’s movements to behave in a coordinated fashion. The mechanics of cell coordination are extremely complex and include both chemical and mechanical communication between cells and between cells and the matrix. Despite the complexity of the physical system, with many variables that cannot be measured in real time, the ECs behave in a predictable manner based on just a few quantities that can be measured in real time. This work presents a methodology for constructing a set of simple stochastic equations for cell motion dependent only on quantities obtained from time lapse data observed from in vitro experiments. Model parameters are identified from time lapse data using a Maximum Likelihood Estimator.

scholarly journals Leukocyte-endothelial adhesion molecules

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2068-2101 ◽  
Author(s):  
TM Carlos ◽  
JM Harlan
Keyword(s):  
Adhesion Molecules ◽  
Sufficient Information ◽  
Leukocyte Integrins ◽  
Endothelial Adhesion Molecules ◽  
And Migration ◽  
Definition Of ◽  
The Individual ◽  
Exciting Area

In the 9 years since the last review on leukocyte and endothelial interactions was published in this journal many of the critical structures involved in leukocyte adherence to and migration across endothelium have been elucidated. With the advent of cell and molecular biology approaches, investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of “anti-adhesion” therapy in humans. The molecular cloning and definition of the adhesive functions of the leukocyte integrins, endothelial members of the Ig gene superfamily, and the selectins has already provided sufficient information to construct an operative paradigm of the molecular basis of leukocyte emigration. The regulation of these adhesion molecules by chemoattractants, cytokines, or chemokines, and the interrelationships of adhesion pathways need to be examined in vitro and, particularly, in vivo. Additional studies are required to dissect the contribution of the individual adhesion molecules to leukocyte emigration in various models of inflammation or immune reaction. Certainly, new adhesion structures will be identified, and the current paradigm of leukocyte emigration will be refined. The promise of new insights into the biology and pathology of the inflammatory and immune response, and the potential for new therapies for a wide variety of diseases assures that this will continue to be an exciting area of investigation.

scholarly journals A SYSTEM OF MATHEMATICAL MODELS FOR THE SIMULATION OF MORPHOLOGICAL PROCESSES IN THE COASTAL AREA

1984 ◽  
Vol 1 (19) ◽  
pp. 98 ◽  
Author(s):  
S. Boer ◽  
H.J. De Vriend ◽  
H.G. Wind
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Coastal Area ◽  
Morphological Changes ◽  
Coastal Engineering ◽  
Coastal Processes ◽  
Morphological Processes ◽  
The Individual ◽  
Near Future

A compound mathematical model (COMOR) for the simulation of morphological changes in the coastal area is being developed. The model is very flexible; it can be composed according to the specific demands of the problem which is considered. So far the model is being applied in the advisory practice to predict initial morphological changes. Recent experiences have shown that the model is quite useful, although at present the knowledge of the individual coastal processes and their interactions is still insufficient to utilize it optimally. However, it is foreseen that in the near future such mathematical models will become a powerful tool in coastal engineering.

scholarly journals Leukocyte-endothelial adhesion molecules

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2068-2101 ◽  
Author(s):  
TM Carlos ◽  
JM Harlan
Keyword(s):  
Adhesion Molecules ◽  
Sufficient Information ◽  
Leukocyte Integrins ◽  
Endothelial Adhesion Molecules ◽  
And Migration ◽  
Definition Of ◽  
The Individual ◽  
Exciting Area

Abstract In the 9 years since the last review on leukocyte and endothelial interactions was published in this journal many of the critical structures involved in leukocyte adherence to and migration across endothelium have been elucidated. With the advent of cell and molecular biology approaches, investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of “anti-adhesion” therapy in humans. The molecular cloning and definition of the adhesive functions of the leukocyte integrins, endothelial members of the Ig gene superfamily, and the selectins has already provided sufficient information to construct an operative paradigm of the molecular basis of leukocyte emigration. The regulation of these adhesion molecules by chemoattractants, cytokines, or chemokines, and the interrelationships of adhesion pathways need to be examined in vitro and, particularly, in vivo. Additional studies are required to dissect the contribution of the individual adhesion molecules to leukocyte emigration in various models of inflammation or immune reaction. Certainly, new adhesion structures will be identified, and the current paradigm of leukocyte emigration will be refined. The promise of new insights into the biology and pathology of the inflammatory and immune response, and the potential for new therapies for a wide variety of diseases assures that this will continue to be an exciting area of investigation.

scholarly journals Mathematical Models for Cellular Organisms

1973 ◽  
Vol 2 (12) ◽  
Author(s):  
Brian H. Mayoh
Keyword(s):  
Mathematical Models ◽  
Final Section ◽  
Spatial Arrangement ◽  
Discrete Events ◽  
Von Neumann ◽  
Cellular Array ◽  
Higher Dimensional ◽  
A Cell ◽  
Definition Of ◽  
The Individual

During the life of a cellular organism, the individual cells grow, divide and die. Our aim in this paper is to examine various mathematical models that represent this process as a sequence of discrete events. <p>In section I and ll we give models in which the development of a cell is not affected by the spatial arrangement of the neighbouring cells. In section lll we drop this restriction for one-dimensional organisms to get the Lindenmayer model. The models in the remaining sections represent attempts to generalize the Lindenmayer model to higher dimensions. The Von-Neumann cellular array model of section IV proves unsatisfactory. The geographical models of section V, Vl and Vll are somewhat better for higher dimensional organisms. The final section gives a precise definition of a class of models, that includes those models presented earlier in the paper. The hope is that biologists will find these models suitable for describing real organisms and that mathematicians will be stimulated to prove biologically interesting theorems about them.</p>

scholarly journals A mathematical model for electrical activity in pig atrial tissue

2021 ◽  
Author(s):  
Victor Peris-Yague ◽  
Tony Rubio ◽  
Funsho E Fakuade ◽  
Niels Voigt ◽  
Stefan Luther ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Human Subjects ◽  
Animal Experiments ◽  
Spatiotemporal Chaos ◽  
Large Animal ◽  
Preclinical Research ◽  
Atrial Tissue

Atrial fibrillation (AF) is the most common sustained form of cardiac arrhythmia occurring in humans. Its effective treatment requires a detailed understanding of the underlying mechanisms at the genetic, molecular, cellular, tissue and organ levels. To study the complex mechanisms underlying the development, maintenance and termination of cardiac arrhythmias, we need preclinical research models. These models range from in vitro cell cultures to in vivo small and large animal hearts. However, translational research requires that the results of these animal experiments are understood in the context of human subjects. Currently, this is achieved through simulations with state-of-the-art mathematical models for human and animal heart tissue. In the context of AF, a model that is extensively used by experimentalists, is that of the pig atria. However, until now, an ionically detailed mathematical model for pig atrial tissue has been lacking, and researchers have been forced to rely on mathematical models from other animal species to understand their experimental observations. In this paper, we present the first ionically detailed mathematical model of porcine atrial electrophysiology. To build the model, we first fitted experimental patch-clamp data from literature to describe the individual currents flowing across the cell membrane. Later, we fine-tuned the model by fitting action potential duration restitution (APDR) curves for different repolarisation levels. The experimental data for the APDR studies was produced in N. Voigt’s lab. We extended our model to the tissue level and demonstrated the ability to maintain stable spiral waves. In agreement with previous experimental results, our model shows that early repolarisation is primarily driven by a calcium-mediated chloride current, IClCa, which is completely inactivated at high pacing frequencies. This is a condition found only in porcine atria. The model shows spatiotemporal chaos with reduced repolarisation.

Der manipulierbare Embryo: Konsequenzen für das Recht

2020 ◽  
Vol 28 (1) ◽  
pp. 53-82
Author(s):  
Hans-Georg Dederer
Keyword(s):  
Developmental Biology ◽  
Human Dignity ◽  
Legal Status ◽  
Basic Law ◽  
Legal Term ◽  
Embryo Protection Act ◽  
Definition Of ◽  
The Individual ◽  
Innovative Techniques

Innovative techniques of developmental biology facilitate the artificial creation of embryo-like entities. This contribution analyses, first, whether certain artificially created embryo-like entities are ‘embryos’ within the meaning of existing statutory law definitions laid down in the Embryo Protection Act, the Stem Cell Act and the Patent Act. These definitions are non-uniform and their interpretation and application with regard to artificially created embryo-like entities is not always conclusive. Accordingly, the legal definitions of the term ‘embryo’ should be harmonised and, thereby, adapted to the state of developmental biology. Any such legislative efforts need to be in conformity with the constitution, primarily with the guarantee of human dignity (Article 1‍(1) of the Basic Law). However, said provision cannot provide guidance to the legislature because the constitutional status of both embryos and embryo-like entities in vitro is highly disputed. It is held that this irresolvable debate is due to a fundamental lack of a widely shared experience that such entities possess a supreme unique value. This article argues that in such a situation it is, in the first instance, for the legislature (i. e. parliament) to determine the legal status of embryos and embryo-like entities in vitro. This argument is based on a particular doctrinal approach according to which the individual right to respect of one’s human dignity arising from Article 1‍(1) BL depends on recognition of the relevant entity as being a ‘human’ or a member of ‘humankind’ respectively. Such recognition has, hitherto, not been accomplished with a view to embryos and embryo-like entities in vitro. Against this backdrop, for the time being, the legislature may determine the legal status of embryos and embryo-like entities in vitro, lay down rules regarding their creation and particular use, and, especially, define the legal term ‘embryo’, albeit within some outer constitutional limits. The article, finally, analyses several elements of, and submits a proposal for, a new legal definition of the term ‘embryo’.

scholarly journals GENERALIZED MATHEMATICAL MODEL OF THE CALIBRATION PROCESSAND THE DIRECT MEASUREMENT OF THE PARAMETERS MULTIPOLE

2018 ◽  
Vol 9 (1) ◽  
pp. 96-105
Author(s):  
A. V. Gusinsky
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Matrix Form ◽  
Measuring System ◽  
Microwave Range ◽  
Measuring Systems ◽  
Error Matrix ◽  
Direct Measurements ◽  
The Matrix ◽  
Measurement Object

The quality of measuring systems of the microwave range, including vector network analyzers, largely depends on the reliability of calibration procedures and direct measurements, which allow to take into account information about the reproducible errors of measuring systems for subsequent correction. The aim of the paper is mathematical modeling of the errors of the measuring system for the generalized case for 2-n pole device.The problems of increasing the accuracy of measuring microwave systems due to compensation of systematic errors determined during calibration are considered. Calibration of measuring systems and correction of the results of direct measurements based on calibration results require the use of appropriate mathematical models of errors. Mathematical models of errors are represented in the form of multipolar errors, included between the object of measurement and the measuring system, which is assumed to be ideal, free of errors. The article proposes a generalized mathematical model of errors, described by a network of errors containing n ports connected to the n-port measuring system, and n ports connected to the n port of the measurement object. To obtain in general form the calibration equation for the 2n-port model of the error multipolar network, its transmission wave matrix [T], recorded in a cellular form, was used, and then a relationship was found between the measurement result in a matrix form with the cellular wave matrix T. A solution for finding the error matrix of matrix equation that connects the matrices known from the results of the corresponding attestation for the standards with the results of measurements during calibration in the matrix form. When solving this equation, a matrix product of «sandwich» type appears due to the cellular wave matrix [T]. The solution is possible when using the Kronecker product of two matrix, the matrix translation operator, the RS operator of the matrix, and the Gaussian elimination method. An equation is obtained for reconstructing the actual values of the scattering matrix of the measurement object, starting from the results of direct measurements in the matrix form and the error matrix. When solving the reconstruction equation, it is advisable to use a matrix inverse to the transmission matrix [T].The developed generalized mathematical model can be used, for example, when it is necessary to measure the parameters of complex microwave devices made on boards (wafer), with probe transitions to measuring ports, where it is important to consider the presence of additional microwave power leaks between ports.

scholarly journals Competitive Organizational Competences of the University

2021 ◽  
Vol 15 (3) ◽  
pp. 31-38
Author(s):  
Artem I. Vasilev ◽  
Keyword(s):  
Professional Activity ◽  
The Matrix ◽  
Organizational Ability ◽  
The One ◽  
Definition Of ◽  
The Individual ◽  
University Leaders ◽  
High Level ◽  
The University ◽  
Organizational Competence

The purpose of this article is to reveal the author’s definition of competitive organizational competencies and to offer a tool for its practical perception – a matrix of perception of competitive competencies. For this, the article reveals the terminological difference between competence and competence and confirms the existence of such a difference in relation to not only the individual, but also the university. With regard to the organization, it is also possible to distinguish the knowledge-resource-expert aspect of the organization’s activities and the functional-active aspect. The organization develops collective, distributed, internal abilities (organizational competence) to perform actions that constitute a specific, specific direction of activity (organizational competence). The work describes a matrix of perception of competitive competencies, specially developed by the author, and proposes to use it as an analytical tool for university leaders. The properties of competence, which, on the one hand, reflect its activity content (i.e., the connection with a specific professional activity), and, on the other hand, have a competitive value and make sense in the context of competitive confrontation, are of priority importance. The matrix reflects the degree of proximity of the competence to the core of the business and the degree of uniqueness and specificity of the competence. The matrix of perception of competitive competencies proposed by the author makes it possible to clearly clarify the key, competitive, sectoral, auxiliary (additional), unique competencies of the university. When defining competitive organizational competence, the author discloses two methodological ways to combine competitive and competence-based approaches: to understand competence as a means or as a goal of competition. The author defines competitive organizational competence as a unique organizational ability that cannot be copied by competitors, which allows it to withstand competition at a high level of competitiveness. In this understanding, competitive competencies are not the goal of competition, but a means of competition, an instrument of competition.

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