SimThyr is a free continuous

dynamic Dynamics (from Greek δυναμικός ''dynamikos'' "powerful", from δύναμις ''dynamis'' " power") or dynamic may refer to: Physics and engineering * Dynamics (mechanics) ** Aerodynamics, the study of the motion of air ** Analytical dyna ...

simulation A simulation is the imitation of the operation of a real-world process or system over time. Simulations require the use of models; the model represents the key characteristics or behaviors of the selected system or process, whereas the ...

program Program, programme, programmer, or programming may refer to: Business and management * Program management, the process of managing several related projects * Time management * Program, a part of planning Arts and entertainment Audio * Programm ...

for the pituitary-thyroid feedback control system. The

open-source Open source is source code that is made freely available for possible modification and redistribution. Products include permission to use the source code, design documents, or content of the product. The open-source model is a decentralized sof ...

program is based on a

nonlinear model In mathematics, nonlinear modelling is empirical or semi-empirical modelling which takes at least some nonlinearities into account. Nonlinear modelling in practice therefore means modelling of phenomena in which independent variables affecting the ...

of thyroid homeostasis. In addition to simulations in the

time domain Time domain refers to the analysis of mathematical functions, physical signals or time series of economic or environmental data, with respect to time. In the time domain, the signal or function's value is known for all real numbers, for the ...

the software supports various methods of

sensitivity analysis Sensitivity analysis is the study of how the uncertainty in the output of a mathematical model or system (numerical or otherwise) can be divided and allocated to different sources of uncertainty in its inputs. A related practice is uncertainty ana ...

. Its simulation engine is

multi-threaded In computer science, a thread of execution is the smallest sequence of programmed instructions that can be managed independently by a scheduler, which is typically a part of the operating system. The implementation of threads and processes dif ...

and supports multiple processor cores. SimThyr provides a

GUI The GUI ( "UI" by itself is still usually pronounced . or ), graphical user interface, is a form of user interface that allows users to interact with electronic devices through graphical icons and audio indicator such as primary notation, inste ...

, which allows for visualising

time series In mathematics, a time series is a series of data points indexed (or listed or graphed) in time order. Most commonly, a time series is a sequence taken at successive equally spaced points in time. Thus it is a sequence of discrete-time data. E ...

, modifying constant structure parameters of the

feedback loop Feedback occurs when outputs of a system are routed back as inputs as part of a chain of cause-and-effect that forms a circuit or loop. The system can then be said to ''feed back'' into itself. The notion of cause-and-effect has to be handled ...

(e.g. for simulation of certain diseases), storing parameter sets as

XML Extensible Markup Language (XML) is a markup language and file format for storing, transmitting, and reconstructing arbitrary data. It defines a set of rules for encoding documents in a format that is both human-readable and machine-readable. ...

files (referred to as "scenarios" in the software) and exporting results of simulations in various formats that are suitable for statistical software. SimThyr is intended for both

educational Education is a purposeful activity directed at achieving certain aims, such as transmitting knowledge or fostering skills and character traits. These aims may include the development of understanding, rationality, kindness, and honesty. Vari ...

purposes and in-silico research.

Mathematical model

The underlying model of thyroid homeostasis is based on fundamental biochemical, physiological and pharmacological principles, e.g. Michaelis-Menten kinetics, non-competitive inhibition and empirically justified

kinetic Kinetic (Ancient Greek: κίνησις “kinesis”, movement or to move) may refer to: * Kinetic theory, describing a gas as particles in random motion * Kinetic energy, the energy of an object that it possesses due to its motion Art and ente ...

parameters. The model has been validated in healthy controls and in cohorts of patients with

hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as ...

and

thyrotoxicosis Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...

Scientific uses

Multiple studies have employed SimThyr for in silico research on the control of

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The t ...

function. The original version was developed to check hypotheses about the generation of

pulsatile In fluid dynamics, a flow with periodic variations is known as pulsatile flow, or as Womersley flow. The flow profiles was first derived by John R. Womersley (1907–1958) in his work with blood flow in arteries. The cardiovascular system of chor ...

TSH release. Later and expanded versions of the software were used to develop the hypothesis of the TSH-T3 shunt in the hypothalamus-pituitary-thyroid axis, to assess the validity of calculated parameters of thyroid homeostasis (including

SPINA-GT Thyroid's secretory capacity (''GT'', also referred to as thyroid's incretory capacity, maximum thyroid hormone output, T4 output or, if calculated from serum levels of thyrotropin and thyroxine, as SPINA-GT) is the maximum stimulated amount of thy ...

and

SPINA-GD The sum activity of peripheral deiodinases (''GD'', also referred to as deiodination capacity, total deiodinase activity or, if calculated from levels of thyroid hormones, as SPINA-GD) is the maximum amount of triiodothyronine produced per time-uni ...

) and to study allostatic mechanisms leading to

non-thyroidal illness syndrome Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from ...

. SimThyr was also used to show that the release rate of thyrotropin is controlled by multiple factors other than T4 and that the relation between free T4 and TSH may be different in

euthyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyr ...

ism,

and

Public perception, reception and discussion of the software

SimThyr is

free Free may refer to: Concept * Freedom, having the ability to do something, without having to obey anyone/anything * Freethought, a position that beliefs should be formed only on the basis of logic, reason, and empiricism * Emancipate, to procur ...

and

software. This ensures the

source code In computing, source code, or simply code, is any collection of code, with or without comment (computer programming), comments, written using a human-readable programming language, usually as plain text. The source code of a Computer program, p ...

to be available, which facilitates scientific discussion and reviewing of the underlying model. Additionally, the fact that it is freely available may result in economical benefits. The software provides an editor that enables users to modify most structure parameters of the information processing structure. This functionality fosters simulation of several functional diseases of the thyroid and the pituitary gland. Parameter sets may be stored as MIRIAM- and

MIASE The minimum information about a simulation experiment (MIASE){{cite journal, author1=D. Waltemath , author2=Richard Adams , author3=Daniel A. Beard , author4=rank T. Bergmann , author5=Upinder S. Bhalla , author6=Randall Britten , author7=Vijayalak ...

-compliant XML files. On the other hand, the complexity of the user interface and the lack of the ability to model treatment effects have been criticized.

References

External links

* of the SimThyr project
Curated information at Zenodo

Curated information at SciCrunch
{{Authority control Free science software Free biosimulation software Medical simulation Free software programmed in Pascal Scientific simulation software Science software for macOS Science software for Windows Mathematical and theoretical biology Computational biology Cross-platform software Biomedical cybernetics Simulation software Human homeostasis Thyroid homeostasis

Mathematical model

Scientific uses

Public perception, reception and discussion of the software

See also

References

External links