{
    "info": {
        "author": "Alexis Pietak, Cecil Curry, et al.",
        "author_email": "alexis.pietak@gmail.com",
        "bugtrack_url": null,
        "classifiers": [
            "Development Status :: 5 - Production/Stable",
            "Environment :: Console",
            "Environment :: MacOS X",
            "Environment :: Win32 (MS Windows)",
            "Environment :: X11 Applications",
            "Intended Audience :: Science/Research",
            "License :: OSI Approved :: BSD License",
            "Natural Language :: English",
            "Operating System :: OS Independent",
            "Topic :: Scientific/Engineering :: Bio-Informatics"
        ],
        "description": ".. # ------------------( DIRECTIVES                         )------------------\n.. # Fallback language applied to all code blocks failing to specify an\n.. # explicit language. Since the majority of all code blocks in this document\n.. # are Bash one-liners intended to be run interactively, this is \"console\".\n.. # For a list of all supported languages, see also:\n.. #     http://build-me-the-docs-please.readthedocs.org/en/latest/Using_Sphinx/ShowingCodeExamplesInSphinx.html#pygments-lexers\n\n.. # FIXME: Sadly, this appears to be unsupported by some ReST parsers and hence\n.. # is disabled until more widely supported. *collective shrug*\n.. # highlight:: console\n\n.. # ------------------( SYNOPSIS                           )------------------\n\n=====\nBETSE\n=====\n\n**BETSE** (**B**\\ io\\ **E**\\ lectric **T**\\ issue **S**\\ imulation **E**\\\nngine) is an open-source cross-platform `discrete exterior calculus`_ simulator\nfor 2D computational multiphysics problems in the life sciences \u2013 including\nelectrodiffusion_, electro-osmosis_, galvanotaxis_, `voltage-gated ion\nchannels`_, `gene regulatory networks`_, and `biochemical reaction networks`_\n(e.g., metabolism).\n\nBETSE is `portably implemented <codebase_>`__ in pure `Python 3`_,\n`continuously stress-tested <testing_>`__ with GitLab-CI_ **\u00d7** Appveyor_ **+**\npy.test_, and `permissively distributed <License_>`__ under the `BSD 2-clause\nlicense`_.\n\n======\nBETSEE\n======\n\nBETSEE_ (\\ **BETSE E**\\ nvironment) is the official open-source cross-platform\ngraphical user interface (GUI) for BETSE. BETSEE_ wraps the low-level\ncommand-line interface (CLI) bundled with BETSE in a high-level interactive\nmodelling environment optimized for both new and advanced users alike.\n\nLike BETSE, BETSEE_ is `portably implemented <BETSEE codebase_>`__ in `Python\n3`_ and `permissively distributed <License_>`__ under the `BSD 2-clause\nlicense`_. Unlike BETSE, BETSEE_ leverages the industry-standard PySide2_-based\n`Qt 5 <Qt_>`_ application framework to deliver a modern scientific workflow.\n\n.. # ------------------( TABLE OF CONTENTS                  )------------------\n.. # Blank line. By default, Docutils appears to only separate the subsequent\n.. # table of contents heading from the prior paragraph by less than a single\n.. # blank line, hampering this table's readability and aesthetic comeliness.\n\n|\n\n.. # Table of contents, excluding the above document heading. While the\n.. # official reStructuredText documentation suggests that a language-specific\n.. # heading will automatically prepend this table, this does *NOT* appear to\n.. # be the case. Instead, this heading must be explicitly declared.\n\n.. contents:: **Contents**\n   :local:\n\n.. # ------------------( DESCRIPTION                        )------------------\n\nInstallation\n============\n\nBETSE currently supports **Linux**, **macOS**, and **Windows** out-of-the-box.\n\nSimple\n--------\n\nFor new users, BETSE is portably installable as follows:\n\n- [\\ *Windows*\\ ] Emulate **Ubuntu Linux** via the `Windows Subsystem for Linux\n  (WSL) <WSL_>`__. [#windows_not]_\n- Install the **Python 3.x** [#python2_not]_ (e.g., 3.6) variant of Anaconda_.\n  [#anaconda_not]_\n- Open a **Bash terminal.** [#terminal]_\n- Run the following commands.\n\n  - Enable conda-forge_.\n\n    .. code-block:: console\n\n       conda config --add channels conda-forge\n\n  - Install **BETSE.** [#conda_package]_\n\n    .. code-block:: console\n\n       conda install betse\n\n  - [\\ *Optional*\\ ] Test **BETSE.** [#test_command]_\n\n    .. code-block:: console\n\n       betse -v try\n\n.. [#windows_not]\n   The `Windows Subsystem for Linux (WSL) <WSL_>`__ and \u2013 hence BETSE itself \u2013\n   is *only* installable under **Windows 10.** Under older Windows versions,\n   BETSE may be installed from a `virtual Linux guest <VirtualBox_>`__.\n\n.. [#python2_not]\n   Do *not* install the **Python 2.7** variant of Anaconda_. BETSE requires\n   **Python 3.x.**\n\n.. [#anaconda_not]\n   If you prefer *not* to install Anaconda_, BETSE dependencies are also\n   `manually installable <Advanced_>`__ via your platform-specific package\n   manager (e.g., Homebrew_ on macOS, APT_ on Ubuntu Linux). Doing so is\n   non-trivial and, where performed incorrectly, could produce a\n   performance-crippled single-core installation of BETSE. Anaconda_ suffers no\n   such issues and is guaranteed to produce a performance-optimized multicore\n   installation of BETSE on *all* supported platforms. We strongly recommend\n   Anaconda_ \u2013 even when you think you know better.\n\n.. [#terminal]\n   To open a `POSIX`_\\ -compatible terminal under:\n\n   - **Windows:**\n\n     #. Install **Ubuntu Linux** via the `Windows Subsystem for Linux (WSL) <WSL_>`__.\n     #. Open an *Ubuntu Linux terminal.*\n\n   - **macOS:**\n\n     #. Open the *Finder*.\n     #. Open the *Applications* folder.\n     #. Open the *Utilities* folder.\n     #. Open *Terminal.app*.\n\n   - **Ubuntu Linux:**\n\n     #. Type ``Ctrl``\\ +\\ ``Alt``\\ +\\ ``t``.\n\n.. [#conda_package]\n\n   This command installs both the `most recent stable release of BETSE <conda\n   package_>`__ *and* all mandatory and most optional dependencies of this\n   release. Older stable releases are installable in a similar manner (e.g.,\n   ``conda install betse=0.7.0`` for BETSE 0.7.0). All `Anaconda packages`_ are\n   kindly hosted by the `non-profit conda-forge organization <conda-forge_>`__.\n\n.. [#test_command]\n\n   This test command:\n\n   #. Enables verbosity with the ``-v`` option, simplifying issue reporting in\n      the event of an unexpected error.\n   #. Creates a ``sample_sim/`` subdirectory in the current directory, providing\n      the default simulation for this release of BETSE. This includes *all*\n      configuration files and resources referenced by these files.\n   #. Runs all simulation phases (e.g., seed, initialization) of this simulation.\n\n   When finished, you may safely either:\n\n   - Remove this subdirectory.\n   - Rename this subdirectory (e.g., to ``my_sim/``) to serve as a basis for\n     subsequent simulations.\n   - Preserve this subdirectory as is.\n\nAdvanced\n--------\n\nFor developers and advanced users, *any* version of BETSE \u2013 including the live\nrepository and prior stable releases \u2013 is manually installable as follows:\n\n#. Install **Python 3.x** and `all dependencies <dependencies_>`__ required by\n   BETSE. Under:\n\n   - **Linux,** install `these dependencies <dependencies_>`__ via your\n     distribution-specific package manager (e.g., APT_ under Debian-based\n     distributions). Do *not* use ``pip``.\\ [#pip_not]_\n   - **macOS,** either:\n\n     - (\\ *Recommended*\\ ) Install the **Python 3.x** variant of Anaconda_.\n     - Or both:\n\n       #. Install a third-party package manager (e.g., Homebrew_, MacPorts_).\n          Apple does *not* provide a package manager out-of-the-box.\n       #. Install `these dependencies <dependencies_>`__ via that package\n          manager. Do *not* use ``pip``.\\ [#pip_not]_\n\n   - **Windows,** install the **Python 3.x** variant of Anaconda_.\\ [#windows]_\n\n#. Open a **terminal.**\n#. **Download** either:\n\n   - **The unstable BETSE repository** as follows:\n\n     #. Install Git_.\n     #. Clone the ``master`` branch of this repository.\n\n        .. code-block:: console\n\n           git clone https://gitlab.com/betse/betse.git\n\n     #. Prepare for installation.\n\n        .. code-block:: console\n\n           cd betse\n\n   - **Any stable BETSE release,** including the most recent, as follows:\n\n     #. Visit our `source tarball archive <tarballs_>`__.\n     #. Click the download icon to the right of the desired release and select\n        *Download tar.gz*.\n     #. Extract the downloaded tarball into the current directory.\n\n        .. code-block:: console\n\n           tar -xvzf betse-*.tar.gz\n\n     #. (\\ *Optional*\\ ) Remove this tarball.\n\n        .. code-block:: console\n\n           rm betse-*.tar.gz\n\n     #. Prepare for installation.\n\n        .. code-block:: console\n\n           cd betse-*\n\n#. **Install BETSE** either:\n\n   - (\\ *Recommended*\\ ) **Editably,** installing a cross-platform symbolic link\n     to the current BETSE codebase. Modifications to this code are applied\n     immediately *without* requiring reinstallation.\n\n     .. code-block:: console\n\n        sudo python3 setup.py develop\n\n   - **Non-editably,** installing a physical copy of the current BETSE codebase.\n     Modifications to this code are ignored and thus require reinstallation.\n\n     .. code-block:: console\n\n        sudo python3 setup.py install\n\n#. (\\ *Optional*\\ ) **Test BETSE,** running all modelling phases of a sample\n   simulation from a new directory.\n\n   .. code-block:: console\n\n      cd /tmp && betse try\n\n\n.. [#pip_not]\n   Do *not* install scientific dependencies (e.g., NumPy_, SciPy_) with either\n   ``pip`` or ``easy_install``; doing so typically degrades BETSE to single-core\n   performance. To optimize BETSE across multiple cores, *always* install these\n   dependencies with your platform-specific package manager (e.g., Homebrew_,\n   APT_).\n\n.. [#windows]\n   Unlike Linux and macOS, Anaconda_ is (\\ *effectively*\\ ) required under\n   Windows. Due to Microsoft's lack of support for `POSIX`_\\ -compliant\n   toolchains, *no* reasonable alternatives for installing multicore-aware\n   scientific dependencies exist.\n\nUsage\n============\n\nBasic\n-----\n\nBETSE installs the ``betse`` command, a low-level command line interface (CLI)\ndesigned for experienced users. The typical CLI-based workflow resembles:\n\n#. Create a default simulation configuration in a new ``my_sim/`` subdirectory\n   of the current directory.\n\n   .. code-block:: console\n\n      betse config my_sim/sim_config.yml\n\n#. [\\ *Optional*\\ ] Edit the new ``my_sim/sim_config.yml`` file with `your\n   favourite text editor <Atom_>`__.\n#. Create a pseudo-random cell cluster from this simulation configuration.\n\n   .. code-block:: console\n\n      betse seed my_sim/sim_config.yml\n\n#. [\\ *Optional*\\ ] Export all enabled plots, animations, and comma-separated\n   value (CSV) files from this cell cluster.\n\n   .. code-block:: console\n\n      betse plot seed my_sim/sim_config.yml\n\n#. Initialize (i.e., calculate steady-state concentrations for) this cell cluster.\n\n   .. code-block:: console\n\n      betse init my_sim/sim_config.yml\n\n#. [\\ *Optional*\\ ] Export all enabled plots, animations, and comma-separated\n   value (CSV) files from this initialization.\n\n   .. code-block:: console\n\n      betse plot init my_sim/sim_config.yml\n\n#. Simulate this initialized cell cluster.\n\n   .. code-block:: console\n\n      betse sim my_sim/sim_config.yml\n\n#. [\\ *Optional*\\ ] Export all enabled plots, animations, and comma-separated\n   value (CSV) files from this simulation.\n\n   .. code-block:: console\n\n      betse plot sim my_sim/sim_config.yml\n\nAlso note that our sister project BETSEE_ installs the ``betsee`` command, a\nhigh-level graphical user interface (GUI) designed for *all* users \u2013 regardless\nof prior experience or familiarity with the command line.\n\nExpert\n--------\n\nBETSE provides a variety of command-line options and subcommands in addition to\nthose synopsized above. The standalone ``betse`` and ``betse --help`` commands\ndescribe these options and subcommands as follows:\n\n.. code-block:: console\n\n   usage: betse [-h] [-v] [-V] [--log-file LOG_FILENAME]\n                [--log-level {all,debug,info,warning,error,critical,none}]\n                [--profile-type {none,call,size}]\n                [--profile-file PROFILE_FILENAME]\n                [--matplotlib-backend MATPLOTLIB_BACKEND_NAME]\n                {config,seed,init,sim,sim-grn,plot,info,try} ...\n\n   The BioElectric Tissue Simulation Engine (BETSE) is a discrete exterior\n   calculus simulator for 2D computational multiphysics problems in the life\n   sciences -- including electrodiffusion, electro-osmosis, galvanotaxis,\n   voltage-gated ion channels, gene regulatory networks, and biochemical\n   reaction networks.\n\n   optional arguments:\n     -h, --help            show this help message and exit\n     -v, --verbose         print and log all messages verbosely\n     -V, --version         print program version and exit\n     --log-file LOG_FILENAME\n                           file to log to (defaults to\n                           \"/home/leycec/.betse/betse.log\")\n     --log-level {all,debug,info,warning,error,critical,none}\n                           minimum level of messages to log to \"--log-file\"\n                           (defaults to \"info\") [overridden by \"--verbose\"]\n     --profile-type {none,call,size}\n                           type of profiling to perform (defaults to \"none\"):\n                           * \"none\", disabling profiling\n                           * \"call\", profiling callables (functions, methods)\n                           * \"size\", profiling object sizes (requires \"pympler\")\n     --profile-file PROFILE_FILENAME\n                           file to profile to unless \"--profile-type=none\"\n                           (defaults to \"/home/leycec/.betse/betse.prof\")\n     --matplotlib-backend MATPLOTLIB_BACKEND_NAME\n                           name of matplotlib backend to use (see: \"betse info\")\n\n   subcommands:\n   Exactly one of the following subcommands must be passed:\n\n     {config,seed,init,sim,sim-grn,plot,info,try}\n       config              create a default config file for BETSE simulations\n       seed                seed a new cell cluster for a config file\n       init                initialize a seeded cell cluster for a config file\n       sim                 simulate an initialized cell cluster for a config file\n       sim-grn             simulate a gene regulatory network for a config file\n       plot                plot an initialized or simulated simulation\n       info                print metadata synopsizing BETSE and current system\n       try                 create, init, simulate, and plot a sample simulation\n\n   subcommand help:\n\n   For help with a specific subcommand, pass the \"-h\" or \"--help\" option to that\n   subcommand. For example, for help with the \"config\" subcommand, run:\n\n       betse config --help\n\nDocumentation\n-------------\n\nBETSE also provides external documentation optimized for offline reading \u2013\ncomplete with explanatory examples, sample plots, and ample screenshots:\n\n- Official `BETSE 1.0 documentation`_. (\\ *PDF format; 75 pages.*\\ )\n- Official `BETSE 0.4 documentation`_. (\\ *PDF format; 72 pages.*\\ )\n- Official `BETSE 0.3 documentation`_. (\\ *PDF format; 77 pages.*\\ )\n\nTutorials\n---------\n\nBETSE provides a range of `hands-on tutorial materials <user_tutorial_>`__,\nincluding simulation files to run key published simulations, as well as a\n`Developer's Tutorial <dev_tutorial_>`__ demonstrating how to load and work\nwith BETSE modules, methods, and simulations in external code projects:\n\n- Official `BETSE Tutorial Simulation Packages <user_tutorial_>`__. (\\ *YAML\n  format.*\\ )\n- Official `BETSE Developer's Tutorial <dev_tutorial_>`__. (\\ *Jupyter\n  Notebook format.*\\ )\n\nIntroduction\n============\n\nBETSE simulates biorealistic electrochemical phenomena in `gap junction`_\\\n-networked 2D cellular collectives. To predict `bioelectric patterns\n<bioelectricity_>`__ and their spatio-temporal dynamics, BETSE:\n\n- Models `ion channel`_ and `gap junction`_ activity.\n- Tracks changes in ion concentration and net ionic charge.\n- Calculates endogenous voltages and currents.\n- Accepts simulation parameters, variables, and options as human-readable,\n  well-commented configuration files in YAML_ format.\n- Exports simulation results to a variety of output formats, including:\n\n  - Publication-quality:\n\n    - Plots, charts, and animations driven by Matplotlib_, the industry\n      standard for open-source plot visualization.\n    - `Directed graphs`_ (i.e., networks) driven by Graphviz_, the industry\n      standard for open-source graph visualization.\n\n  - Internet-friendly compressed video driven by any of various popular\n    open-source video encoders, including FFmpeg_, Libav_, and MEncoder_.\n  - Post-processable tabular data (e.g., `comma-separated values (CSV)\n    <comma-separated values_>`__).\n\n- Imports bitmask images defining the shapes of:\n\n  - Cell clusters.\n  - Cell cluster regions localizing `ion channel`_ activity, typically\n    signifying disparate types of adjacent tissue.\n\nTo assemble simple concepts into complex simulations, BETSE supplies a richly\nconfigurable, highly scalable biological toolset consisting of:\n\nIons\n----\n\nSimulations may enable arbitrary combinations of the principal ions implicated\nin bioelectrical signaling \u2013 including:\n\n- Sodium_ (*Na*\\ :sup:`+`).\n- Potassium_ (*K*\\ :sup:`+`).\n- Chloride_ (*Cl*\\ :sup:`-`).\n- Calcium_ (*Ca*\\ :sup:`2+`).\n- Hydrogen_ (*H*\\ :sup:`+`).\n- `Anionic proteins`_ (*P*\\ :sup:`-`).\n- Bicarbonate_ (*HCO*\\ :sup:`-`\\ :sub:`3`).\n\nIon Channels\n------------\n\nIndividual cells in simulations may enable arbitrary combinations of\n`voltage-gated ion channels`_, each implementing the `Hodgkin-Huxley (HH)\nformalism`_ with experimentally-derived parameters sourced from reputable\n`knowledge-based systems`_ (e.g., Channelpedia_). Explicitly supported channel\ntypes include:\n\n- HCN1_, HCN2_, and HCN4_.\n- `L-type Ca`_, `T-type Ca`_, and |P/Q-type Ca|_.\n- Kir2.1_.\n- Kv1.1_, Kv1.2_, Kv1.5_. Kv3.3_, and Kv3.4_.\n- Nav1.2_, Nav1.3_, and Nav1.6_.\n- `Leak <leak channels_>`__ and `ligand-gated channels`_, including:\n\n  - |Calcium-gated K+ channels|_.\n\nCustom ion channels parametrized by user-selected constants may be trivially\ndefined in the same manner (e.g., via a YAML_\\ -formatted configuration file).\n\nIon Pumps and Exchangers\n------------------------\n\nFor fine-grained control over cell dynamics, notable ion pumps and exchangers\nmay also be selectively enabled \u2013 including:\n\n- |Ca2+-ATPase|_.\n- |H+/K+-ATPase|_.\n- |Na+/K+-ATPase|_.\n- V-ATPase_.\n\nCustom ion pumps and exchangers parametrized by user-selected constants may be\ntrivially defined in the same manner (e.g., via a YAML_\\ -formatted\nconfiguration file).\n\nExtracellular Space\n-------------------\n\nCells form interconnected intracellular networks via voltage-sensitive `gap\njunction connections <gap junction_>`__ embedded within an `extracellular\nenvironment`_, maintained by `tight junctions`_ at the cell cluster periphery.\nSimulation of this environment enables exploration of `local field\npotentials`_, `transepithelial potential`_, and `ephaptic coupling`_ between\ncells.\n\nBiological Networks\n-------------------\n\nSimulation of `gene regulatory <gene regulatory networks_>`__ and `biochemical\nreaction networks`_ at both the cellular and mitochondrial level supports deep\nspatial analysis of otherwise intractable biological processes. Metabolism,\ndisease, aging, and other `genetic <genetics_>`__ and `epigenetic\n<epigenetics_>`__ phenomena commonly associated with quasi-`Big Data`_ are all\nvalid targets for exhaustive study with BETSE.\n\nTo integrate these potent control systems with bioelectrical signaling, the\n`activity <enzyme activity_>`__-modulated interaction between `gene products`_\nand similar biochemicals is fully integrated with `ion channels <ion\nchannel_>`__, `ion pumps`_, and `gap junctions`_.\n\nValidation\n==========\n\nBETSE is peer-reviewed software receiving continual evidence-based scrutiny.\nSimulation output is reproducibly synchronized with experimental observations on\n`membrane permeability`_, `resting potential`_, ion concentration, and similar\nreal-world biophysical quantities. Predictable outcomes have been demonstrated\nfor such well-known cases as:\n\n-  `Transmembrane voltage changes <transmembrane voltage_>`__ on perturbations\n   to single cell membrane states and environmental ion concentrations.\n-  `Transepithelial potential differences (TEPD) <transepithelial\n   potential_>`__.\n-  Bioelectrical signals at large-scale cellular wound sites.\n\nCitation\n========\n\nBETSE is formally described in our `introductory paper <2016 article_>`__.\nThird-party papers, theses, and other texts leveraging BETSE should ideally\ncite the following:\n\n    `Alexis Pietak`_ and `Michael Levin`_, 2016. |2016 article name|_\n    |2016 article supplement|_ [#supplement]_ |2016 journal name|_ *4*\\ (55).\n    :sup:`https://doi.org/10.3389/fbioe.2016.00055`\n\nSubsequent papers expanding the BETSE architecture with additional theory,\nexperimental results, and comparative metrics include:\n\n    * `Alexis Pietak`_ and `Michael Levin`_, 2017. |2017 article name|_\n      |2017 article supplement|_ [#supplement]_ |2017 journal name|_ *14*\\ (134),\n      p.20170425. :sup:`https://doi.org/10.1098/rsif.2017.0425`\n    * Vaibhav P. Pai, `Alexis Pietak`_, Valerie Willocq, Bin Ye, Nian-Qing Shi,\n      and `Michael Levin`_, 2018. |2018 hcn2 article name|_ |2018 hcn2 article\n      supplement|_ [#supplement]_ |2018 hcn2 journal name|_ *9*\\ (1), p.998.\n      :sup:`https://doi.org/10.1038/s41467-018-03334-5`\n    * Javier Cervera, `Alexis Pietak`_, `Michael Levin`_, and Salvador Mafe,\n      2018. |2018 coupling article name|_ |2018 coupling journal name|_ *128*,\n      pp.45\u201461. :sup:`https://doi.org/10.1016/j.bioelechem.2018.04.013`\n    * `Alexis Pietak`_ and `Michael Levin`_, 2018. |2018 review article name|_\n      |2018 review journal name|_\n      :sup:`https://doi.org/10.1016/j.pbiomolbio.2018.03.008`\n    * `Alexis Pietak`_, Johanna Bischof, Joshua LaPalme, Junji Morokuma, and\n      `Michael Levin`_, 2019. |2019 article name|_ |2019 journal name|_\n      :sup:`https://doi.org/10.1371/journal.pcbi.1006904`\n\n.. # FIXME: Add an image thumbnail for the first article above displaying the\n.. # cover image selected by the prior journal for that edition's cover article.\n\n.. # Note that, for unknown reasons, this footnote *MUST* be refenced above and\n.. # defined here rather than in the supplement replacements defined below.\n\n.. [#supplement]\n   This article's supplement extends the cursory theory presented by this\n   article with a rigorous treatment of the mathematics, formalisms, and\n   abstractions required to fully reproduce this work. If theoretical questions\n   remain after completing the main article, please consult this supplement.\n\nContact\n=======\n\nTo contact `Dr. Pietak`_, the principal developer of the BETSE codebase and\nfirst or second author of all above papers, cordially direct correspondence to\neither:\n\n* The `anonymous contact form <Organic Mechanics Contact_>`__ at `Organic\n  Mechanics`_, the personal archives of all material published to date by\n  `Dr. Pietak`_ \u2013 including papers, presentations, textbooks, and additional\n  theoretical work.\n* The personal e-mail account of `Dr. Pietak`_: [#e-mail]_\n\n  * *Username:* **alexis** ``{dot}`` **pietak**\n  * *Hostname:* **gmail** ``{dot}`` **com**\n\nTo report a software issue (e.g., bug, crash, or other unexpected behaviour)\n*or* request a new feature in BETSE, consider `submitting a new issue <issue\nsubmission_>`__ to our `issue tracker`_. Thanks in advance; it's only through\ngenerous user contributions that your user experience can continue to improve.\n\n.. [#e-mail]\n   To protect Dr. Pietak's e-mail address against `automated harvesting <e-mail\n   harvesting_>`__, this address has been intentionally obfuscated. Reconstruct\n   the original address by:\n\n   * Replacing the ``{dot}`` substring with the ``.`` charecter.\n   * Concatenating the username and hostname strings with the ``@`` character.\n\n   For this reason, consider directing correspondence to the `anonymous contact\n   form <Organic Mechanics Contact_>`__ at `Organic Mechanics`_ instead.\n\nAuthors\n=======\n\nBETSE comes courtesy a dedicated community of `authors <author list_>`__ and\ncontributors_ \u2013 without whom this project would be computationally impoverished,\nbiologically misaligned, and simply unusable.\n\n**Thanks, all.**\n\nFunding\n=======\n\nBETSE is currently independently financed as a volunteer open-source project.\nPrior grant funding sources include (in chronological order):\n\n#. For the five year period spanning 2015\u20142019, BETSE was graciously associated\n   with the `Paul Allen Discovery Center`_ at `Tufts University`_ and supported\n   by a `Paul Allen Discovery Center award`_ from the `Paul G. Allen Frontiers\n   Group`_ .\n\nSee Also\n========\n\nFor prospective users:\n\n-  `Installation <dependencies_>`__, detailing BETSE's installation with\n   exhaustive platform-specific instructions.\n\nFor prospective contributors:\n\n-  `Development <doc/md/DEVELOP.md>`__, detailing development of the BETSE\n   codebase \u2013 philosophy, workflow, and otherwise.\n-  `Testing <doc/md/TEST.md>`__, detailing testing of the BETSE codebase \u2013\n   `continuous integration`_, manual testing, and otherwise.\n-  `Freezing <doc/md/FREEZE.md>`__, detailing conversion of the BETSE codebase\n   into redistributable platform-specific executable binaries.\n\nLicense\n=======\n\nBETSE is open-source software `released <license_>`__ under the permissive `BSD\n2-clause license`_.\n\nThe logo prominently displayed on this `project page <project_>`__ is a flat\n`Noun Project`_ icon entitled `\"Cow,\" <Cows collection_>`__ `kindly released\n<Noun Project license_>`__ under the permissive `BSD-compatible <license\ncompatibility_>`__ `CC BY 3.0 license`_ by `Maxim Kulikov`_.\n\n.. # ------------------( LINKS ~ betse                      )------------------\n.. _codebase:\n   https://gitlab.com/betse/betse/tree/master\n.. _conda package:\n   https://anaconda.org/conda-forge/betse\n.. _contributors:\n   https://gitlab.com/betse/betse/graphs/master\n.. _issue submission:\n   https://gitlab.com/betse/betse/issues/new?issue%5Bassignee_id%5D=&issue%5Bmilestone_id%5D=\n.. _issue tracker:\n   https://gitlab.com/betse/betse/issues\n.. _project:\n   https://gitlab.com/betse/betse\n.. _testing:\n   https://gitlab.com/betse/betse/pipelines\n.. _tarballs:\n   https://gitlab.com/betse/betse/tags\n\n.. # ------------------( LINKS ~ betse : docs               )------------------\n.. _BETSE 1.0 documentation:\n   https://www.dropbox.com/s/3rsbrjq2ljal8dl/BETSE_Documentation_April10th2019.pdf?dl=0\n.. _BETSE 0.4 documentation:\n   https://www.dropbox.com/s/n8qfms2oks9cvv2/BETSE04_Documentation_Dec1st2016.pdf?dl=0\n.. _BETSE 0.3 documentation:\n   https://www.dropbox.com/s/fsxhjpipbiog0ru/BETSE_Documentation_Nov1st2015.pdf?dl=0\n\n.. # ------------------( LINKS ~ betse : local              )------------------\n.. _author list:\n   doc/md/AUTHORS.md\n.. _dev_tutorial:\n   doc/md/DEV_DEMO.md\n.. _user_tutorial:\n   doc/md/TUTORIALS.md\n.. _dependencies:\n   doc/md/INSTALL.md\n.. _license:\n   LICENSE\n\n.. # ------------------( LINKS ~ betsee                     )------------------\n.. _BETSEE:\n   https://gitlab.com/betse/betsee\n.. _BETSEE codebase:\n   https://gitlab.com/betse/betsee/tree/master\n\n.. # ------------------( LINKS ~ academia                   )------------------\n.. _Michael Levin:\n.. _Levin, Michael:\n   https://ase.tufts.edu/biology/labs/levin\n.. _Channelpedia:\n   http://channelpedia.epfl.ch\n.. _Paul Allen Discovery Center:\n   http://www.alleninstitute.org/what-we-do/frontiers-group/discovery-centers/allen-discovery-center-tufts-university\n.. _Paul Allen Discovery Center award:\n   https://www.alleninstitute.org/what-we-do/frontiers-group/news-press/press-resources/press-releases/paul-g-allen-frontiers-group-announces-allen-discovery-center-tufts-university\n.. _Paul G. Allen Frontiers Group:\n   https://www.alleninstitute.org/what-we-do/frontiers-group\n.. _Tufts University:\n   https://www.tufts.edu\n\n.. # ------------------( LINKS ~ academia : ally            )------------------\n.. _Alexis Pietak:\n.. _Pietak, Alexis:\n.. _Dr. Pietak:\n   https://www.researchgate.net/profile/Alexis_Pietak\n.. _Organic Mechanics:\n   https://www.omecha.org\n.. _Organic Mechanics Contact:\n   https://www.omecha.org/contact\n\n.. # ------------------( LINKS ~ paper : 2016               )------------------\n.. _2016 article:\n   http://journal.frontiersin.org/article/10.3389/fbioe.2016.00055/abstract\n\n.. |2016 article name| replace::\n   **Exploring instructive physiological signaling with the bioelectric tissue\n   simulation engine (BETSE).**\n.. _2016 article name:\n   http://journal.frontiersin.org/article/10.3389/fbioe.2016.00055/abstract\n\n.. |2016 article supplement| replace::\n   **(**\\ Supplement\\ **).**\n.. _2016 article supplement:\n   https://www.frontiersin.org/articles/file/downloadfile/203679_supplementary-materials_datasheets_1_pdf/octet-stream/Data%20Sheet%201.PDF/1/203679\n\n.. |2016 journal name| replace::\n   *Frontiers in Bioengineering and Biotechnology,*\n.. _2016 journal name:\n   http://journal.frontiersin.org/journal/bioengineering-and-biotechnology\n\n.. # ------------------( LINKS ~ paper ~ 2017               )------------------\n.. |2017 article name| replace::\n   **Bioelectric gene and reaction networks: computational modelling of genetic, biochemical and bioelectrical dynamics in pattern regulation.**\n.. _2017 article name:\n   http://rsif.royalsocietypublishing.org/content/14/134/20170425\n\n.. |2017 article supplement| replace::\n   **(**\\ Supplement\\ **).**\n.. _2017 article supplement:\n   https://figshare.com/collections/Supplementary_material_from_Bioelectric_gene_and_reaction_networks_computational_modelling_of_genetic_biochemical_and_bioelectrical_dynamics_in_pattern_regulation_/3878404\n\n.. |2017 journal name| replace::\n   *Journal of The Royal Society Interface,*\n.. _2017 journal name:\n   http://rsif.royalsocietypublishing.org\n\n.. # ------------------( LINKS ~ paper ~ 2018 : hcn2        )------------------\n.. |2018 hcn2 article name| replace::\n   **HCN2 rescues brain defects by enforcing endogenous voltage pre-patterns.**\n.. _2018 hcn2 article name:\n   https://www.nature.com/articles/s41467-018-03334-5\n\n.. |2018 hcn2 article supplement| replace::\n   **(**\\ Supplement\\ **).**\n.. _2018 hcn2 article supplement:\n   https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-018-03334-5/MediaObjects/41467_2018_3334_MOESM1_ESM.pdf\n\n.. |2018 hcn2 journal name| replace::\n   *Nature Communications.*\n.. _2018 hcn2 journal name:\n   https://www.nature.com\n\n.. # ------------------( LINKS ~ paper ~ 2018 : coupling    )------------------\n.. |2018 coupling article name| replace::\n   **Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach.**\n.. _2018 coupling article name:\n   https://www.sciencedirect.com/science/article/pii/S156753941830063X?via%3Dihub\n\n.. |2018 coupling journal name| replace::\n   *Bioelectrochemistry.*\n.. _2018 coupling journal name:\n   https://www.sciencedirect.com/journal/bioelectrochemistry\n\n.. # ------------------( LINKS ~ paper ~ 2018 : review      )------------------\n.. |2018 review article name| replace::\n   **Bioelectrical control of positional information in development and regeneration: A review of conceptual and computational advances.**\n.. _2018 review article name:\n   https://www.sciencedirect.com/science/article/pii/S0079610718300415\n\n.. |2018 review journal name| replace::\n   *Progress in Biophysics and Molecular Biology.*\n.. _2018 review journal name:\n   https://www.sciencedirect.com/journal/progress-in-biophysics-and-molecular-biology\n\n.. # ------------------( LINKS ~ paper ~ 2019               )------------------\n.. |2019 article name| replace::\n   **Neural control of body-plan axis in regenerating planaria.**\n.. _2019 article name:\n   https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006904\n\n.. |2019 journal name| replace::\n   *PLOS Computational Biology.*\n.. _2019 journal name:\n   https://journals.plos.org/ploscompbiol\n\n.. # ------------------( LINKS ~ science                    )------------------\n.. _bioelectricity:\n   https://en.wikipedia.org/wiki/Bioelectromagnetics\n.. _biochemical reaction networks:\n   http://www.nature.com/subjects/biochemical-reaction-networks\n.. _discrete exterior calculus:\n   https://en.wikipedia.org/wiki/Discrete_exterior_calculus\n.. _electrodiffusion:\n   https://en.wikipedia.org/wiki/Nernst%E2%80%93Planck_equation\n.. _electro-osmosis:\n   https://en.wikipedia.org/wiki/Electro-osmosis\n.. _enzyme activity:\n   https://en.wikipedia.org/wiki/Enzyme_assay\n.. _ephaptic coupling:\n   https://en.wikipedia.org/wiki/Ephaptic_coupling\n.. _epigenetics:\n   https://en.wikipedia.org/wiki/Epigenetics\n.. _extracellular environment:\n   https://en.wikipedia.org/wiki/Extracellular\n.. _finite volume:\n   https://en.wikipedia.org/wiki/Finite_volume_method\n.. _galvanotaxis:\n   https://en.wiktionary.org/wiki/galvanotaxis\n.. _gap junction:\n.. _gap junctions:\n   https://en.wikipedia.org/wiki/Gap_junction\n.. _gene products:\n   https://en.wikipedia.org/wiki/Gene_product\n.. _gene regulatory networks:\n   https://en.wikipedia.org/wiki/Gene_regulatory_network\n.. _genetics:\n   https://en.wikipedia.org/wiki/Genetics\n.. _genetic algorithms:\n   https://en.wikipedia.org/wiki/Genetic_algorithm\n.. _Hodgkin-Huxley (HH) formalism:\n   https://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model\n.. _local field potentials:\n   https://en.wikipedia.org/wiki/Local_field_potential\n.. _membrane permeability:\n   https://en.wikipedia.org/wiki/Cell_membrane\n.. _resting potential:\n   https://en.wikipedia.org/wiki/Resting_potential\n.. _tight junctions:\n   https://en.wikipedia.org/wiki/Tight_junction\n.. _transmembrane voltage:\n   https://en.wikipedia.org/wiki/Membrane_potential\n.. _transepithelial potential:\n   https://en.wikipedia.org/wiki/Transepithelial_potential_difference\n\n.. # ------------------( LINKS ~ science : ions             )------------------\n.. _anionic proteins:\n   https://en.wikipedia.org/wiki/Ion#anion\n.. _bicarbonate: https://en.wikipedia.org/wiki/Bicarbonate\n.. _calcium:     https://en.wikipedia.org/wiki/Calcium_in_biology\n.. _chloride:    https://en.wikipedia.org/wiki/Chloride\n.. _hydrogen:    https://en.wikipedia.org/wiki/Hydron_(chemistry)\n.. _sodium:      https://en.wikipedia.org/wiki/Sodium_in_biology\n.. _potassium:   https://en.wikipedia.org/wiki/Potassium_in_biology\n\n.. # ------------------( LINKS ~ science : channels         )------------------\n.. _ion channel:\n   https://en.wikipedia.org/wiki/Ion_channel\n.. _leak channels:\n   https://en.wikipedia.org/wiki/Leak_channel\n.. _ligand-gated channels:\n   https://en.wikipedia.org/wiki/Ligand-gated_ion_channel\n.. _voltage-gated ion channels:\n   https://en.wikipedia.org/wiki/Voltage-gated_ion_channel\n\n.. |calcium-gated K+ channels| replace::\n   Calcium-gated K\\ :sup:`+` channels\n.. _calcium-gated K+ channels:\n   https://en.wikipedia.org/wiki/Calcium-activated_potassium_channel\n\n.. # ------------------( LINKS ~ science : channels : type  )------------------\n.. _HCN1:   http://channelpedia.epfl.ch/ionchannels/61\n.. _HCN2:   http://channelpedia.epfl.ch/ionchannels/62\n.. _HCN4:   http://channelpedia.epfl.ch/ionchannels/64\n.. _Kir2.1: http://channelpedia.epfl.ch/ionchannels/42\n.. _Kv1.1:  http://channelpedia.epfl.ch/ionchannels/1\n.. _Kv1.2:  http://channelpedia.epfl.ch/ionchannels/2\n.. _Kv1.5:  http://channelpedia.epfl.ch/ionchannels/5\n.. _Kv3.3:  http://channelpedia.epfl.ch/ionchannels/13\n.. _Kv3.4:  http://channelpedia.epfl.ch/ionchannels/14\n.. _Nav1.2: http://channelpedia.epfl.ch/ionchannels/121\n.. _Nav1.3: http://channelpedia.epfl.ch/ionchannels/122\n.. _Nav1.6: http://channelpedia.epfl.ch/ionchannels/125\n.. _L-type Ca:   http://channelpedia.epfl.ch/ionchannels/212\n.. _T-type Ca:   https://en.wikipedia.org/wiki/T-type_calcium_channel\n\n.. |P/Q-type Ca| replace:: :sup:`P`\\ /\\ :sub:`Q`-type Ca\n.. _P/Q-type Ca:\n   http://channelpedia.epfl.ch/ionchannels/78\n\n.. # ------------------( LINKS ~ science : pumps : type     )------------------\n.. _ion pumps:\n   https://en.wikipedia.org/wiki/Active_transport\n\n.. # ------------------( LINKS ~ science : pumps : type     )------------------\n.. _V-ATPase: https://en.wikipedia.org/wiki/V-ATPase\n\n.. |Ca2+-ATPase| replace:: Ca\\ :sup:`2+`-ATPase\n.. _Ca2+-ATPase: https://en.wikipedia.org/wiki/Calcium_ATPase\n\n.. |H+/K+-ATPase| replace:: H\\ :sup:`+`/K\\ :sup:`+`-ATPase\n.. _H+/K+-ATPase: https://en.wikipedia.org/wiki/Hydrogen_potassium_ATPase\n\n.. |Na+/K+-ATPase| replace:: Na\\ :sup:`+`/K\\ :sup:`+`-ATPase\n.. _Na+/K+-ATPase: https://en.wikipedia.org/wiki/Na%2B/K%2B-ATPase\n\n.. # ------------------( LINKS ~ science : computer         )------------------\n.. _Big Data:\n   https://en.wikipedia.org/wiki/Big_data\n.. _comma-separated values:\n   https://en.wikipedia.org/wiki/Comma-separated_values\n.. _continuous integration:\n   https://en.wikipedia.org/wiki/Continuous_integration\n.. _directed graphs:\n   https://en.wikipedia.org/wiki/Directed_graph\n.. _e-mail harvesting:\n   https://en.wikipedia.org/wiki/Email_address_harvesting\n.. _genenic algorithms:\n   https://en.wikipedia.org/wiki/Genetic_algorithm\n.. _knowledge-based systems:\n   https://en.wikipedia.org/wiki/Knowledge-based_systems\n\n.. # 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------------------( LINKS ~ software : conda           )------------------\n.. _Anaconda:\n   https://www.anaconda.com/download\n.. _Anaconda packages:\n   https://anaconda.org\n.. _conda-forge:\n   https://conda-forge.org\n\n.. # ------------------( LINKS ~ software : pyside2         )------------------\n.. _PySide2:\n   https://wiki.qt.io/PySide2\n.. _PySide2 5.6:\n   https://code.qt.io/cgit/pyside/pyside.git/log/?h=5.6\n.. _PySide2 installation:\n   https://wiki.qt.io/PySide2_GettingStarted\n.. _PySide2 PPA:\n   https://launchpad.net/~thopiekar/+archive/ubuntu/pyside-git\n.. _Qt:\n   https://www.qt.io\n.. _Qt 5.6:\n   https://wiki.qt.io/Qt_5.6_Release\n\n.. # ------------------( LINKS ~ software : icons           )------------------\n.. _Cows collection:\n   https://thenounproject.com/maxim221/collection/cows\n.. _Maxim Kulikov:\n   https://thenounproject.com/maxim221\n.. _Noun Project:\n   https://thenounproject.com\n.. _Noun Project license:\n   https://thenounproject.com/legal\n\n.. # ------------------( LINKS ~ software : licenses        )------------------\n.. _license compatibility:\n   https://en.wikipedia.org/wiki/License_compatibility#Compatibility_of_FOSS_licenses\n.. _BSD 2-clause license:\n   https://opensource.org/licenses/BSD-2-Clause\n.. _CC BY 3.0 license:\n   https://creativecommons.org/licenses/by/3.0\n\n\n",
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