- Author:
- AnandR <a.rampadarath@auckland.ac.nz>
- Date:
- 2019-04-05 14:25:01+13:00
- Desc:
- Added some semgen annotated models (AnandR)
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/584/rawfile/ade7933153a72bb89e0b02d75db92d6e4be285f5/semgen_annotated_models/vasalou_2010.cellml
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<article>
<articleinfo>
<title>A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>This model runs in both OpenCell and COR to replicate the published results (figure 2). This CellML model translation is based on the curated SBML model in the BioModels database (BIOMD0000000246.xml) which in turn was based on the original author's Matlab code. Note that in order to replicate figure 2 the model has to be run for at least 200 hours to allow the oscillations to stabilise (and for 500 hours to clearly see the stablisation).</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>ABSTRACT: The suprachiasmatic nucleus (SCN) of the hypothalamus is a multicellular system that drives daily rhythms in mammalian behavior and physiology. Although the gene regulatory network that produces daily oscillations within individual neurons is well characterized, less is known about the electrophysiology of the SCN cells and how firing rate correlates with circadian gene expression. We developed a firing rate code model to incorporate known electrophysiological properties of SCN pacemaker cells, including circadian dependent changes in membrane voltage and ion conductances. Calcium dynamics were included in the model as the putative link between electrical firing and gene expression. Individual ion currents exhibited oscillatory patterns matching experimental data both in current levels and phase relationships. VIP and GABA neurotransmitters, which encode synaptic signals across the SCN, were found to play critical roles in daily oscillations of membrane excitability and gene expression. Blocking various mechanisms of intracellular calcium accumulation by simulated pharmacological agents (nimodipine, IP3- and ryanodine-blockers) reproduced experimentally observed trends in firing rate dynamics and core-clock gene transcription. The intracellular calcium concentration was shown to regulate diverse circadian processes such as firing frequency, gene expression and system periodicity. The model predicted a direct relationship between firing frequency and gene expression amplitudes, demonstrated the importance of intracellular pathways for single cell behavior and provided a novel multiscale framework which captured characteristics of the SCN at both the electrophysiological and gene regulatory levels.</para>
<para>The original paper reference is cited below:</para>
<para>
A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus, Vasalou C, Henson MA, 2010,
<emphasis>PLoS Computational Biology</emphasis>
, 6, e1000706.
<ulink url="http://www.ncbi.nlm.nih.gov/pubmed/20300645">PubMed ID: 20300645</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram1">
<mediaobject>
<imageobject>
<imagedata fileref="vasalou_henson_2010.png" />
</imageobject>
</mediaobject>
<caption>Schematic representation of the SCN neuron model</caption>
</informalfigure>
<informalfigure float="0" id="fig_cell_diagram1">
<mediaobject>
<imageobject>
<imagedata fileref="leloup_2003.png" />
</imageobject>
</mediaobject>
<caption>
Leloup and Goldbeter 2003 model for circadian oscillations in mammals involving interlocked negative and positive regulations of
<emphasis>Per</emphasis>
,
<emphasis>Cry</emphasis>
,
<emphasis>Bmal1</emphasis>
, and
<emphasis>Rev-Erb</emphasis>
genes by their protein products.
</caption>
</informalfigure>
</sect1>
</article>
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<times />
<ci>P_Na</ci>
<ci>Na_ex</ci>
</apply>
<apply>
<times />
<ci>P_Cl</ci>
<ci>Cl_in</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="c_calculation">
<eq />
<ci>c</ci>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>P_K</ci>
<ci>K_ex</ci>
</apply>
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>P_Ca</ci>
<ci>Ca_ex</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.001</cn>
</apply>
<apply>
<times />
<ci>P_Na</ci>
<ci>Na_ex</ci>
</apply>
<apply>
<times />
<ci>P_Cl</ci>
<ci>Cl_in</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="P_K_calculation">
<eq />
<ci>P_K</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_PK</ci>
<apply>
<power />
<apply>
<divide />
<ci>BC</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="nanoM">1</cn>
</apply>
<ci>npk</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_PK</ci>
<apply>
<power />
<apply>
<divide />
<ci>BC</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="nanoM">1</cn>
</apply>
<ci>npk</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Res_calculation">
<eq />
<ci>Res</ci>
<apply>
<divide />
<apply>
<times />
<ci>V_R</ci>
<ci>V_rest</ci>
</apply>
<apply>
<plus />
<ci>K_R</ci>
<ci>V_rest</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>K_in</ci>
<apply>
<divide />
<ci>K_ex</ci>
<ci>theta_K</ci>
</apply>
</apply>
<apply>
<eq />
<ci>Na_in</ci>
<apply>
<divide />
<ci>Na_ex</ci>
<ci>theta_Na</ci>
</apply>
</apply>
<apply>
<eq />
<ci>theta_K</ci>
<apply>
<exp />
<apply>
<divide />
<ci>E_K</ci>
<apply>
<times />
<ci>k_q</ci>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="milliV">1000.0</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>theta_Na</ci>
<apply>
<exp />
<apply>
<divide />
<ci>E_Na</ci>
<apply>
<times />
<ci>k_q</ci>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="milliV">1000.0</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>E_K</ci>
<apply>
<divide />
<apply>
<times />
<ci>E_K_0</ci>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
</apply>
<apply>
<plus />
<ci>T_room</ci>
<ci>T_abs</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>E_Na</ci>
<apply>
<divide />
<apply>
<times />
<ci>E_Na_0</ci>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
</apply>
<apply>
<plus />
<ci>T_room</ci>
<ci>T_abs</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>E_L</ci>
<apply>
<divide />
<apply>
<times />
<ci>E_L_0</ci>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
</apply>
<apply>
<plus />
<ci>T_room</ci>
<ci>T_abs</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>E_Ca</ci>
<apply>
<times />
<apply>
<divide />
<apply>
<times />
<ci>k_q</ci>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
</apply>
<apply>
<ln />
<apply>
<divide />
<ci>Ca_ex</ci>
<ci>Ca_in</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="milliV">1000.0</cn>
</apply>
</apply>
<apply>
<eq />
<ci>E_inhib</ci>
<apply>
<times />
<apply>
<minus />
<ci>k_q</ci>
</apply>
<apply>
<plus />
<ci>T</ci>
<ci>T_abs</ci>
</apply>
<apply>
<ln />
<apply>
<divide />
<ci>Cl_ex</ci>
<ci>Cl_in</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="milliV">1000.0</cn>
</apply>
</apply>
<apply id="i_Na_calculation">
<eq />
<ci>i_Na</ci>
<apply>
<times />
<ci>g_Na</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
<apply id="i_Na_abs_calculation">
<eq />
<ci>i_Na_abs</ci>
<apply>
<root />
<apply>
<power />
<ci>i_Na</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply id="g_K_calculation">
<eq />
<ci>g_K</ci>
<apply>
<plus />
<ci>g_K0</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_gk</ci>
<ci>MP</ci>
</apply>
<apply>
<plus />
<ci>K_gk</ci>
<ci>MP</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_K_calculation">
<eq />
<ci>i_K</ci>
<apply>
<times />
<ci>g_K</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply id="g_Ca_calculation">
<eq />
<ci>g_Ca</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_Ca</ci>
<apply>
<power />
<ci>MP</ci>
<ci>nca</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_Ca</ci>
<apply>
<power />
<ci>MP</ci>
<ci>nca</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_Ca_calculation">
<eq />
<ci>i_Ca</ci>
<apply>
<times />
<ci>g_Ca</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
<apply id="g_KCa_calculation">
<eq />
<ci>g_KCa</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_KCa</ci>
<apply>
<power />
<ci>CC</ci>
<ci>nkca</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_KCa</ci>
<apply>
<power />
<ci>CC</ci>
<ci>nkca</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_KCa_calculation">
<eq />
<ci>i_KCa</ci>
<apply>
<times />
<ci>g_KCa</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply id="g_L_calculation">
<eq />
<ci>g_L</ci>
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Res</ci>
</apply>
</apply>
<apply id="i_L_calculation">
<eq />
<ci>i_L</ci>
<apply>
<times />
<ci>g_L</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_L</ci>
</apply>
</apply>
</apply>
<apply id="g_ex_calculation">
<eq />
<ci>g_ex</ci>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>v_ex1</ci>
<apply>
<power />
<ci>i_Na_abs</ci>
<ci>nex1</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_ex1</ci>
<apply>
<power />
<ci>i_Na_abs</ci>
<ci>nex1</ci>
</apply>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>v_ex2</ci>
<apply>
<power />
<ci>Ca_in</ci>
<ci>nex2</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_ex2</ci>
<apply>
<power />
<ci>Ca_in</ci>
<ci>nex2</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="i_ex_calculation">
<eq />
<ci>i_ex</ci>
<apply>
<times />
<ci>g_ex</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_ex</ci>
</apply>
</apply>
</apply>
<apply id="i_inhib_calculation">
<eq />
<ci>i_inhib</ci>
<apply>
<times />
<ci>g_inhib</ci>
<apply>
<minus />
<ci>V_rest</ci>
<ci>E_inhib</ci>
</apply>
</apply>
</apply>
<apply id="GABA_calculation">
<eq />
<ci>GABA</ci>
<apply>
<plus />
<ci>GABA0</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_GABA</ci>
<ci>VIP</ci>
</apply>
<apply>
<plus />
<ci>K_GABA</ci>
<ci>VIP</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_calculation">
<eq />
<ci>beta</ci>
<apply>
<divide />
<ci>VIP</ci>
<apply>
<plus />
<ci>VIP</ci>
<ci>K_D</ci>
</apply>
</apply>
</apply>
<apply id="v_sPC_calculation">
<eq />
<ci>v_sPC</ci>
<apply>
<plus />
<ci>v_sP0</ci>
<apply>
<divide />
<apply>
<times />
<ci>C_T</ci>
<ci>CB</ci>
</apply>
<apply>
<plus />
<ci>K_C</ci>
<ci>CB</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Cl_in_calculation">
<eq />
<ci>Cl_in</ci>
<apply>
<plus />
<ci>Cl0</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_Cl1</ci>
<ci>MP</ci>
</apply>
<apply>
<plus />
<ci>K_Cl1</ci>
<ci>MP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>v_Cl2</ci>
<apply>
<power />
<ci>GABA</ci>
<ci>nCl</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_Cl2</ci>
<apply>
<power />
<ci>GABA</ci>
<ci>nCl</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="V_K_calculation">
<eq />
<ci>V_K</ci>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V_MK</ci>
<ci>Ca_in</ci>
</apply>
<apply>
<plus />
<ci>k_MK</ci>
<ci>Ca_in</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>V_b</ci>
<ci>beta</ci>
</apply>
<apply>
<plus />
<ci>k_b</ci>
<ci>beta</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ca_in" cmeta:id="Ca_in">
<variable cmeta:id="Ca_in.Ca_in" initial_value="0.1" name="Ca_in" public_interface="out" units="microM" />
<variable cmeta:id="Ca_in.beta_IP3" initial_value="0.5" name="beta_IP3" units="dimensionless" />
<variable cmeta:id="Ca_in.Ca_store" initial_value="0.1" name="Ca_store" units="nanoM" />
<variable cmeta:id="Ca_in.v0" name="v0" units="microM_per_hour" />
<variable cmeta:id="Ca_in.v1" name="v1" units="microM_per_hour" />
<variable cmeta:id="Ca_in.v2" name="v2" units="microM_per_hour" />
<variable cmeta:id="Ca_in.v3" name="v3" units="microM_per_hour" />
<variable cmeta:id="Ca_in.v_kk" initial_value="3.3" name="v_kk" units="per_microM_per_hour" />
<variable cmeta:id="Ca_in.v_v0" initial_value="0.09" name="v_v0" units="microM_per_hour" />
<variable cmeta:id="Ca_in.kf" initial_value="0.001" name="kf" units="per_hour" />
<variable cmeta:id="Ca_in.k" name="k" units="per_microM_per_hour" />
<variable cmeta:id="Ca_in.nkk" initial_value="0.1" name="nkk" units="dimensionless" />
<variable cmeta:id="Ca_in.nv0" initial_value="4.5" name="nv0" units="dimensionless" />
<variable cmeta:id="Ca_in.m" initial_value="6.0" name="m" units="dimensionless" />
<variable cmeta:id="Ca_in.n" initial_value="2.2" name="n" units="dimensionless" />
<variable cmeta:id="Ca_in.p" initial_value="4.2" name="p" units="dimensionless" />
<variable cmeta:id="Ca_in.v" initial_value="2.0" name="v" units="dimensionless" />
<variable cmeta:id="Ca_in.K_kk" initial_value="0.02" name="K_kk" units="nanoM_0_1" />
<variable cmeta:id="Ca_in.K_v0" initial_value="4.5" name="K_v0" units="nanoM_4_5" />
<variable cmeta:id="Ca_in.K_2" initial_value="5.0" name="K_2" units="microM" />
<variable cmeta:id="Ca_in.K_R" initial_value="3.0" name="K_R" units="microM" />
<variable cmeta:id="Ca_in.K_A" initial_value="0.67" name="K_A" units="microM" />
<variable cmeta:id="Ca_in.v_M1" initial_value="0.0003" name="v_M1" units="microM_per_hour" />
<variable cmeta:id="Ca_in.v_M2" initial_value="149.5" name="v_M2" units="microM_per_hour" />
<variable cmeta:id="Ca_in.v_M3" initial_value="400.0" name="v_M3" units="microM_per_hour" />
<variable cmeta:id="Ca_in.time" name="time" public_interface="in" units="hour" />
<variable cmeta:id="Ca_in.MP" name="MP" public_interface="in" units="nanoM" />
<variable cmeta:id="Ca_in.CC" name="CC" public_interface="in" units="nanoM" />
<variable cmeta:id="Ca_in.BC" name="BC" public_interface="in" units="nanoM" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Ca_diff_eq">
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_in</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<ci>v0</ci>
<ci>v1</ci>
<ci>v3</ci>
<apply>
<times />
<ci>kf</ci>
<ci>Ca_store</ci>
</apply>
</apply>
<apply>
<plus />
<ci>v2</ci>
<apply>
<times />
<ci>k</ci>
<apply>
<power />
<ci>Ca_in</ci>
<ci>v</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="Ca_store_diff_eq">
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_store</ci>
</apply>
<apply>
<minus />
<ci>v2</ci>
<apply>
<plus />
<ci>v3</ci>
<apply>
<times />
<ci>kf</ci>
<ci>Ca_store</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="k_calculation">
<eq />
<ci>k</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_kk</ci>
<apply>
<power />
<ci>CC</ci>
<ci>nkk</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_kk</ci>
<apply>
<power />
<ci>CC</ci>
<ci>nkk</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="v0_calculation">
<eq />
<ci>v0</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_v0</ci>
<apply>
<power />
<ci>BC</ci>
<ci>nv0</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_v0</ci>
<apply>
<power />
<ci>BC</ci>
<ci>nv0</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="v1_calculation">
<eq />
<ci>v1</ci>
<apply>
<times />
<ci>v_M1</ci>
<ci>beta_IP3</ci>
</apply>
</apply>
<apply id="v2_calculation">
<eq />
<ci>v2</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_M2</ci>
<apply>
<power />
<ci>Ca_in</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>K_2</ci>
<ci>n</ci>
</apply>
<apply>
<power />
<ci>Ca_in</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="v3_calculation">
<eq />
<ci>v3</ci>
<apply>
<divide />
<apply>
<times />
<apply>
<divide />
<apply>
<times />
<ci>v_M3</ci>
<apply>
<power />
<ci>Ca_store</ci>
<ci>m</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>K_R</ci>
<ci>m</ci>
</apply>
<apply>
<power />
<ci>Ca_store</ci>
<ci>m</ci>
</apply>
</apply>
</apply>
<apply>
<power />
<ci>Ca_in</ci>
<ci>p</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>K_A</ci>
<ci>p</ci>
</apply>
<apply>
<power />
<ci>Ca_in</ci>
<ci>p</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="VIP" cmeta:id="VIP">
<variable cmeta:id="VIP.VIP" initial_value="0.0" name="VIP" public_interface="out" units="nanoM" />
<variable cmeta:id="VIP.v_VIP" initial_value="0.5" name="v_VIP" units="flux" />
<variable cmeta:id="VIP.K_VIP" initial_value="15.0" name="K_VIP" units="hertz_1_9" />
<variable cmeta:id="VIP.kd_VIP" initial_value="0.5" name="kd_VIP" units="nanoM_0_8_per_hour" />
<variable cmeta:id="VIP.nd_VIP" initial_value="0.2" name="nd_VIP" units="dimensionless" />
<variable cmeta:id="VIP.n_VIP" initial_value="1.9" name="n_VIP" units="dimensionless" />
<variable cmeta:id="VIP.time" name="time" public_interface="in" units="hour" />
<variable cmeta:id="VIP.fr" name="fr" public_interface="in" units="hertz" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="VIP_diff_eq">
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>VIP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>v_VIP</ci>
<apply>
<power />
<ci>fr</ci>
<ci>n_VIP</ci>
</apply>
</apply>
<apply>
<plus />
<ci>K_VIP</ci>
<apply>
<power />
<ci>fr</ci>
<ci>n_VIP</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<ci>kd_VIP</ci>
<apply>
<power />
<ci>VIP</ci>
<ci>nd_VIP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MP" cmeta:id="MP">
<variable cmeta:id="MP_MP" initial_value="2.8" name="MP" public_interface="out" units="nanoM" />
<variable cmeta:id="MP.vmP" initial_value="1.1" name="vmP" units="flux" />
<variable cmeta:id="MP.kdmp" initial_value="0.01" name="kdmp" units="first_order_rate_constant" />
<variable cmeta:id="MP.KAP" initial_value="0.6" name="KAP" units="nanoM" />
<variable cmeta:id="MP.KmP" initial_value="0.31" name="KmP" units="nanoM" />
<variable cmeta:id="MP.n" name="n" public_interface="in" units="dimensionless" />
<variable cmeta:id="MP.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="MP.time" name="time" public_interface="in" units="hour" />
<variable cmeta:id="MP.v_sPC" name="v_sPC" public_interface="in" units="flux" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>MP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>v_sPC</ci>
<apply>
<power />
<ci>BN</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>KAP</ci>
<ci>n</ci>
</apply>
<apply>
<power />
<ci>BN</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>vmP</ci>
<ci>MP</ci>
</apply>
<apply>
<plus />
<ci>KmP</ci>
<ci>MP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdmp</ci>
<ci>MP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MC" cmeta:id="MC">
<variable cmeta:id="MC_MC" initial_value="2.0" name="MC" public_interface="out" units="nanoM" />
<variable cmeta:id="MC.vsC" initial_value="1.1" name="vsC" units="flux" />
<variable cmeta:id="MC.vmC" initial_value="1.0" name="vmC" units="flux" />
<variable cmeta:id="MC.kdmc" initial_value="0.01" name="kdmc" units="first_order_rate_constant" />
<variable cmeta:id="MC.KAC" initial_value="0.6" name="KAC" units="nanoM" />
<variable cmeta:id="MC.KmC" initial_value="0.4" name="KmC" units="nanoM" />
<variable cmeta:id="MC.n" name="n" public_interface="in" units="dimensionless" />
<variable cmeta:id="MC.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="MC.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>MC</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>vsC</ci>
<apply>
<power />
<ci>BN</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>KAC</ci>
<ci>n</ci>
</apply>
<apply>
<power />
<ci>BN</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>vmC</ci>
<ci>MC</ci>
</apply>
<apply>
<plus />
<ci>KmC</ci>
<ci>MC</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdmc</ci>
<ci>MC</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MB" cmeta:id="MB">
<variable cmeta:id="MB_MB" initial_value="7.94" name="MB" public_interface="out" units="nanoM" />
<variable cmeta:id="MB.vsB" initial_value="1.0" name="vsB" units="flux" />
<variable cmeta:id="MB.vmB" initial_value="0.8" name="vmB" units="flux" />
<variable cmeta:id="MB.kdmb" initial_value="0.01" name="kdmb" units="first_order_rate_constant" />
<variable cmeta:id="MB.KIB" initial_value="2.2" name="KIB" units="nanoM" />
<variable cmeta:id="MB.KmB" initial_value="0.4" name="KmB" units="nanoM" />
<variable cmeta:id="MB.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="MB.m" name="m" public_interface="in" units="dimensionless" />
<variable cmeta:id="MB.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>MB</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>vsB</ci>
<apply>
<power />
<ci>KIB</ci>
<ci>m</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>KIB</ci>
<ci>m</ci>
</apply>
<apply>
<power />
<ci>BN</ci>
<ci>m</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>vmB</ci>
<ci>MB</ci>
</apply>
<apply>
<plus />
<ci>KmB</ci>
<ci>MB</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdmb</ci>
<ci>MB</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PC" cmeta:id="PC">
<variable cmeta:id="PC_PC" initial_value="0.4" name="PC" public_interface="out" units="nanoM" />
<variable cmeta:id="PC.ksP" name="ksP" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PC.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="PC.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="PC.k3" name="k3" public_interface="in" units="second_order_rate_constant" />
<variable cmeta:id="PC.k4" name="k4" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PC.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PC.V1P" name="V1P" public_interface="in" units="flux" />
<variable cmeta:id="PC.V2P" name="V2P" public_interface="in" units="flux" />
<variable cmeta:id="PC.PCP" name="PCP" public_interface="in" units="nanoM" />
<variable cmeta:id="PC.PCC" name="PCC" public_interface="in" units="nanoM" />
<variable cmeta:id="PC.CC" name="CC" public_interface="in" units="nanoM" />
<variable cmeta:id="PC.MP" name="MP" public_interface="in" units="nanoM" />
<variable cmeta:id="PC.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>PC</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>ksP</ci>
<ci>MP</ci>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>V2P</ci>
<ci>PCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>PCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>k4</ci>
<ci>PCC</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V1P</ci>
<ci>PC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>PC</ci>
</apply>
</apply>
<apply>
<times />
<ci>k3</ci>
<ci>PC</ci>
<ci>CC</ci>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>PC</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="CC" cmeta:id="CC">
<variable cmeta:id="CC_CC" initial_value="12.0" name="CC" public_interface="out" units="nanoM" />
<variable cmeta:id="CC.ksC" name="ksC" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="CC.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="CC.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="CC.k3" name="k3" public_interface="in" units="second_order_rate_constant" />
<variable cmeta:id="CC.k4" name="k4" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="CC.kdnc" name="kdnc" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="CC.V1C" name="V1C" public_interface="in" units="flux" />
<variable cmeta:id="CC.V2C" name="V2C" public_interface="in" units="flux" />
<variable cmeta:id="CC.CCP" name="CCP" public_interface="in" units="nanoM" />
<variable cmeta:id="CC.PC" name="PC" public_interface="in" units="nanoM" />
<variable cmeta:id="CC.PCC" name="PCC" public_interface="in" units="nanoM" />
<variable cmeta:id="CC.MC" name="MC" public_interface="in" units="nanoM" />
<variable cmeta:id="CC.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>CC</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>ksC</ci>
<ci>MC</ci>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>V2C</ci>
<ci>CCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>CCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>k4</ci>
<ci>PCC</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V1C</ci>
<ci>CC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>CC</ci>
</apply>
</apply>
<apply>
<times />
<ci>k3</ci>
<ci>PC</ci>
<ci>CC</ci>
</apply>
<apply>
<times />
<ci>kdnc</ci>
<ci>CC</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCP" cmeta:id="PCP">
<variable cmeta:id="PCP_PCP" initial_value="0.13" name="PCP" public_interface="out" units="nanoM" />
<variable cmeta:id="PCP.vdPC" name="vdPC" public_interface="in" units="flux" />
<variable cmeta:id="PCP.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCP.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCP.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="PCP.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCP.V1P" name="V1P" public_interface="in" units="flux" />
<variable cmeta:id="PCP.V2P" name="V2P" public_interface="in" units="flux" />
<variable cmeta:id="PCP.PC" name="PC" public_interface="in" units="nanoM" />
<variable cmeta:id="PCP.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>PCP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V1P</ci>
<ci>PC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>PC</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V2P</ci>
<ci>PCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>PCP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdPC</ci>
<ci>PCP</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>PCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>PCP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="CCP" cmeta:id="CCP">
<variable cmeta:id="CCP_CCP" initial_value="9.0" name="CCP" public_interface="out" units="nanoM" />
<variable cmeta:id="CCP.vdCC" name="vdCC" public_interface="in" units="flux" />
<variable cmeta:id="CCP.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="CCP.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="CCP.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="CCP.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="CCP.V1C" name="V1C" public_interface="in" units="flux" />
<variable cmeta:id="CCP.V2C" name="V2C" public_interface="in" units="flux" />
<variable cmeta:id="CCP.CC" name="CC" public_interface="in" units="nanoM" />
<variable cmeta:id="CCP.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>CCP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V1C</ci>
<ci>CC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>CC</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V2C</ci>
<ci>CCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>CCP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdCC</ci>
<ci>CCP</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>CCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>CCP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCC" cmeta:id="PCC">
<variable cmeta:id="PCC_PCC" initial_value="1.26" name="PCC" public_interface="out" units="nanoM" />
<variable cmeta:id="PCC.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCC.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCC.k1" name="k1" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCC.k2" name="k2" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCC.k3" name="k3" public_interface="in" units="second_order_rate_constant" />
<variable cmeta:id="PCC.k4" name="k4" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCC.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCC.V1PC" name="V1PC" public_interface="in" units="flux" />
<variable cmeta:id="PCC.V2PC" name="V2PC" public_interface="in" units="flux" />
<variable cmeta:id="PCC.PCCP" name="PCCP" public_interface="in" units="nanoM" />
<variable cmeta:id="PCC.PCN" name="PCN" public_interface="in" units="nanoM" />
<variable cmeta:id="PCC.PC" name="PC" public_interface="in" units="nanoM" />
<variable cmeta:id="PCC.CC" name="CC" public_interface="in" units="nanoM" />
<variable cmeta:id="PCC.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>PCC</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V2PC</ci>
<ci>PCCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>PCCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>k3</ci>
<ci>PC</ci>
<ci>CC</ci>
</apply>
<apply>
<times />
<ci>k2</ci>
<ci>PCN</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V1PC</ci>
<ci>PCC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>PCC</ci>
</apply>
</apply>
<apply>
<times />
<ci>k4</ci>
<ci>PCC</ci>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>PCC</ci>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>PCC</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCN" cmeta:id="PCN">
<variable cmeta:id="PCN_PCN" initial_value="0.16" name="PCN" public_interface="out" units="nanoM" />
<variable cmeta:id="PCN.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCN.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCN.k1" name="k1" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCN.k2" name="k2" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCN.k7" name="k7" public_interface="in" units="second_order_rate_constant" />
<variable cmeta:id="PCN.k8" name="k8" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCN.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCN.V3PC" name="V3PC" public_interface="in" units="flux" />
<variable cmeta:id="PCN.V4PC" name="V4PC" public_interface="in" units="flux" />
<variable cmeta:id="PCN.PCNP" name="PCNP" public_interface="in" units="nanoM" />
<variable cmeta:id="PCN.PCC" name="PCC" public_interface="in" units="nanoM" />
<variable cmeta:id="PCN.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="PCN.IN" name="IN" public_interface="in" units="nanoM" />
<variable cmeta:id="PCN.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>PCN</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V4PC</ci>
<ci>PCNP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>PCNP</ci>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>PCC</ci>
</apply>
<apply>
<times />
<ci>k8</ci>
<ci>IN</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V3PC</ci>
<ci>PCN</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>PCN</ci>
</apply>
</apply>
<apply>
<times />
<ci>k2</ci>
<ci>PCN</ci>
</apply>
<apply>
<times />
<ci>k7</ci>
<ci>BN</ci>
<ci>PCN</ci>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>PCN</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCCP" cmeta:id="PCCP">
<variable cmeta:id="PCCP_PCCP" initial_value="0.2" name="PCCP" public_interface="out" units="nanoM" />
<variable cmeta:id="PCCP.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCCP.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCCP.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="PCCP.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCCP.V1PC" name="V1PC" public_interface="in" units="flux" />
<variable cmeta:id="PCCP.V2PC" name="V2PC" public_interface="in" units="flux" />
<variable cmeta:id="PCCP.vdPCC" name="vdPCC" public_interface="in" units="flux" />
<variable cmeta:id="PCCP.PCC" name="PCC" public_interface="in" units="nanoM" />
<variable cmeta:id="PCCP.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>PCCP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V1PC</ci>
<ci>PCC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>PCC</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V2PC</ci>
<ci>PCCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>PCCP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdPCC</ci>
<ci>PCCP</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>PCCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>PCCP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCNP" cmeta:id="PCNP">
<variable cmeta:id="PCNP_PCNP" initial_value="0.091" name="PCNP" public_interface="out" units="nanoM" />
<variable cmeta:id="PCNP.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCNP.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="PCNP.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="PCNP.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="PCNP.V3PC" name="V3PC" public_interface="in" units="flux" />
<variable cmeta:id="PCNP.V4PC" name="V4PC" public_interface="in" units="flux" />
<variable cmeta:id="PCNP.vdPCN" name="vdPCN" public_interface="in" units="flux" />
<variable cmeta:id="PCNP.PCN" name="PCN" public_interface="in" units="nanoM" />
<variable cmeta:id="PCNP.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>PCNP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V3PC</ci>
<ci>PCN</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>PCN</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V4PC</ci>
<ci>PCNP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>PCNP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdPCN</ci>
<ci>PCNP</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>PCNP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>PCNP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="BC" cmeta:id="BC">
<variable cmeta:id="BC_BC" initial_value="2.41" name="BC" public_interface="out" units="nanoM" />
<variable cmeta:id="BC.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="BC.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="BC.ksB" name="ksB" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BC.k5" name="k5" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BC.k6" name="k6" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BC.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BC.V1B" name="V1B" public_interface="in" units="flux" />
<variable cmeta:id="BC.V2B" name="V2B" public_interface="in" units="flux" />
<variable cmeta:id="BC.MB" name="MB" public_interface="in" units="nanoM" />
<variable cmeta:id="BC.BCP" name="BCP" public_interface="in" units="nanoM" />
<variable cmeta:id="BC.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="BC.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>BC</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V2B</ci>
<ci>BCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>BCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>k6</ci>
<ci>BN</ci>
</apply>
<apply>
<times />
<ci>ksB</ci>
<ci>MB</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V1B</ci>
<ci>BC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>BC</ci>
</apply>
</apply>
<apply>
<times />
<ci>k5</ci>
<ci>BC</ci>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>BC</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="BCP" cmeta:id="BCP">
<variable cmeta:id="BCP_BCP" initial_value="0.48" name="BCP" public_interface="out" units="nanoM" />
<variable cmeta:id="BCP.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="BCP.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="BCP.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="BCP.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BCP.V1B" name="V1B" public_interface="in" units="flux" />
<variable cmeta:id="BCP.V2B" name="V2B" public_interface="in" units="flux" />
<variable cmeta:id="BCP.vdBC" name="vdBC" public_interface="in" units="flux" />
<variable cmeta:id="BCP.BC" name="BC" public_interface="in" units="nanoM" />
<variable cmeta:id="BCP.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>BCP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V1B</ci>
<ci>BC</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>BC</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V2B</ci>
<ci>BCP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>BCP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdBC</ci>
<ci>BCP</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>BCP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>BCP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="BN" cmeta:id="BN">
<variable cmeta:id="BN_BN" initial_value="1.94" name="BN" public_interface="out" units="nanoM" />
<variable cmeta:id="BN.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="BN.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="BN.k5" name="k5" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BN.k6" name="k6" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BN.k7" name="k7" public_interface="in" units="second_order_rate_constant" />
<variable cmeta:id="BN.k8" name="k8" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BN.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BN.V3B" name="V3B" public_interface="in" units="flux" />
<variable cmeta:id="BN.V4B" name="V4B" public_interface="in" units="flux" />
<variable cmeta:id="BN.BNP" name="BNP" public_interface="in" units="nanoM" />
<variable cmeta:id="BN.BC" name="BC" public_interface="in" units="nanoM" />
<variable cmeta:id="BN.PCN" name="PCN" public_interface="in" units="nanoM" />
<variable cmeta:id="BN.IN" name="IN" public_interface="in" units="nanoM" />
<variable cmeta:id="BN.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>BN</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V4B</ci>
<ci>BNP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>BNP</ci>
</apply>
</apply>
<apply>
<times />
<ci>k5</ci>
<ci>BC</ci>
</apply>
<apply>
<times />
<ci>k8</ci>
<ci>IN</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V3B</ci>
<ci>BN</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>BN</ci>
</apply>
</apply>
<apply>
<times />
<ci>k6</ci>
<ci>BN</ci>
</apply>
<apply>
<times />
<ci>k7</ci>
<ci>BN</ci>
<ci>PCN</ci>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>BN</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="BNP" cmeta:id="BNP">
<variable cmeta:id="BNP_BNP" initial_value="0.32" name="BNP" public_interface="out" units="nanoM" />
<variable cmeta:id="BNP.Kp" name="Kp" public_interface="in" units="nanoM" />
<variable cmeta:id="BNP.Kdp" name="Kdp" public_interface="in" units="nanoM" />
<variable cmeta:id="BNP.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="BNP.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="BNP.V3B" name="V3B" public_interface="in" units="flux" />
<variable cmeta:id="BNP.V4B" name="V4B" public_interface="in" units="flux" />
<variable cmeta:id="BNP.vdBN" name="vdBN" public_interface="in" units="flux" />
<variable cmeta:id="BNP.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="BNP.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>BNP</ci>
</apply>
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V3B</ci>
<ci>BN</ci>
</apply>
<apply>
<plus />
<ci>Kp</ci>
<ci>BN</ci>
</apply>
</apply>
<apply>
<plus />
<apply>
<divide />
<apply>
<times />
<ci>V4B</ci>
<ci>BNP</ci>
</apply>
<apply>
<plus />
<ci>Kdp</ci>
<ci>BNP</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdBN</ci>
<ci>BNP</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>BNP</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>BNP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="IN" cmeta:id="IN">
<variable cmeta:id="IN_IN" initial_value="0.05" name="IN" public_interface="out" units="nanoM" />
<variable cmeta:id="IN.Kd" name="Kd" public_interface="in" units="nanoM" />
<variable cmeta:id="IN.kdn" name="kdn" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="IN.k7" name="k7" public_interface="in" units="second_order_rate_constant" />
<variable cmeta:id="IN.k8" name="k8" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="IN.vdIN" name="vdIN" public_interface="in" units="flux" />
<variable cmeta:id="IN.PCN" name="PCN" public_interface="in" units="nanoM" />
<variable cmeta:id="IN.BN" name="BN" public_interface="in" units="nanoM" />
<variable cmeta:id="IN.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>IN</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>k7</ci>
<ci>BN</ci>
<ci>PCN</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>k8</ci>
<ci>IN</ci>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vdIN</ci>
<ci>IN</ci>
</apply>
<apply>
<plus />
<ci>Kd</ci>
<ci>IN</ci>
</apply>
</apply>
<apply>
<times />
<ci>kdn</ci>
<ci>IN</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="CB" cmeta:id="CB">
<variable cmeta:id="CB_CB" initial_value="0.12" name="CB" public_interface="out" units="nanoM" />
<variable cmeta:id="CB.K1CB" initial_value="0.01" name="K1CB" units="nanoM" />
<variable cmeta:id="CB.K2CB" initial_value="0.01" name="K2CB" units="nanoM" />
<variable cmeta:id="CB.WT" initial_value="1.0" name="WT" units="hour" />
<variable cmeta:id="CB.vP" initial_value="1.0" name="vP" units="nanoM" />
<variable cmeta:id="CB.V_K" name="V_K" public_interface="in" units="nanoM" />
<variable cmeta:id="CB.time" name="time" public_interface="in" units="hour" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>CB</ci>
</apply>
<apply>
<divide />
<apply>
<minus />
<apply>
<divide />
<apply>
<times />
<ci>V_K</ci>
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="nanoM">1.0</cn>
<ci>CB</ci>
</apply>
</apply>
<apply>
<minus />
<apply>
<plus />
<ci>K1CB</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="nanoM">1.0</cn>
</apply>
<ci>CB</ci>
</apply>
</apply>
<apply>
<divide />
<apply>
<times />
<ci>vP</ci>
<ci>CB</ci>
</apply>
<apply>
<plus />
<ci>K2CB</ci>
<ci>CB</ci>
</apply>
</apply>
</apply>
<ci>WT</ci>
</apply>
</apply>
</math>
</component>
<component name="model_parameters">
<variable cmeta:id="model_parameters.k1" initial_value="0.45" name="k1" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.k2" initial_value="0.2" name="k2" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.k3" initial_value="0.4" name="k3" public_interface="out" units="second_order_rate_constant" />
<variable cmeta:id="model_parameters.k4" initial_value="0.2" name="k4" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.k5" initial_value="0.4" name="k5" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.k6" initial_value="0.2" name="k6" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.k7" initial_value="0.5" name="k7" public_interface="out" units="second_order_rate_constant" />
<variable cmeta:id="model_parameters.k8" initial_value="0.1" name="k8" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.kdnc" initial_value="0.12" name="kdnc" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.kdn" initial_value="0.01" name="kdn" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.ksB" initial_value="0.12" name="ksB" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.ksC" initial_value="1.6" name="ksC" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.ksP" initial_value="0.6" name="ksP" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="model_parameters.m" initial_value="2.0" name="m" public_interface="out" units="dimensionless" />
<variable cmeta:id="model_parameters.n" initial_value="4.0" name="n" public_interface="out" units="dimensionless" />
<variable cmeta:id="model_parameters.Kd" initial_value="0.3" name="Kd" public_interface="out" units="nanoM" />
<variable cmeta:id="model_parameters.Kdp" initial_value="0.1" name="Kdp" public_interface="out" units="nanoM" />
<variable cmeta:id="model_parameters.Kp" initial_value="0.1" name="Kp" public_interface="out" units="nanoM" />
<variable cmeta:id="model_parameters.V1C" initial_value="0.6" name="V1C" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V1P" initial_value="0.4" name="V1P" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V1B" initial_value="0.5" name="V1B" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V2B" initial_value="0.1" name="V2B" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V3B" initial_value="0.5" name="V3B" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V4B" initial_value="0.2" name="V4B" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V1PC" initial_value="0.4" name="V1PC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V2C" initial_value="0.1" name="V2C" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V2P" initial_value="0.3" name="V2P" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V2PC" initial_value="0.1" name="V2PC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V3PC" initial_value="0.4" name="V3PC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.V4PC" initial_value="0.1" name="V4PC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdBC" initial_value="0.5" name="vdBC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdBN" initial_value="0.6" name="vdBN" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdCC" initial_value="0.7" name="vdCC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdIN" initial_value="0.8" name="vdIN" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdPC" initial_value="0.7" name="vdPC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdPCC" initial_value="0.7" name="vdPCC" public_interface="out" units="flux" />
<variable cmeta:id="model_parameters.vdPCN" initial_value="0.7" name="vdPCN" public_interface="out" units="flux" />
</component>
<connection>
<map_components component_1="IN" component_2="PCN" />
<map_variables variable_1="IN" variable_2="IN" />
</connection>
<connection>
<map_components component_1="model_parameters" component_2="BC" />
<map_variables variable_1="Kp" variable_2="Kp" />
<map_variables variable_1="kdn" variable_2="kdn" />
<map_variables variable_1="ksB" variable_2="ksB" />
<map_variables variable_1="Kdp" variable_2="Kdp" />
<map_variables variable_1="V2B" variable_2="V2B" />
<map_variables variable_1="k6" variable_2="k6" />
<map_variables variable_1="k5" variable_2="k5" />
<map_variables variable_1="V1B" variable_2="V1B" />
</connection>
<connection>
<map_components component_1="environment" component_2="BC" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="PCN" component_2="PCNP" />
<map_variables variable_1="PCN" variable_2="PCN" />
</connection>
<connection>
<map_components component_1="VIP" component_2="membrane" />
<map_variables variable_1="VIP" variable_2="VIP" />
</connection>
<connection>
<map_components component_1="environment" component_2="MP" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="PC" component_2="PCC" />
<map_variables variable_1="PC" variable_2="PC" />
</connection>
<connection>
<map_components component_1="environment" component_2="MC" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="environment" component_2="PCCP" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="PCC" component_2="PC" />
<map_variables variable_1="PCC" variable_2="PCC" />
</connection>
<connection>
<map_components component_1="membrane" component_2="CB" />
<map_variables variable_1="V_K" variable_2="V_K" />
</connection>
<connection>
<map_components component_1="BN" component_2="MC" />
<map_variables variable_1="BN" variable_2="BN" />
</connection>
<connection>
<map_components component_1="membrane" component_2="VIP" />
<map_variables variable_1="fr" variable_2="fr" />
</connection>
<connection>
<map_components component_1="PCCP" component_2="PCC" />
<map_variables variable_1="PCCP" variable_2="PCCP" />
</connection>
<connection>
<map_components component_1="environment" component_2="VIP" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="CC" component_2="Ca_in" />
<map_variables variable_1="CC" variable_2="CC" />
</connection>
<connection>
<map_components component_1="CCP" component_2="CC" />
<map_variables variable_1="CCP" variable_2="CCP" />
</connection>
<connection>
<map_components component_1="PCN" component_2="BN" />
<map_variables variable_1="PCN" variable_2="PCN" />
</connection>
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<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of BMAL1 in the suprachiasmatic nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PC.PCC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_41">
<semsim:physicalPropertyOf rdf:resource="#entity_42" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosophorylated Per-Cry complex in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CC.PC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_46">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_41" dcterms:description="">
<ro:part_of rdf:resource="#entity_12" />
<semsim:name>Lumped Per1, per2 and per3</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of mRNA translated to cyctolic, unphosphorylated Per</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.i_KCa">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_14">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_3" dcterms:description="">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_3">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_21">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/go/GO:0015269" />
</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasMediatorParticipant>
<semsim:name>Calcium-activated potassium current (BK current).</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00318" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Calcium-activated potassium current.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CC.CCP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_45">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_43" dcterms:description="">
<ro:part_of>
<rdf:Description rdf:about="#entity_24">
<ro:part_of rdf:resource="#entity_2" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:226054" />
</rdf:Description>
</ro:part_of>
<semsim:name>Phosphorylated lumped CRY1 and CRY2</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phoshorylated CRY (lumped CRY1 and CRY2) protein in the cytosol of the neuron.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.i_inhib">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_16">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_5" dcterms:description="">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_4">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_22">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/go/GO:0004890" />
</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasMediatorParticipant>
<semsim:name>Inhibitory postsynaptic current (IPSCs)</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00318" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Inhibitory postsynaptic currents (IPSCs), conveyed by the
GABA neurotransmitter and its GABA A receptor.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#MC_MC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_35">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_37">
<ro:part_of>
<rdf:Description rdf:about="#entity_38" dcterms:description="">
<semsim:name>Lumped CRY1 and CRY2 proteins</semsim:name>
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:67122" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of corresponding mRNA of CRY (CRY1 and CRY2 lumped).</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane" dc:title="membrane">
<dcterms:alternative>cell membrane</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.CC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_30">
<semsim:physicalPropertyOf rdf:resource="#entity_29" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated CRY (lumped CRY1 and CRY2) protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CCP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#CC.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#BNP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#PCC.PCCP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_54">
<semsim:physicalPropertyOf rdf:resource="#entity_42" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated Per-Cry complex in the cytosol of a neuron.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCCP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#vasalou_2010" semsim:modelName="vasalou_2010" bqmodel:isDescribedBy="20300645" />
<rdf:Description rdf:about="#membrane.Na_in">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_2">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_3">
<ro:part_of>
<rdf:Description rdf:about="#entity_4">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:226054" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29101" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of sodium in the cytosol</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CC_CC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_44">
<semsim:physicalPropertyOf rdf:resource="#entity_29" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated CRY (lumped CRY1 and CRY2) protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.i_Ca">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_12">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_1" dcterms:description="">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_1">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_18" />
</rdf:Description>
</semsim:hasMediatorParticipant>
<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_1" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_17" />
</rdf:Description>
</semsim:hasSinkParticipant>
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_1" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_16" />
</rdf:Description>
</semsim:hasSourceParticipant>
<semsim:name>Ca(2+) influx into the cytosol.</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00318" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Calcium current through the membrane of the SCN neuron.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.CB">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_22">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of CREB</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BNP_BNP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_78">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated BMAL1 protein in the suprachiasmatic Nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.E_Na">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_4">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_6">
<ro:part_of rdf:resource="#entity_1" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29101" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01581" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Nernst potential for Sodium.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.g_K">
<dcterms:description>COnductance of potassium channels</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#IN.BN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_82">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of BMAL1 in the suprachiasmatic nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.BC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_31">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_25">
<ro:part_of rdf:resource="#entity_24" />
<semsim:hasPhysicalDefinition rdf:resource="http://purl.obolibrary.org/obo/PR_000004305" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated, cytosolic BMAL1 protein.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BC.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#membrane.CC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_21">
<semsim:physicalPropertyOf rdf:resource="#entity_29" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated CRY (lumped CRY1 and CRY2) protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCP.PC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_50">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of mRNA translated to cyctolic, unphosphorylated Per</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCN_PCN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_58">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_44">
<ro:part_of rdf:resource="#entity_36" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/go/GO:1990512" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of nuclear form of of unphosphorylated Per-Cry complex.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCC.PCN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_55">
<semsim:physicalPropertyOf rdf:resource="#entity_44" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of nuclear form of of unphosphorylated Per-Cry complex.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#environment.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#PC.PCP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_40">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phoshorylated PER (Lumped Per1, per2 and per3) in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BN.IN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_77">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Inactive complex between PER–CRY and CLOCK–BMAL1 in nucleus</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PC.CC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_42">
<semsim:physicalPropertyOf rdf:resource="#entity_29" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated CRY (lumped CRY1 and CRY2) protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#PCCP.PCC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_64">
<semsim:physicalPropertyOf rdf:resource="#entity_42" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosophorylated Per-Cry complex in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.K_in">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_3">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_5">
<ro:part_of rdf:resource="#entity_4" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29103" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Potassium concentration within the cytosol</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#MB.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#membrane.V_K">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_0">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Intracellular protein kinase concentration.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.VIP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_20">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_28">
<ro:part_of rdf:resource="#entity_2" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:80331" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of intracellular Vasoactive intestinal peptide.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.Ca_store">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_24">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_30">
<ro:part_of>
<rdf:Description rdf:about="#entity_31" dcterms:description="">
<semsim:name>IP3 and Ryanodine stores</semsim:name>
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>IP3 and ryanodine dependent Calcium stores.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#MP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#MC.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#membrane.Ca_in">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_17">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_23">
<ro:part_of rdf:resource="#entity_24" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of intracellular calcium in the neuron.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.BC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_18">
<semsim:physicalPropertyOf rdf:resource="#entity_25" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated, cytosolic BMAL1 protein.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BNP.BN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_79">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of BMAL1 in the suprachiasmatic nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.g_ex">
<dcterms:description>Conductance of the excitatory current</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCC_PCC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_53">
<semsim:physicalPropertyOf rdf:resource="#entity_42" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosophorylated Per-Cry complex in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#MP.BN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_34">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of BMAL1 in the suprachiasmatic nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CB.V_K">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_84">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Intracellular protein kinase concentration.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCNP_PCNP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_65">
<semsim:physicalPropertyOf rdf:resource="#entity_44" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated nuclear form of Per-Cry complex</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.Ca_in">
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<dcterms:description>Concentration of intracellular calcium in the neuron.</dcterms:description>
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<rdf:Description rdf:about="#BC_BC">
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<rdf:Description rdf:about="#property_67">
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<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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<dcterms:description>Concentration of unphosphorylated, cytosolic BMAL1 protein.</dcterms:description>
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<rdf:Description rdf:about="#BCP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#PC.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#PCNP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
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<rdf:Description rdf:about="#BN.BNP">
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<rdf:Description rdf:about="#property_74">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated BMAL1 protein in the suprachiasmatic Nucleus.</dcterms:description>
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<rdf:Description rdf:about="#membrane.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
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<rdf:Description rdf:about="#membrane.i_Na">
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<rdf:Description rdf:about="#property_11">
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<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/go/GO:0005272" />
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<rdf:Description rdf:about="#sink_0" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_6" />
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<rdf:Description rdf:about="#source_0" semsim:hasMultiplier="1.0">
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<rdf:Description rdf:about="#entity_13">
<ro:part_of rdf:resource="#entity_14" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29101" />
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</semsim:hasSourceParticipant>
<semsim:name>Na+ flow across membrane</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00318" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Sodium current across membrane</dcterms:description>
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<rdf:Description rdf:about="#CCP_CCP">
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<rdf:Description rdf:about="#property_51">
<semsim:physicalPropertyOf rdf:resource="#entity_43" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phoshorylated CRY (lumped CRY1 and CRY2) protein in the cytosol of the neuron.</dcterms:description>
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<rdf:Description rdf:about="#membrane.E_Ca">
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<rdf:Description rdf:about="#property_5">
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<rdf:Description rdf:about="#entity_7">
<ro:part_of rdf:resource="#entity_1" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29108" />
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<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01581" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Calcium reverse membrane potential.</dcterms:description>
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<rdf:Description rdf:about="#BN.BC">
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<rdf:Description rdf:about="#property_75">
<semsim:physicalPropertyOf rdf:resource="#entity_25" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated, cytosolic BMAL1 protein.</dcterms:description>
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<rdf:Description rdf:about="#BCP_BCP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_71">
<semsim:physicalPropertyOf rdf:resource="#entity_25" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated BMAL1 protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BN.PCN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_76">
<semsim:physicalPropertyOf rdf:resource="#entity_44" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of nuclear form of of unphosphorylated Per-Cry complex.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCN.PCNP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_59">
<semsim:physicalPropertyOf rdf:resource="#entity_44" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated nuclear form of Per-Cry complex</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BN.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#MP_MP">
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<rdf:Description rdf:about="#property_33">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_26">
<ro:part_of>
<rdf:Description rdf:about="#entity_27" dcterms:description="">
<ro:part_of>
<rdf:Description rdf:about="#entity_10">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:54527" />
</rdf:Description>
</ro:part_of>
<semsim:name>Lumped Per1, per2 and per3</semsim:name>
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:67122" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Transcription of Per (Per1, per2 and Per3 gene) into the corresponding mRNA.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCC.PC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_56">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of mRNA translated to cyctolic, unphosphorylated Per</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#IN.PCN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_81">
<semsim:physicalPropertyOf rdf:resource="#entity_44" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of nuclear form of of unphosphorylated Per-Cry complex.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.GABA">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_9">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_9">
<ro:part_of rdf:resource="#entity_10" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:84786" />
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</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of gamma-aminobutyric acid in the neuron</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCNP.PCN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_66">
<semsim:physicalPropertyOf rdf:resource="#entity_44" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of nuclear form of of unphosphorylated Per-Cry complex.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCN.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#PCN.BN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_61">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of BMAL1 in the suprachiasmatic nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.E_inhib">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_8">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01581" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.MP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_29">
<semsim:physicalPropertyOf rdf:resource="#entity_26" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Transcription of Per (Per1, per2 and Per3 gene) into the corresponding mRNA.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCP_PCP">
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<rdf:Description rdf:about="#property_49">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phoshorylated PER (Lumped Per1, per2 and per3) in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CC.PCC">
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<rdf:Description rdf:about="#property_47">
<semsim:physicalPropertyOf rdf:resource="#entity_42" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosophorylated Per-Cry complex in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#BC.BCP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_69">
<semsim:physicalPropertyOf rdf:resource="#entity_25" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated BMAL1 protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.v0">
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<rdf:Description rdf:about="#property_25">
<semsim:physicalPropertyOf rdf:resource="#process_1" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Influx of Calcium into the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#VIP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#membrane.V_rest">
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<rdf:Description rdf:about="#property_1">
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<rdf:Description rdf:about="#entity_0">
<ro:part_of rdf:resource="#entity_1" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:30322" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00378" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Membrane resting potential</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#MB.BN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_38">
<semsim:physicalPropertyOf rdf:resource="#entity_35" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of BMAL1 in the suprachiasmatic nucleus.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.g_Ca">
<dcterms:description>Conductance of Ca2+ channels</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.i_L">
<dcterms:description>Leakage current across membrane.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.v1">
<dcterms:description>IP3-sensitive calcium stores flow rate</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCCP_PCCP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_63">
<semsim:physicalPropertyOf rdf:resource="#entity_42" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of phosphorylated Per-Cry complex in the cytosol of a neuron.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CCP.CC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_52">
<semsim:physicalPropertyOf rdf:resource="#entity_29" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated CRY (lumped CRY1 and CRY2) protein in the cytosol.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#IN_IN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_80">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Inactive complex between PER–CRY and CLOCK–BMAL1 in nucleus</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#VIP.VIP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_32">
<semsim:physicalPropertyOf rdf:resource="#entity_28" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of intracellular Vasoactive intestinal peptide.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.Cl_in">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_10">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_11">
<ro:part_of rdf:resource="#entity_12" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:17996" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Intracellular Cl- concentration.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.i_K">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_13">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_2" dcterms:description="">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_2">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_20">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/go/GO:0005267" />
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<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_2" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_8" />
</rdf:Description>
</semsim:hasSinkParticipant>
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_2" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_19">
<ro:part_of rdf:resource="#entity_14" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29103" />
</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasSourceParticipant>
<semsim:name>Potassium current</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00318" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Potassium current through the membrane of the SCN neuron.</dcterms:description>
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<rdf:Description rdf:about="#membrane.MP">
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<rdf:Description rdf:about="#property_19">
<semsim:physicalPropertyOf rdf:resource="#entity_26" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Transcription of Per (Per1, per2 and Per3 gene) into the corresponding mRNA.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.v2">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_26">
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<rdf:Description rdf:about="#process_6" dcterms:description="">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_5">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_34">
<semsim:hasPhysicalDefinition rdf:resource="http://purl.obolibrary.org/obo/PR_Q15413" />
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</semsim:hasPhysicalEntityReference>
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<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_3" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_32">
<ro:part_of>
<rdf:Description rdf:about="#entity_33" dcterms:description="">
<semsim:name>ryanodine stores</semsim:name>
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</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:hasPhysicalEntityReference>
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</semsim:hasSinkParticipant>
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_3" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_17" />
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</semsim:hasSourceParticipant>
<semsim:name>Ca(2+) transport from the cytosol to the ryanodine stores</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00593" />
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<dcterms:description>Transport of calcium from the cytosol to the ryanodine stores</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PC_PC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_39">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of mRNA translated to cyctolic, unphosphorylated Per</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PC.MP">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_43">
<semsim:physicalPropertyOf rdf:resource="#entity_26" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Transcription of Per (Per1, per2 and Per3 gene) into the corresponding mRNA.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCC.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#MB_MB">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_37">
<semsim:physicalPropertyOf rdf:resource="#entity_39" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of corresponding mRNA of BMAL1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#CC.MC">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_48">
<semsim:physicalPropertyOf rdf:resource="#entity_37" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of corresponding mRNA of CRY (CRY1 and CRY2 lumped).</dcterms:description>
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<rdf:Description rdf:about="#BCP.BC">
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<rdf:Description rdf:about="#property_72">
<semsim:physicalPropertyOf rdf:resource="#entity_25" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of unphosphorylated, cytosolic BMAL1 protein.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.g_KCa">
<dcterms:description>Conductance of Calcium-activated potassium channels</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#PCP.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Ca_in.v3">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_27">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_7" dcterms:description="">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_6">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_34" />
</rdf:Description>
</semsim:hasMediatorParticipant>
<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_4" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_17" />
</rdf:Description>
</semsim:hasSinkParticipant>
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_4" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_32" />
</rdf:Description>
</semsim:hasSourceParticipant>
<semsim:name>Ca(2+) transport from ryanodine stores to the cytosol of the neuron.</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00593" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Release of Calcium from the stores into the cytosol</dcterms:description>
</rdf:Description>
</rdf:RDF>
</model>
