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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Phys.</journal-id>
<journal-title>Frontiers in Physics</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Phys.</abbrev-journal-title>
<issn pub-type="epub">2296-424X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">1123370</article-id>
<article-id pub-id-type="doi">10.3389/fphy.2023.1123370</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Physics</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Fractional critical slowing down in some biological models</article-title>
<alt-title alt-title-type="left-running-head">Alharbey and Hassan</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fphy.2023.1123370">10.3389/fphy.2023.1123370</ext-link>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Alharbey</surname>
<given-names>R. A.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/888467/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hassan</surname>
<given-names>S. S.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="fn" rid="fn1">
<sup>&#x2020;</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Mathematics Department</institution>, <institution>Faculty of Science</institution>, <institution>King Abdulaziz University</institution>, <addr-line>Jeddah</addr-line>, <country>Saudi Arabia</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Mathematics</institution>, <institution>College of Science</institution>, <institution>University of Bahrain</institution>, <addr-line>Sakhir</addr-line>, <country>Kingdom of Bahrain</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2072452/overview">Samir A. El-Tantawy</ext-link>, Port Said University, Egypt</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2162464/overview">Yasser Sharaby</ext-link>, Suez University, Egypt</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/787110/overview">Xing Lu</ext-link>, Beijing Jiaotong University, China</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: R. A. Alharbey, <email>rania.math@gmail.com</email>
</corresp>
<fn fn-type="equal" id="fn1">
<label>
<sup>&#x2020;</sup>
</label>
<p>These authors have contributed equally to this work</p>
</fn>
<fn fn-type="other">
<p>This article was submitted to Mathematical Physics, a section of the journal Frontiers in Physics</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>07</day>
<month>03</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>11</volume>
<elocation-id>1123370</elocation-id>
<history>
<date date-type="received">
<day>14</day>
<month>12</month>
<year>2022</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>01</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2023 Alharbey and Hassan.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Alharbey and Hassan</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>The critical slowing down (CSD) phenomenon of the switching time in response to perturbation <italic>&#x3b2;</italic> (0 &#x3c; <italic>&#x3b2;</italic> &#x3c; 1) of the control parameters at the critical points of the steady state bistable curves, associated with two biological models (the spruce budworm outbreak model and the Thomas reaction model for enzyme membrane) is investigated within fractional derivative forms of order <italic>&#x3b1;</italic> (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1) that allows for memory mechanism. We use two definitions of fractional derivative, namely, Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives. Both definitions of fractional derivative yield the <italic>same</italic> qualitative results. The interplay of the two parameters <italic>&#x3b1;</italic> (as memory index) and <italic>&#x3b2;</italic> shows that the time delay <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> can be reduced or increased, compared with the ordinary derivative case (<italic>&#x3b1;</italic> &#x3d; 1). Further, <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> fits: (<italic>i</italic>) as function of <italic>&#x3b2;</italic> the scaling inverse square root formula <inline-formula id="inf1">
<mml:math id="m1">
<mml:mn>1</mml:mn>
<mml:mo>/</mml:mo>
<mml:msqrt>
<mml:mrow>
<mml:mi>&#x3b2;</mml:mi>
</mml:mrow>
</mml:msqrt>
</mml:math>
</inline-formula> at fixed fractional derivative index (<italic>&#x3b1;</italic> &#x3c; 1) and, (<italic>ii</italic>) as a function of <italic>&#x3b1;</italic> (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1) an exponentially increasing form at fixed perturbation parameter <italic>&#x3b2;</italic>.</p>
</abstract>
<kwd-group>
<kwd>critical slowing down</kwd>
<kwd>Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives</kwd>
<kwd>switching timedelay</kwd>
<kwd>bistable behaviour</kwd>
<kwd>mathematical models in biology</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Bistable systems in many branches of sciences (physics, biology, &#x2026; ) and engineering are characterized by the co-existence of two stable states, where the system switches from one stable state to other state by means of changing one or some of the system control parameters [<xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref>]. The associated transient phenomena of lengthening the switching time between these two stable states, called critical slowing down (CSD), happens upon perturbing one of the parameters at the critical (switching-on or -off) points of the charactertistic bistable curve [<xref ref-type="bibr" rid="B5">5</xref>&#x2013;<xref ref-type="bibr" rid="B8">8</xref>]. It has been suggested that, CSD may serve as a universal indicator of how a complex physical system (such as brain, ecosystems, climate and financial markets) approaches a threshold [<xref ref-type="bibr" rid="B9">9</xref>&#x2013;<xref ref-type="bibr" rid="B12">12</xref>], and as well serving as an indicator of transitions in two-species biological models, which exhibit Hopf bifurcation or hysteresis transition [<xref ref-type="bibr" rid="B13">13</xref>]. For our specific current concern, the CSD phenomenon has recently been investigated by us in [<xref ref-type="bibr" rid="B14">14</xref>] for some biological bistable models, namely.<list list-type="simple">
<list-item>
<p>(a) The spruce budworm outbreak model [<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B15">15</xref>];</p>
</list-item>
<list-item>
<p>(b) The Thomas-reaction (enzyme membrane) model [<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B16">16</xref>].</p>
</list-item>
</list>
</p>
<p>Specifically, our investigation in [<xref ref-type="bibr" rid="B14">14</xref>] was concerned with the nature of transition between the two stable states, and the verification of the inverse square root scaling law, for the switching time delay (<italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub>) at the critical switching-on and -off points, independent of the type of non-linearity in the model rate equations. The model rate equation in model a) is of first order ordinary differential equation (ODE), while in model b) the model rate equations are coupled first order ODEs.On the other hand, fractional calculus, a field of mathematics that deals with the analysis of derivatives and integrals of fractional (or even complex) order, has its applications in diverse areas of science and engineering. The associated fractional differential equations (FDEs) are widely and successfully used in mathematical modelling in a variety of fields. We refer the reader to the extensive list of major works and applications in the area of fractional calculus cited in ([<xref ref-type="bibr" rid="B17">17</xref>&#x2013;<xref ref-type="bibr" rid="B20">20</xref>] and refs. therein). In ordinary calculus, the first order derivative of a function <italic>f</italic>(<italic>t</italic>), namely <inline-formula id="inf2">
<mml:math id="m2">
<mml:msup>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
<mml:mrow>
<mml:mo stretchy="false">(</mml:mo>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mo stretchy="false">)</mml:mo>
</mml:mrow>
<mml:mo>&#x3d;</mml:mo>
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>t</mml:mi>
</mml:mrow>
</mml:mfrac>
</mml:math>
</inline-formula> is the instantaneous rate of change of <italic>f</italic>(<italic>t</italic>) over the infinitesimal time period, <italic>t</italic> &#x2192; 0, that is, local time effect. In fractional calculus, the physical meaning is non-local, as the time domain is manifested as a memory (or time delay) effect and the current state of the system depends on its earlier history. Moreover, in fitting with test data of various models of memory phenomena, the order of the fractional derivative serves as an index of memory [<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>]. FDEs of arbitrary real order are not in general easy to solve analytically [<xref ref-type="bibr" rid="B23">23</xref>]. However, the numerical method based on Laplace transform technique is a basic one and applicable for a wide class of initial value problems for FDEs, [<xref ref-type="bibr" rid="B23">23</xref>&#x2013;<xref ref-type="bibr" rid="B26">26</xref>]. Recent fundamental computational methods are found in [<xref ref-type="bibr" rid="B27">27</xref>, <xref ref-type="bibr" rid="B28">28</xref>]; and refs, therein.</p>
<p>Experimentally speaking, fractional derivative models (FDMs) are in excellent agreement with experimental data in many branches of science and engineering. Two specific examples we quote.<list list-type="simple">
<list-item>
<p>1. A recent experimental study of viscoelastic properties of some soft biological tissues under harmonic mechanical loading shows that the FD Voigt model performed better, compared with integer order derivative models [<xref ref-type="bibr" rid="B29">29</xref>].</p>
</list-item>
<list-item>
<p>2. FDM (Maxwell&#x2019;s model) describing the viscoelastic Creep damage of some fruits is more efficient and well fitted with experimental data [<xref ref-type="bibr" rid="B30">30</xref>].</p>
</list-item>
</list>
</p>
<p>Further, CSD or more generally instability mechanism and chaos, have been investigated at large in fractional order dynamical systems in fields, like, fluid flow [<xref ref-type="bibr" rid="B31">31</xref>&#x2013;<xref ref-type="bibr" rid="B35">35</xref>], neurology and biological phenomena ([<xref ref-type="bibr" rid="B36">36</xref>&#x2013;<xref ref-type="bibr" rid="B38">38</xref>]; refs. therein) to account successfully for memory (time-delay) and special non-local effects. For example.<list list-type="simple">
<list-item>
<p>1. The Landau model that describes the fluid flow from laminar to turbulent has been examined within a fractional rate equation model [<xref ref-type="bibr" rid="B35">35</xref>] in order to account for memory effect. This transition to turbulence due to CSD shows that the turbulent fluctuations depend on memory of inverse power law decay in agreement with experiment [<xref ref-type="bibr" rid="B39">39</xref>]-slower than in the case of no memory (ordinary derivative case) of turbulent fluctuations decaying exponentially,</p>
</list-item>
<list-item>
<p>2. Capacitive memory due to fractional order cardiomyocyte dynamical model [<xref ref-type="bibr" rid="B37">37</xref>] alters the electrical signaling in cardiac cells in a manner that promote or suppress electrical instability (known as alternans).</p>
</list-item>
<list-item>
<p>3. The use of a fractional order mathematical model to study the signaling process in nerve cells (like, neuron) due to incorporated strong memory effects [<xref ref-type="bibr" rid="B36">36</xref>] has been interpreted as a neuronal disorder (Parkinson disease).</p>
</list-item>
</list>
</p>
<p>The concern of the present paper is to adopt the corresponding FDEs in both models a) [<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B15">15</xref>] and b) [<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B16">16</xref>], referred to above, in order to incorporate for memory effects and examine effects of the fractional derivative order parameter (<italic>&#x3b1;</italic>), (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1) on the time delay (<italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub>) associated with the CSD phenomena examined in the no-memory case [<xref ref-type="bibr" rid="B14">14</xref>]. We use and compare two definitions of fractional derivatives, namely, Caputo&#x2019;s [<xref ref-type="bibr" rid="B40">40</xref>] and Caputo-Fabrizio&#x2019;s [<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>] definitions. Both definitions have the advantage of dealing with initial conditions of the variables and their integer derivatives suitable in most physical processes, like models a) [<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B15">15</xref>] and b) [<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B16">16</xref>] referred to above. As a main result, it is found that Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s definitions of fractional derivatives yield the <italic>same</italic> qualitative results of reduced time delay <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> at fixed perturbation of the concerned control parameter, with smaller values of the fractional derivative order <italic>&#x3b1;</italic>. The small <italic>quantitative difference</italic> in <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> is due to the different convoluted kernels (that model the memory or delay effect) in [<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B40">40</xref>].This paper is presented as follows. In section 2), we present the model differential equations in both ordinary and Caputo&#x2019;s fractional derivative forms, for both models. In section 3), we present the computational results for the transient switching. Section 4) presents a summary of the results. In <xref ref-type="sec" rid="s10">Supplementary Appendix A</xref>, a brief background of the model ODEs (eqa (1) and. 2) below) representing the two biological models referred to above is given, while <xref ref-type="sec" rid="s10">Supplementary Appendix B</xref> presents a guideline for Euler&#x2019;s numerical method to solve fractional FDE.</p>
</sec>
<sec id="s2">
<title>2 The model equations</title>
<p>Here, we first present the model DEs of the two biological models (the Spruce-budworm and Thomas reaction models) in their ordinary derivative forms. (A brief background of these model ODEs are given in <xref ref-type="sec" rid="s10">Supplementary Appendix A</xref>). Second, we present the corresponding fractional derivative forms, according to the two formulations of Caputo&#x2019;s [<xref ref-type="bibr" rid="B40">40</xref>] and Caputo-Fabrizio&#x2019;s definitions [<xref ref-type="bibr" rid="B21">21</xref>].</p>
<sec id="s2-1">
<title>2.1 Ordinary derivative case</title>
<sec id="s2-1-1">
<title>2.1.1 The spruce budworm Model</title>
<p>This model ([<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B15">15</xref>]) provides a good example for understanding the dynamics of the interaction between trees and insects. The model rate equation for the insect (budworms) population has the form:<disp-formula id="e1">
<mml:math id="m3">
<mml:mtable class="eqnarray">
<mml:mtr>
<mml:mtd columnalign="right">
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfrac>
<mml:mi>N</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:mo>&#x3d;</mml:mo>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:mi>N</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2212;</mml:mo>
<mml:mfrac>
<mml:mrow>
<mml:mi>N</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mi>K</mml:mi>
</mml:mrow>
</mml:mfrac>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>F</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>N</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>/</mml:mo>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>N</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x2b;</mml:mo>
<mml:msup>
<mml:mrow>
<mml:mi>B</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfenced>
</mml:mtd>
</mml:mtr>
<mml:mtr>
<mml:mtd columnalign="right"/>
<mml:mtd columnalign="left">
<mml:mo>&#x2261;</mml:mo>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:msub>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>o</mml:mi>
</mml:mrow>
</mml:msub>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>N</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
</mml:mtd>
</mml:mtr>
</mml:mtable>
</mml:math>
<label>(1)</label>
</disp-formula>where <italic>N</italic>(<italic>&#x3c4;</italic>) is the budworm&#x2019;s population, <italic>&#x3c4;</italic> &#x3d; <italic>rt</italic> is normalised time, <italic>r</italic> is the linear birth rate and <italic>K</italic> is the constant carrying capacity which is related to the foliage (food) available on the trees in the absence of birds. The constant <italic>F</italic> &#x3d; <italic>p</italic>
<sub>
<italic>o</italic>
</sub>
<italic>A</italic>/<italic>r</italic> is the predation population with rate <italic>p</italic>
<sub>
<italic>o</italic>
</sub> and <italic>A</italic> is the (positive) predator attack rate and <italic>B</italic> is the threshold measure of the budworm population. The predation will approach an upper level value, <inline-formula id="inf3">
<mml:math id="m4">
<mml:mi>l</mml:mi>
<mml:mi>i</mml:mi>
<mml:msub>
<mml:mrow>
<mml:mi>m</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>N</mml:mi>
<mml:mo>&#x2192;</mml:mo>
<mml:mi>&#x221e;</mml:mi>
</mml:mrow>
</mml:msub>
<mml:mi>F</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>N</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mo>/</mml:mo>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>N</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mo>&#x2b;</mml:mo>
<mml:msup>
<mml:mrow>
<mml:mi>B</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x3d;</mml:mo>
<mml:mi>F</mml:mi>
</mml:math>
</inline-formula> as <italic>N</italic> increases.</p>
</sec>
<sec id="s2-1-2">
<title>2.1.2 The Thomas reaction model</title>
<p>The mechanism of this model is based on a basic reaction in an enzyme membrane, between the substrate oxygen and uric acid. The model equations of the system in a dimensionless form are [<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B16">16</xref>]:<disp-formula id="e2a">
<mml:math id="m5">
<mml:mtable class="eqnarray">
<mml:mtr>
<mml:mtd columnalign="right">
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfrac>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:mo>&#x3d;</mml:mo>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:mi>a</mml:mi>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>&#x2113;</mml:mi>
<mml:mfrac>
<mml:mrow>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2b;</mml:mo>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x2b;</mml:mo>
<mml:mi>k</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>u</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfrac>
</mml:mtd>
</mml:mtr>
<mml:mtr>
<mml:mtd columnalign="right"/>
<mml:mtd columnalign="left">
<mml:mo>&#x2261;</mml:mo>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:msub>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>1</mml:mn>
</mml:mrow>
</mml:msub>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
</mml:mtd>
</mml:mtr>
</mml:mtable>
</mml:math>
<label>(2a)</label>
</disp-formula>
<disp-formula id="e2b">
<mml:math id="m6">
<mml:mtable class="eqnarray">
<mml:mtr>
<mml:mtd columnalign="right">
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfrac>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:mo>&#x3d;</mml:mo>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:mi>&#x3b3;</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>b</mml:mi>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>&#x2113;</mml:mi>
<mml:mfrac>
<mml:mrow>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2b;</mml:mo>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x2b;</mml:mo>
<mml:mi>k</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>u</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfrac>
</mml:mtd>
</mml:mtr>
<mml:mtr>
<mml:mtd columnalign="right"/>
<mml:mtd columnalign="left">
<mml:mo>&#x2261;</mml:mo>
</mml:mtd>
<mml:mtd columnalign="left">
<mml:msub>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msub>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mo>.</mml:mo>
</mml:mtd>
</mml:mtr>
</mml:mtable>
</mml:math>
<label>(2b)</label>
</disp-formula>Here, <italic>u</italic> and <italic>v</italic> represent the uric acid and the oxygen being supplied at constant rates <italic>a</italic> and <italic>&#x3b3;b</italic>, respectively, where, <italic>a</italic>, <italic>&#x2113;</italic>, <italic>k</italic>, <italic>&#x3b3;</italic> and <italic>b</italic> are all positive real constants. The factor <inline-formula id="inf4">
<mml:math id="m7">
<mml:mi>u</mml:mi>
<mml:mrow>
<mml:mo stretchy="false">(</mml:mo>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mo stretchy="false">)</mml:mo>
</mml:mrow>
<mml:mi>v</mml:mi>
<mml:mrow>
<mml:mo stretchy="false">(</mml:mo>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mo stretchy="false">)</mml:mo>
</mml:mrow>
<mml:mo>/</mml:mo>
<mml:mspace width="0.3333em"/>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2b;</mml:mo>
<mml:mi>u</mml:mi>
<mml:mrow>
<mml:mo stretchy="false">(</mml:mo>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mo stretchy="false">)</mml:mo>
</mml:mrow>
<mml:mo>&#x2b;</mml:mo>
<mml:mi>k</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>u</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msup>
<mml:mrow>
<mml:mo stretchy="false">(</mml:mo>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mo stretchy="false">)</mml:mo>
</mml:mrow>
</mml:mrow>
</mml:mfenced>
</mml:math>
</inline-formula> exhibits <italic>substrate inhibition:</italic> it increases (decreases) when <italic>u</italic> is small (large), with measure of inhibition&#x2019;s severity equal to <italic>k</italic>.</p>
<p>In [<xref ref-type="bibr" rid="B14">14</xref>], the model Equations 1, 2 were analysed in detail (theoretically and computationally) regarding regions of bistability, the CSD phenomenon at the critical (switch-up and -down) points of the bistable curves and the verification of the inverse square root scaling law of the switching time delay [<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B41">41</xref>].</p>
</sec>
</sec>
<sec id="s2-2">
<title>2.2 Fractional derivative cases</title>
<p>In this case, Equations 1, 2 take the following forms;<disp-formula id="e3">
<mml:math id="m8">
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>N</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x3d;</mml:mo>
<mml:msub>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>o</mml:mi>
</mml:mrow>
</mml:msub>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>N</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
</mml:math>
<label>(3)</label>
</disp-formula>and,<disp-formula id="e4a">
<mml:math id="m9">
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x3d;</mml:mo>
<mml:msub>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>1</mml:mn>
</mml:mrow>
</mml:msub>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
</mml:math>
<label>(4a)</label>
</disp-formula>
<disp-formula id="e4b">
<mml:math id="m10">
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>&#x3d;</mml:mo>
<mml:msub>
<mml:mrow>
<mml:mi>f</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mn>2</mml:mn>
</mml:mrow>
</mml:msub>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>u</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
<mml:mi>v</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mo>,</mml:mo>
</mml:math>
<label>(4b)</label>
</disp-formula>respectively, where <inline-formula id="inf5">
<mml:math id="m11">
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
</mml:math>
</inline-formula> denotes the fractional derivative of order <italic>&#x3b1;</italic> (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1). There is no unique definition of fractional calculus (FC), derivatives and integrals. Definitions of FC are too many and still -up to date - increasing. Here, we use and compare two definitions of fractional derivatives of a continuous function <italic>f</italic>(<italic>&#x3c4;</italic>) on (0, <italic>&#x3c4;</italic>), namely, Caputo&#x2019;s [<xref ref-type="bibr" rid="B40">40</xref>] and Caputo-Fabrizio&#x2019;s [<xref ref-type="bibr" rid="B21">21</xref>] derivatives.</p>
<sec id="s2-2-1">
<title>2.2.1 Caputo&#x2019;s fractional derivative [<xref ref-type="bibr" rid="B40">40</xref>]</title>
<p>&#x2009;&#x2009;&#x2009;&#x2009;&#x2009;Caputo&#x2019;s fractional derivative of <italic>f</italic>(<italic>&#x3c4;</italic>) is defined as the convolution of the kernel power function <italic>&#x3c4;</italic>
<sup>&#x2212;<italic>&#x3b1;</italic>
</sup>, 0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1 with the first order (ordinary derivative) <italic>f</italic>&#x2032;<italic>&#x3c4;</italic>) on the closed interval [0, <italic>&#x3c4;</italic>],<disp-formula id="e5">
<mml:math id="m12">
<mml:msub>
<mml:mrow>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>f</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mi mathvariant="italic">Cap</mml:mi>
</mml:mrow>
</mml:msub>
<mml:mo>&#x3d;</mml:mo>
<mml:mfrac>
<mml:mrow>
<mml:mn>1</mml:mn>
</mml:mrow>
<mml:mrow>
<mml:mi mathvariant="normal">&#x393;</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfrac>
<mml:msubsup>
<mml:mrow>
<mml:mo>&#x222b;</mml:mo>
</mml:mrow>
<mml:mrow>
<mml:mn>0</mml:mn>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:msubsup>
<mml:mfrac>
<mml:mrow>
<mml:mn>1</mml:mn>
</mml:mrow>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
<mml:mo>&#x2212;</mml:mo>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>f</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfenced>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
<mml:mo>,</mml:mo>
</mml:math>
<label>(5)</label>
</disp-formula>with &#x393;(<italic>x</italic>) is the gamma function.</p>
</sec>
<sec id="s2-2-2">
<title>2.2.2 Caputo-Fabrizio&#x2019;s derivative [<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>]</title>
<p>&#x2009;&#x2009;&#x2009;&#x2009;&#x2009;This fractional derivative of <italic>f</italic>(<italic>&#x3c4;</italic>) is defined as the convolution of the kernel exponential function <italic>e</italic>
<sup>&#x2212;<italic>&#x3b1;&#x3c4;</italic>/(1&#x2212;<italic>&#x3b1;</italic>)</sup>, 0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1, with <italic>f</italic>&#x2032;(<italic>&#x3c4;</italic>) on the closed interval [0, <italic>&#x3c4;</italic>],<disp-formula id="e6">
<mml:math id="m13">
<mml:msub>
<mml:mrow>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>f</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
<mml:mrow>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>C</mml:mi>
<mml:mi>a</mml:mi>
<mml:mi>p</mml:mi>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>F</mml:mi>
<mml:mi>a</mml:mi>
<mml:mi>b</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:msub>
<mml:mo>&#x3d;</mml:mo>
<mml:mfrac>
<mml:mrow>
<mml:mn>1</mml:mn>
</mml:mrow>
<mml:mrow>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfrac>
<mml:msubsup>
<mml:mrow>
<mml:mo>&#x222b;</mml:mo>
</mml:mrow>
<mml:mrow>
<mml:mn>0</mml:mn>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:msubsup>
<mml:msup>
<mml:mrow>
<mml:mi>e</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>&#x3b1;</mml:mi>
<mml:mo>/</mml:mo>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mn>1</mml:mn>
<mml:mo>&#x2212;</mml:mo>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:mfenced>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
<mml:mo>&#x2212;</mml:mo>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfenced>
</mml:mrow>
</mml:msup>
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mi>f</mml:mi>
<mml:mfenced open="(" close=")">
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfenced>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>t</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mo>&#x2032;</mml:mo>
</mml:mrow>
</mml:msup>
<mml:mo>,</mml:mo>
</mml:math>
<label>(6)</label>
</disp-formula>
</p>
</sec>
</sec>
</sec>
<sec id="s3">
<title>3 Transient switching and time delay</title>
<p>The switching time at the critical (switch-on and -off) points of the characteristic steady state bistable curves (<italic>N</italic> vs <italic>K</italic>) according to the FDE 3), or (<italic>u</italic> and <italic>v</italic> vs <italic>a</italic>) according to the FDEs 4) with both Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives, Eqs. <xref ref-type="disp-formula" rid="e5">5</xref> and <xref ref-type="disp-formula" rid="e6">6</xref>, respectively, are investigated by solving these FDEs numerically using the fractional Euler&#x2019;s method developed in [<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B48">48</xref>] (see <xref ref-type="sec" rid="s10">Supplementary Appendix B</xref> for guidelines). This is done by replacing the control (input) parameter <italic>K</italic> in Equations 1&#x2013;3) by <italic>K</italic>
<sub>
<italic>c</italic>
</sub> &#xb1; <italic>&#x3b2;</italic>, or <italic>a</italic> in Equations 2, 4 by <italic>a</italic>
<sub>
<italic>c</italic>
</sub> &#xb1; <italic>&#x3b2;</italic>, where <italic>&#x3b2;</italic> (0 &#x3c; <italic>&#x3b2;</italic> &#x3c; 1) is a small real perturbation of the relevant control parameter, and <italic>K</italic>
<sub>
<italic>c</italic>
</sub>, <italic>a</italic>
<sub>
<italic>c</italic>
</sub> are the initial (switch-on or switch-off) points of the bistable curves. Results are compared with the ordinary derivatives case (<italic>&#x3b1;</italic> &#x3d; 1) [<xref ref-type="bibr" rid="B14">14</xref>].</p>
<sec id="s3-1">
<title>3.1 The spruce budworm model</title>
<p>The switching-on and off -points, <italic>A</italic>
<sub>
<italic>on</italic>
</sub> and <italic>A</italic>
<sub>
<italic>off</italic>
</sub>, respectively, of the steady state bistable curve (<italic>N</italic> vs. <italic>K</italic>) according to the ODE, Eq. <xref ref-type="disp-formula" rid="e1">1</xref>, or the FDE; Eq. <xref ref-type="disp-formula" rid="e3">3</xref>, i. e., <inline-formula id="inf6">
<mml:math id="m14">
<mml:mfrac>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>N</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
</mml:mfrac>
<mml:mo>&#x3d;</mml:mo>
<mml:mfrac>
<mml:mrow>
<mml:msup>
<mml:mrow>
<mml:mi>d</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
<mml:mi>N</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>d</mml:mi>
<mml:msup>
<mml:mrow>
<mml:mi>&#x3c4;</mml:mi>
</mml:mrow>
<mml:mrow>
<mml:mi>&#x3b1;</mml:mi>
</mml:mrow>
</mml:msup>
</mml:mrow>
</mml:mfrac>
<mml:mo>&#x3d;</mml:mo>
<mml:mn>0</mml:mn>
</mml:math>
</inline-formula>, are shown in <xref ref-type="fig" rid="F1">Figure 1</xref>, for fixed values of the parameters <italic>F</italic> and <italic>B</italic> (c.f [<xref ref-type="bibr" rid="B14">14</xref>]). For fixed positive perturbation parameter <italic>&#x3b2;</italic> &#x3d; 0.1, the time delay <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> to switch up to the upper branch of the bistable curve, <xref ref-type="fig" rid="F2">Figure 2</xref>, is reduced in both cases of the fractional derivatives with smaller values of <italic>&#x3b1;</italic>, (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1), compared with the ordinary derivative case (<italic>&#x3b1;</italic> &#x3d; 1). This is confirmed in <xref ref-type="fig" rid="F3">Figure 3</xref> where for fixed 0 &#x3c; <italic>&#x3b2;</italic> &#x3c; 1, <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> vs. <italic>&#x3b1;</italic> best fits exponentially increasing function for <italic>&#x3b1;</italic> &#x2208; (0, 1) in both cases of fractional derivatives. Note in <xref ref-type="fig" rid="F2">Figure 2</xref>, <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> is slightly reduced in the case of Caputo-Fabrizio&#x2019;s fractional derivative, compared with Caputo&#x2019;s fractional derivative case. Further, for fixed fractional parameter <italic>&#x3b1;</italic> &#x3d; 0.25, for example, the lesser the perturbation parameter <italic>&#x3b2;</italic>, the larger is <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> (i.e. slowing down)- <xref ref-type="fig" rid="F4">Figures 4&#x2013;</xref> like the case of <italic>&#x3b1;</italic> &#x3d; 1 [<xref ref-type="bibr" rid="B14">14</xref>]. For fixed negative value of perturbation- <xref ref-type="fig" rid="F5">Figures 5&#x2013;</xref> at the switching-off point <italic>A</italic>
<sub>
<italic>off</italic>
</sub> (in <xref ref-type="fig" rid="F1">Figure 1</xref>), we have the same qualitative behaviour as in <xref ref-type="fig" rid="F2">Figure 2</xref>, but with smooth delayed switching to the lower branch.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>The steady state bistable curve of <italic>N</italic> against <italic>K</italic>, at fixed values of the parameters <italic>F</italic> &#x3d;0.85, <italic>B</italic> &#x3d;0.5. The switching-on and -off points: <italic>A</italic>
<sub>
<italic>on</italic>
</sub> &#x3d;(3.6631,0.61299) and <italic>A</italic>
<sub>
<italic>off</italic>
</sub> &#x3d;(3.0199,1.2793).</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g001.tif"/>
</fig>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>The transient population <italic>N</italic>(<italic>&#x3c4;</italic>) <italic>versus</italic> the normalised time <italic>&#x3c4;</italic> &#x3d; <italic>&#x3b3;t</italic> (as log scale), for control parameter with positive perturbation, <italic>K</italic> &#x3d; <italic>K</italic>
<sub>
<italic>c</italic>
</sub> &#x2b; <italic>&#x3b2;</italic>; <italic>K</italic>
<sub>
<italic>c</italic>
</sub> &#x3d;3.6631&#xa0;at the switching-on point, <italic>A</italic>
<sub>
<italic>on</italic>
</sub>, of <xref ref-type="fig" rid="F1">Figure 1</xref> and fixed <italic>&#x3b2;</italic> &#x3d;0.1, and for <italic>&#x3b1;</italic> &#x3d;1 (ordinary derivative) and 0.25 (Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives).</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g002.tif"/>
</fig>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Time-delay, <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub>, <italic>versus</italic> the fractional derivative parameter <italic>&#x3b1;</italic> at fixed <italic>&#x3b2;</italic> &#x3d;0.1. Circles represent the numerical results and the solid lines <italic>C</italic>
<sub>1</sub>, <italic>C</italic>
<sub>2</sub> represent the exponential fitting, 4.9<italic>e</italic>
<sup>2.2<italic>&#x3b1;</italic>
</sup> in the case of Caputo&#x2019;s derivative, and 3.8<italic>e</italic>
<sup>2.3<italic>&#x3b1;</italic>
</sup> in the case of Caputo-Fabrizio&#x2019;s derivative, respectively.</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g003.tif"/>
</fig>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>As <xref ref-type="fig" rid="F2">Figure 2</xref>, but at fixed value of <italic>&#x3b1;</italic> &#x3d;0.25, and different <italic>&#x3b2;</italic> &#x3d;0.01,0.3 in the case of: <bold>(A)</bold> Caputo&#x2019;s, and <bold>(B)</bold> Caputo-Fabrizio&#x2019;s, fractional derivatives.</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g004.tif"/>
</fig>
<fig id="F5" position="float">
<label>FIGURE 5</label>
<caption>
<p>Data as in <xref ref-type="fig" rid="F2">Figure 2</xref>, but with negative perturbation, <italic>K</italic>
<sub>
<italic>c</italic>
</sub> &#x2212; <italic>&#x3b2;</italic> at <italic>A</italic>
<sub>
<italic>off</italic>
</sub>, where <italic>K</italic>
<sub>
<italic>c</italic>
</sub> &#x3d;3.0199.</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g005.tif"/>
</fig>
<p>In both cases of positive and negative perturbations <italic>&#x3b2;</italic>) at the switching-on and -off points, <italic>A</italic>
<sub>
<italic>on</italic>
</sub> and <italic>A</italic>
<sub>
<italic>off</italic>
</sub>, respectively, the time delay formula <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> &#x223c;&#x7c;<italic>&#x3b2;</italic>&#x7c;<sup>&#x2212;1/2</sup> (inverse square root scaling law) essentially holds in the both cases of Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1), <xref ref-type="fig" rid="F6">Figure 6</xref>, similar to the ordinary derivative case (<italic>&#x3b1;</italic> &#x3d; 1) [<xref ref-type="bibr" rid="B14">14</xref>], but with different proportionality factor.</p>
<fig id="F6" position="float">
<label>FIGURE 6</label>
<caption>
<p>Time-delay, <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub>, <italic>versus</italic> the perturbation parameter <italic>&#x3b2;</italic> at the switching-on point <italic>A</italic>
<sub>
<italic>on</italic>
</sub> in <xref ref-type="fig" rid="F1">Figure 1</xref>. Circles represent the numerical results and the dashed lines represent the corresponding fittings, <inline-formula id="inf7">
<mml:math id="m15">
<mml:mi>&#x3bb;</mml:mi>
<mml:mo>/</mml:mo>
<mml:msqrt>
<mml:mrow>
<mml:mi>&#x3b2;</mml:mi>
</mml:mrow>
</mml:msqrt>
</mml:math>
</inline-formula>. <bold>(A)</bold> The case of ordinary derivative (<italic>&#x3b1;</italic> &#x3d;1). <bold>(B)</bold> The case of Caputo&#x2019;s fractional derivative (<italic>&#x3b1;</italic> &#x3d;0.25). <bold>(C)</bold> As <bold>(B)</bold> but with Caputo-Fabrizio&#x2019;s fractional derivative.</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g006.tif"/>
</fig>
</sec>
<sec id="s3-2">
<title>3.2 The Thomas reaction model</title>
<p>The steady state bistable curves for the Oxygen and uric acid concentrations <italic>u</italic>, <italic>v</italic>, respectively, against the supplied rate <italic>a</italic>, according to Eq. 2 or 4) are shown in <xref ref-type="fig" rid="F7">Figure 7</xref>, for fixed values of other system parameters [<xref ref-type="bibr" rid="B14">14</xref>]. For positive perturbation <italic>&#x3b2;</italic> in the ordinary derivative case (<italic>&#x3b1;</italic> &#x3d; 1) at the switching-on point, <italic>A</italic>
<sub>
<italic>on</italic>
</sub> in <xref ref-type="fig" rid="F7">Figure 7</xref>, the transient oxygen concentration <italic>u</italic>(<italic>&#x3c4;</italic>), <xref ref-type="fig" rid="F8">Figure 8</xref>, shows similar qualitative behaviour of reducing <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> in both cases of Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives, but with smaller quantitive difference. The same behaviour occurs with negative perturbation at the switching-off point <italic>A</italic>
<sub>
<italic>off</italic>
</sub> in <xref ref-type="fig" rid="F7">Figure 7</xref>. Similar qualitative behaviour is also exhibited for the transient uric acid concentration <italic>v</italic>(<italic>t</italic>) for <italic>&#x3b1;</italic> &#x3d; 1 [<xref ref-type="bibr" rid="B14">14</xref>] and <italic>&#x3b1;</italic> &#x3c; 1. The time delay <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> in both cases of <italic>u</italic>(<italic>&#x3c4;</italic>) and <italic>v</italic>(<italic>&#x3c4;</italic>) against the fractional parameter <italic>&#x3b1;</italic> and the perturbation parameter <italic>&#x3b2;</italic> shows similar qualitative behaviour as in <xref ref-type="fig" rid="F3">Figures 3</xref>, <xref ref-type="fig" rid="F6">6</xref>, respectively.</p>
<fig id="F7" position="float">
<label>FIGURE 7</label>
<caption>
<p>The steady state bistable curves, <italic>u</italic> and 0.12<italic>v</italic>, <italic>versus</italic> the control parameter, <italic>a</italic>, for fixed parameters <italic>K</italic> &#x3d;20, <italic>B</italic> &#x3d;100, <italic>&#x3b3;</italic> &#x3d; <italic>l</italic> &#x3d;1.</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g007.tif"/>
</fig>
<fig id="F8" position="float">
<label>FIGURE 8</label>
<caption>
<p>The transient Oxygen concentration, <italic>u</italic>(<italic>&#x3c4;</italic>), <italic>versus</italic> the normalised time, <italic>&#x3c4;</italic> with positive perturbation, <italic>&#x3ba;</italic> &#x3d; <italic>a</italic>
<sub>
<italic>c</italic>
</sub> &#x2b; <italic>&#x3b2;</italic>, <italic>a</italic>
<sub>
<italic>c</italic>
</sub> &#x3d;9.3643, at the switching-on point <italic>A</italic>
<sub>
<italic>on</italic>
</sub> of <xref ref-type="fig" rid="F7">Figure 7</xref> with fixed <italic>&#x3b2;</italic> &#x3d;0.1 for <italic>&#x3b1;</italic> &#x3d;1 (ordinary derivative) and 0.25 (Caputo&#x2019;s and Caputo-Fabrizio&#x2019;s fractional derivatives).</p>
</caption>
<graphic xlink:href="fphy-11-1123370-g008.tif"/>
</fig>
</sec>
</sec>
<sec id="s4">
<title>4 Summary</title>
<p>Fractional order mathematical models generalise the concept of ordinary differentiation to incorporate memory (time delay) and spatial non-local effects, and hence provide extra fractional parameters to interpret/predict the dynamical behaviour of the concerned model and capture more of its details.In this paper, we have investigated the switching time response at the critical switching-on and -off points of the bistable curves related to two biological models, namely, the spruce budworm outbreak model [<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B15">15</xref>] and the Thomas reaction model for enzyme membrane [<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B16">16</xref>] within fractional order models. Two definitions of fractional derivatives of order <italic>&#x3b1;</italic>, (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1) have been used, namely, Caputo&#x2019;s [<xref ref-type="bibr" rid="B40">40</xref>] and Caputo-Fabrizio&#x2019;s [<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>] fractional derivatives. Our study shows the following.<list list-type="simple">
<list-item>
<p>(i) The two definitions use convolution kernels of different variability that model the memory effect, namely, as power function [<xref ref-type="bibr" rid="B40">40</xref>] and as exponential function [<xref ref-type="bibr" rid="B21">21</xref>]. Both definitions yield the <italic>same</italic> qualitative results, (ii)-(iv) below, for the two biological models referred to above. The small quantitative variance in the results is due to the different mathematical forms for the memory or delay effect.</p>
</list-item>
<list-item>
<p>(ii) The switching time <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> due to the perturbation in the control (input) parameter, at the critical points of the bistable curves, is reduced further in the fractional derivative case (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1), compared with the ordinary derivative case (<italic>&#x3b1;</italic> &#x3d; 1) [<xref ref-type="bibr" rid="B14">14</xref>],</p>
</list-item>
<list-item>
<p>(iii) For fixed perturbation <italic>&#x3b2;</italic>, <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> as a function of the fractional derivative parameter, <italic>&#x3b1;</italic>, (0 &#x3c; <italic>&#x3b1;</italic> &#x3c; 1) fits an exponential form, i.e., <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> is reduced with strong memory index (<italic>&#x3b1;</italic> &#x226A; 1) and,</p>
</list-item>
<list-item>
<p>(iv) The switching time <italic>&#x3c4;</italic>
<sub>
<italic>D</italic>
</sub> as a function of the perturbation parameter <italic>&#x3b2;</italic> fits the scaled inverse square root law <inline-formula id="inf8">
<mml:math id="m16">
<mml:mfrac>
<mml:mrow>
<mml:mn>1</mml:mn>
</mml:mrow>
<mml:mrow>
<mml:msqrt>
<mml:mrow>
<mml:mi>&#x3b2;</mml:mi>
</mml:mrow>
</mml:msqrt>
</mml:mrow>
</mml:mfrac>
</mml:math>
</inline-formula> at fixed fractional derivative index (<italic>&#x3b1;</italic> &#x3c; 1) as in the ordinary derivative case (<italic>&#x3b1;</italic> &#x3d; 1) [<xref ref-type="bibr" rid="B14">14</xref>]. This is a further indication of the universality of this inverse square root law in both cases of ordinary and fractional derivative formulations. Experimental affirmation of this law in optical bistable models within ordinary derivative formation was reported in [<xref ref-type="bibr" rid="B42">42</xref>].</p>
</list-item>
</list>
</p>
<p>In general, fractional order models provide deeper insight into the system dynamics with memory taken, into effect and further motivate for experimental observation.Finally, we refer to some very recent works [<xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B44">44</xref>] on biological models of COVID-19. In [<xref ref-type="bibr" rid="B43">43</xref>], the authors investigated various parameter estimation methods of COVID-19 incubation period using lognormal and Gamma distribution assumptions. The expressions for the maximum likelihood estimation, expectation maximisation algorithm and newly proposed algorithm [<xref ref-type="bibr" rid="B43">43</xref>] are termed as double or single (Riemann) integrals: these integral expressions can be converted to fractional integrals (i.e usual Riemann integral with memory or non-local, convolution kernel of fractional index, e.g. [<xref ref-type="bibr" rid="B23">23</xref>]), and so to have extra fractional order parameter. The other biological model of COVID-19 [<xref ref-type="bibr" rid="B44">44</xref>] is concerned with the stability and sensitivity analysis, and optimal control strategies of a suggested epidemic control of COVID-19. The adopted model of ODEs can be converted to FDEs and so to investigate the memory effect in this epidemic model. The formulation of the models in [<xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B44">44</xref>] within fractional calculus will certainly add details concerning memory/non-local effects.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="s5">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="sec" rid="s10">Supplementary Material</xref>, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec id="s6">
<title>Author contributions</title>
<p>RA: Conceptualization, Methodology, Software SH: Data curation, Writing- Original draft preparation. RA: Visualization, Investigation. SH: Supervision: RA: Software, Validation: SH: Writing- Reviewing and Editing. All authors contributed to the article and approved the submitted version.</p>
</sec>
<sec id="s7">
<title>Funding</title>
<p>The authors received the fund by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah under grant No. (G-184-247-1443).</p>
</sec>
<sec sec-type="COI-statement" id="s8">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="s9">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec id="s10">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fphy.2023.1123370/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fphy.2023.1123370/full&#x23;supplementary-material</ext-link>
</p>
<supplementary-material xlink:href="DataSheet1.pdf" id="SM1" mimetype="application/pdf" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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