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<div class="moz-cite-prefix">Dear Sheri and FIS Colleagues,</div>
<div class="moz-cite-prefix"><br>
</div>
<div class="moz-cite-prefix">Thanks a lot for your impressive text.
The interpenetration of logic-computation and biology-immunology
for the analysis of the "algorithmic" defense of self versus the
non-self raises a number of relevant issues. I will refer to a
few.<br>
</div>
<div class="moz-cite-prefix">You briefly mention Barbieri's code
biology & codepoieis on the complexification of eukaryotes vs.
prokaryotes (my own take comes from Villarreal, "ex viruses
omnia", enlarging McClintock on mobile elements). It is very
interesting to discuss the new forms of vulnerability of the
multicellulars precisely by those viral ancestries at the same
time evolutionary associates & foes. The innate branch of the
immune system probably already had predecessors in unicellular
eukaryotes (there is an ancestral form of "protosynapse" between
them that predates the immune and the neuronal synapses). The
relationship between immune and nervous systems is so deep... you
can be quite right searching for both self vs. non-self
recognition-strategies in both of them. There is also the
intriguing presence and tentative regulation of around 20 trillion
bacteria (also fungi & viruses) of more than 2,000 species
into the gut microbiome. The way immune & neural enteric
system intermingle in the sheparding of that "ecosystemic cattle"
is amazing. Probably it could be another instance of mixed
algorithmic strategy not far away from your own search scope. <br>
</div>
<div class="moz-cite-prefix">Months ago, a leading researcher on
ribosome structure/function/evolution lectured in this list--Youri
Timsit. I wonder whether he has been around and read the present
text, at least in the comment on ribosomes. <br>
</div>
<div class="moz-cite-prefix">Going to Mirror System Neurons, my
opinion is that other species apart from primates use it, see for
instance domestic dogs' amazing mind reading capabilities. Perhaps
in the very inner representations of self (sensory, motor,
visceral, plus the different pain systems) you may find other
instances of advanced self vs. non-self operatives. <br>
</div>
<div class="moz-cite-prefix">And cancer? That means a dramatic
breach of the self organization. The transformation of self into
an invader non-self. We start to understand a little bit into the
sets of mutations of the different cancer types. Whatever formal
approaches will be of help.<br>
</div>
<div class="moz-cite-prefix"><br>
</div>
<div class="moz-cite-prefix">Sorry that I cannot discuss on the
suggestive formalisms you utilize--other FISers will do. At the
time being these are my initial, mostly biological, comments. <br>
</div>
<div class="moz-cite-prefix"><br>
</div>
<div class="moz-cite-prefix">Thanks again,</div>
<div class="moz-cite-prefix">--Pedro<br>
</div>
<div class="moz-cite-prefix"><br>
</div>
<div class="moz-cite-prefix">El 25/10/2022 a las 20:42, Markose,
Sheri escribió:<br>
</div>
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<p class="MsoNormal"><span
style="font-family:"Arial",sans-serif">Dear
Colleagues - I look forward to your valuable comments.<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-family:"Arial",sans-serif"><o:p> </o:p></span></p>
<p style="margin:0cm;text-align:center;background:white"
align="center"><a name="_Hlk116426332" moz-do-not-send="true"><b><span
style="font-size:11.0pt;color:black;border:none
windowtext 1.0pt;padding:0cm">G</span></b></a><span
style="mso-bookmark:_Hlk116426332"><span
style="font-size:11.0pt;color:black">ö<b><span
style="border:none windowtext 1.0pt;padding:0cm">delian
Self-Referential Genomic Information Processing:
Complex Self-Other Interactions and Novelty Production</span></b></span></span><span
style="mso-bookmark:_Hlk116426332"><b><span
style="font-size:11.0pt;border:none windowtext
1.0pt;padding:0cm"><o:p></o:p></span></b></span></p>
<p style="margin:0cm;background:white"><span
style="mso-bookmark:_Hlk116426332"><b><span
style="font-size:11.0pt;color:black;border:none
windowtext 1.0pt;padding:0cm"><o:p> </o:p></span></b></span></p>
<p style="margin:0cm;background:white"><span
style="mso-bookmark:_Hlk116426332"><b><i><span
style="font-size:11.0pt;color:black;border:none
windowtext 1.0pt;padding:0cm">Overview for Foundations
of Information Science Discussion –
<o:p></o:p></span></i></b></span></p>
<p style="margin:0cm;background:white"><span
style="mso-bookmark:_Hlk116426332"><b><i><span
style="font-size:11.0pt;color:black;border:none
windowtext 1.0pt;padding:0cm">Sheri Markose
25-10-2022<o:p></o:p></span></i></b></span></p>
<ol style="margin-top:0cm" type="1" start="1">
<li style="margin-top:0cm;margin-bottom:0cm;mso-list:l0 level1
lfo1;background:white">
<span style="mso-bookmark:_Hlk116426332"><b><span
style="font-size:11.0pt;color:black;border:none
windowtext 1.0pt;padding:0cm">Background
</span></b></span><span
style="mso-bookmark:_Hlk116426332"><b><span
style="font-size:11.0pt;border:none windowtext
1.0pt;padding:0cm"><o:p></o:p></span></b></span></li>
</ol>
<p style="margin:0cm;background:white"><span
style="mso-bookmark:_Hlk116426332"><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm">Complexity, evolvability, novelty
production and ‘thinking outside the box’ in biology and
humans have for most part relied on models of randomness
or on statistical white noise error terms.
</span></span><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm"><o:p></o:p></span></p>
<p style="margin:0cm;background:white"><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm"> The digitization of
inheritable information in the genome encoded in a near
universal alphabet (A,T,C,G/U) has been called the
‘algorithmic takeover of biology’ by Walker and Davis
(2013). The Faustian pact at the genesis of life
colourfully portrayed by Freeman Dyson as ‘ the takeover of
a replicative digital virus of an analogue metabolism’
accords with the perspective of Forterre, Zimmer, Villareal,
Koonin and others. </span><span
style="font-size:11.0pt;color:black">This underpins the
remarkable fact that in nature only life and biology as we
know it and the artifacts of genomic intelligence (GI)
thereof are explicitly code based digital systems. </span><span
style="font-size:11.0pt"><o:p></o:p></span></p>
<p class="MsoBodyText2" style="line-height:normal"><span
style="font-size:11.0pt"> Genomic
intelligence is a concept introduced in
<a
href="https://urldefense.com/v3/__https://doi.org/10.3390/e23040405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqV3O-kDY$"
moz-do-not-send="true">Markose (2021)</a> specifically to
characterize the Gödelization of code-based information
processing in genomic systems with the distinctive
self-referential conditions of Gödel Incompleteness results
that appear to have been acquired for complexification over
the course of evolution of multicellular eukaryote life,
<a
href="https://urldefense.com/v3/__https://doi.org/10.1016/j.biosystems.2022.104718__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqPn2Rp5k$"
moz-do-not-send="true">Markose (2022)</a>. <a
name="bbib59" moz-do-not-send="true">
To explain the latter in contrast to the relative stasis
of prokaryotes, which has remain unchanged since
inception,
</a></span><span style="mso-bookmark:bbib59"></span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib10__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqdTKw3lg$"
moz-do-not-send="true"><span style="mso-bookmark:bbib59"><span
style="font-size:11.0pt;color:#0C7DBB">Barbieri (2012</span></span><span
style="mso-bookmark:bbib59"></span></a><span
style="mso-bookmark:bbib59"><span
style="font-size:11.0pt;color:#2E2E2E">; </span></span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib13__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq0lIhVMs$"
moz-do-not-send="true"><span style="mso-bookmark:bbib59"><span
style="font-size:11.0pt;color:#0C7DBB">2018)</span></span><span
style="mso-bookmark:bbib59"></span></a><span
style="mso-bookmark:bbib59"><span style="font-size:11.0pt">,for
instance, has resorted to Code Biology and Codeopoiesis,
viz. biotic code based explanations to complement the
more popular thermodynamic explanations of
self-organization and
</span></span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/topics/mathematics/autopoiesis__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqDFaksjk$"
title="Learn more about autopoiesis from ScienceDirect's
AI-generated Topic Pages" moz-do-not-send="true"><span
style="mso-bookmark:bbib59"><span
style="font-size:11.0pt;color:#2E2E2E">autopoiesis</span></span><span
style="mso-bookmark:bbib59"></span></a><span
style="mso-bookmark:bbib59"><span
style="font-size:11.0pt;color:#2E2E2E">.
</span></span><span style="mso-bookmark:bbib59"></span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib59__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqIQhnjCw$"
moz-do-not-send="true"><span style="mso-bookmark:bbib59"><span
style="font-size:11.0pt;color:#0C7DBB">Igamberdiev
(2021)</span></span><span style="mso-bookmark:bbib59"></span></a><span
style="mso-bookmark:bbib59"></span><span
style="font-size:11.0pt;color:#2E2E2E"> gives general
principles, but no concrete evidence, for why “living
systems during evolution continuously realize the proof of
Gödel's theorems (1931).” <o:p></o:p></span></p>
<p style="margin:0cm;background:white"><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm"> Significantly, while
debunking the idea that the primary source of evolutionary
changes arise from random transcription/replication errors,
t</span><span
style="font-size:11.0pt;color:black;background:white">he
epochal discovery by Nobel Laureate
<a name="bbib88" moz-do-not-send="true">Barbara </a></span><span
style="mso-bookmark:bbib88"></span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib88__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqajIC2C4$"
moz-do-not-send="true"><span style="mso-bookmark:bbib88"><span
style="font-size:11.0pt;color:#0C7DBB">McClintock (1984)</span></span><span
style="mso-bookmark:bbib88"></span></a><span
style="mso-bookmark:bbib88"></span><span
style="font-size:11.0pt;color:black;background:white"> of
viral transposable elements that conduct cut-paste
(transposons) and copy-paste (retrotransposon) gives a code
based explanation for genomic evolvability, brain
plasticity and novel phenotype primarily in eukaryotes.
This underscores the truism that primarily only software can
change software and also that viral hacking by such internal
and external biotic malware is the Achilles heel of genomic
digital systems.<span
style="background:yellow;mso-highlight:yellow">
</span> </span><span
style="font-size:11.0pt;background:white"><o:p></o:p></span></p>
<ol style="margin-top:0cm" type="1" start="2">
<li style="margin-top:0cm;margin-bottom:0cm;mso-list:l0 level1
lfo1;background:white">
<b><span style="font-size:11.0pt;color:black;border:none
windowtext 1.0pt;padding:0cm">Unpacking the Evidence</span></b><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm">
<b>for </b></span><b><span
style="font-size:11.0pt;color:black">Gödelization of
Biology</span></b><span
style="font-size:11.0pt;color:black">
</span><b><span style="font-size:11.0pt;border:none
windowtext 1.0pt;padding:0cm"><o:p></o:p></span></b></li>
</ol>
<p style="margin:0cm;background:white"><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm"> While operations
on encoded information fall under the purview of Computation
Theory and Recursion Function Theory (<b>RFT</b>), till
recently there was no evidence for how this and </span><span
style="font-size:11.0pt;color:#2E2E2E">Gödel's theorems
apply to</span><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm"> biology. Markose (</span><span
style="font-size:11.0pt;color:black"><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib61__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq6qlj9z0$"
moz-do-not-send="true"><span style="border:none windowtext
1.0pt;padding:0cm">2022</span></a><span
style="border:none windowtext 1.0pt;padding:0cm">) unpacks
the recent breakthroughs here. </span></span><span
style="font-size:11.0pt;border:none windowtext
1.0pt;padding:0cm"><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> Gödelization
of information processing starts, firstly, with unique
identifiers or Gödel numbers for digital entities well known
in the digital economy and taking the form of bio-peptide
unique identifiers including ‘zip codes’ in organisms as
discovered in the Nobel prize winning work of Blobel (2009).
It appears all signalling in bio-ICT relies on peptide
identifiers from transcription factors to neuron-neuron
links.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> Two
other
<span style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white">
distinctive </span>Gödelian<span
style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white"> features found in
genomic intelligence, using epithets from Hofstadter
(1999) are self-reference (<b>Self-Ref</b>) or the online
machine execution involving the Diagonal operator and
offline virtual self-representation (<b>Self-Rep</b>) of
the former.
</span>The breakthrough on the significance of these staples
of <b>RFT</b> found in textbooks such as Rogers (1967) and
Cutland (1980), starts with the insight from Gershenfeld (<a
name="bbib48" moz-do-not-send="true"></a><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib48__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqGSrl56A$"
moz-do-not-send="true"><span style="mso-bookmark:bbib48"><span
style="color:#0C7DBB">2012</span></span><span
style="mso-bookmark:bbib48"></span></a><span
style="mso-bookmark:bbib48"></span><span
style="color:#2E2E2E">, </span><a name="bbib49"
moz-do-not-send="true"></a><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib49__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqpGCiPPQ$"
moz-do-not-send="true"><span style="mso-bookmark:bbib49"><span
style="color:#0C7DBB">2017</span></span><span
style="mso-bookmark:bbib49"></span></a><span
style="mso-bookmark:bbib49"></span><span
style="color:#2E2E2E"> Chapter 3 p. 109</span></span><span
style="font-size:11.0pt;font-family:"Georgia",serif;color:#2E2E2E">)</span><span
style="font-size:11.0pt"> as to what the
self-referential/Diagonal operator means for biology, where
a program
<i>g </i>builds<i> </i>machine </span><i><span
style="font-size:11.0pt;font-family:Symbol">f
</span></i><span style="font-size:11.0pt">to run <i>g </i>(typically
denoted as </span>
<i><span style="font-size:11.0pt;font-family:Symbol">f</span></i><i><sub><span
style="font-size:11.0pt">g</span></sub></i><i><span
style="font-size:11.0pt">(g)</span></i><span
style="font-size:11.0pt">). Gershenfeld (</span><span
style="font-size:11.0pt"><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib48__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqGSrl56A$"
moz-do-not-send="true"><span style="color:#0C7DBB">2012</span></a>)
says what 21 century digital fabrication is trying to
achieve is something biology solved 3.7 billion years ago
with the self-assembly programs associated with the ribosome
and other transcriptase machinery involved in gene
expression for the morphology, somatic identity and
regulatory control of the organism. <o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> Despite
the central role assigned to self-reference for the sentient
self in advanced organisms (<a
href="https://urldefense.com/v3/__https://scholar.google.se/citations?view_op=view_citation&hl=sv&user=ZW8RWdAAAAAJ&citation_for_view=ZW8RWdAAAAAJ:Y0pCki6q_DkC__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqclXIy_8$"
moz-do-not-send="true">Gardenfors 2003</a>, <a
href="https://urldefense.com/v3/__https://doi.org/10.1016/j.neuroimage.2005.12.002__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqKaUbmro$"
moz-do-not-send="true">Northoff et. al, 2006</a> ,
<a name="bbib94" moz-do-not-send="true"></a><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib94__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqkgZx_Ng$"
moz-do-not-send="true"><span style="mso-bookmark:bbib94"><span
style="color:#0C7DBB">Newen (2018)</span></span><span
style="mso-bookmark:bbib94"></span></a><span
style="mso-bookmark:bbib94"></span> , <a
href="https://urldefense.com/v3/__https://doi.org/10.1016/j.pbiomolbio.2018.10.002__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqM9CMK80$"
moz-do-not-send="true">Miller et.al., 2018</a> , etc) only
<a name="bbib114" moz-do-not-send="true"></a><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib114__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqPf630Ss$"
moz-do-not-send="true"><span style="mso-bookmark:bbib114"><span
style="color:#0C7DBB">Tsuda (2014)</span></span><span
style="mso-bookmark:bbib114"></span></a><span
style="mso-bookmark:bbib114"></span><span
style="color:#2E2E2E"> </span>and Markose (2017,
2021,2022) have noted how the evolutionary development of <b>Self-Rep</b>
mirror structures as in
<span style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white">
the</span> Gödel Meta-Representation Theorem (Rogers,1967)
is necessary for biotic elements to make statements about
themselves, first having self-assembled themselves. This
<i>offline</i> embodied <b>Self-Rep</b>, which contrasts
with no such structures in prokaryotes, was a paradigm shift
<span style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white">
in the Adaptive Immune System (AIS) some 500 million years
ago in the lineage of jawed fish, called the Big Bang of
Immunology, Janeway et. al (2005). This latterly appears
as Mirror Neuron System (MNS) mostly in primate brains
first discovered by the Parma Group of neuroscientists. <o:p></o:p></span></span></p>
<p class="MsoFootnoteText"><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm;background:white"> </span><span
style="font-size:11.0pt">The
<b><span style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white">AIS</span></b><span
style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white"> demonstrates virtual
offline mirrored self-representation (<b>Self-Rep</b>) in
the MHC1 T cell receptors of ~85 % of expressed genes viz.
<i>halted </i>machine executions of genomic self-assembly
codes that determine the somatic and phenotype identity
for the organism. As will be seen, these Self-Repped gene
codes in the Thymus, called the <i>Thymic Self </i> (</span><a
href="https://urldefense.com/v3/__https://www.frontiersin.org/articles/10.3389/fpsyt.2020.540676/full__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqRtkoQzk$"
moz-do-not-send="true"><span style="border:none windowtext
1.0pt;padding:0cm;background:white">Ramon and Faure,
2021</span></a><span style="color:black;border:none
windowtext 1.0pt;padding:0cm;background:white">) or ‘the
science of self’ (</span><a
href="https://urldefense.com/v3/__https://link.springer.com/article/10.1007/s00281-020-00831-y__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq71KRW4U$"
moz-do-not-send="true"><span style="border:none windowtext
1.0pt;padding:0cm;background:white">Greenen, 2021</span></a><span
style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white">) are primarily used
to identify the hostile other, viz. negation function
operators of non-self antigens. In turn, the Mirror
Neuron System (<b>MNS</b>) reuses codes of self-actions
from the sensory-motor cortex for social cognition and
inference regarding conspecifics via virtual simulations
in the <b>MNS</b> (</span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib35__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqek3WNP4$"
moz-do-not-send="true"><span style="color:#0C7DBB">Fadiga
et al. (1995)</span></a><span style="color:#2E2E2E">; </span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib46__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqHLWVVsM$"
moz-do-not-send="true"><span style="color:#0C7DBB">Gallese
et al. (1996)</span></a><span style="color:#2E2E2E">; </span><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib102__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqmxeFzqA$"
moz-do-not-send="true"><span style="color:#0C7DBB">Rizzolatti
et al. (1996)</span></a>).
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> It
is conjectured that an identical
<b>RFT</b> machinery is involved in the self-other nexus in
both the <b>AIS</b> and
<b>MNS</b>. The graphics for <b>Self-Rep</b> Mirror
Mapping in the <b>AIS</b> and
<b>MNS</b> is given in <a
href="https://urldefense.com/v3/__https://www.mdpi.com/1099-4300/23/4/405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq8Rs91D0$"
moz-do-not-send="true">Figure 1 in Markose (2021)</a>.<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span
style="font-size:11.0pt;background:lime;mso-highlight:lime"><o:p> </o:p></span></p>
<ol style="margin-top:0cm" type="1" start="3">
<li class="MsoListParagraph"
style="margin-bottom:0cm;margin-left:0cm;mso-add-space:auto;line-height:normal;mso-list:l0
level1 lfo1">
<b><span style="font-family:"Times New
Roman",serif">Detection of Non-Self Antigen in AIS:
N</span></b><b><span style="font-family:"Times New
Roman",serif">ew Diversity-Selector Model and Gödel
Sentence in Genomic Blockchain Distributed Ledger (BCDL)
<o:p></o:p></span></b></li>
</ol>
<p class="MsoFootnoteText"><b><span
style="font-size:11.0pt;font-family:Symbol"> </span></b><span
style="font-size:11.0pt">The most significant of all
breakthroughs here is the one made by the game theorist
Binmore (1987) who raised the ‘spectre of Gödel (1931)’ in
the form of Gödel’s Liar who will negate or falsify what can
be computed/predicted. Binmore effectively mooted the
adversarial digital game which is co-extensive with life
itself (Markose, 2017, 2021). This constitutes the
<i>fourth</i> condition of Gödel systems and involves an
adversarial agent in the form of a virus or a hacker whose
actions cannot be constrained in anyway.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> The
Gödel Incompleteness result that generates the Gödel
Sentence permits a code qua biotic element to self-report
“I’m under attack”, when it has been hacked/negated by a
novel malware. This marks an endogenous exit from listable
sets, a necessary condition for novelty and the production
of novel antibodies, to avoid the irrational state of
logical inconsistency of formal systems (<a
href="https://urldefense.com/v3/__https://www.jstor.org/stable/j.ctt1b7x7ww__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqtrLoY_E$"
moz-do-not-send="true">Smullyan,1961</a>). The genomic
Gödel Sentence in terms of 21 century nomenclature is a <i>hash</i>
that helps demonstrate endogenously that the outputs of
expressed genes have been maliciously altered. Note,
</span>that halting self-assembly gene codes, <i>g</i> <span
style="font-family:Symbol">
Î</span><span style="font-family:Symbol"> </span><b>G </b>that
create the organism are theorems of the genomic system
<span style="font-size:11.0pt">theorems and is disjoint from
known non-theorems or what the immunologist Burnett (1958)
famously called ‘forbidden codes’ if allowed to run will
‘negate’ the theorems and cause harm.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> Indeed,
how the
<b>AIS</b> identifies novel software attacks on own gene
codes, <i>g</i> , by malware/parasite negating functions
<i>f<sub>p</sub></i><sup>¬ !</sup> , which belongs to an
uncountable infinite set that cannot be mechanically listed,
is stupendous case of uber bio-cybersecurity.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> <span
style="color:black;border:none windowtext
1.0pt;padding:0cm;background:white">The AIS implements
‘out of the box’ astronomic anticipative search for novel
non-self antigens necessary for </span>novel anti-body
production and cognition <span
style="color:black;background:white">
in humans manifests unbounded proteanism for novel
extended phenotypes, Dawkins (1987), in the form of
artifacts outside of ourselves</span>.
<span style="color:black;background:white">This facility
found only in the <b>AIS</b> relying on the Recombination
Activator genes (<b>RAG</b> 1 and 2) and in the human
brain for neural receptor diversity runs into orders of
magnitude of 10<sup>20</sup> – 10<sup>30</sup> that exceed
the pre-scripted germline genome size many times over.
</span><span style="background:white"><o:p></o:p></span></span></p>
<p class="MsoFootnoteText"><span
style="font-size:11.0pt;color:#555555;background:white"> </span><span
style="font-size:11.0pt"> The Rogers (1967) fixed point
indexes for yet to happen
<i>f<sub>p</sub></i><sup>¬ !</sup> attacks by the non-self
antigens are generated in the
<b>AIS</b> in most ingenious fashion: a large number of
codes/indexes purported to be of different
<a name="_Hlk117013984" moz-do-not-send="true"><i>f<sub>p</sub></i><sup>¬
!</sup> </a>on each <b>self-repped</b>
<i> g </i>are generated in the T-Cell Receptors. This is
the most spectacular case of predictive coding. Suppose that
the g.n for the specific tuple {<i> f<sub>p</sub></i><sup>¬
</sup>, <i>g<sub>n</sub></i> } denoted by <i>g<sup>¬</sup></i>.
When the attack by
<i>f<sub>p</sub></i><sup>¬ !</sup> takes place in real time
in the periphery involving the said pair {<i> f<sub>p</sub></i><sup>¬
</sup>, <i>g<sub>n</sub></i> }, the experientially driven
peripheral MHC1 receptor must record this and if this
‘syncs’ with the one that was speculatively generated in the
thymic MHC1 receptors, two parts of the fixed point come
together to construct a genomic Gödel Sentence. <i> </i><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> This
molecular genomic diversity-selector model follows a unique
self-referential blockchain distributed ledger that is
different, in terms of the self-referential design, from
man-made
<b>BCDLs</b> first invented circa 2009. <span
style="color:black;border:none windowtext
1.0pt;padding:0cm">
The genomic </span><b>BCDL </b><span
style="color:black;border:none windowtext
1.0pt;padding:0cm">manifests secure digital and
decentralized record keeping where no internal or external
bio-malware can compromise the immutability of the life’s
building blocks and no novel blocks can be added that is
not consistent with extant blocks. <o:p>
</o:p></span></span></p>
<p class="MsoFootnoteText"><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm"> There are no doubt
</span><span
style="font-size:11.0pt;color:black;background:white">macroscopic
environmental and population level pressures of the
Neo-Darwinian style natural selection arising from
conspecific or multi-species competition for survival in
terms of those which reproduce more and those which die out.
There is growing evidence that at level of bio-digital smart
controls of the eukaryote genome and homeostasis, selective
pressures are based on the principles of a unique
self-referential
</span><b><span
style="font-size:11.0pt;color:black;border:none windowtext
1.0pt;padding:0cm">BCDL</span></b><span
style="font-size:11.0pt;color:black;background:white">
</span><span style="font-size:11.0pt;background:white"><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span
style="font-size:11.0pt;color:black;background:white"> In
conclusion, genomic intelligence in vertebrates that has
reached its apogee in humans is highly empathic as the
conspecific/other is the projection of self; greatly
Machiavellian having co-evolved with adversarial viral
agents; geared toward unbounded proteanism from the get-go
starting with transposon based diversity of
<b>RAG</b> genes in the immune system and stringently
self-regulated by a <b>BCD</b>L driven by the principle of
autonomy of the life of the organism and an agenda to be
hack-free.
</span><span style="font-size:11.0pt;background:white"><o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-family:"Arial",sans-serif"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">Points
for discussion and areas where I would like collaborators
and those I can learn from as in my day job I’m an
economist
<o:p></o:p></span></b></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">#1</span></b><span
style="font-size:11.0pt"> I fully concur with the latter
part of
</span><span style="font-size:11.0pt"><a
href="https://urldefense.com/v3/__https://doi.org/10.1016/j.pbiomolbio.2018.10.002__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqM9CMK80$"
moz-do-not-send="true">Miller/Torday (2018)</a> statement
:
<o:p></o:p></span></p>
<p style="margin:0cm;background:white"><span
style="font-size:11.0pt;color:#2E2E2E">“As self-referential
cognition is demonstrated by all living organisms, life can
be equated with the sustenance of cellular </span><span
style="font-size:11.0pt;color:black"><a
href="https://urldefense.com/v3/__https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/homeostasis__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq8F9h1Jc$"
title="Learn more about homeostasis from ScienceDirect's
AI-generated Topic Pages" moz-do-not-send="true"><span
style="color:#2E2E2E">homeostasis</span></a></span><span
style="font-size:11.0pt;color:#2E2E2E"> in the continuous
defence of 'self'.” </span><span
style="font-size:11.0pt;color:black">However, Miller/Torday
do not use any of the code based
<b>RFT</b> Gödel style <b>Self-Ref</b> mirror structures
for genomic information processing.</span><span
style="font-size:11.0pt"><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">
No doubt prokaryote CRISPR based identification of non-self
antigens is highly sophisticated and so are the innate
immune system strategies which primarily entail analog
defences of
</span><span style="font-size:11.0pt">setting up barriers,
toxicity, raising temperature by inflammation and ingestion
by phagocytes. Prokaryotes distinctively do not have the
mirror
<b>Self-Rep </b>offline structures of self as in the Rogers
(1967) <b>RFT</b> fixed point theorems which permit
bio-molecules to self-report changes to their own codes. My
take on homeostasis in eukaryotes post jawed fish is that
bio software data security and hence the autonomy of self
was taken to the next level: the design of how codes can
self-report they have been changed by bio malware by
utilizing hashes like the Gödel Sentence.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"> It
will be interesting to compare the bacteria-phage arms race
in prokaryotes with the one in the
<b>AIS</b> antibody production outlined above. I have
reached out to John Mattick and Silvia Sanchez Ramon on
these issues.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">#2.</span></b><span
style="font-size:11.0pt"> In Markose (2021) I indicate that
the generation of genomic Gödel Sentences for detection of
novel the non-self antigen is necessary for novel antibody
production is a testable hypothesis. Those who died of Covid
19 were found not to be capable of antibody production and
instead were subjected by a cytokine storm brought about by
the analog defences of toxicity and inflammation of the
innate immune system.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt"># 3</span></b><span
style="font-size:11.0pt"> A common
<b>Self-Rep</b> mirror <b>RFT</b> machinery for self-other
recognition in the <b>
AIS </b>and social cognition following from the Mirror
Neuron Systems in primates has been conjectured. Similar
conjectures have been made at least since Irun Cohen, but
without any
<b>RFT</b> to guide the discussions. </span><span
style="font-size:11.0pt"><a
href="https://urldefense.com/v3/__https://www.mdpi.com/1099-4300/23/4/405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq8Rs91D0$"
moz-do-not-send="true">Figure 1 in Markose (2021)</a>
shows how a knock-out of the circuitry for self’s updates on
non-self activity vis-ŕ-vis self (the RHS entry in the <i>offline</i>
<b>Self-Rep</b> </span><span
style="font-size:11.0pt;font-family:Symbol">s</span><span
style="font-size:11.0pt">(g,g) operator ) known to be
controlled by interferon gamma as in
<a
href="https://urldefense.com/v3/__https://www.nature.com/articles/nature18626__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqF1KRYvk$"
moz-do-not-send="true">Jonathan Kipnis Group 2016</a>
experiment on rats, could lead to loss of immune
capabilities as well as their sociability. Note, the
Markose
<b>RFT</b> machinery for the self-other nexus is a different
explanation to the evo-devo one given by Kipnis et.al.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">#4</span></b><span
style="font-size:11.0pt"> Finally, it is a matter of
incredulity that over 90 years have passed since Gödel
(1931) for evidence to be found that the staples of
<b>Self-Ref</b> and <b>Self-Rep</b> and the Gödel Sentence
are ubiquitous in Biology. A number of factors can be
adduced. Even those who espouse that code-based operations
are relevant in cognition such as in the Computational
Theory of Mind never mention
<b>Self-Ref</b> and <b>Self-Rep</b>, let alone that the
Gödel Sentence is like a </span>
<i><span style="font-size:11.0pt">hash </span></i><span
style="font-size:11.0pt">which permits a software document
to endogenously self-report it has been hacked. There is a
strong anti-machine view which overlooks the encoded basis
of the genome and biology and claims that biology is a
non-digital natural process that is creative in some
vitalistic way.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoNormal"><b><span style="font-family:"Times New
Roman",serif">References
<o:p></o:p></span></b></p>
<p class="MsoNormal"><b><span style="font-family:"Times New
Roman",serif">#Blog on University of Essex Website:
<i>How we became smart – a journey of discovery through
the world of game theory and genomic intelligence</i>
<a
href="https://urldefense.com/v3/__https://www.essex.ac.uk/blog/posts/2021/10/26/how-we-became-smart__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqVgSsoLo$"
moz-do-not-send="true">https://www.essex.ac.uk/blog/posts/2021/10/26/how-we-became-smart</a>
<o:p></o:p></span></b></p>
<p class="MsoNormal"><b><span style="font-family:"Times New
Roman",serif"><br>
#</span></b><span style="font-family:"Times New
Roman",serif">Markose, S.M, 2022,
</span><span style="font-family:"Times New
Roman",serif;color:#505050;mso-fareast-language:EN-GB">Complexification
of eukaryote phenotype: Adaptive immuno-cognitive systems as
unique Gödelian blockchain distributed ledger,
</span><span style="font-family:"Times New
Roman",serif;color:#323232;mso-fareast-language:EN-GB">Biosystems,
ISSN: 0303-2647, Vol: 220,
</span><a
href="https://urldefense.com/v3/__https://doi.org/10.1016/j.biosystems.2022.104718__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqPn2Rp5k$"
target="_blank" title="Persistent link using digital object
identifier" moz-do-not-send="true"><span
style="font-family:"Times New
Roman",serif;color:#0C7DBB">https://doi.org/10.1016/j.biosystems.2022.104718</span></a><span
class="MsoHyperlink"><span style="font-family:"Times
New Roman",serif;color:#0C7DBB">
<o:p></o:p></span></span></p>
<p class="MsoNormal"><u><span style="font-family:"Times New
Roman",serif;color:#0C7DBB"><br>
<span class="MsoHyperlink"><span style="color:#0C7DBB">#</span></span></span></u><span
style="font-family:"Times New
Roman",serif;color:black;background:white">Markose,
S.M, 2021, </span><a
href="https://urldefense.com/v3/__https://doi.org/10.3390/e23040405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqV3O-kDY$"
moz-do-not-send="true"><span style="font-family:"Times
New Roman",serif;color:#70B85D;border:none windowtext
1.0pt;padding:0cm;background:white">“Genomic Intelligence
as Über Bio-Cybersecurity: The Gödel Sentence in
Immuno-Cognitive Systems”</span></a><span
style="font-family:"Times New
Roman",serif;color:black;background:white">, </span><em><span
style="font-family:"Calibri",sans-serif;color:black;border:none
windowtext 1.0pt;padding:0cm;background:white">Entropy. </span></em><span
style="font-family:"Times New
Roman",serif;color:black;background:white">23(4), 405;
ttps://doi.org/10.3390/e23040405 <o:p></o:p></span></p>
<p class="MsoNormal"><span class="info"><span
style="font-family:"Times New
Roman",serif;color:black;border:none windowtext
1.0pt;padding:0cm;background:white"><br>
Markose, S.M, 2017, Complex type 4 structure changing
dynamics of digital agents: Nash equilibria or a game with
arms race in innovations. </span></span><span class="info"><i><span
style="font-family:"Times New
Roman",serif;color:black;border:none windowtext
1.0pt;padding:0cm">Journal of Dynamics & Games</span></i></span><span
class="info"><span style="font-family:"Times New
Roman",serif;color:black;border:none windowtext
1.0pt;padding:0cm;background:white">, 2017, 4 (3) :
255-284. doi: </span></span><a
href="https://urldefense.com/v3/__http://dx.doi.org/10.3934/jdg.2017015__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqC_UOvRc$"
moz-do-not-send="true"><span style="font-family:"Times
New Roman",serif;color:#70B85D;border:none windowtext
1.0pt;padding:0cm">10.3934/jdg.2017015</span></a><span
style="font-family:"Times New
Roman",serif;color:black;background:white">
<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-family:"Arial",sans-serif"><o:p> </o:p></span></p>
<p class="MsoNormal"><span
style="font-family:"Arial",sans-serif"><o:p> </o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;font-family:"Arial",sans-serif">-------------------<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;font-family:"Arial",sans-serif">Professor
Sheri Markose<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;font-family:"Arial",sans-serif">Economics
Department<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;font-family:"Arial",sans-serif">University
of Essex<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;font-family:"Arial",sans-serif">UK
<o:p></o:p></span></p>
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