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</o:shapelayout></xml><![endif]--></head><body lang=JA link=blue vlink=purple><div class=WordSection1><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'>At 4:50PM 05/14/2016, Plamen L. Simeonov wrote:<o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p><p class=MsoNormal><b><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif'>The key question in such a “deep holistic” physically-phenomenological physiology (</span></b><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif'>3φ<u>)</u><b> is how to define or comprehend (self-organized) criticality operationally within the unifying framework of biomathematics and biocomputation</b>.</span><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p><p class=MsoNormal style='background:white'><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'> Let me start with paraphrasing this statement in a pedestrian manner. Consider, for instance, the serious physiological issue of metastatic melanoma. The microenvironment of the melanoma cells seems to affect the gene expression programs with use of a lot of transcription factors. What is unique to the genotypic conditions of melanoma tumors is that the malignant cells within the same tumor displays transcriptional heterogeneity associated with the cell cycle, spatial context and a drug-resistance program, etc. That is to say, a subset of genes expressed by one cell type may influence the propagation of other cell types as riding on the vehicle of intercellular communication for tumor phenotype </span><span lang=EN style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F4E79;mso-style-textfill-fill-color:#1F4E79;mso-style-textfill-fill-alpha:100.0%'><a href="http://science.sciencemag.org/content/352/6282/189"><span style='color:black;mso-style-textfill-fill-color:black;mso-style-textfill-fill-alpha:100.0%'><span style='color:black;mso-style-textfill-fill-color:black;mso-style-textfill-fill-alpha:100.0%'>(science.sciencemag.org/content/352/6282/189</span></span></a></span><span lang=EN style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#10253F'> </span><span lang=EN style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F4E79;mso-style-textfill-fill-color:#1F4E79;mso-style-textfill-fill-alpha:100.0%'>). </span><span lang=EN-US><o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'> <o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'> One strenuous problem surrounding metastatic melanoma is in the difficulty in conceiving of its global state description because of its metastatic nature. The situation would seem almost similar to the unattainability of the macro-state description at the critical point of a phase transition in statistical mechanics as Alex Hankey called our attention to. In contrast, the unattainability of a state description is everywhere in biology. Exchange of matter that is ubiquitous in biology makes its state description unlikely right in the middle of the exchange process, while the state description might recover either before or after the exchange event. <o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'> In any case, one decisive event making criticality durable must have been the origins of life on our Earth, as taking advantage of a lot of counterfactual conditionals on the ground of first come, first served. <o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'> Koichiro Matsuno<o:p></o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p><p class=MsoNormal><span lang=EN-US style='font-size:10.0pt;font-family:"Arial",sans-serif;color:#1F497D'><o:p> </o:p></span></p></div></body></html>