0000000000554193
AUTHOR
G. Barbaraci
Digital control circuitry for the p53 dynamics in cancer cell and apoptosis
Experimental work and theoretical models deduce a "digital" response of the p53 transcription factor when genomic integrity is damaged. The mutual influence of p53 and its antagonist, the Mdm2 oncogene, is closed in feedback. This paper proposes an aerospace architecture for translating the p53/Mdm2/DNA damage network into a digital circuitry in which the optimal control theory is applied for obtaining the requested dynamic evolutions of some considered cell species for repairing a DNA damage. The purpose of this paper is not to improve the analysis of the actual mathematical models but to demonstrate the usefulness of such digital circuitry design to detect and predict the cell species dyn…
On p21 tracking property in cancer cell unravelled bio-digitally in silico. Are apoptosis principles universal?
Upon severe DNA damage, p21 acts in a dual mode; on the one hand, it inhibits the cyclin-CDK complex for arresting the G2/M transition and on the other hand, it indirectly becomes an apoptotic factor by activating--in sequence--the retinoblastoma protein, E2F1 and APAF1 expressions. But, in a cancer cells proliferation, the mechanisms of, and participants in, the apoptosis failure remain unclear. Since the p21/p53/Mdm2 proteins network normally involves a digital response in a cancer cell, through an original design of a cell signalling-protein simulator, we demonstrate, in silico, that apoptosis phase instability is fully reciprocated by p21 mRNA irregular dynamics which operates according…
Digital control circuitry of cancer cell and its apoptosis
This study, through a typical aerospace systems architecture, suggests an engineering design of a human cancer cell circuitry in which a digital optimal control matrix is assigned to repair the DNA damage level and/or to trigger its apoptosis. Here, the conceived machinery is proposed taking into account the state of the art in cancer investigation. However, it could be further generalized. The most recent studies on cancer pathologies give a predominant role to the oncosuppressor protein p53 and its antagonist, the oncogene Mdm2. Experimental and theoretical approaches are in agreement in deducing a “digital” response of the p53 when genomic integrity is damaged. Once DNA damage is present…
On MR Differential with Limited Slip
Design of a magnetorheological (MR) sports car differential is presented in this paper, with the aim of the total mass reduction and the torque maintenance. The torque output is controlled by adjusting the applied magnetic field. The nominal output torque of the differential is derived by using Bingham plastic constitutive model; the choice of the materials occurs to minimize the thickness of the circuit, but preliminary sizing based on electromagnetic theory does not lead to satisfactory results. Electromagnetic finite element analysis (FEA) is performed to estimate the effective distribution of the magnetic field. The shear stress distribution in MR Fluid is theoretically predicted using …