1,282 research outputs found
Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms
This paper develops a point-mutation model describing the evolutionary
dynamics of a population of adult stem cells. Such a model may prove useful for
quantitative studies of tissue aging and the emergence of cancer. We consider
two modes of chromosome segregation: (1) Random segregation, where the daughter
chromosomes of a given parent chromosome segregate randomly into the stem cell
and its differentiating sister cell. (2) ``Immortal DNA strand''
co-segregation, for which the stem cell retains the daughter chromosomes with
the oldest parent strands. Immortal strand co-segregation is a mechanism,
originally proposed by Cairns (J. Cairns, {\it Nature} {\bf 255}, 197 (1975)),
by which stem cells preserve the integrity of their genomes. For random
segregation, we develop an ordered strand pair formulation of the dynamics,
analogous to the ordered strand pair formalism developed for quasispecies
dynamics involving semiconservative replication with imperfect lesion repair
(in this context, lesion repair is taken to mean repair of postreplication
base-pair mismatches). Interestingly, a similar formulation is possible with
immortal strand co-segregation, despite the fact that this segregation
mechanism is age-dependent. From our model we are able to mathematically show
that, when lesion repair is imperfect, then immortal strand co-segregation
leads to better preservation of the stem cell lineage than random chromosome
segregation. Furthermore, our model allows us to estimate the optimal lesion
repair efficiency for preserving an adult stem cell population for a given
period of time. For human stem cells, we obtain that mispaired bases still
present after replication and cell division should be left untouched, to avoid
potentially fixing a mutation in both DNA strands.Comment: 9 pages, 3 figure
Ab initio study of alanine polypeptide chains twisting
We have investigated the potential energy surfaces for alanine chains
consisting of three and six amino acids. For these molecules we have calculated
potential energy surfaces as a function of the Ramachandran angles Phi and Psi,
which are widely used for the characterization of the polypeptide chains. These
particular degrees of freedom are essential for the characterization of
proteins folding process. Calculations have been carried out within ab initio
theoretical framework based on the density functional theory and accounting for
all the electrons in the system. We have determined stable conformations and
calculated the energy barriers for transitions between them. Using a
thermodynamic approach, we have estimated the times of characteristic
transitions between these conformations. The results of our calculations have
been compared with those obtained by other theoretical methods and with the
available experimental data extracted from the Protein Data Base. This
comparison demonstrates a reasonable correspondence of the most prominent
minima on the calculated potential energy surfaces to the experimentally
measured angles Phi and Psi for alanine chains appearing in native proteins. We
have also investigated the influence of the secondary structure of polypeptide
chains on the formation of the potential energy landscape. This analysis has
been performed for the sheet and the helix conformations of chains of six amino
acids.Comment: 24 pages, 10 figure
A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations
A major goal of modern computational biology is to simulate the collective
behaviour of large cell populations starting from the intricate web of
molecular interactions occurring at the microscopic level. In this paper we
describe a simplified model of cell metabolism, growth and proliferation,
suitable for inclusion in a multicell simulator, now under development
(Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the
proliferation dynamics of tumor cells which adapt their behaviour to respond to
changes in the biochemical composition of the environment. This modeling of
nutrient metabolism and cell cycle at a mesoscopic scale level leads to a
continuous flow of information between the two disparate spatiotemporal scales
of molecular and cellular dynamics that can be simulated with modern computers
and tested experimentally.Comment: 58 pages, 7 figures, 3 tables, pdf onl
Mean-field cooperativity in chemical kinetics
We consider cooperative reactions and we study the effects of the interaction
strength among the system components on the reaction rate, hence realizing a
connection between microscopic and macroscopic observables. Our approach is
based on statistical mechanics models and it is developed analytically via
mean-field techniques. First of all, we show that, when the coupling strength
is set positive, the model is able to consistently recover all the various
cooperative measures previously introduced, hence obtaining a single unifying
framework. Furthermore, we introduce a criterion to discriminate between weak
and strong cooperativity, based on a measure of "susceptibility". We also
properly extend the model in order to account for multiple attachments
phenomena: this is realized by incorporating within the model -body
interactions, whose non-trivial cooperative capability is investigated too.Comment: 25 pages, 4 figure
Deliverable 6.1 - Demonstration prototype of the EuroMix model toolbox
This document describes in short the new features in a demonstration prototype of the EuroMix toolbox, developed as MCRA 8.2.
An important aim of the EuroMix project is to develop and implement a web-based platform (the EuroMix toolbox) including data and models accessible to all key-actors in risk assessment and risk management.
In the EuroMix project the development of a mixture selection module based on exposure was prioritised, because the choice of chemicals for the experiments depended on this. A mixture selection module was therefore developed, based on a method called sparse non-negative matrix under-approximation (SNMU). The mixture selection module was then applied to French and Dutch data, leading to a list of suggested chemicals for each adverse outcome pathway in the project
‘Teamwerk in de wijk’. Overkoepelende rapportage 2021-2022
The politics and administration of institutional chang
Teamwerk in de wijk: een rapportage over het functioneren van wijkteams in vijf gemeentelijke organisaties 2020-2021
The politics and administration of institutional chang
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