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What can mathematical, computational and robotic models tell us about the origins of syntax?
Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach
The evolutionary dynamics of a system of cancerous cells in a model of
chronic myeloid leukemia (CML) is investigated by a statistical approach.
Cancer progression is explored by applying a Monte Carlo method to simulate the
stochastic behavior of cell reproduction and death in a population of blood
cells which can experience genetic mutations. In CML front line therapy is
represented by the tyrosine kinase inhibitor imatinib which strongly affects
the reproduction of leukemic cells only. In this work, we analyze the effects
of a targeted therapy on the evolutionary dynamics of normal, first-mutant and
cancerous cell populations. Several scenarios of the evolutionary dynamics of
imatinib-treated leukemic cells are described as a consequence of the efficacy
of the different modeled therapies. We show how the patient response to the
therapy changes when an high value of the mutation rate from healthy to
cancerous cells is present. Our results are in agreement with clinical
observations. Unfortunately, development of resistance to imatinib is observed
in a proportion of patients, whose blood cells are characterized by an
increasing number of genetic alterations. We find that the occurrence of
resistance to the therapy can be related to a progressive increase of
deleterious mutations.Comment: Submitted to Central European Journal of Physic
Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib
Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic
Nonlinear deterministic equations in biological evolution
We review models of biological evolution in which the population frequency
changes deterministically with time. If the population is self-replicating,
although the equations for simple prototypes can be linearised, nonlinear
equations arise in many complex situations. For sexual populations, even in the
simplest setting, the equations are necessarily nonlinear due to the mixing of
the parental genetic material. The solutions of such nonlinear equations
display interesting features such as multiple equilibria and phase transitions.
We mainly discuss those models for which an analytical understanding of such
nonlinear equations is available.Comment: Invited review for J. Nonlin. Math. Phy
New Studies of the Pulsar Wind Nebula in the Supernova Remnant CTB 80
We investigated the kinematics of the pulsar wind nebula (PWN) associated
with PSR B1951+32 in the old supernova remnant CTB 80 using the Fabry-Perot
interferometer of the 6m Special Astrophysical Observatory telescope. In
addition to the previously known expansion of the system of bright filaments
with a velocity of 100-200km/s, we detected weak high-velocity features in the
H-alpha line at least up to velocities of 400-450km/s. We analyzed the
morphology of the PWN in the H-alpha, [SII], and [OIII] lines using HST data
and discuss its nature. The shape of the central filamentary shell, which is
determined by the emission in the [OIII] line and in the radio continuum, is
shown to be consistent with the bow-shock model for a significant (about 60
degrees) inclination of the pulsar's velocity vector to the plane of the sky.
In this case, the space velocity of the pulsar is twice higher than its
tangential velocity, i.e., it reaches ~500 km/s, and PSR B1951+32 is the first
pulsar whose line-of-sight velocity (of about 400 km/s) has been estimated from
the PWN observations. The shell-like H-alpha-structures outside the bow shock
front in the east and the west may be associated with both the pulsar's jets
and the pulsar-wind breakthrough due to the layered structure of the extended
CTB 80 shell.Comment: to appear in Astronomy Letters, 12 pages, 6 postscript figures, two
in colour; for a version with high resolution figures see
http://www.sao.ru/hq/grb/team/vkom/CTB80_fine.pd
Niche as a determinant of word fate in online groups
Patterns of word use both reflect and influence a myriad of human activities
and interactions. Like other entities that are reproduced and evolve, words
rise or decline depending upon a complex interplay between {their intrinsic
properties and the environments in which they function}. Using Internet
discussion communities as model systems, we define the concept of a word niche
as the relationship between the word and the characteristic features of the
environments in which it is used. We develop a method to quantify two important
aspects of the size of the word niche: the range of individuals using the word
and the range of topics it is used to discuss. Controlling for word frequency,
we show that these aspects of the word niche are strong determinants of changes
in word frequency. Previous studies have already indicated that word frequency
itself is a correlate of word success at historical time scales. Our analysis
of changes in word frequencies over time reveals that the relative sizes of
word niches are far more important than word frequencies in the dynamics of the
entire vocabulary at shorter time scales, as the language adapts to new
concepts and social groupings. We also distinguish endogenous versus exogenous
factors as additional contributors to the fates of words, and demonstrate the
force of this distinction in the rise of novel words. Our results indicate that
short-term nonstationarity in word statistics is strongly driven by individual
proclivities, including inclinations to provide novel information and to
project a distinctive social identity.Comment: Supporting Information is available here:
http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00
Ectopic A-lattice seams destabilize microtubules
Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe
Individual biases, cultural evolution, and the statistical nature of language universals: the case of colour naming systems
Language universals have long been attributed to an innate Universal Grammar. An alternative explanation states that linguistic universals emerged independently in every language in response to shared cognitive or perceptual biases. A computational model has recently shown how this could be the case, focusing on the paradigmatic example of the universal properties of colour naming patterns, and producing results in quantitative agreement with the experimental data. Here we investigate the role of an individual perceptual bias in the framework of the model. We study how, and to what extent, the structure of the bias influences the corresponding linguistic universal patterns. We show that the cultural history of a group of speakers introduces population-specific constraints that act against the pressure for uniformity arising from the individual bias, and we clarify the interplay between these two forces
The role of cell location and spatial gradients in the evolutionary dynamics of colon and intestinal crypts
BACKGROUND: Colon and intestinal crypts serve as an important model system for adult stem cell proliferation and differentiation. We develop a spatial stochastic model to study the rate of somatic evolution in a normal crypt, focusing on the production of two-hit mutants that inactivate a tumor suppressor gene. We investigate the effect of cell division pattern along the crypt on mutant production, assuming that the division rate of each cell depends on its location. RESULTS: We find that higher probability of division at the bottom of the crypt, where the stem cells are located, leads to a higher rate of double-hit mutant production. The optimal case for delaying mutations occurs when most of the cell divisions happen at the top of the crypt. We further consider an optimization problem where the “evolutionary” penalty for double-hit mutant generation is complemented with a “functional” penalty that assures that fully differentiated cells at the top of the crypt cannot divide. CONCLUSION: The trade-off between the two types of objectives leads to the selection of an intermediate division pattern, where the cells in the middle of the crypt divide with the highest rate. This matches the pattern of cell divisions obtained experimentally in murine crypts. REVIEWERS: This article was reviewed by David Axelrod (nominated by an Editorial Board member, Marek Kimmel), Yang Kuang and Anna Marciniak-Czochra. For the full reviews, please go to the Reviewers’ comments section. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13062-016-0141-6) contains supplementary material, which is available to authorized users
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