Near-infrared spectroscopy of 1999 JU3, the target of the Hayabusa 2 mission

Context. Primitive asteroids contain complex organic material and ices relevant to the origin of life on Earth. These types of asteroids are the target of several-sample return missions to be launched in the next years. 1999 JU3 is the target of the Japanese Aerospace Exploration Agency's Hayabusa 2 mission. Aims. 1999 JU3 has been previously identified as a C-class asteroid. Spectroscopic observations at longer wavelengths will help to constrain its composition. Methods. We obtained spectroscopy of 1999 JU3 from 0.85 to 2.2 microns, with the 3.6 m Telescopio Nazionale Galileo using the low resolution mode of the Near Infrared Camera Spectrograph. Results. We present a near-infrared spectrum of 1999 JU3 from 0.85 to 2.2microns that is consistent with previously published spectra and with its C-type classification. Conclusions. Our spectrum confirms the primitive nature of 1999 JU3 and its interest as target of the sample-return mission Hayabusa 2.Comment: Research Note: 3 pages 1 Figure Received December 2012; accepted 4 March 201

Additional spectra of asteroid 1996 FG3, backup target of the ESA MarcoPolo-R mission

Near-Earth binary asteroid (175706) 1996 FG3 is the current backup target of the ESA MarcoPolo-R mission, selected for the study phase of ESA M3 missions. It is a primitive (C-type) asteroid that shows significant variation in its visible and near-infrared spectra. Here we present new spectra of 1996 FG3 and we compare our new data with other published spectra, analysing the variation in the spectral slope. The asteroid will not be observable again over the next three years at least. We obtained the spectra using DOLORES and NICS instruments at the Telescopio Nazionale Galileo (TNG), a 3.6m telescope located at El Roque de los Muchachos Observatory in La Palma, Spain. To compare with other published spectra of the asteroid, we computed the spectral slope S', and studied any plausible correlation of this quantity with the phase angle (alpha). In the case of visible spectra, we find a variation in spectral slope of Delta S' = 0.15 +- 0.10 %/10^3 A/degree for 3 < alpha < 18 degrees, in good agreement with the values found in the literature for the phase reddening effect. In the case of the near-infrared, we find a variation in the slope of Delta S' = 0.04 +- 0.08 %/10^3 A/degree for 6 < alpha < 51 degrees. Our computed variation in S' agrees with the only two values found in the literature for the phase reddening in the near-infrared. The variation in the spectral slope of asteroid 1996 FG3 shows a trend with the phase angle at the time of the observations, both in the visible and the near-infrared. It is worth noting that, to fully explain this spectral variability we should take into account other factors, like the position of the secondary component of the binary asteroid 1999 FG3 with respect to the primary, or the spin axis orientation at the time of the observations. More data are necessary for an analysis of this kind.Comment: 4 pages, 3 figures, Accepted in A&A 25 June 201

First-Order Regular and Degenerate Identification Differential Problems

We are concerned with both regular and degenerate first-order identification problems related to systems of differential equations of weakly parabolic type in Banach spaces. Several applications to partial differential equations and systems will be given in a subsequent paper to show the fullness of our abstract results

Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations

This work was supported in part by the French National Research Agency through the “ANR blanche” project Kibord [ANR-13-BS01-0004].Background: A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through in silico studies. Results: To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use. Conclusions: Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome, i.e., extinction of sensitive cells and selection of highly resistant cells. Also, our mathematical results formalise the idea that the use of cytotoxic agents at high doses can act as a double-edged sword by promoting the outgrowth of drug resistant cellular clones. Overall, our theoretical work offers a formal basis for the development of anti-cancer therapeutic protocols that go beyond the ‘maximum-tolerated-dose paradigm’, as they may be more effective than traditional protocols at keeping the size of cancer cell populations under control while avoiding the expansion of drug tolerant clones.Publisher PDFPeer reviewe

Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations

Background: A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through in silico studies. Results: To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use. Conclusions: Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome, i.e., extinction of sensitive cells and selection of highly resistant cells. Also, our mathematical results formalise the idea that the use of cytotoxic agents at high doses can act as a double-edged sword by promoting the outgrowth of drug resistant cellular clones. Overall, our theoretical work offers a formal basis for the development of anti-cancer therapeutic protocols that go beyond the 'maximum-tolerated-dose paradigm', as they may be more effective than traditional protocols at keeping the size of cancer cell populations under control while avoiding the expansion of drug tolerant clones. Reviewers: This article was reviewed by Angela Pisco, Sébastien Benzekry and Heiko Enderling

Effects of an advection term in nonlocal lotka-volterra equations

Nonlocal Lotka-Volterra equations have the property that solutions concentrate as Dirac masses in the limit of small diffusion. In this paper, we show how the presence of an advection term changes the location of the concentration points in the limit of small diffusion and slow drift. The mathematical interest lies in the formalism of constrained Hamilton-Jacobi equations. Our motivations come from previous models of evolutionary dynamics in phenotype-structured populations [R.H. Chisholm, T. Lorenzi, A. Lorz, et al., Cancer Res., 75, 930-939, 2015], where the diffusion operator models the effects of heritable variations in gene expression, while the advection term models the effect of stress-induced adaptation

Cell population heterogeneity and evolution towards drug resistance in cancer: Biological and mathematical assessment, theoretical treatment optimisation

Background Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level. Scope of review We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies. Major conclusions Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies. General significance Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled “System Genetics” Guest Editor: Dr. Yudong Cai and Dr. Tao Huang

Dissecting the dynamics of epigenetic changes in phenotype-structured populations exposed to fluctuating environments

International audienceAn enduring puzzle in evolutionary biology is to understand how individuals and populations adapt to fluctuating environments. Here we present an integro-differential model of adaptive dynamics in a phenotype-structured population whose fitness landscape evolves in time due to periodic environmental oscillations. The analytical tractability of our model allows for a systematic investigation of the relative contributions of heritable variations in gene expression, environmental changes and natural selection as drivers of phenotypic adaptation. We show that environmental fluctuations can induce the population to enter an unstable and fluctuation-driven epigenetic state. We demonstrate that this can trigger the emergence of oscillations in the size of the population, and we establish a full characterisation of such oscillations. Moreover, the results of our analyses provide a formal basis for the claim that higher rates of epimutations can bring about higher levels of intrapopulation heterogeneity, whilst intense selection pressures can deplete variation in the phenotypic pool of asexual populations. Finally, our work illustrates how the dynamics of the population size is led by a strong synergism between the rate of phenotypic variation and the frequency of environmental oscillations, and identifies possible ecological conditions that promote the maximisation of the population size in fluctuating environments

Evolutionary dynamics of phenotype-structured populations : from individual-level mechanisms to population-level consequences

This research was supported in part by the Australian Research Council (DP140100339) and by the French National Research Agency through the ANR blanche project Kibord [ANR-13-BS01-0004] and the “ANR JC” project Modevol [ANR-13-JS01-0009]. TL was also supported in part by the Hadamard Mathematics Labex, backed by the Fondation Mathématique Jacques Hadamard, through a grant overseen by the French National Research Agency [ANR-11-LABX-0056-LMH]. LD was also supported in part by Université Sorbonne Paris Cité “Investissements d’Avenir”[ANR-11-IDEX-0005].Epigenetic mechanisms are increasingly recognised as integral to the adaptation of species that face environmental changes. In particular, empirical work has provided important insights into the contribution of epigenetic mechanisms to the persistence of clonal species, from which a number of verbal explanations have emerged that are suited to logical testing by proof-of-concept mathematical models. Here, we present a stochastic agent-based model and a related deterministic integrodifferential equation model for the evolution of a phenotype-structured population composed of asexually-reproducing and competing organisms which are exposed to novel environmental conditions. This setting has relevance to the study of biological systems where colonising asexual populations must survive and rapidly adapt to hostile environments, like pathogenesis, invasion and tumour metastasis. We explore how evolution might proceed when epigenetic variation in gene expression can change the reproductive capacity of individuals within the population in the new environment. Simulations and analyses of our models clarify the conditions under which certain evolutionary paths are possible, and illustrate that whilst epigenetic mechanisms may facilitate adaptation in asexual species faced with environmental change, they can also lead to a type of “epigenetic load” and contribute to extinction. Moreover, our results offer a formal basis for the claim that constant environments favour individuals with low rates of stochastic phenotypic variation. Finally, our model provides a “proof of concept” of the verbal hypothesis that phenotypic stability is a key driver in rescuing the adaptive potential of an asexual lineage, and supports the notion that intense selection pressure can, to an extent, offset the deleterious effects of high phenotypic instability and biased epimutations, and steer an asexual population back from the brink of an evolutionary dead end.PostprintPeer reviewe

Evolutionary dynamics of phenotype-structured populations: from individual-level mechanisms to population-level consequences

Epigenetic mechanisms are increasingly recognised as integral to the adaptation of species that face environmental changes. In particular, empirical work has provided important insights into the contribution of epigenetic mechanisms to the persistence of clonal species, from which a number of verbal explanations have emerged that are suited to logical testing by proof-of-concept mathematical models. Here, we present a stochastic agent-based model and a related deterministic integrodifferential equation model for the evolution of a phenotype-structured population composed of asexually-reproducing and competing organisms which are exposed to novel environmental conditions. This setting has relevance to the study of biological systems where colonising asexual populations must survive and rapidly adapt to hostile environments, like pathogenesis, invasion and tumour metastasis. We explore how evolution might proceed when epigenetic variation in gene expression can change the reproductive capacity of individuals within the population in the new environment. Simulations and analyses of our models clarify the conditions under which certain evolutionary paths are possible and illustrate that while epigenetic mechanisms may facilitate adaptation in asexual species faced with environmental change, they can also lead to a type of “epigenetic load” and contribute to extinction. Moreover, our results offer a formal basis for the claim that constant environments favour individuals with low rates of stochastic phenotypic variation. Finally, our model provides a “proof of concept” of the verbal hypothesis that phenotypic stability is a key driver in rescuing the adaptive potential of an asexual lineage and supports the notion that intense selection pressure can, to an extent, offset the deleterious effects of high phenotypic instability and biased epimutations, and steer an asexual population back from the brink of an evolutionary dead end