Jean Clairambault | INRIA - Academia.edu (original) (raw)

Papers by Jean Clairambault

Early Human Development, 1993

related to a changed balance between the sympathetic and parasympathetic nervous systems with a d... more related to a changed balance between the sympathetic and parasympathetic nervous systems with a diminished parasympathetic component of heart rate control in prematures reaching term, as compared to newborns.

Early Human Development, 1992

To complete traditional time-and frequency-domain analyses, new methods derived from non-linear s... more To complete traditional time-and frequency-domain analyses, new methods derived from non-linear systems analysis have recently been developed for time series studies. A panel of the most widely used methods of heart rate analysis is given with computations on mouse data, before and after a single atropine injection.

Journal of Materials Processing Technology, 1991

Heart rate variability (HRV) analysis of 24 healthy newborn sleeping babies was performed by a sh... more Heart rate variability (HRV) analysis of 24 healthy newborn sleeping babies was performed by a short-time Fourier transform in three frequency bands, reflecting the activity of both branches of the autonomic nervous system (ANS), vagal and sympathetic. The means of the three extracted time signals, computed over records of 512 heartbeats, were used as a material for principal component analysis, and for discriminant factor analyses, to separate sleep states and conceptional age (CA) groups. This study suggests that sleep state discrimination, on the basis of an opposition between high (purely vagal in its origin) and low (vagal and sympathetic) frequency HRV, is regularly improved from 31 to 41 weeks CA; and a strong increase in ANS activity, mainly vagal, as reflected by high-frequency HRV, occurs precociously, not later than 38 weeks CA

Cardiovascular Research, 1996

Journal of Molecular Medicine-jmm, 1997

Heart rate is a function of at least three factors located in the sinus node, including the pace... more Heart rate is a function of at least three factors located in the sinus node, including the pacemaker and the activity of the sympathetic and vagal pathways. Heart rate varies during breathing and exercising. The is far from being a purely academic question because, after myocardial infarction or in cardiac insufficiency, reduced heart rate variability (HRV) represents the most valuable prognostic factor. HRV is usually considered index of the sympathovagal balance and is explored using time domain analysis, such as spectral analysis. Nevertheless, methods such as the Fast Fourier Transformation are not applicable to small rodents which have an unstable heart rate with asymmetric oscillations. Nonlinear methods show chaotic behavior under some conditions. A time and frequency domain method of analysis, the Wigner-Villé Transform, has been proposed for the study of HRV in both humans and small rodents, as a compromise between linear and nonlinear methods. We developed a method to quantify both arrhythmias and HRV in unanesthetized rodents. Such a method allows study of the relationship between the physiological parameters and the myocardial phenotype. Ventricular premature beats are more frequent in 16-month-old spontaneously hypertensive rats than in age-matched controls. In addition, HRV is attenuated in spontaneously hypertensive rats, as in compensatory cardiac hypertrophy in humans, and such attenuation is considered a prognostic index. Converting enzyme inhibition reduces in parallel arterial hypertension, cardiac hypertrophy, and ventricular fibrosis; it prevents ventricular premature beats and normalizes heart rate variability. It can be demonstrated that the incidence of ventricular premature beats is linked to the myocardial phenotype in terms of both cardiac hypertrophy and fibrosis. The two factors act as independent variables. HRV is correlated with the incidence of arrhythmias, suggesting that the beneficial effects of converting enzyme inhibition are related to prevention of arrhythmias.

Cardiovascular Drugs and Therapy, 1997

Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HR... more Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HRV) is presently one of the best indices to predict fatal issues in cardiac failure and after myocardial infarction. HRV depends on various reflexes. In addition, parallel studies of HRV and the myocardial adrenergic and muscarinic transduction system in experimental models of cardiac hypertrophy (CH) have suggested that the myocardial phenotype at the sinus-node level may also play a role. A transgenic strain of mice with atrial overexpression of the 677-1 receptors was generated with attenuated HRV, which demonstrates that the phenotype itself is a determinant of HRV. HRV is explored by noninvasive techniques, including simple determination of the standard error of the mean, time-domain analysis, and Fourier transformation. We recently developed a time and frequency domain method of analysis, the smoothed pseudo-Wigner-Ville transformation, which allows better exploration of nonstationarity. Nonlinear methods have also been applied due to the extreme complexity of the biological determinants, and have provided evidence of a chaotic attractor in certain conditions. It is proposed that in steady state a very simple process, which is not completely deterministic, could better explain intermit interval regulations than chaotic behavior. In contrast, under extreme circumstances the regulation proceeds using chaotic behavior. Arrhythmias and HRV can be quantitated in 16-month-old unanesthetized spontaneously hypertensive rats (SHR). Ventricular premature beats are more frequent in SHR than in age-matched controls; they disappear after converting enzyme inhibition (CEI) relative to the reduction of both cardiac hypertrophy and ventricular fibrosis. HRV is attenuated in SHR, as it is in compensatory CH in humans. When CH is prevented, HRV returns to normal. CEI is therefore antiarrhythmic. Another pharmacological application of this concept concerns the bradycardic agents that may improve HRV.

To study the autonomic nervous system maturation in newborns, the authors analyzed the heart rate... more To study the autonomic nervous system maturation in newborns, the authors analyzed the heart rate variability in correlation with sleep states and body movements. They used SIGNAL, a data flow parallel and synchronous language, designed for real time system programming. It answers the needs of this heart rate analysis sytem by processing large amounts of polygraphic signals at various sampling rates, and expressing relationships among their rhythms. The methods used and the implementation in the SIGNAL language are described

How far is neuroepithelial cell proliferation in the developing central nervous system a determin... more How far is neuroepithelial cell proliferation in the developing central nervous system a deterministic process? Or, to put it in a more precise way, how accurately can it be described by a deterministic mathematical model? To provide tracks to answer this question, a deterministic system of transport and diffusion partial differential equations, both physiologically and spatially structured, is introduced as a model to describe the spatially organized process of cell proliferation during the development of the central nervous system. As an initial step towards dealing with the three-dimensional case, a unidimensional version of the model is presented. Numerical analysis and numerical tests are performed. In this work we also achieve a first experimental validation of the proposed model, by using cell proliferation data recorded from histological sections obtained during the development of the optic tectum in the chick embryo.

We address the following question: Can one sustain, on the basis of mathematical models, that for... more We address the following question: Can one sustain, on the basis of mathematical models, that for cancer cells, the loss of control by circadian rhythm favours a faster population growth? This question, which comes from the observation that tumour growth in mice is enhanced by experimental disruption of the circadian rhythm, may be tackled by mathematical modelling of the cell cycle. For this purpose we consider an age-structured population model with control of death (apoptosis) rates and phase transitions, and two eigenvalues: one for periodic control coefficients (via a variant of Floquet theory in infinite dimension) and one for constant coefficients (taken as the time average of the periodic case). We show by a direct proof that, surprisingly enough considering the abovementioned observation, the periodic eigenvalue is always greater than the steady state eigenvalue when the sole apoptosis rate is concerned. We also show by numerical simulations when transition rates between the phases of the cell cycle are concerned, that, without further hypotheses, no natural hierarchy between the two eigenvalues exists. This at least shows that, if such models are to take account the abovementioned observation, control of death rates inside phases is not sufficient, and that transition rates between phases are a key target in proliferation control.

We study the growth rate of a cell population that follows an age-structured PDE with time-period... more We study the growth rate of a cell population that follows an age-structured PDE with time-periodic coefficients. Our motivation comes from the comparison between experimental tumor growth curves in mice endowed with intact or disrupted circadian clocks, known to exert their influence on the cell division cycle. We compare the growth rate of the model controlled by a time-periodic control on its coefficients with the growth rate of stationary models of the same nature, but with averaged coefficients. We firstly derive a delay differential equation which allows us to prove several inequalities and equalities on the growth rates. We also discuss about the necessity to take into account the structure of the cell division cycle for chronotherapy modeling. Numerical simulations illustrate the results.

Journal of Mathematical Biology, 2008

We present a nonlinear model of the dynamics of a cell population divided into proliferative and ... more We present a nonlinear model of the dynamics of a cell population divided into proliferative and quiescent compartments. The proliferative phase represents the complete cell cycle (G 1−S−G 2−M) of a population committed to divide at its end. The model is structured by the time spent by a cell in the proliferative phase, and by the amount of Cyclin D/(CDK4 or 6) complexes. Cells can transit from one compartment to the other, following transition rules which differ according to the tissue state: healthy or tumoral. The asymptotic behaviour of solutions of the nonlinear model is analysed in two cases, exhibiting tissue homeostasis or tumour exponential growth. The model is simulated and its analytic predictions are confirmed numerically.

We study proliferation in tissues from the point of view of physiologically structured partial di... more We study proliferation in tissues from the point of view of physiologically structured partial differential models, focusing on age synchronisation in the cell division cycle in cell populations and its control at phase transition checkpoints.

Mathematical and Computer Modelling, 2008

We analyse both theoretically and numerically a nonlinear model of the dynamics of a cell populat... more We analyse both theoretically and numerically a nonlinear model of the dynamics of a cell population divided into proliferative and quiescent compartments that is described in [F. Bekkal Brikci, J. Clairambault, B. Ribba, B. Perthame, An age-and-cyclinstructured cell population model with proliferation and quiescence, INRIA Research Report No 5941, 2006]. It is a physiological age and molecule-structured population model for the cell division cycle, which aims at representing both healthy and tumoral tissues. A noticeable feature of this model is to exhibit tissue homeostasis for healthy tissue and unlimited growth for tumoral tissue. In particular, the present paper analyses model parameters for which a tumoral tissue exhibits polynomial growth and not mere exponential growth. Polynomial tumour growth has been recently advocated by several authors, on the basis either of experimental observations or of individual cell-based simulations which take space limitations into account. This model is able to take such polynomial growth behaviour into account without considerations of space, by proposing exchange functions between the proliferative and quiescent compartments.

Comptes Rendus Mathematique, 2006

We address the following question: can one sustain, on the basis of mathematical models, that for... more We address the following question: can one sustain, on the basis of mathematical models, that for cancer cells, the loss of control by circadian rhythm favours a faster growth? This question, which comes from the observation that tumour growth in mice is enhanced by experimental disruption of the circadian rhythm, may be tackled by mathematical modelling of the cell cycle. For this purpose we consider an age-structured population model with control of death (apoptosis) rates and phase transitions, and two eigenvalues: one for periodic control coefficients (via a variant of Floquet theory in infinite dimension) and one for constant coefficients (taken as the time average of the periodic case). We show by a direct proof that, surprisingly enough considering the above-mentioned observation, the periodic eigenvalue is always greater than the steady state eigenvalue when the sole apoptosis rate is concerned. We also show by numerical simulations when transition rates between the phases of the cell cycle are concerned, that, without further hypotheses, no natural hierarchy between the two eigenvalues exists. This at least shows that, if such models are to take account of the above-mentioned observation, control of death rates inside phases is not sufficient, and that transition rates between phases are a key target in proliferation control. To cite this article: J. Clairambault et al., C. R. Acad. Sci. Paris, Ser. I 342 (2006).  2005 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Comptes Rendus Mathematique, 2007

Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictat... more Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictate rhythms of approximately 24 h (circa diem) to many physiological processes. This includes metabolism (e.g., temperature, hormonal blood levels) and cell proliferation. It has been observed in tumor-bearing laboratory rodents that a severe disruption of these physiological rhythms results in accelerated tumor growth.

Mathematical Modelling of Natural Phenomena, 2009

Mathematical and Computer Modelling, 2011