260 research outputs found
Implication du virus Epstein-Barr ainsi que de la protéine virale EBNA1 dans la modification de l’épissage alternatif et dans le développement du cancer de l’estomac
Le virus Epstein-Barr est un des virus dotés de propriétés oncogéniques. Ceci est inquiétant car le virus est présent sous forme d’infection latente dans 95% de la population adulte au niveau mondial. Bien que ce virus soit associé surtout aux lymphomes, d’autres types de cancer sont aussi connus par leur association à cette infection tels que le carcinome gastrique. En fait, 10% de tous les cas de carcinome gastrique sont associés à la présence du virus Epstein-Barr. Plusieurs protéines du virus ont été étudiées individuellement afin d’établir leurs propriétés oncogéniques. Parmi celles-ci, la protéine virale EBNA1 joue un rôle important au niveau de la carcinogénèse et son expression est détectée au niveau des tissus gastriques cancéreux associés à l’infection par le virus Epstein-Barr.
Des études réalisées au cours de ces dernières années montrent la relation entre un patron aberrant de l’épissage alternatif des ARN messagers et différents types de cancer, comme le cancer du sein et de la prostate. Les travaux de recherche présentés dans ce mémoire visent à établir si le virus Epstein-Barr est capable de changer le patron d’épissage alternatif au niveau des tissus cancéreux de l’estomac. L’utilisation de données de séquençage à haut débit fait sur des tissus cancéreux et tissus sains d’estomac (infectés ou non par le virus Epstein-Barr) permettra d’estimer les changements au niveau du patron d’épissage alternatif en relation à l’état des tissus et de la présence du virus Epstein-Barr. Les résultats obtenus nous montrent que l’épissage alternatif de plus de 500 gènes est altéré lorsque le virus est présent. Parmi ces gènes plusieurs codent pour des facteurs d’épissage, des facteurs de transcription, et des suppresseurs de tumeurs qui pourraient être impliqués dans le processus de développement du cancer.
Finalement, nos résultats montrent que le patron d’épissage alternatif d’une cellule est modifié lorsque celle-ci est infectée par le virus Epstein-Barr ou qu’elle exprime une de ses protéines virales EBNA1, et ces altérations touchent plusieurs gènes impliqués dans des processus biologiques et qui semblent favoriser le développement du cancer
Geometric Integration of Hamiltonian Systems Perturbed by Rayleigh Damping
Explicit and semi-explicit geometric integration schemes for dissipative
perturbations of Hamiltonian systems are analyzed. The dissipation is
characterized by a small parameter , and the schemes under study
preserve the symplectic structure in the case . In the case
the energy dissipation rate is shown to be asymptotically
correct by backward error analysis. Theoretical results on monotone decrease of
the modified Hamiltonian function for small enough step sizes are given.
Further, an analysis proving near conservation of relative equilibria for small
enough step sizes is conducted.
Numerical examples, verifying the analyses, are given for a planar pendulum
and an elastic 3--D pendulum. The results are superior in comparison with a
conventional explicit Runge-Kutta method of the same order
Fluctuating "Pulled" Fronts: the Origin and the Effects of a Finite Particle Cutoff
Recently it has been shown that when an equation that allows so-called pulled
fronts in the mean-field limit is modelled with a stochastic model with a
finite number of particles per correlation volume, the convergence to the
speed for is extremely slow -- going only as .
In this paper, we study the front propagation in a simple stochastic lattice
model. A detailed analysis of the microscopic picture of the front dynamics
shows that for the description of the far tip of the front, one has to abandon
the idea of a uniformly translating front solution. The lattice and finite
particle effects lead to a ``stop-and-go'' type dynamics at the far tip of the
front, while the average front behind it ``crosses over'' to a uniformly
translating solution. In this formulation, the effect of stochasticity on the
asymptotic front speed is coded in the probability distribution of the times
required for the advancement of the ``foremost bin''. We derive expressions of
these probability distributions by matching the solution of the far tip with
the uniformly translating solution behind. This matching includes various
correlation effects in a mean-field type approximation. Our results for the
probability distributions compare well to the results of stochastic numerical
simulations. This approach also allows us to deal with much smaller values of
than it is required to have the asymptotics to be valid.Comment: 26 pages, 11 figures, to appear in Phys. rev.
Review and Comparison of Computational Approaches for Joint Longitudinal and Time‐to‐Event Models
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151312/1/insr12322.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151312/2/insr12322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151312/3/Supplement_ReviewComputationalJointModels_final.pd
Genetic analyses of celiac disease in a Spanish population confirm association with CELIAC3 but not with CELIAC4
[EN] Genetic predisposition to celiac disease (CD) is determined primarily by the human leukocyte antigen (HLA) genes (CELIAC1 region; 6p21), although many loci are involved in disease susceptibility. First, we have analysed a large series of CD patients from the Spanish Mediterranean region who had previously been characterised for the HLA complex. We have investigated how relevant regions contribute to CD susceptibility: CELIAC3 (CD28/CTLA4/ICOS region on 2q33) and CELIAC4 (19p13) as well as the tumour necrosis factor alpha (TNF-alpha) and the linfotoxin loci by case-control and association analyses. We highlight the association with the +49*A allele of cytotoxic T-lymphocyte-associated antigen 4 locus (P = 0.01), and the -308*A of TNF-alpha locus (P = 0.0008) in DQ2 individuals, although an independent role for TNF-alpha as risk factor has not been proven. Moreover, we do not confirm the association with the CELIAC4 region polymorphisms described in other populations.We are grateful for the kind collaboration of patients and families and Asociación de Celíacos de la Comunidad Valenciana (ACECOVA). This work was supported by the Fondo de Investigacio¿n Sanitaria (grant PI02573) and by the CSIC Intramural Frontiers Project (PROFICEL). ED holds a fellowship from the Fundacio¿n La Fe. English text revised by F. BarracloughCapilla, A.; Donat, E.; Planelles, D.; Espinós-Armero, CÁ.; Ribes-Koninckx, C.; Palau, F. (2007). Genetic analyses of celiac disease in a Spanish population confirm association with CELIAC3 but not with CELIAC4. Tissue Antigens. 70(4):324-329. https://doi.org/10.1111/j.1399-0039.2007.00899.x32432970
Asymptotic Scaling of the Diffusion Coefficient of Fluctuating "Pulled" Fronts
We present a (heuristic) theoretical derivation for the scaling of the
diffusion coefficient for fluctuating ``pulled'' fronts. In agreement
with earlier numerical simulations, we find that as ,
approaches zero as , where is the average number of particles per
correlation volume in the stable phase of the front. This behaviour of
stems from the shape fluctuations at the very tip of the front, and is
independent of the microscopic model.Comment: Some minor algebra corrected, to appear in Rapid Comm., Phys. Rev.
Bayesian analysis of a disability model for lung cancer survival
Bayesian reasoning, survival analysis and multi-state models are used to assess survival times for Stage IV non-small-cell lung cancer patients and the evolution of the disease over time. Bayesian estimation is done using minimum informative priors for the Weibull regression survival model, leading to an automatic inferential procedure. Markov chain Monte Carlo methods have been used for approximating posterior distributions and the Bayesian information criterion has been considered for covariate selection. In particular, the posterior distribution of the transition probabilities, resulting from the multi-state model, constitutes a very interesting tool which could be useful to help oncologists and patients make efficient and effective decisions.This study has been partially supported by the Ministerio de Ciencia e Innovación [grant number MTM2010- 19528], Mutua Madrileña [grant AP75942010], Ministero dell'Istruzione, dell'Universitá e della Ricerca of Italy and the visiting professor program of the Regione Autonoma della Sardegna
Kinematic reduction of reaction-diffusion fronts with multiplicative noise: Derivation of stochastic sharp-interface equations
We study the dynamics of generic reaction-diffusion fronts, including pulses
and chemical waves, in the presence of multiplicative noise. We discuss the
connection between the reaction-diffusion Langevin-like field equations and the
kinematic (eikonal) description in terms of a stochastic moving-boundary or
sharp-interface approximation. We find that the effective noise is additive and
we relate its strength to the noise parameters in the original field equations,
to first order in noise strength, but including a partial resummation to all
orders which captures the singular dependence on the microscopic cutoff
associated to the spatial correlation of the noise. This dependence is
essential for a quantitative and qualitative understanding of fluctuating
fronts, affecting both scaling properties and nonuniversal quantities. Our
results predict phenomena such as the shift of the transition point between the
pushed and pulled regimes of front propagation, in terms of the noise
parameters, and the corresponding transition to a non-KPZ universality class.
We assess the quantitative validity of the results in several examples
including equilibrium fluctuations, kinetic roughening, and the noise-induced
pushed-pulled transition, which is predicted and observed for the first time.
The analytical predictions are successfully tested against rigorous results and
show excellent agreement with numerical simulations of reaction-diffusion field
equations with multiplicative noise.Comment: 17 pages, 6 figure
Bayesian estimation of incomplete data using conditionally specified priors
In this paper, a class of conjugate prior for estimating incomplete count data based on a broad class of conjugate prior distributions is presented. The new class of prior distributions arises from a conditional perspective, making use of the conditional specification methodology and can be considered as the generalisation of the form of prior distributions that have been used previously in the estimation of in- complete count data well. Finally, some examples of simulated and real data are given
The universality class of fluctuating pulled fronts
It has recently been proposed that fluctuating ``pulled'' fronts propagating
into an unstable state should not be in the standard KPZ universality class for
rough interface growth. We introduce an effective field equation for this class
of problems, and show on the basis of it that noisy pulled fronts in {\em d+1}
bulk dimensions should be in the universality class of the {\em (d+1)+1}D KPZ
equation rather than of the {\em d+1}D KPZ equation. Our scenario ties together
a number of heretofore unexplained observations in the literature, and is
supported by previous numerical results.Comment: 4 pages, 2 figure
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