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We generalize the popular ensemble Kalman filter to an ensemble transform filter, in which the prior distribution can take the form of a Gaussian mixture or a Gaussian kernel density estimator. The design of the filter is based on a continuous formulation of the Bayesian filter analysis step. We call the new filter algorithm the ensemble Gaussian-mixture filter (EGMF). The EGMF is implemented for three simple test problems (Brownian dynamics in one dimension, Langevin dynamics in two dimensions and the three-dimensional Lorenz-63 model). It is demonstrated that the EGMF is capable of tracking systems with non-Gaussian uni- and multimodal ensemble distributions.
A partial transformation alpha on an n-element chain X-n is called order-preserving if x <= y implies x alpha <= y alpha for all x, y in the domain of alpha and it is called extensive if x <= x alpha for all x in the domain of alpha. The set of all partial order-preserving extensive transformations on X-n forms a semiband POEn. We determine the maximal subsemigroups as well as the maximal subsemibands of POEn.
Clustering of gene expression data is often done with the latent aim of dimension reduction, by finding groups of genes that have a common response to potentially unknown stimuli. However, what is poorly understood to date is the behaviour of a low dimensional signal embedded in high dimensions. This paper introduces a multicollinear model which is based on random matrix theory results, and shows potential for the characterisation of a gene cluster's correlation matrix. This model projects a one dimensional signal into many dimensions and is based on the spiked covariance model, but rather characterises the behaviour of the corresponding correlation matrix. The eigenspectrum of the correlation matrix is empirically examined by simulation, under the addition of noise to the original signal. The simulation results are then used to propose a dimension estimation procedure of clusters from data. Moreover, the simulation results warn against considering pairwise correlations in isolation, as the model provides a mechanism whereby a pair of genes with 'low' correlation may simply be due to the interaction of high dimension and noise. Instead, collective information about all the variables is given by the eigenspectrum.
The chemical master equation (CME) is the fundamental evolution equation of the stochastic description of biochemical reaction kinetics. In most applications it is impossible to solve the CME directly due to its high dimensionality. Instead, indirect approaches based on realizations of the underlying Markov jump process are used, such as the stochastic simulation algorithm (SSA). In the SSA, however, every reaction event has to be resolved explicitly such that it becomes numerically inefficient when the system's dynamics include fast reaction processes or species with high population levels. In many hybrid approaches, such fast reactions are approximated as continuous processes or replaced by quasi-stationary distributions in either a stochastic or a deterministic context. Current hybrid approaches, however, almost exclusively rely on the computation of ensembles of stochastic realizations. We present a novel hybrid stochastic-deterministic approach to solve the CME directly. Our starting point is a partitioning of the molecular species into discrete and continuous species that induces a partitioning of the reactions into discrete-stochastic and continuous-deterministic processes. The approach is based on a WKB (Wentzel-Kramers-Brillouin) ansatz for the conditional probability distribution function (PDF) of the continuous species (given a discrete state) in combination with Laplace's method of integral approximation. The resulting hybrid stochastic-deterministic evolution equations comprise a CME with averaged propensities for the PDF of the discrete species that is coupled to an evolution equation of the related expected levels of the continuous species for each discrete state. In contrast to indirect hybrid methods, the impact of the evolution of discrete species on the dynamics of the continuous species has to be taken into account explicitly. The proposed approach is efficient whenever the number of discrete molecular species is small. We illustrate the performance of the new hybrid stochastic-deterministic approach in an application to model systems of biological interest.
The Gaussian Graphical Model (GGM) is a popular tool for incorporating sparsity into joint multivariate distributions. The G-Wishart distribution, a conjugate prior for precision matrices satisfying general GGM constraints, has now been in existence for over a decade. However, due to the lack of a direct sampler, its use has been limited in hierarchical Bayesian contexts, relegating mixing over the class of GGMs mostly to situations involving standard Gaussian likelihoods. Recent work has developed methods that couple model and parameter moves, first through reversible jump methods and later by direct evaluation of conditional Bayes factors and subsequent resampling. Further, methods for avoiding prior normalizing constant calculations-a serious bottleneck and source of numerical instability-have been proposed. We review and clarify these developments and then propose a new methodology for GGM comparison that blends many recent themes. Theoretical developments and computational timing experiments reveal an algorithm that has limited computational demands and dramatically improves on computing times of existing methods. We conclude by developing a parsimonious multivariate stochastic volatility model that embeds GGM uncertainty in a larger hierarchical framework. The method is shown to be capable of adapting to swings in market volatility, offering improved calibration of predictive distributions.
We propose a conversion method from alarm-based to rate-based earthquake forecast models. A differential probability gain g(alarm)(ref) is the absolute value of the local slope of the Molchan trajectory that evaluates the performance of the alarm-based model with respect to the chosen reference model. We consider that this differential probability gain is constant over time. Its value at each point of the testing region depends only on the alarm function value. The rate-based model is the product of the event rate of the reference model at this point multiplied by the corresponding differential probability gain. Thus, we increase or decrease the initial rates of the reference model according to the additional amount of information contained in the alarm-based model. Here, we apply this method to the Early Aftershock STatistics (EAST) model, an alarm-based model in which early aftershocks are used to identify space-time regions with a higher level of stress and, consequently, a higher seismogenic potential. The resulting rate-based model shows similar performance to the original alarm-based model for all ranges of earthquake magnitude in both retrospective and prospective tests. This conversion method offers the opportunity to perform all the standard evaluation tests of the earthquake testing centers on alarm-based models. In addition, we infer that it can also be used to consecutively combine independent forecast models and, with small modifications, seismic hazard maps with short- and medium-term forecasts.
We consider compact Riemannian spin manifolds without boundary equipped with orthogonal connections. We investigate the induced Dirac operators and the associated commutative spectral triples. In case of dimension four and totally anti-symmetric torsion we compute the Chamseddine-Connes spectral action, deduce the equations of motions and discuss critical points.
We show that it is possible to approximate the zeta-function of a curve over a finite field by meromorphic functions which satisfy the same functional equation and moreover satisfy (respectively do not satisfy) an analog of the Riemann hypothesis. In the other direction, it is possible to approximate holomorphic functions by simple manipulations of such a zeta-function. No number theory is required to understand the theorems and their proofs, for it is known that the zeta-functions of curves over finite fields are very explicit meromorphic functions. We study the approximation properties of these meromorphic functions.
Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to integrate cell-level kinetic models and pharmacokinetic compartment models. Incorporating target dynamics into pharmacokinetic models is especially useful for the development of therapeutic antibodies because their effect and pharmacokinetics are inherently interdependent. The approach is illustrated by analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies targeting the epidermal growth factor receptor. We build a multi-level model for anti-EGFR antibodies by combining a systems biology model with in vitro determined parameters and a pharmacokinetic model based on in vivo pharmacokinetic data. Using this model, we investigated in silico the impact of biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect saturates with increasing drug-receptor affinity, thereby limiting the impact of increasing antibody affinity on improving the effect. This indicates that observed differences in the therapeutic effects of high affinity antibodies in the market and in clinical development may result mainly from Fc-mediated indirect mechanisms such as antibody-dependent cell cytotoxicity.
Retrieval of aerosol extinction coefficient profiles from Raman lidar data by inversion method
(2012)
We regard the problem of differentiation occurring in the retrieval of aerosol extinction coefficient profiles from inelastic Raman lidar signals by searching for a stable solution of the resulting Volterra integral equation. An algorithm based on a projection method and iterative regularization together with the L-curve method has been performed on synthetic and measured lidar signals. A strategy to choose a suitable range for the integration within the framework of the retrieval of optical properties is proposed here for the first time to our knowledge. The Monte Carlo procedure has been adapted to treat the uncertainty in the retrieval of extinction coefficients.