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In this chapter, an overview of systematic eradication of basic science foci in European universities in the last two decades is given. This happens under the slogan of optimisation of the university education to the needs and demands of the society. It is pointed out that reliance on “market demands” brings with it long-term deficiencies in the maintenance of basic and advanced knowledge construction in societies necessary for long-term future technological advances. University policies that claim improvement of higher education towards more immediate efficiency may end up with the opposite effect of affecting its quality and long term expected positive impact on society.
Uniformly valid confidence intervals post model selection in regression can be constructed based on Post-Selection Inference (PoSI) constants. PoSI constants are minimal for orthogonal design matrices, and can be upper bounded in function of the sparsity of the set of models under consideration, for generic design matrices. In order to improve on these generic sparse upper bounds, we consider design matrices satisfying a Restricted Isometry Property (RIP) condition. We provide a new upper bound on the PoSI constant in this setting. This upper bound is an explicit function of the RIP constant of the design matrix, thereby giving an interpolation between the orthogonal setting and the generic sparse setting. We show that this upper bound is asymptotically optimal in many settings by constructing a matching lower bound.
We consider composite-composite testing problems for the expectation in the Gaussian sequence model where the null hypothesis corresponds to a closed convex subset C of R-d. We adopt a minimax point of view and our primary objective is to describe the smallest Euclidean distance between the null and alternative hypotheses such that there is a test with small total error probability. In particular, we focus on the dependence of this distance on the dimension d and variance 1/n giving rise to the minimax separation rate. In this paper we discuss lower and upper bounds on this rate for different smooth and non-smooth choices for C.
We consider truncated SVD (or spectral cut-off, projection) estimators for a prototypical statistical inverse problem in dimension D. Since calculating the singular value decomposition (SVD) only for the largest singular values is much less costly than the full SVD, our aim is to select a data-driven truncation level (m) over cap is an element of {1, . . . , D} only based on the knowledge of the first (m) over cap singular values and vectors. We analyse in detail whether sequential early stopping rules of this type can preserve statistical optimality. Information-constrained lower bounds and matching upper bounds for a residual based stopping rule are provided, which give a clear picture in which situation optimal sequential adaptation is feasible. Finally, a hybrid two-step approach is proposed which allows for classical oracle inequalities while considerably reducing numerical complexity.
S-test results for the USGS and RELM forecasts. The differences between the simulated log-likelihoods and the observed log-likelihood are labelled on the horizontal axes, with scaling adjustments for the 40year.retro experiment. The horizontal lines represent the confidence intervals, within the 0.05 significance level, for each forecast and experiment. If this range contains a log-likelihood difference of zero, the forecasted log-likelihoods are consistent with the observed, and the forecast passes the S-test (denoted by thin lines). If the minimum difference within this range does not contain zero, the forecast fails the S-test for that particular experiment, denoted by thick lines. Colours distinguish between experiments (see Table 2 for explanation of experiment durations). Due to anomalously large likelihood differences, S-test results for Wiemer-Schorlemmer.ALM during the 10year.retro and 40year.retro experiments are not displayed. The range of log-likelihoods for the Holliday-et-al.PI forecast is lower than for the other forecasts due to relatively homogeneous forecasted seismicity rates and use of a small fraction of the RELM testing region.
We prove that the Atiyah–Singer Dirac operator in L2 depends Riesz continuously on L∞ perturbations of complete metrics g on a smooth manifold. The Lipschitz bound for the map depends on bounds on Ricci curvature and its first derivatives as well as a lower bound on injectivity radius. Our proof uses harmonic analysis techniques related to Calderón’s first commutator and the Kato square root problem. We also show perturbation results for more general functions of general Dirac-type operators on vector bundles.
Understanding and reducing complex systems pharmacology models based on a novel input-response index
(2018)
A growing understanding of complex processes in biology has led to large-scale mechanistic models of pharmacologically relevant processes. These models are increasingly used to study the response of the system to a given input or stimulus, e.g., after drug administration. Understanding the input–response relationship, however, is often a challenging task due to the complexity of the interactions between its constituents as well as the size of the models. An approach that quantifies the importance of the different constituents for a given input–output relationship and allows to reduce the dynamics to its essential features is therefore highly desirable. In this article, we present a novel state- and time-dependent quantity called the input–response index that quantifies the importance of state variables for a given input–response relationship at a particular time. It is based on the concept of time-bounded controllability and observability, and defined with respect to a reference dynamics. In application to the brown snake venom–fibrinogen (Fg) network, the input–response indices give insight into the coordinated action of specific coagulation factors and about those factors that contribute only little to the response. We demonstrate how the indices can be used to reduce large-scale models in a two-step procedure: (i) elimination of states whose dynamics have only minor impact on the input–response relationship, and (ii) proper lumping of the remaining (lower order) model. In application to the brown snake venom–fibrinogen network, this resulted in a reduction from 62 to 8 state variables in the first step, and a further reduction to 5 state variables in the second step. We further illustrate that the sequence, in which a recursive algorithm eliminates and/or lumps state variables, has an impact on the final reduced model. The input–response indices are particularly suited to determine an informed sequence, since they are based on the dynamics of the original system. In summary, the novel measure of importance provides a powerful tool for analysing the complex dynamics of large-scale systems and a means for very efficient model order reduction of nonlinear systems.
The increasing availability of earth observations necessitates mathematical methods to optimally combine such data with hydrologic models. Several algorithms exist for such purposes, under the umbrella of data assimilation (DA). However, DA methods are often applied in a suboptimal fashion for complex real-world problems, due largely to several practical implementation issues. One such issue is error characterization, which is known to be critical for a successful assimilation. Mischaracterized errors lead to suboptimal forecasts, and in the worst case, to degraded estimates even compared to the no assimilation case. Model uncertainty characterization has received little attention relative to other aspects of DA science. Traditional methods rely on subjective, ad hoc tuning factors or parametric distribution assumptions that may not always be applicable. We propose a novel data-driven approach (named SDMU) to model uncertainty characterization for DA studies where (1) the system states are partially observed and (2) minimal prior knowledge of the model error processes is available, except that the errors display state dependence. It includes an approach for estimating the uncertainty in hidden model states, with the end goal of improving predictions of observed variables. The SDMU is therefore suited to DA studies where the observed variables are of primary interest. Its efficacy is demonstrated through a synthetic case study with low-dimensional chaotic dynamics and a real hydrologic experiment for one-day-ahead streamflow forecasting. In both experiments, the proposed method leads to substantial improvements in the hidden states and observed system outputs over a standard method involving perturbation with Gaussian noise.
SmB6 is predicted to be the first member of the intersection of topological insulators and Kondo insulators, strongly correlated materials in which the Fermi level lies in the gap of a many-body resonance that forms by hybridization between localized and itinerant states. While robust, surface-only conductivity at low temperature and the observation of surface states at the expected high symmetry points appear to confirm this prediction, we find both surface states at the (100) surface to be topologically trivial. We find the (Gamma) over bar state to appear Rashba split and explain the prominent (X) over bar state by a surface shift of the many-body resonance. We propose that the latter mechanism, which applies to several crystal terminations, can explain the unusual surface conductivity. While additional, as yet unobserved topological surface states cannot be excluded, our results show that a firm connection between the two material classes is still outstanding.
We give a new and very short proof of a theorem of Greiner asserting that a positive and contractive -semigroup on an -space is strongly convergent in case it has a strictly positive fixed point and contains an integral operator. Our proof is a streamlined version of a much more general approach to the asymptotic theory of positive semigroups developed recently by the authors. Under the assumptions of Greiner's theorem, this approach becomes particularly elegant and simple. We also give an outlook on several generalisations of this result.
This paper is concerned with the filtering problem in continuous time. Three algorithmic solution approaches for this problem are reviewed: (i) the classical Kalman-Bucy filter, which provides an exact solution for the linear Gaussian problem; (ii) the ensemble Kalman-Bucy filter (EnKBF), which is an approximate filter and represents an extension of the Kalman-Bucy filter to nonlinear problems; and (iii) the feedback particle filter (FPF), which represents an extension of the EnKBF and furthermore provides for a consistent solution in the general nonlinear, non-Gaussian case. The common feature of the three algorithms is the gain times error formula to implement the update step (to account for conditioning due to the observations) in the filter. In contrast to the commonly used sequential Monte Carlo methods, the EnKBF and FPF avoid the resampling of the particles in the importance sampling update step. Moreover, the feedback control structure provides for error correction potentially leading to smaller simulation variance and improved stability properties. The paper also discusses the issue of nonuniqueness of the filter update formula and formulates a novel approximation algorithm based on ideas from optimal transport and coupling of measures. Performance of this and other algorithms is illustrated for a numerical example.
From monthly mean observatory data spanning 1957-2014, geomagnetic field secular variation values were calculated by annual differences. Estimates of the spherical harmonic Gauss coefficients of the core field secular variation were then derived by applying a correlation based modelling. Finally, a Fourier transform was applied to the time series of the Gauss coefficients. This process led to reliable temporal spectra of the Gauss coefficients up to spherical harmonic degree 5 or 6, and down to periods as short as 1 or 2 years depending on the coefficient. We observed that a k(-2) slope, where k is the frequency, is an acceptable approximation for these spectra, with possibly an exception for the dipole field. The monthly estimates of the core field secular variation at the observatory sites also show that large and rapid variations of the latter happen. This is an indication that geomagnetic jerks are frequent phenomena and that significant secular variation signals at short time scales - i.e. less than 2 years, could still be extracted from data to reveal an unexplored part of the core dynamics.
The global prevalence of rapid and extensive land use change necessitates hydrologic modelling methodologies capable of handling non-stationarity. This is particularly true in the context of Hydrologic Forecasting using Data Assimilation. Data Assimilation has been shown to dramatically improve forecast skill in hydrologic and meteorological applications, although such improvements are conditional on using bias-free observations and model simulations. A hydrologic model calibrated to a particular set of land cover conditions has the potential to produce biased simulations when the catchment is disturbed. This paper sheds new light on the impacts of bias or systematic errors in hydrologic data assimilation, in the context of forecasting in catchments with changing land surface conditions and a model calibrated to pre-change conditions. We posit that in such cases, the impact of systematic model errors on assimilation or forecast quality is dependent on the inherent prediction uncertainty that persists even in pre-change conditions. Through experiments on a range of catchments, we develop a conceptual relationship between total prediction uncertainty and the impacts of land cover changes on the hydrologic regime to demonstrate how forecast quality is affected when using state estimation Data Assimilation with no modifications to account for land cover changes. This work shows that systematic model errors as a result of changing or changed catchment conditions do not always necessitate adjustments to the modelling or assimilation methodology, for instance through re-calibration of the hydrologic model, time varying model parameters or revised offline/online bias estimation.
For a given subcritical discrete Schrodinger operator H on a weighted infinite graph X, we construct a Hardy-weight w which is optimal in the following sense. The operator H - lambda w is subcritical in X for all lambda < 1, null-critical in X for lambda = 1, and supercritical near any neighborhood of infinity in X for any lambda > 1. Our results rely on a criticality theory for Schrodinger operators on general weighted graphs.
For an arbitrary euclidean field F we introduce a central extension (G(F), Phi) of SL(2, F) admitting a left-ordering and study its algebraic properties. The elements of G(F) are order preserving bijections of the convex hull of Q in F. If F = R then G(F) is isomorphic to the classical universal covering group of the Lie group SL(2, R). Among other results we show that G(F) is a perfect group which possesses a rank 1 cone of exceptional type. We also prove that its centre is an infinite cyclic group and investigate its normal subgroups.
Background and objective Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort (R) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Methods Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort (R) or 20 mg of Infacort (R)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Results Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline (cort),15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing < 20 kg. Conclusions Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing < 20 kg.
The simultaneous detection of energy, momentum and temporal information in electron spectroscopy is the key aspect to enhance the detection efficiency in order to broaden the range of scientific applications. Employing a novel 60 degrees wide angle acceptance lens system, based on an additional accelerating electron optical element, leads to a significant enhancement in transmission over the previously employed 30 degrees electron lenses. Due to the performance gain, optimized capabilities for time resolved electron spectroscopy and other high transmission applications with pulsed ionizing radiation have been obtained. The energy resolution and transmission have been determined experimentally utilizing BESSY II as a photon source. Four different and complementary lens modes have been characterized. (C) 2017 The Authors. Published by Elsevier B.V.
We prove finiteness and diameter bounds for graphs having a positive Ricci-curvature bound in the Bakry–Émery sense. Our first result using only curvature and maximal vertex degree is sharp in the case of hypercubes. The second result depends on an additional dimension bound, but is independent of the vertex degree. In particular, the second result is the first Bonnet–Myers type theorem for unbounded graph Laplacians. Moreover, our results improve diameter bounds from Fathi and Shu (Bernoulli 24(1):672–698, 2018) and Horn et al. (J für die reine und angewandte Mathematik (Crelle’s J), 2017, https://doi.org/10.1515/crelle-2017-0038) and solve a conjecture from Cushing et al. (Bakry–Émery curvature functions of graphs, 2016).
Lie group method in combination with Magnus expansion is utilized to develop a universal method applicable to solving a Sturm–Liouville Problem (SLP) of any order with arbitrary boundary conditions. It is shown that the method has ability to solve direct regular and some singular SLPs of even orders (tested up to order eight), with a mix of boundary conditions (including non-separable and finite singular endpoints), accurately and efficiently.
The present technique is successfully applied to overcome the difficulties in finding suitable sets of eigenvalues so that the inverse SLP problem can be effectively solved.
Next, a concrete implementation to the inverse Sturm–Liouville problem
algorithm proposed by Barcilon (1974) is provided. Furthermore, computational feasibility and applicability of this algorithm to solve inverse Sturm–Liouville problems of order n=2,4 is verified successfully. It is observed that the method is successful even in the presence of significant noise, provided that the assumptions of the algorithm are satisfied.
In conclusion, this work provides methods that can be adapted successfully for solving a direct (regular/singular) or inverse SLP of an arbitrary order with arbitrary boundary conditions.
We complete the picture how the asymptotic behavior of a dynamical system is reflected by properties of the associated Perron-Frobenius operator. Our main result states that strong convergence of the powers of the Perron-Frobenius operator is equivalent to setwise convergence of the underlying dynamic in the measure algebra. This situation is furthermore characterized by uniform mixing-like properties of the system.
ShapeRotator
(2018)
The quantification of complex morphological patterns typically involves comprehensive shape and size analyses, usually obtained by gathering morphological data from all the structures that capture the phenotypic diversity of an organism or object. Articulated structures are a critical component of overall phenotypic diversity, but data gathered from these structures are difficult to incorporate into modern analyses because of the complexities associated with jointly quantifying 3D shape in multiple structures. While there are existing methods for analyzing shape variation in articulated structures in two-dimensional (2D) space, these methods do not work in 3D, a rapidly growing area of capability and research. Here, we describe a simple geometric rigid rotation approach that removes the effect of random translation and rotation, enabling the morphological analysis of 3D articulated structures. Our method is based on Cartesian coordinates in 3D space, so it can be applied to any morphometric problem that also uses 3D coordinates (e.g., spherical harmonics). We demonstrate the method by applying it to a landmark-based dataset for analyzing shape variation using geometric morphometrics. We have developed an R tool (ShapeRotator) so that the method can be easily implemented in the commonly used R package geomorph and MorphoJ software. This method will be a valuable tool for 3D morphological analyses in articulated structures by allowing an exhaustive examination of shape and size diversity.
We analyze a general class of self-adjoint difference operators H-epsilon = T-epsilon + V-epsilon on l(2)((epsilon Z)(d)), where V-epsilon is a multi-well potential and v(epsilon) is a small parameter. We give a coherent review of our results on tunneling up to new sharp results on the level of complete asymptotic expansions (see [30-35]). Our emphasis is on general ideas and strategy, possibly of interest for a broader range of readers, and less on detailed mathematical proofs. The wells are decoupled by introducing certain Dirichlet operators on regions containing only one potential well. Then the eigenvalue problem for the Hamiltonian H-epsilon is treated as a small perturbation of these comparison problems. After constructing a Finslerian distance d induced by H-epsilon, we show that Dirichlet eigenfunctions decay exponentially with a rate controlled by this distance to the well. It follows with microlocal techniques that the first n eigenvalues of H-epsilon converge to the first n eigenvalues of the direct sum of harmonic oscillators on R-d located at several wells. In a neighborhood of one well, we construct formal asymptotic expansions of WKB-type for eigenfunctions associated with the low-lying eigenvalues of H-epsilon. These are obtained from eigenfunctions or quasimodes for the operator H-epsilon acting on L-2(R-d), via restriction to the lattice (epsilon Z)(d). Tunneling is then described by a certain interaction matrix, similar to the analysis for the Schrodinger operator (see [22]), the remainder is exponentially small and roughly quadratic compared with the interaction matrix. We give weighted l(2)-estimates for the difference of eigenfunctions of Dirichlet-operators in neighborhoods of the different wells and the associated WKB-expansions at the wells. In the last step, we derive full asymptotic expansions for interactions between two "wells" (minima) of the potential energy, in particular for the discrete tunneling effect. Here we essentially use analysis on phase space, complexified in the momentum variable. These results are as sharp as the classical results for the Schrodinger operator in [22].
Rapid population and economic growth in Southeast Asia has been accompanied by extensive land use change with consequent impacts on catchment hydrology. Modeling methodologies capable of handling changing land use conditions are therefore becoming ever more important and are receiving increasing attention from hydrologists. A recently developed data-assimilation-based framework that allows model parameters to vary through time in response to signals of change in observations is considered for a medium-sized catchment (2880 km(2)) in northern Vietnam experiencing substantial but gradual land cover change. We investigate the efficacy of the method as well as the importance of the chosen model structure in ensuring the success of a time-varying parameter method. The method was used with two lumped daily conceptual models (HBV and HyMOD) that gave good-quality streamflow predictions during pre-change conditions. Although both time-varying parameter models gave improved streamflow predictions under changed conditions compared to the time-invariant parameter model, persistent biases for low flows were apparent in the HyMOD case. It was found that HyMOD was not suited to representing the modified baseflow conditions, resulting in extreme and unrealistic time-varying parameter estimates. This work shows that the chosen model can be critical for ensuring the time-varying parameter framework successfully models streamflow under changing land cover conditions. It can also be used to determine whether land cover changes (and not just meteorological factors) contribute to the observed hydrologic changes in retrospective studies where the lack of a paired control catchment precludes such an assessment.
We establish essential steps of an iterative approach to operator algebras, ellipticity and Fredholm property on stratified spaces with singularities of second order. We cover, in particular, corner-degenerate differential operators. Our constructions are focused on the case where no additional conditions of trace and potential type are posed, but this case works well and will be considered in a forthcoming paper as a conclusion of the present calculus.
Earthquake rates are driven by tectonic stress buildup, earthquake-induced stress changes, and transient aseismic processes. Although the origin of the first two sources is known, transient aseismic processes are more difficult to detect. However, the knowledge of the associated changes of the earthquake activity is of great interest, because it might help identify natural aseismic deformation patterns such as slow-slip events, as well as the occurrence of induced seismicity related to human activities. For this goal, we develop a Bayesian approach to identify change-points in seismicity data automatically. Using the Bayes factor, we select a suitable model, estimate possible change-points, and we additionally use a likelihood ratio test to calculate the significance of the change of the intensity. The approach is extended to spatiotemporal data to detect the area in which the changes occur. The method is first applied to synthetic data showing its capability to detect real change-points. Finally, we apply this approach to observational data from Oklahoma and observe statistical significant changes of seismicity in space and time.
Paleoearthquakes and historic earthquakes are the most important source of information for the estimation of long-term earthquake recurrence intervals in fault zones, because corresponding sequences cover more than one seismic cycle. However, these events are often rare, dating uncertainties are enormous, and missing or misinterpreted events lead to additional problems. In the present study, I assume that the time to the next major earthquake depends on the rate of small and intermediate events between the large ones in terms of a clock change model. Mathematically, this leads to a Brownian passage time distribution for recurrence intervals. I take advantage of an earlier finding that under certain assumptions the aperiodicity of this distribution can be related to the Gutenberg-Richter b value, which can be estimated easily from instrumental seismicity in the region under consideration. In this way, both parameters of the Brownian passage time distribution can be attributed with accessible seismological quantities. This allows to reduce the uncertainties in the estimation of the mean recurrence interval, especially for short paleoearthquake sequences and high dating errors. Using a Bayesian framework for parameter estimation results in a statistical model for earthquake recurrence intervals that assimilates in a simple way paleoearthquake sequences and instrumental data. I present illustrative case studies from Southern California and compare the method with the commonly used approach of exponentially distributed recurrence times based on a stationary Poisson process.
Cell-free protein synthesis as a novel tool for directed glycoengineering of active erythropoietin
(2018)
As one of the most complex post-translational modification, glycosylation is widely involved in cell adhesion, cell proliferation and immune response. Nevertheless glycoproteins with an identical polypeptide backbone mostly differ in their glycosylation patterns. Due to this heterogeneity, the mapping of different glycosylation patterns to their associated function is nearly impossible. In the last years, glycoengineering tools including cell line engineering, chemoenzymatic remodeling and site-specific glycosylation have attracted increasing interest. The therapeutic hormone erythropoietin (EPO) has been investigated in particular by various groups to establish a production process resulting in a defined glycosylation pattern. However commercially available recombinant human EPO shows batch-to-batch variations in its glycoforms. Therefore we present an alternative method for the synthesis of active glycosylated EPO with an engineered O-glycosylation site by combining eukaryotic cell-free protein synthesis and site-directed incorporation of non-canonical amino acids with subsequent chemoselective modifications.
This article assesses the distance between the laws of stochastic differential equations with multiplicative Levy noise on path space in terms of their characteristics. The notion of transportation distance on the set of Levy kernels introduced by Kosenkova and Kulik yields a natural and statistically tractable upper bound on the noise sensitivity. This extends recent results for the additive case in terms of coupling distances to the multiplicative case. The strength of this notion is shown in a statistical implementation for simulations and the example of a benchmark time series in paleoclimate.
Frühe mathematische Bildung
(2018)
Im vorliegenden Beitrag werden aktuelle Forschungstrends im Bereich der frühen mathematischen Bildung im Kontext jüngst formulierter Zieldimensionen für die frühe mathematische Bildung (siehe Benz et al., 2017) dargestellt. Es wird auf spielbasierte Fördermaßnahmen, Kompetenzen im Bereich „Raum und Form“, den Einfluss sprachlicher Parameter auf die Entwicklung mathematischer Kompetenzen sowie auf mathematikbezogene Kompetenzen frühpädagogischer Fachkräfte eingegangen. Darüber hinaus werden die Ergebnisse einer aktuellen Feldstudie zur Förderung früher mathematischer Kompetenzen (siehe Dillon, Kannan, Dean, Spelke & Duflo, 2017) vorgestellt. Abschließend wird die Entwicklung und Implementierung anschlussfähiger Bildungskonzepte als eine der zentralen Herausforderungen zukünftiger Forschungs- und Bildungsbemühungen diskutiert
We consider the problem of low rank matrix recovery in a stochastically noisy high-dimensional setting. We propose a new estimator for the low rank matrix, based on the iterative hard thresholding method, that is computationally efficient and simple. We prove that our estimator is optimal in terms of the Frobenius risk and in terms of the entry-wise risk uniformly over any change of orthonormal basis, allowing us to provide the limiting distribution of the estimator. When the design is Gaussian, we prove that the entry-wise bias of the limiting distribution of the estimator is small, which is of interest for constructing tests and confidence sets for low-dimensional subsets of entries of the low rank matrix.
Die Bienaymé-Galton-Watson Prozesse können für die Untersuchung von speziellen und sich entwickelnden Populationen verwendet werden. Die Populationen umfassen Individuen, welche sich identisch, zufällig, selbstständig und unabhängig voneinander fortpflanzen und die jeweils nur eine Generation existieren. Die n-te Generation ergibt sich als zufällige Summe der Individuen der (n-1)-ten Generation. Die Relevanz dieser Prozesse begründet sich innerhalb der Historie und der inner- und außermathematischen Bedeutung. Die Geschichte der Bienaymé-Galton-Watson-Prozesse wird anhand der Entwicklung des Konzeptes bis heute dargestellt. Dabei werden die Wissenschaftler:innen verschiedener Disziplinen angeführt, die Erkenntnisse zu dem Themengebiet beigetragen und das Konzept in ihren Fachbereichen angeführt haben. Somit ergibt sich die außermathematische Signifikanz. Des Weiteren erhält man die innermathematische Bedeutsamkeit mittels des Konzeptes der Verzweigungsprozesse, welches auf die Bienaymé-Galton-Watson Prozesse zurückzuführen ist. Die Verzweigungsprozesse stellen eines der aussagekräftigsten Modelle für die Beschreibung des Populationswachstums dar. Darüber hinaus besteht die derzeitige Wichtigkeit durch die Anwendungsmöglichkeit der Verzweigungsprozesse und der Bienaymé-Galton-Watson Prozesse innerhalb der Epidemiologie. Es werden die Ebola- und die Corona-Pandemie als Anwendungsfelder angeführt. Die Prozesse dienen als Entscheidungsstütze für die Politik und ermöglichen Aussagen über die Auswirkungen von Maßnahmen bezüglich der Pandemien. Neben den Prozessen werden ebenfalls der bedingte Erwartungswert bezüglich diskreter Zufallsvariablen, die wahrscheinlichkeitserzeugende Funktion und die zufällige Summe eingeführt. Die Konzepte vereinfachen die Beschreibung der Prozesse und bilden somit die Grundlage der Betrachtungen. Außerdem werden die benötigten und weiterführenden Eigenschaften der grundlegenden Themengebiete und der Prozesse aufgeführt und bewiesen. Das Kapitel erreicht seinen Höhepunkt bei dem Beweis des Kritikalitätstheorems, wodurch eine Aussage über das Aussterben des Prozesses in verschiedenen Fällen und somit über die Aussterbewahrscheinlichkeit getätigt werden kann. Die Fälle werden anhand der zu erwartenden Anzahl an Nachkommen eines Individuums unterschieden. Es zeigt sich, dass ein Prozess bei einer zu erwartenden Anzahl kleiner gleich Eins mit Sicherheit ausstirbt und bei einer Anzahl größer als Eins, die Population nicht in jedem Fall aussterben muss. Danach werden einzelne Beispiele, wie der linear fractional case, die Population von Fibroblasten (Bindegewebszellen) von Mäusen und die Entstehungsfragestellung der Prozesse, angeführt. Diese werden mithilfe der erlangten Ergebnisse untersucht und einige ausgewählte zufällige Dynamiken werden im nachfolgenden Kapitel simuliert. Die Simulationen erfolgen durch ein in Python erstelltes Programm und werden mithilfe der Inversionsmethode realisiert. Die Simulationen stellen beispielhaft die Entwicklungen in den verschiedenen Kritikalitätsfällen der Prozesse dar. Zudem werden die Häufigkeiten der einzelnen Populationsgrößen in Form von Histogrammen angebracht. Dabei lässt sich der Unterschied zwischen den einzelnen Fällen bestätigen und es wird die Anwendungsmöglichkeit der Bienaymé-Galton-Watson Prozesse bei komplexeren Problemen deutlich. Histogramme bekräftigen, dass die einzelnen Populationsgrößen nur endlich oft vorkommen. Diese Aussage wurde von Galton aufgeworfen und in der Extinktions-Explosions-Dichotomie verwendet. Die dargestellten Erkenntnisse über das Themengebiet und die Betrachtung des Konzeptes werden mit einer didaktischen Analyse abgeschlossen. Die Untersuchung beinhaltet die Berücksichtigung der Fundamentalen Ideen, der Fundamentalen Ideen der Stochastik und der Leitidee „Daten und Zufall“. Dabei ergibt sich, dass in Abhängigkeit der gewählten Perspektive die Anwendung der Bienaymé-Galton-Watson Prozesse innerhalb der Schule plausibel ist und von Vorteil für die Schüler:innen sein kann. Für die Behandlung wird exemplarisch der Rahmenlehrplan für Berlin und Brandenburg analysiert und mit dem Kernlehrplan Nordrhein-Westfalens verglichen. Die Konzeption des Lehrplans aus Berlin und Brandenburg lässt nicht den Schluss zu, dass die Bienaymé-Galton-Watson Prozesse angewendet werden sollten. Es lässt sich feststellen, dass die zugrunde liegende Leitidee nicht vollumfänglich mit manchen Fundamentalen Ideen der Stochastik vereinbar ist. Somit würde eine Modifikation hinsichtlich einer stärkeren Orientierung des Lehrplans an den Fundamentalen Ideen die Anwendung der Prozesse ermöglichen. Die Aussage wird durch die Betrachtung und Übertragung eines nordrhein-westfälischen Unterrichtsentwurfes für stochastische Prozesse auf die Bienaymé-Galton-Watson Prozesse unterstützt. Darüber hinaus werden eine Concept Map und ein Vernetzungspentagraph nach von der Bank konzipiert um diesen Aspekt hervorzuheben.
We consider a statistical inverse learning (also called inverse regression) problem, where we observe the image of a function f through a linear operator A at i.i.d. random design points X-i , superposed with an additive noise. The distribution of the design points is unknown and can be very general. We analyze simultaneously the direct (estimation of Af) and the inverse (estimation of f) learning problems. In this general framework, we obtain strong and weak minimax optimal rates of convergence (as the number of observations n grows large) for a large class of spectral regularization methods over regularity classes defined through appropriate source conditions. This improves on or completes previous results obtained in related settings. The optimality of the obtained rates is shown not only in the exponent in n but also in the explicit dependency of the constant factor in the variance of the noise and the radius of the source condition set.
Left-right (L-R) asymmetry in the body plan is determined by nodal flow in vertebrate embryos. Shinohara et al. (Shinohara K et al. 2012 Nat. Commun. 3, 622 (doi:10.1038/ncomms1624)) used Dpcd and Rfx3 mutant mouse embryos and showed that only a few cilia were sufficient to achieve L-R asymmetry. However, the mechanism underlying the breaking of symmetry by such weak ciliary flow is unclear. Flow-mediated signals associated with the L-R asymmetric organogenesis have not been clarified, and two different hypotheses-vesicle transport and mechanosensing-are now debated in the research field of developmental biology. In this study, we developed a computational model of the node system reported by Shinohara et al. and examined the feasibilities of the two hypotheses with a small number of cilia. With the small number of rotating cilia, flow was induced locally and global strong flow was not observed in the node. Particles were then effectively transported only when they were close to the cilia, and particle transport was strongly dependent on the ciliary positions. Although the maximum wall shear rate was also influenced by ciliary position, the mean wall shear rate at the perinodal wall increased monotonically with the number of cilia. We also investigated the membrane tension of immotile cilia, which is relevant to the regulation of mechanotransduction. The results indicated that tension of about 0.1 mu Nm(-1) was exerted at the base even when the fluid shear rate was applied at about 0.1 s(-1). The area of high tension was also localized at the upstream side, and negative tension appeared at the downstream side. Such localization may be useful to sense the flow direction at the periphery, as time-averaged anticlockwise circulation was induced in the node by rotation of a few cilia. Our numerical results support the mechanosensing hypothesis, and we expect that our study will stimulate further experimental investigations of mechanotransduction in the near future.
Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
In paper (Flad and Harutyunyan in Discrete Contin Dyn Syst 420-429, 2011) is shown that the Hamiltonian of the helium atom in the Born-Oppenheimer approximation, in the case if two particles coincide, is an edge-degenerate operator, which is elliptic in the corresponding edge calculus. The aim of this paper is an analogous investigation in the case if all three particles coincide. More precisely, we show that the Hamiltonian in the mentioned case is a corner-degenerate operator, which is elliptic as an operator in the corner analysis.
Transition metals in inorganic systems and metalloproteins can occur in different oxidation states, which makes them ideal redox-active catalysts. To gain a mechanistic understanding of the catalytic reactions, knowledge of the oxidation state of the active metals, ideally in operando, is therefore critical. L-edge X-ray absorption spectroscopy (XAS) is a powerful technique that is frequently used to infer the oxidation state via a distinct blue shift of L-edge absorption energies with increasing oxidation state. A unified description accounting for quantum-chemical notions whereupon oxidation does not occur locally on the metal but on the whole molecule and the basic understanding that L-edge XAS probes the electronic structure locally at the metal has been missing to date. Here we quantify how charge and spin densities change at the metal and throughout the molecule for both redox and core-excitation processes. We explain the origin of the L-edge XAS shift between the high-spin complexes Mn-II(acac)(2) and Mn-III(acac)(3) as representative model systems and use ab initio theory to uncouple effects of oxidation-state changes from geometric effects. The shift reflects an increased electron affinity of Mn-III in the core-excited states compared to the ground state due to a contraction of the Mn 3d shell upon core-excitation with accompanied changes in the classical Coulomb interactions. This new picture quantifies how the metal-centered core hole probes changes in formal oxidation state and encloses and substantiates earlier explanations. The approach is broadly applicable to mechanistic studies of redox-catalytic reactions in molecular systems where charge and spin localization/delocalization determine reaction pathways.
Given two weighted graphs (X, b(k), m(k)), k = 1, 2 with b(1) similar to b(2) and m(1) similar to m(2), we prove a weighted L-1-criterion for the existence and completeness of the wave operators W-+/- (H-2, H-1, I-1,I-2), where H-k denotes the natural Laplacian in l(2)(X, m(k)) w.r.t. (X, b(k), m(k)) and I-1,I-2 the trivial identification of l(2)(X, m(1)) with l(2) (X, m(2)). In particular, this entails a general criterion for the absolutely continuous spectra of H-1 and H-2 to be equal.
We prove that if u is a locally Lipschitz continuous function on an open set chi subset of Rn + 1 satisfying the nonlinear heat equation partial derivative(t)u = Delta(vertical bar u vertical bar(p-1) u), p > 1, weakly away from the zero set u(-1) (0) in chi, then u is a weak solution to this equation in all of chi.
Spiele und spieltypische Elemente wie das Sammeln von Treuepunkten sind aus dem Alltag kaum wegzudenken. Zudem werden sie zunehmend in Unternehmen oder in Lernumgebungen eingesetzt. Allerdings ist die Methode Gamification bisher für den pädagogischen Kontext wenig klassifiziert und für Lehrende kaum zugänglich gemacht worden.
Daher zielt diese Bachelorarbeit darauf ab, eine systematische Strukturierung und Aufarbeitung von Gamification sowie innovative Ansätze für die Verwendung spieltypischer Elemente im Unterricht, konkret dem Mathematikunterricht, zu präsentieren. Dies kann eine Grundlage für andere Fachgebiete, aber auch andere Lehrformen bieten und so die Umsetzbarkeit von Gamification in eigenen Lehrveranstaltungen aufzeigen.
In der Arbeit wird begründet, weshalb und mithilfe welcher Elemente Gamification die Motivation und Leistungsbereitschaft der Lernenden langfristig erhöhen, die Sozial- und Personalkompetenzen fördern sowie die Lernenden zu mehr Aktivität anregen kann. Zudem wird Gamification explizit mit grundlegenden mathematikdidaktischen Prinzipien in Verbindung gesetzt und somit die Relevanz für den Mathematikunterricht hervorgehoben.
Anschließend werden die einzelnen Elemente von Gamification wie Punkte, Level, Abzeichen, Charaktere und Rahmengeschichte entlang einer eigens für den pädagogischen Kontext entwickelten Klassifikation „FUN“ (Feedback – User specific elements – Neutral elements) schematisch beschrieben, ihre Funktionen und Wirkung dargestellt sowie Einsatzmöglichkeiten im Unterricht aufgezeigt. Dies beinhaltet Ideen zu lernförderlichem Feedback, Differenzierungsmöglichkeiten und Unterrichtsrahmengestaltung, die in Lehrveranstaltungen aller Art umsetzbar sein können. Die Bachelorarbeit umfasst zudem ein spezifisches Beispiel, einen Unterrichtsentwurf einer gamifizierten Mathematikstunde inklusive des zugehörigen Arbeitsmaterials, anhand dessen die Verwendung von Gamification deutlich wird.
Gamification offeriert oftmals Vorteile gegenüber dem traditionellen Unterricht, muss jedoch wie jede Methode an den Inhalt und die Zielgruppe angepasst werden. Weiterführende Forschung könnte sich mit konkreten motivationalen Strukturen, personenspezifischen Unterschieden sowie mit mathematischen Inhalten wie dem Problemlösen oder dem Wechsel zwischen verschiedenen Darstellungen hinsichtlich gamifizierter Lehrformen beschäftigen.
While patients are known to respond differently to drug therapies, current clinical practice often still follows a standardized dosage regimen for all patients. For drugs with a narrow range of both effective and safe concentrations, this approach may lead to a high incidence of adverse events or subtherapeutic dosing in the presence of high patient variability. Model-informedprecision dosing (MIPD) is a quantitative approach towards dose individualization based on mathematical modeling of dose-response relationships integrating therapeutic drug/biomarker monitoring (TDM) data. MIPD may considerably improve the efficacy and safety of many drug therapies. Current MIPD approaches, however, rely either on pre-calculated dosing tables or on simple point predictions of the therapy outcome. These
approaches lack a quantification of uncertainties and the ability to account for effects that are delayed. In addition, the underlying models are not improved while applied to patient data. Therefore, current approaches are not well suited for informed clinical decision-making based on a differentiated understanding of the individually predicted therapy outcome.
The objective of this thesis is to develop mathematical approaches for MIPD, which (i) provide efficient fully Bayesian forecasting of the individual therapy outcome including associated uncertainties, (ii) integrate Markov decision processes via reinforcement learning (RL) for a comprehensive decision framework for dose individualization, (iii) allow for continuous learning across patients and hospitals. Cytotoxic anticancer chemotherapy with its major dose-limiting toxicity, neutropenia, serves as a therapeutically relevant application example.
For more comprehensive therapy forecasting, we apply Bayesian data assimilation (DA) approaches, integrating patient-specific TDM data into mathematical models of chemotherapy-induced neutropenia that build on prior population analyses. The value of uncertainty quantification is demonstrated as it allows reliable computation of the patient-specific probabilities of relevant clinical quantities, e.g., the neutropenia grade. In view of novel home monitoring devices that increase the amount of TDM data available, the data processing of
sequential DA methods proves to be more efficient and facilitates handling of the variability between dosing events.
By transferring concepts from DA and RL we develop novel approaches for MIPD. While DA-guided dosing integrates individualized uncertainties into dose selection, RL-guided dosing provides a framework to consider delayed effects of dose selections. The combined
DA-RL approach takes into account both aspects simultaneously and thus represents a holistic approach towards MIPD. Additionally, we show that RL can be used to gain insights into important patient characteristics for dose selection. The novel dosing strategies substantially reduce the occurrence of both subtherapeutic and life-threatening neutropenia grades in a simulation study based on a recent clinical study (CEPAC-TDM trial) compared to currently used MIPD approaches.
If MIPD is to be implemented in routine clinical practice, a certain model bias with respect to the underlying model is inevitable, as the models are typically based on data from comparably small clinical trials that reflect only to a limited extent the diversity in real-world patient populations. We propose a sequential hierarchical Bayesian inference framework that enables continuous cross-patient learning to learn the underlying model parameters of the target patient population. It is important to note that the approach only requires summary information of the individual patient data to update the model. This separation of the individual inference from population inference enables implementation across different centers of care.
The proposed approaches substantially improve current MIPD approaches, taking into account new trends in health care and aspects of practical applicability. They enable progress towards more informed clinical decision-making, ultimately increasing patient benefits beyond the current practice.
Local observations indicate that climate change and shifting disturbance regimes are causing permafrost degradation. However, the occurrence and distribution of permafrost region disturbances (PRDs) remain poorly resolved across the Arctic and Subarctic. Here we quantify the abundance and distribution of three primary PRDs using time-series analysis of 30-m resolution Landsat imagery from 1999 to 2014. Our dataset spans four continental-scale transects in North America and Eurasia, covering similar to 10% of the permafrost region. Lake area loss (-1.45%) dominated the study domain with enhanced losses occurring at the boundary between discontinuous and continuous permafrost regions. Fires were the most extensive PRD across boreal regions (6.59%), but in tundra regions (0.63%) limited to Alaska. Retrogressive thaw slumps were abundant but highly localized (< 10(-5)%). Our analysis synergizes the global-scale importance of PRDs. The findings highlight the need to include PRDs in next-generation land surface models to project the permafrost carbon feedback.
This thesis focuses on the study of marked Gibbs point processes, in particular presenting some results on their existence and uniqueness, with ideas and techniques drawn from different areas of statistical mechanics: the entropy method from large deviations theory, cluster expansion and the Kirkwood--Salsburg equations, the Dobrushin contraction principle and disagreement percolation.
We first present an existence result for infinite-volume marked Gibbs point processes. More precisely, we use the so-called entropy method (and large-deviation tools) to construct marked Gibbs point processes in R^d under quite general assumptions. In particular, the random marks belong to a general normed space S and are not bounded. Moreover, we allow for interaction functionals that may be unbounded and whose range is finite but random. The entropy method relies on showing that a family of finite-volume Gibbs point processes belongs to sequentially compact entropy level sets, and is therefore tight.
We then present infinite-dimensional Langevin diffusions, that we put in interaction via a Gibbsian description. In this setting, we are able to adapt the general result above to show the existence of the associated infinite-volume measure. We also study its correlation functions via cluster expansion techniques, and obtain the uniqueness of the Gibbs process for all inverse temperatures β and activities z below a certain threshold. This method relies in first showing that the correlation functions of the process satisfy a so-called Ruelle bound, and then using it to solve a fixed point problem in an appropriate Banach space. The uniqueness domain we obtain consists then of the model parameters z and β for which such a problem has exactly one solution.
Finally, we explore further the question of uniqueness of infinite-volume Gibbs point processes on R^d, in the unmarked setting. We present, in the context of repulsive interactions with a hard-core component, a novel approach to uniqueness by applying the discrete Dobrushin criterion to the continuum framework. We first fix a discretisation parameter a>0 and then study the behaviour of the uniqueness domain as a goes to 0. With this technique we are able to obtain explicit thresholds for the parameters z and β, which we then compare to existing results coming from the different methods of cluster expansion and disagreement percolation.
Throughout this thesis, we illustrate our theoretical results with various examples both from classical statistical mechanics and stochastic geometry.
In the present paper, we study the problem of existence of honest and adaptive confidence sets for matrix completion. We consider two statistical models: the trace regression model and the Bernoulli model. In the trace regression model, we show that honest confidence sets that adapt to the unknown rank of the matrix exist even when the error variance is unknown. Contrary to this, we prove that in the Bernoulli model, honest and adaptive confidence sets exist only when the error variance is known a priori. In the course of our proofs, we obtain bounds for the minimax rates of certain composite hypothesis testing problems arising in low rank inference.
We analyze a general class of difference operators Hε=Tε+Vε on ℓ2((εZ)d), where Vε is a multi-well potential and ε is a small parameter. We derive full asymptotic expansions of the prefactor of the exponentially small eigenvalue splitting due to interactions between two “wells” (minima) of the potential energy, i.e., for the discrete tunneling effect. We treat both the case where there is a single minimal geodesic (with respect to the natural Finsler metric induced by the leading symbol h0(x,ξ) of Hε) connecting the two minima and the case where the minimal geodesics form an ℓ+1 dimensional manifold, ℓ≥1. These results on the tunneling problem are as sharp as the classical results for the Schrödinger operator in Helffer and Sjöstrand (Commun PDE 9:337–408, 1984). Technically, our approach is pseudo-differential and we adapt techniques from Helffer and Sjöstrand [Analyse semi-classique pour l’équation de Harper (avec application à l’équation de Schrödinger avec champ magnétique), Mémoires de la S.M.F., 2 series, tome 34, pp 1–113, 1988)] and Helffer and Parisse (Ann Inst Henri Poincaré 60(2):147–187, 1994) to our discrete setting.
Contributions to the theoretical analysis of the algorithms with adversarial and dependent data
(2021)
In this work I present the concentration inequalities of Bernstein's type for the norms of Banach-valued random sums under a general functional weak-dependency assumption (the so-called $\cC-$mixing). The latter is then used to prove, in the asymptotic framework, excess risk upper bounds of the regularised Hilbert valued statistical learning rules under the τ-mixing assumption on the underlying training sample. These results (of the batch statistical setting) are then supplemented with the regret analysis over the classes of Sobolev balls of the type of kernel ridge regression algorithm in the setting of online nonparametric regression with arbitrary data sequences. Here, in particular, a question of robustness of the kernel-based forecaster is investigated. Afterwards, in the framework of sequential learning, the multi-armed bandit problem under $\cC-$mixing assumption on the arm's outputs is considered and the complete regret analysis of a version of Improved UCB algorithm is given. Lastly, probabilistic inequalities of the first part are extended to the case of deviations (both of Azuma-Hoeffding's and of Burkholder's type) to the partial sums of real-valued weakly dependent random fields (under the type of projective dependence condition).
One of the crucial components in seismic hazard analysis is the estimation of the maximum earthquake magnitude and associated uncertainty. In the present study, the uncertainty related to the maximum expected magnitude mu is determined in terms of confidence intervals for an imposed level of confidence. Previous work by Salamat et al. (Pure Appl Geophys 174:763-777, 2017) shows the divergence of the confidence interval of the maximum possible magnitude m(max) for high levels of confidence in six seismotectonic zones of Iran. In this work, the maximum expected earthquake magnitude mu is calculated in a predefined finite time interval and imposed level of confidence. For this, we use a conceptual model based on a doubly truncated Gutenberg-Richter law for magnitudes with constant b-value and calculate the posterior distribution of mu for the time interval T-f in future. We assume a stationary Poisson process in time and a Gutenberg-Richter relation for magnitudes. The upper bound of the magnitude confidence interval is calculated for different time intervals of 30, 50, and 100 years and imposed levels of confidence alpha = 0.5, 0.1, 0.05, and 0.01. The posterior distribution of waiting times T-f to the next earthquake with a given magnitude equal to 6.5, 7.0, and7.5 are calculated in each zone. In order to find the influence of declustering, we use the original and declustered version of the catalog. The earthquake catalog of the territory of Iran and surroundings are subdivided into six seismotectonic zones Alborz, Azerbaijan, Central Iran, Zagros, Kopet Dagh, and Makran. We assume the maximum possible magnitude m(max) = 8.5 and calculate the upper bound of the confidence interval of mu in each zone. The results indicate that for short time intervals equal to 30 and 50 years and imposed levels of confidence 1 - alpha = 0.95 and 0.90, the probability distribution of mu is around mu = 7.16-8.23 in all seismic zones.
We study the Volterra property of a class of anisotropic pseudo-differential operators on R x B for a manifold B with edge Y and time-variable t. This exposition belongs to a program for studying parabolicity in such a situation. In the present consideration we establish non-smoothing elements in a subalgebra with anisotropic operator-valued symbols of Mellin type with holomorphic symbols in the complex Mellin covariable from the cone theory, where the covariable t of t extends to symbolswith respect to t to the lower complex v half-plane. The resulting space ofVolterra operators enlarges an approach of Buchholz (Parabolische Pseudodifferentialoperatoren mit operatorwertigen Symbolen. Ph. D. thesis, Universitat Potsdam, 1996) by necessary elements to a new operator algebra containing Volterra parametrices under an appropriate condition of anisotropic ellipticity. Our approach avoids some difficulty in choosing Volterra quantizations in the edge case by generalizing specific achievements from the isotropic edge-calculus, obtained by Seiler (Pseudodifferential calculus on manifolds with non-compact edges, Ph. D. thesis, University of Potsdam, 1997), see also Gil et al. (in: Demuth et al (eds) Mathematical research, vol 100. Akademic Verlag, Berlin, pp 113-137, 1997; Osaka J Math 37: 221-260, 2000).