@unpublished{RabinovichSchulzeTarkhanov1999,
  author    = {Rabinovich, Vladimir and Schulze, Bert-Wolfgang and Tarkhanov, Nikolai Nikolaevich},
  title     = {Boundary value problems in domains with corners},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-25552},
  year      = {1999},
  abstract  = {We describe Fredholm boundary value problems for differential equations in domains with intersecting cuspidal edges on the boundary.},
  language  = {en}
}
@unpublished{NazaikinskiiSchulzeSternin1999,
  author    = {Nazaikinskii, Vladimir E. and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Quantization methods in differential equations : Chapter 2: Quantization of Lagrangian modules},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-25582},
  year      = {1999},
  abstract  = {In this chapter we use the wave packet transform described in Chapter 1 to quantize extended classical states represented by so-called Lagrangian sumbanifolds of the phase space. Functions on a Lagrangian manifold form a module over the ring of classical Hamiltonian functions on the phase space (with respect to pointwise multiplication). The quantization procedure intertwines this multiplication with the action of the corresponding quantum Hamiltonians; hence we speak of quantization of Lagrangian modules. The semiclassical states obtained by this quantization procedure provide asymptotic solutions to differential equations with a small parameter. Locally, such solutions can be represented by WKB elements. Global solutions are given by Maslov's canonical operator [2]; also see, e.g., [3] and the references therein. Here the canonical operator is obtained in the framework of the universal quantization procedure provided by the wave packet transform. This procedure was suggested in [4] (see also the references there) and further developed in [5]; our exposition is in the spirit of these papers. Some further bibliographical remarks can be found in the beginning of Chapter 1.},
  language  = {en}
}
@unpublished{SavinSchulzeSternin2000,
  author    = {Savin, Anton and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Elliptic operators in subspaces},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-25701},
  year      = {2000},
  abstract  = {We construct elliptic theory in the subspaces, determined by pseudodifferential projections. The finiteness theorem as well as index formula are obtained for elliptic operators acting in the subspaces. Topological (K-theoretic) aspects of the theory are studied in detail.},
  language  = {en}
}
@unpublished{SchulzeSterninSavin1999,
  author    = {Schulze, Bert-Wolfgang and Sternin, Boris and Savin, Anton},
  title     = {The homotopy classification and the index of boundary value problems for general elliptic operators},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-25568},
  year      = {1999},
  abstract  = {We give the homotopy classification and compute the index of boundary value problems for elliptic equations. The classical case of operators that satisfy the Atiyah-Bott condition is studied first. We also consider the general case of boundary value problems for operators that do not necessarily satisfy the Atiyah-Bott condition.},
  language  = {en}
}
@unpublished{ManicciaSchulze2002,
  author    = {Maniccia, L. and Schulze, Bert-Wolfgang},
  title     = {An algebra of meromorphic corner symbols},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26360},
  year      = {2002},
  abstract  = {Operators on manifolds with corners that have base configurations with geometric singularities can be analysed in the frame of a conormal symbolic structure which is in spirit similar to the one for conical singularities of Kondrat'ev's work. Solvability of elliptic equations and asymptotics of solutions are determined by meromorphic conormal symbols. We study the case when the base has edge singularities which is a natural assumption in a number of applications. There are new phenomena, caused by a specific kind of higher degeneracy of the underlying symbols. We introduce an algebra of meromorphic edge operators that depend on complex parameters and investigate meromorphic inverses in the parameter-dependent elliptic case. Among the examples are resolvents of elliptic differential operators on manifolds with edges.},
  language  = {en}
}
@unpublished{OliaroSchulze2002,
  author    = {Oliaro, Alessandro and Schulze, Bert-Wolfgang},
  title     = {Parameter-dependent boundary value problems on manifolds with edges},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26424},
  year      = {2002},
  abstract  = {As is known from Kondratyev's work, boundary value problems for elliptic operators on a manifold with conical singularities and boundary are controlled by a principal symbolic hierarchy, where the conormal symbols belong to the typical new components, compared with the smooth case, with interior and boundary symbols. A similar picture may be expected on manifolds with corners when the base of the cone itself is a manifold with conical or edge singularities. This is a natural situation in a number of applications, though with essential new difficulties. We investigate here corresponding conormal symbols in terms of a calculus of holomorphic parameter-dependent edge boundary value problems on the base. We show that a certain kernel cut-off procedure generates all such holomorphic families, modulo smoothing elements, and we establish conormal symbols as an algebra as is necessary for a parametrix constructions in the elliptic case.},
  language  = {en}
}
@unpublished{CoriascoSchulze2002,
  author    = {Coriasco, Sandro and Schulze, Bert-Wolfgang},
  title     = {Edge problems on configurations with model cones of different dimensions},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26438},
  year      = {2002},
  abstract  = {Elliptic equations on configurations W = W1 ∪ ... ∪ Wn with edge Y and components Wj of different dimension can be treated in the frame of pseudo-differential analysis on manifolds with geometric singularities, here, edges. Starting from edge-degenerate operators on Wj, j = 1, ..., N, we construct an algebra with extra "transmission" conditions on Y that satisfy an analogue of the Shapiro-Lopatinskij condition. Ellipticity refers to a two-component symbolic hierarchy with an interior and an edge part; the latter one is operator-valued, operating on the union of different dimensional model cones. We construct parametrices within our calculus, where exchange of information between the various components is encoded in Green and Mellin operators that are smoothing on W\Y. Moreover, we obtain regularity of solutions in weighted edge spaces with asymptotics.},
  language  = {en}
}
@unpublished{SchulzeSeiler2002,
  author    = {Schulze, Bert-Wolfgang and Seiler, J{\"o}rg},
  title     = {Pseudodifferential boundary value problems with global projection conditions},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26233},
  year      = {2002},
  abstract  = {Contents: Introduction 1 Operators with the transmission property 1.1 Operators on a manifold with boundary 1.2 Conditions with pseudodifferential projections 1.3 Projections and Fredholm families 2 Boundary value problems not requiring the transmission property 2.1 Interior operators 2.2 Edge amplitude functions 2.3 Boundary value problems 3 Operators with global projection conditions 3.1 Construction for boundary symbols 3.2 Ellipticity of boundary value problems with projection data 3.3 Operators of order zero},
  language  = {en}
}
@unpublished{NazaikinskiiSchulzeSternin2001,
  author    = {Nazaikinskii, Vladimir and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Localization problem in index theory of elliptic operators},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26175},
  year      = {2001},
  abstract  = {This is a survey of recent results concerning the general index locality principle, associated surgery, and their applications to elliptic operators on smooth manifolds and manifolds with singularities as well as boundary value problems. The full version of the paper is submitted for publication in Russian Mathematical Surveys.},
  language  = {en}
}
@unpublished{NazaikinskiiSavinSchulzeetal.2002,
  author    = {Nazaikinskii, Vladimir and Savin, Anton and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Elliptic theory on manifolds with nonisolated singularities : III. The spectral flow of families of conormal symbols},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26386},
  year      = {2002},
  abstract  = {When studyind elliptic operators on manifolds with nonisolated singularities one naturally encounters families of conormal symbols (i.e. operators elliptic with parameter p ∈ IR in the sense of Agranovich-Vishik) parametrized by the set of singular points. For homotopies of such families we define the notion of spectral flow, which in this case is an element of the K-group of the parameter space. We prove that the spectral flow is equal to the index of some family of operators on the infinite cone.},
  language  = {en}
}
@unpublished{HarutjunjanSchulze2002,
  author    = {Harutjunjan, G. and Schulze, Bert-Wolfgang},
  title     = {Reduction of orders in boundary value problems without the transmission property},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26220},
  year      = {2002},
  abstract  = {Given an algebra of pseudo-differential operators on a manifold, an elliptic element is said to be a reduction of orders, if it induces isomorphisms of Sobolev spaces with a corresponding shift of smoothness. Reductions of orders on a manifold with boundary refer to boundary value problems. We consider smooth symbols and ellipticity without additional boundary conditions which is the relevant case on a manifold with boundary. Starting from a class of symbols that has been investigated before for integer orders in boundary value problems with the transmission property we study operators of arbitrary real orders that play a similar role for operators without the transmission property. Moreover, we show that order reducing symbols have the Volterra property and are parabolic of anisotropy 1; analogous relations are formulated for arbitrary anisotropies. We finally investigate parameter-dependent operators, apply a kernel cut-off construction with respect to the parameter and show that corresponding holomorphic operator-valued Mellin symbols reduce orders in weighted Sobolev spaces on a cone with boundary.},
  language  = {en}
}
@unpublished{NazaikinskiiSavinSchulzeetal.2002,
  author    = {Nazaikinskii, Vladimir and Savin, Anton and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Elliptic theory on manifolds with nonisolated singularities : IV. Obstructions to elliptic problems on manifolds with edges},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26415},
  year      = {2002},
  abstract  = {The obstruction to the existence of Fredholm problems for elliptic differentail operators on manifolds with edges is a topological invariant of the operator. We give an explicit general formula for this invariant. As an application we compute this obstruction for geometric operators.},
  language  = {en}
}
@unpublished{NazaikinskiiSavinSchulzeetal.2002,
  author    = {Nazaikinskii, Vladimir and Savin, Anton and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Elliptic theory on manifolds with nonisolated singularities : II. Products in elliptic theory on manifolds with edges},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26335},
  year      = {2002},
  abstract  = {Exterior tensor products of elliptic operators on smooth manifolds and manifolds with conical singularities are used to obtain examples of elliptic operators on manifolds with edges that do not admit well-posed edge boundary and coboundary conditions.},
  language  = {en}
}
@unpublished{NazaikinskiiSavinSchulzeetal.2003,
  author    = {Nazaikinskii, Vladimir and Savin, Anton and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Differential operators on manifolds with singularities : analysis and topology : Chapter 5: Manifolds with isolated singularities},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26659},
  year      = {2003},
  abstract  = {Contents: Chapter 5: Manifolds with Isolated Singularities 5.1. Differential Operators and the Geometry of Singularities 5.1.1. How do isolated singularities arise? Examples 5.1.2. Definition and methods for the description of manifolds with isolated singularities 5.1.3. Bundles. The cotangent bundle 5.2. Asymptotics of Solutions, Function Spaces,Conormal Symbols 5.2.1. Conical singularities 5.2.2. Cuspidal singularities 5.3. A Universal Representation of Degenerate Operators and the Finiteness Theorem 5.3.1. The cylindrical representation 5.3.2. Continuity and compactness 5.3.3. Ellipticity and the finiteness theorem 5.4. Calculus of ΨDO 5.4.1. General ΨDO 5.4.2. The subalgebra of stabilizing ΨDO 5.4.3. Ellipticity and the finiteness theorem},
  language  = {en}
}
@unpublished{DinesSchulze2003,
  author    = {Dines, Nicoleta and Schulze, Bert-Wolfgang},
  title     = {Mellin-edge representations of elliptic operators},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26627},
  year      = {2003},
  abstract  = {We construct a class of elliptic operators in the edge algebra on a manifold M with an embedded submanifold Y interpreted as an edge. The ellipticity refers to a principal symbolic structure consisting of the standard interior symbol and an operator-valued edge symbol. Given a differential operator A on M for every (sufficiently large) s we construct an associated operator As in the edge calculus. We show that ellipticity of A in the usual sense entails ellipticity of As as an edge operator (up to a discrete set of reals s). Parametrices P of A then correspond to parametrices Ps of As, interpreted as Mellin-edge representations of P.},
  language  = {en}
}
@unpublished{KrainerSchulze2004,
  author    = {Krainer, Thomas and Schulze, Bert-Wolfgang},
  title     = {The conormal symbolic structure of corner boundary value problems},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26662},
  year      = {2004},
  abstract  = {Ellipticity of operators on manifolds with conical singularities or parabolicity on space-time cylinders are known to be linked to parameter-dependent operators (conormal symbols) on a corresponding base manifold. We introduce the conormal symbolic structure for the case of corner manifolds, where the base itself is a manifold with edges and boundary. The specific nature of parameter-dependence requires a systematic approach in terms of meromorphic functions with values in edge-boundary value problems. We develop here a corresponding calculus, and we construct inverses of elliptic elements.},
  language  = {en}
}
@unpublished{NazaikinskiiSavinSchulzeetal.2004,
  author    = {Nazaikinskii, Vladimir and Savin, Anton and Schulze, Bert-Wolfgang and Sternin, Boris},
  title     = {Differential operators on manifolds with singularities : analysis and topology : Chapter 7: The index problem on manifolds with singularities},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26700},
  year      = {2004},
  abstract  = {Contents: Chapter 7: The Index Problemon Manifolds with Singularities Preface 7.1. The Simplest Index Formulas 7.1.1. General properties of the index 7.1.2. The index of invariant operators on the cylinder 7.1.3. Relative index formulas 7.1.4. The index of general operators on the cylinder 7.1.5. The index of operators of the form 1 + G with a Green operator G 7.1.6. The index of operators of the form 1 + G on manifolds with edges 7.1.7. The index on bundles with smooth base and fiber having conical points 7.2. The Index Problem for Manifolds with Isolated Singularities 7.2.1. Statement of the index splitting problem 7.2.2. The obstruction to the index splitting 7.2.3. Computation of the obstruction in topological terms 7.2.4. Examples. Operators with symmetries 7.3. The Index Problem for Manifolds with Edges 7.3.1. The index excision property 7.3.2. The obstruction to the index splitting 7.4. Bibliographical Remarks},
  language  = {en}
}
@unpublished{HarutjunjanSchulze2004,
  author    = {Harutjunjan, Gohar and Schulze, Bert-Wolfgang},
  title     = {Boundary problems with meromorphic symbols in cylindrical domains},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-26735},
  year      = {2004},
  abstract  = {We show relative index formulas for boundary value problems in cylindrical domains and Sobolev spaces with different weigths at ±∞. The amplitude functions are meromorphic in the axial covariable and take values in the space of boundary value problems on the cross section of the cylinder.},
  language  = {en}
}
@article{HanischLudewig2022,
  author    = {Hanisch, Florian and Ludewig, Matthias},
  title     = {The fermionic integral on loop space and the Pfaffian line bundle},
  series = {Journal of mathematical physics},
  volume    = {63},
  journal   = {Journal of mathematical physics},
  number    = {12},
  publisher = {American Inst. of Physics},
  address   = {College Park, Md.},
  issn      = {0022-2488},
  doi       = {10.1063/5.0060355},
  pages     = {26},
  year      = {2022},
  abstract  = {As the loop space of a Riemannian manifold is infinite-dimensional, it is a non-trivial problem to make sense of the "top degree component " of a differential form on it. In this paper, we show that a formula from finite dimensions generalizes to assign a sensible "top degree component " to certain composite forms, obtained by wedging with the exponential (in the exterior algebra) of the canonical presymplectic 2-form on the loop space. This construction is a crucial ingredient for the definition of the supersymmetric path integral on the loop space.},
  language  = {en}
}
@article{Metzger2023,
  author    = {Metzger, Jan},
  title     = {Refined position estimates for surfaces of Willmore type in Riemannian manifolds},
  series = {Communications in analysis and geometry},
  volume    = {30},
  journal   = {Communications in analysis and geometry},
  number    = {10},
  publisher = {International Press of Boston},
  address   = {Somerville, Mass.},
  issn      = {1019-8385},
  doi       = {10.4310/CAG.2022.v30.n10.a5},
  pages     = {2315 -- 2346},
  year      = {2023},
  abstract  = {In this paper we consider surfaces which are critical points of the Willmore functional subject to constrained area. In the case of small area we calculate the corrections to the intrinsic geometry induced by the ambient curvature. These estimates together with the choice of an adapted geometric center of mass lead to refined position estimates in relation to the scalar curvature of the ambient manifold.},
  language  = {en}
}
@article{RœllyZass2020,
  author    = {Rœlly, Sylvie and Zass, Alexander},
  title     = {Marked Gibbs point processes with unbounded interaction},
  series = {Journal of statistical physics},
  volume    = {179},
  journal   = {Journal of statistical physics},
  number    = {4},
  publisher = {Springer},
  address   = {New York},
  issn      = {0022-4715},
  doi       = {10.1007/s10955-020-02559-3},
  pages     = {972 -- 996},
  year      = {2020},
  abstract  = {We construct marked Gibbs point processes in R-d under quite general assumptions. Firstly, we allow for interaction functionals that may be unbounded and whose range is not assumed to be uniformly bounded. Indeed, our typical interaction admits an a.s. finite but random range. Secondly, the random marks-attached to the locations in R-d-belong to a general normed space G. They are not bounded, but their law should admit a super-exponential moment. The approach used here relies on the so-called entropy method and large-deviation tools in order to prove tightness of a family of finite-volume Gibbs point processes. An application to infinite-dimensional interacting diffusions is also presented.},
  language  = {en}
}
@article{Seyedhosseini2022,
  author    = {Seyedhosseini, Mehran},
  title     = {A variant of Roe algebras for spaces with cylindrical ends with applications in relative higher index theory},
  series = {Journal of noncommutative geometry},
  volume    = {16},
  journal   = {Journal of noncommutative geometry},
  number    = {2},
  publisher = {European Mathematical Society},
  address   = {Zurich},
  issn      = {1661-6952},
  doi       = {10.4171/JNCG/457},
  pages     = {595 -- 624},
  year      = {2022},
  abstract  = {In this paper, we define a variant of Roe algebras for spaces with cylindrical ends and use this to study questions regarding existence and classification of metrics of positive scalar curvature on such manifolds which are collared on the cylindrical end. We discuss how our constructions are related to relative higher index theory as developed by Chang, Weinberger, and Yu and use this relationship to define higher rho-invariants for positive scalar curvature metrics on manifolds with boundary. This paves the way for the classification of these metrics. Finally, we use the machinery developed here to give a concise proof of a result of Schick and the author, which relates the relative higher index with indices defined in the presence of positive scalar curvature on the boundary.},
  language  = {en}
}
@phdthesis{Hecher2021,
  author    = {Hecher, Markus},
  title     = {Advanced tools and methods for treewidth-based problem solving},
  doi       = {10.25932/publishup-51251},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512519},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xv, 184},
  year      = {2021},
  abstract  = {In the last decades, there was a notable progress in solving the well-known Boolean satisfiability (Sat) problem, which can be witnessed by powerful Sat solvers. One of the reasons why these solvers are so fast are structural properties of instances that are utilized by the solver's interna. This thesis deals with the well-studied structural property treewidth, which measures the closeness of an instance to being a tree. In fact, there are many problems parameterized by treewidth that are solvable in polynomial time in the instance size when parameterized by treewidth. In this work, we study advanced treewidth-based methods and tools for problems in knowledge representation and reasoning (KR). Thereby, we provide means to establish precise runtime results (upper bounds) for canonical problems relevant to KR. Then, we present a new type of problem reduction, which we call decomposition-guided (DG) that allows us to precisely monitor the treewidth when reducing from one problem to another problem. This new reduction type will be the basis for a long-open lower bound result for quantified Boolean formulas and allows us to design a new methodology for establishing runtime lower bounds for problems parameterized by treewidth. Finally, despite these lower bounds, we provide an efficient implementation of algorithms that adhere to treewidth. Our approach finds suitable abstractions of instances, which are subsequently refined in a recursive fashion, and it uses Sat solvers for solving subproblems. It turns out that our resulting solver is quite competitive for two canonical counting problems related to Sat.},
  language  = {en}
}
@article{PohleAdamBeumer2022,
  author    = {Pohle, Jennifer and Adam, Timo and Beumer, Larissa},
  title     = {Flexible estimation of the state dwell-time distribution in hidden semi-Markov models},
  series = {Computational statistics \& data analysis},
  volume    = {172},
  journal   = {Computational statistics \& data analysis},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0167-9473},
  doi       = {10.1016/j.csda.2022.107479},
  pages     = {15},
  year      = {2022},
  abstract  = {Hidden semi-Markov models generalise hidden Markov models by explicitly modelling the time spent in a given state, the so-called dwell time, using some distribution defined on the natural numbers. While the (shifted) Poisson and negative binomial distribution provide natural choices for such distributions, in practice, parametric distributions can lack the flexibility to adequately model the dwell times. To overcome this problem, a penalised maximum likelihood approach is proposed that allows for a flexible and data-driven estimation of the dwell-time distributions without the need to make any distributional assumption. This approach is suitable for direct modelling purposes or as an exploratory tool to investigate the latent state dynamics. The feasibility and potential of the suggested approach is illustrated in a simulation study and by modelling muskox movements in northeast Greenland using GPS tracking data. The proposed method is implemented in the R-package PHSMM which is available on CRAN.},
  language  = {en}
}
@article{BiskabornSmithNoetzlietal.2019,
  author    = {Biskaborn, Boris and Smith, Sharon L. and Noetzli, Jeannette and Matthes, Heidrun and Vieira, Goncalo and Streletskiy, Dmitry A. and Schoeneich, Philippe and Romanovsky, Vladimir E. and Lewkowicz, Antoni G. and Abramov, Andrey and Allard, Michel and Boike, Julia and Cable, William L. and Christiansen, Hanne H. and Delaloye, Reynald and Diekmann, Bernhard and Drozdov, Dmitry and Etzelmueller, Bernd and Grosse, Guido and Guglielmin, Mauro and Ingeman-Nielsen, Thomas and Isaksen, Ketil and Ishikawa, Mamoru and Johansson, Margareta and Johannsson, Halldor and Joo, Anseok and Kaverin, Dmitry and Kholodov, Alexander and Konstantinov, Pavel and Kroeger, Tim and Lambiel, Christophe and Lanckman, Jean-Pierre and Luo, Dongliang and Malkova, Galina and Meiklejohn, Ian and Moskalenko, Natalia and Oliva, Marc and Phillips, Marcia and Ramos, Miguel and Sannel, A. Britta K. and Sergeev, Dmitrii and Seybold, Cathy and Skryabin, Pavel and Vasiliev, Alexander and Wu, Qingbai and Yoshikawa, Kenji and Zheleznyak, Mikhail and Lantuit, Hugues},
  title     = {Permafrost is warming at a global scale},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2041-1723},
  doi       = {10.1038/s41467-018-08240-4},
  pages     = {11},
  year      = {2019},
  abstract  = {Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007-2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 +/- 0.15 degrees C. Over the same period, discontinuous permafrost warmed by 0.20 +/- 0.10 degrees C. Permafrost in mountains warmed by 0.19 +/- 0.05 degrees C and in Antarctica by 0.37 +/- 0.10 degrees C. Globally, permafrost temperature increased by 0.29 +/- 0.12 degrees C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged.},
  language  = {en}
}
@book{OPUS4-43561,
  title     = {Implementation research on problem solving in school settings},
  series = {Ars inveniendi et dejudicandi ; 13},
  journal   = {Ars inveniendi et dejudicandi ; 13},
  editor    = {Kuzle, Ana and Rott, Benjamin and Gebel, Inga},
  publisher = {WTM-Verlag},
  address   = {M{\"u}nster},
  isbn      = {978-3-95987-116-7},
  pages     = {IV, 220},
  year      = {2019},
  language  = {en}
}
@article{EngbertRabeKliegletal.2021,
  author    = {Engbert, Ralf and Rabe, Maximilian Michael and Kliegl, Reinhold and Reich, Sebastian},
  title     = {Sequential data assimilation of the stochastic SEIR epidemic model for regional COVID-19 dynamics},
  series = {Bulletin of mathematical biology : official journal of the Society for Mathematical Biology},
  volume    = {83},
  journal   = {Bulletin of mathematical biology : official journal of the Society for Mathematical Biology},
  number    = {1},
  publisher = {Springer},
  address   = {New York},
  issn      = {0092-8240},
  doi       = {10.1007/s11538-020-00834-8},
  pages     = {16},
  year      = {2021},
  abstract  = {Newly emerging pandemics like COVID-19 call for predictive models to implement precisely tuned responses to limit their deep impact on society. Standard epidemic models provide a theoretically well-founded dynamical description of disease incidence. For COVID-19 with infectiousness peaking before and at symptom onset, the SEIR model explains the hidden build-up of exposed individuals which creates challenges for containment strategies. However, spatial heterogeneity raises questions about the adequacy of modeling epidemic outbreaks on the level of a whole country. Here, we show that by applying sequential data assimilation to the stochastic SEIR epidemic model, we can capture the dynamic behavior of outbreaks on a regional level. Regional modeling, with relatively low numbers of infected and demographic noise, accounts for both spatial heterogeneity and stochasticity. Based on adapted models, short-term predictions can be achieved. Thus, with the help of these sequential data assimilation methods, more realistic epidemic models are within reach.},
  language  = {en}
}
@phdthesis{Fischer2024,
  author    = {Fischer, Florian},
  title     = {Hardy inequalities on graphs},
  doi       = {10.25932/publishup-64773},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-647730},
  school      = {Universit{\"a}t Potsdam},
  pages     = {vi, 160},
  year      = {2024},
  abstract  = {Die Dissertation befasst sich mit einer zentralen Ungleichung der nicht-linearen Potentialtheorie, der Hardy-Ungleichung. Sie besagt, dass das nicht-lineare Energiefunktional von unten durch eine p-te Potenz einer gewichteten p-Norm abgesch{\"a}tzt werden kann, p>1. Das Energiefunktional besteht dabei aus einem Divergenz- und einem beliebigen Potentialteil. Als zugrundeliegender Raum wurden hier lokal summierbare unendliche Graphen gew{\"a}hlt. Bisherige Ver{\"o}ffentlichungen zu Hardy-Ungleichungen auf Graphen haben vor allem den Spezialfall p=2 betrachtet, oder lokal endliche Graphen ohne Potentialteil. Zwei grundlegende Fragestellungen ergeben sich nun ganz nat{\"u}rlich: F{\"u}r welche Graphen gibt {\"u}berhaupt es eine Hardy-Ungleichung? Und, wenn es sie gibt, gibt es einen Weg um ein optimales Gewicht zu erhalten? Antworten auf diese Fragen werden in Theorem 10.1 und Theorem 12.1 gegeben. Theorem 10.1 gibt eine Reihe an Charakterisierungen an; unter anderem gibt es eine Hardy-Ungleichung auf einem Graphen genau dann, wenn es eine Greensche Funktion gibt. Theorem 12.1 gibt eine explizite Formel an, um optimale Hardy-Gewichte f{\"u}r lokal endliche Graphen unter einigen technischen Zusatzannahmen zu berechnen. In Beispielen wird gezeigt, dass Greensche Funktionen gute Kandidaten sind um in die Formel eingesetzt zu werden. Um diese beiden Theoreme beweisen zu k{\"o}nnen, m{\"u}ssen eine Vielzahl an Techniken erarbeitet werden, welche in den ersten Kapiteln behandelt werden. Dabei sind eine Verallgemeinerung der Grundzustandstransformation (Theorem 4.1), ein Agmon-Allegretto-Piepenbrink-artiges Resultat (Theorem 6.1) und das Vergleichsprinzip (Proposition 7.3) besonders hervorzuheben, da diese Resultate sehr h{\"a}ufig angewendet werden und somit das Fundament der Dissertation bilden. Es wird zudem darauf Wert gelegt die Theorie durch Beispiele zu veranschaulichen. Hierbei wird der Fokus auf die nat{\"u}rlichen Zahlen, Euklidische Gitter, B{\"a}ume und Sterne gelegt. Als Abschluss werden noch eine nicht-lineare Version der Heisenbergschen Unsch{\"a}rferelation und eine Rellich-Ungleichung aus der Hardy-Ungleichung geschlussfolgert.},
  language  = {en}
}
@article{Zass2021,
  author    = {Zass, Alexander},
  title     = {Gibbs point processes on path space},
  series = {Markov processes and related fields},
  volume    = {28},
  journal   = {Markov processes and related fields},
  number    = {3},
  publisher = {Polymat},
  address   = {Moscow},
  issn      = {1024-2953},
  pages     = {329 -- 364},
  year      = {2021},
  abstract  = {We present general existence and uniqueness results for marked models with pair interactions, exemplified through Gibbs point processes on path space. More precisely, we study a class of infinite-dimensional diffusions under Gibbsian interactions, in the context of marked point configurations: the starting points belong to R-d, and the marks are the paths of Langevin diffusions. We use the entropy method to prove existence of an infinite-volume Gibbs point process and use cluster expansion tools to provide an explicit activity domain in which uniqueness holds.},
  language  = {en}
}
@article{HuangHuangReichetal.2022,
  author    = {Huang, Daniel Zhengyu and Huang, Jiaoyang and Reich, Sebastian and Stuart, Andrew M.},
  title     = {Efficient derivative-free Bayesian inference for large-scale inverse problems},
  series = {Inverse problems : an international journal of inverse problems, inverse methods and computerised inversion of data},
  volume    = {38},
  journal   = {Inverse problems : an international journal of inverse problems, inverse methods and computerised inversion of data},
  number    = {12},
  publisher = {IOP Publ. Ltd.},
  address   = {Bristol},
  issn      = {0266-5611},
  doi       = {10.1088/1361-6420/ac99fa},
  pages     = {40},
  year      = {2022},
  abstract  = {We consider Bayesian inference for large-scale inverse problems, where computational challenges arise from the need for repeated evaluations of an expensive forward model. This renders most Markov chain Monte Carlo approaches infeasible, since they typically require O(10(4)) model runs, or more. Moreover, the forward model is often given as a black box or is impractical to differentiate. Therefore derivative-free algorithms are highly desirable. We propose a framework, which is built on Kalman methodology, to efficiently perform Bayesian inference in such inverse problems. The basic method is based on an approximation of the filtering distribution of a novel mean-field dynamical system, into which the inverse problem is embedded as an observation operator. Theoretical properties are established for linear inverse problems, demonstrating that the desired Bayesian posterior is given by the steady state of the law of the filtering distribution of the mean-field dynamical system, and proving exponential convergence to it. This suggests that, for nonlinear problems which are close to Gaussian, sequentially computing this law provides the basis for efficient iterative methods to approximate the Bayesian posterior. Ensemble methods are applied to obtain interacting particle system approximations of the filtering distribution of the mean-field model; and practical strategies to further reduce the computational and memory cost of the methodology are presented, including low-rank approximation and a bi-fidelity approach. The effectiveness of the framework is demonstrated in several numerical experiments, including proof-of-concept linear/nonlinear examples and two large-scale applications: learning of permeability parameters in subsurface flow; and learning subgrid-scale parameters in a global climate model. Moreover, the stochastic ensemble Kalman filter and various ensemble square-root Kalman filters are all employed and are compared numerically. The results demonstrate that the proposed method, based on exponential convergence to the filtering distribution of a mean-field dynamical system, is competitive with pre-existing Kalman-based methods for inverse problems.},
  language  = {en}
}
@article{ShlapunovTarchanov2022,
  author    = {Shlapunov, Alexander A. and Tarchanov, Nikolaj Nikolaevič},
  title     = {Inverse image of precompact sets and regular solutions to the Navier-Stokes equations},
  series = {Vestnik Udmurtskogo Universiteta. Matematika, mechanika, kompʹjuternye nauki},
  volume    = {32},
  journal   = {Vestnik Udmurtskogo Universiteta. Matematika, mechanika, kompʹjuternye nauki},
  number    = {2},
  publisher = {Udmurtskij gosudarstvennyj universitet},
  address   = {Iževsk},
  issn      = {1994-9197},
  doi       = {10.35634/vm220208},
  pages     = {278 -- 297},
  year      = {2022},
  abstract  = {We consider the initial value problem for the Navier-Stokes equations over R-3 x [0, T] with time T > 0 in the spatially periodic setting. We prove that it induces open injective mappings A(s): B-1(s) -> B-2(s-1) where B-1(s), B-2(s-1) are elements from scales of specially constructed function spaces of Bochner-Sobolev typeparametrized with the smoothness index s is an element of N. Finally, we prove that a map Asis surjective if and only if the inverse image A(s)(- 1) (K) of any pre compact set K from the range of the map Asis bounded in the Bochner space L-s([0, T], L-r(T-3))with the Ladyzhenskaya-Prodi-Serrin numbers s, r.},
  language  = {en}
}
@misc{KrauseKloftHuisingaetal.2019,
  author    = {Krause, Andreas and Kloft, Charlotte and Huisinga, Wilhelm and Karlsson, Mats and Pinheiro, Jos{\´e} and Bies, Robert and Rogers, James and Mentr{\´e}, France and Musser, Bret J.},
  title     = {Comment on Jaki et al., A proposal for a new PhD level curriculum on quantitative methods for drug development},
  series = {Pharmaceutical statistics : the journal of applied statistics in the pharmaceutical industry},
  volume    = {18},
  journal   = {Pharmaceutical statistics : the journal of applied statistics in the pharmaceutical industry},
  number    = {3},
  publisher = {Wiley},
  address   = {Hoboken},
  organization    = {ASA Special Interest Grp Stat Phar ASA Special Interest Grp Stat Phar},
  issn      = {1539-1604},
  pages     = {278 -- 281},
  year      = {2019},
  language  = {en}
}
@phdthesis{Seuring2000,
  author    = {Seuring, Markus},
  title     = {Output space compaction for testing and concurrent checking},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0000165},
  school      = {Universit{\"a}t Potsdam},
  year      = {2000},
  abstract  = {In der Dissertation werden neue Entwurfsmethoden f{\"u}r Kompaktoren f{\"u}r die Ausg{\"a}nge von digitalen Schaltungen beschrieben, die die Anzahl der zu testenden Ausg{\"a}nge drastisch verkleinern und dabei die Testbarkeit der Schaltungen nur wenig oder gar nicht verschlechtern. Der erste Teil der Arbeit behandelt f{\"u}r kombinatorische Schaltungen Methoden, die die Struktur der Schaltungen beim Entwurf der Kompaktoren ber{\"u}cksichtigen. Verschiedene Algorithmen zur Analyse von Schaltungsstrukturen werden zum ersten Mal vorgestellt und untersucht. Die Komplexit{\"a}t der vorgestellten Verfahren zur Erzeugung von Kompaktoren ist linear bez{\"u}glich der Anzahl der Gatter in der Schaltung und ist damit auf sehr große Schaltungen anwendbar. Im zweiten Teil wird erstmals ein solches Verfahren f{\"u}r sequentielle Schaltkreise beschrieben. Dieses Verfahren baut im wesentlichen auf das erste auf. Der dritte Teil beschreibt eine Entwurfsmethode, die keine Informationen {\"u}ber die interne Struktur der Schaltung oder {\"u}ber das zugrundeliegende Fehlermodell ben{\"o}tigt. Der Entwurf basiert alleine auf einem vorgegebenen Satz von Testvektoren und die dazugeh{\"o}renden Testantworten der fehlerfreien Schaltung. Ein nach diesem Verfahren erzeugter Kompaktor maskiert keinen der Fehler, die durch das Testen mit den vorgegebenen Vektoren an den Ausg{\"a}ngen der Schaltung beobachtbar sind.},
  language  = {en}
}
@article{MuellerSchoellGroenlandScherfClaveletal.2020,
  author    = {Mueller-Schoell, Anna and Groenland, Stefanie L. and Scherf-Clavel, Oliver and van Dyk, Madele and Huisinga, Wilhelm and Michelet, Robin and Jaehde, Ulrich and Steeghs, Neeltje and Huitema, Alwin D. R. and Kloft, Charlotte},
  title     = {Therapeutic drug monitoring of oral targeted antineoplastic drugs},
  series = {European journal of clinical pharmacology},
  volume    = {77},
  journal   = {European journal of clinical pharmacology},
  number    = {4},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0031-6970},
  doi       = {10.1007/s00228-020-03014-8},
  pages     = {441 -- 464},
  year      = {2020},
  abstract  = {Purpose This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window.},
  language  = {en}
}
@article{GrisicEserHuisingaetal.2020,
  author    = {Grisic, Ana-Marija and Eser, Alexander and Huisinga, Wilhelm and Reinisch, Walter and Kloft, Charlotte},
  title     = {Quantitative relationship between infliximab exposure and inhibition of C-reactive protein synthesis to support inflammatory bowel disease management},
  series = {British journal of clinical pharmacology},
  volume    = {87},
  journal   = {British journal of clinical pharmacology},
  number    = {5},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0306-5251},
  doi       = {10.1111/bcp.14648},
  pages     = {2374 -- 2384},
  year      = {2020},
  abstract  = {Aim Quantitative and kinetic insights into the drug exposure-disease response relationship might enhance our knowledge on loss of response and support more effective monitoring of inflammatory activity by biomarkers in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX). This study aimed to derive recommendations for dose adjustment and treatment optimisation based on mechanistic characterisation of the relationship between IFX serum concentration and C-reactive protein (CRP) concentration. <br /> Methods Data from an investigator-initiated trial included 121 patients with IBD during IFX maintenance treatment. Serum concentrations of IFX, antidrug antibodies (ADA), CRP, and disease-related covariates were determined at the mid-term and end of a dosing interval. Data were analysed using a pharmacometric nonlinear mixed-effects modelling approach. An IFX exposure-CRP model was generated and applied to evaluate dosing regimens to achieve CRP remission. <br /> Results The generated quantitative model showed that IFX has the potential to inhibit up to 72\% (9\% relative standard error [RSE]) of CRP synthesis in a patient. IFX concentration leading to 90\% of the maximum CRP synthesis inhibition was 18.4 mu g/mL (43\% RSE). Presence of ADA was the most influential factor on IFX exposure. With standard dosing strategy, >= 55\% of ADA+ patients experienced CRP nonremission. Shortening the dosing interval and co-therapy with immunomodulators were found to be the most beneficial strategies to maintain CRP remission. <br /> Conclusions With the generated model we could for the first time establish a robust relationship between IFX exposure and CRP synthesis inhibition, which could be utilised for treatment optimisation in IBD patients.},
  language  = {en}
}
@article{KluweMicheletMuellerSchoelletal.2020,
  author    = {Kluwe, Franziska and Michelet, Robin and M{\"u}ller-Sch{\"o}ll, Anna and Maier, Corinna and Klopp-Schulze, Lena and van Dyk, Madele and Mikus, Gerd and Huisinga, Wilhelm and Kloft, Charlotte},
  title     = {Perspectives on model-informed precision dosing in the digital health era},
  series = {Clinical pharmacology \& therapeutics},
  volume    = {109},
  journal   = {Clinical pharmacology \& therapeutics},
  number    = {1},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0009-9236},
  doi       = {10.1002/cpt.2049},
  pages     = {29 -- 36},
  year      = {2020},
  language  = {en}
}
@article{NassarHohmannMicheletetal.2022,
  author    = {Nassar, Yomna M. and Hohmann, Nicolas and Michelet, Robin and Gottwalt, Katharina and Meid, Andreas D. and Burhenne, J{\"u}rgen and Huisinga, Wilhelm and Haefeli, Walter E. and Mikus, Gerd and Kloft, Charlotte},
  title     = {Quantification of the Time Course of CYP3A Inhibition, Activation, and Induction Using a Population Pharmacokinetic Model of Microdosed Midazolam Continuous Infusion},
  series = {Clinical Pharmacokinetics},
  volume    = {61},
  journal   = {Clinical Pharmacokinetics},
  number    = {11},
  publisher = {Springer},
  address   = {Northcote},
  issn      = {0312-5963},
  doi       = {10.1007/s40262-022-01175-6},
  pages     = {1595 -- 1607},
  year      = {2022},
  abstract  = {Background Cytochrome P450 (CYP) 3A contributes to the metabolism of many approved drugs. CYP3A perpetrator drugs can profoundly alter the exposure of CYP3A substrates. However, effects of such drug-drug interactions are usually reported as maximum effects rather than studied as time-dependent processes. Identification of the time course of CYP3A modulation can provide insight into when significant changes to CYP3A activity occurs, help better design drug-drug interaction studies, and manage drug-drug interactions in clinical practice. Objective We aimed to quantify the time course and extent of the in vivo modulation of different CYP3A perpetrator drugs on hepatic CYP3A activity and distinguish different modulatory mechanisms by their time of onset, using pharmacologically inactive intravenous microgram doses of the CYP3A-specific substrate midazolam, as a marker of CYP3A activity. Methods Twenty-four healthy individuals received an intravenous midazolam bolus followed by a continuous infusion for 10 or 36 h. Individuals were randomized into four arms: within each arm, two individuals served as a placebo control and, 2 h after start of the midazolam infusion, four individuals received the CYP3A perpetrator drug: voriconazole (inhibitor, orally or intravenously), rifampicin (inducer, orally), or efavirenz (activator, orally). After midazolam bolus administration, blood samples were taken every hour (rifampicin arm) or every 15 min (remaining study arms) until the end of midazolam infusion. A total of 1858 concentrations were equally divided between midazolam and its metabolite, 1'-hydroxymidazolam. A nonlinear mixed-effects population pharmacokinetic model of both compounds was developed using NONMEM (R). CYP3A activity modulation was quantified over time, as the relative change of midazolam clearance encountered by the perpetrator drug, compared to the corresponding clearance value in the placebo arm. Results Time course of CYP3A modulation and magnitude of maximum effect were identified for each perpetrator drug. While efavirenz CYP3A activation was relatively fast and short, reaching a maximum after approximately 2-3 h, the induction effect of rifampicin could only be observed after 22 h, with a maximum after approximately 28-30 h followed by a steep drop to almost baseline within 1-2 h. In contrast, the inhibitory impact of both oral and intravenous voriconazole was prolonged with a steady inhibition of CYP3A activity followed by a gradual increase in the inhibitory effect until the end of sampling at 8 h. Relative maximum clearance changes were +59.1\%, +46.7\%, -70.6\%, and -61.1\% for efavirenz, rifampicin, oral voriconazole, and intravenous voriconazole, respectively. Conclusions We could distinguish between different mechanisms of CYP3A modulation by the time of onset. Identification of the time at which clearance significantly changes, per perpetrator drug, can guide the design of an optimal sampling schedule for future drug-drug interaction studies. The impact of a short-term combination of different perpetrator drugs on the paradigm CYP3A substrate midazolam was characterized and can define combination intervals in which no relevant interaction is to be expected.},
  language  = {en}
}
@misc{WeisserStueblerMatheisetal.2017,
  author    = {Weisser, Karin and St{\"u}bler, Sabine and Matheis, Walter and Huisinga, Wilhelm},
  title     = {Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products},
  series = {Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology},
  volume    = {88},
  journal   = {Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology},
  publisher = {Elsevier},
  address   = {San Diego},
  issn      = {0273-2300},
  doi       = {10.1016/j.yrtph.2017.02.018},
  pages     = {310 -- 321},
  year      = {2017},
  abstract  = {As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.},
  language  = {en}
}
@article{WichaHuisingaKloft2017,
  author    = {Wicha, Sebastian G. and Huisinga, Wilhelm and Kloft, Charlotte},
  title     = {Translational pharmacometric evaluation of typical antibiotic broad-spectrum combination therapies against staphylococcus aureus exploiting in vitro information},
  series = {CPT: pharmacometrics \& systems pharmacology},
  volume    = {6},
  journal   = {CPT: pharmacometrics \& systems pharmacology},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {2163-8306},
  doi       = {10.1002/psp4.12197},
  pages     = {512 -- 522},
  year      = {2017},
  abstract  = {Broad-spectrum antibiotic combination therapy is frequently applied due to increasing resistance development of infective pathogens. The objective of the present study was to evaluate two common empiric broad-spectrum combination therapies consisting of either linezolid (LZD) or vancomycin (VAN) combined with meropenem (MER) against Staphylococcus aureus (S. aureus) as the most frequent causative pathogen of severe infections. A semimechanistic pharmacokinetic-pharmacodynamic (PK-PD) model mimicking a simplified bacterial life-cycle of S. aureus was developed upon time-kill curve data to describe the effects of LZD, VAN, and MER alone and in dual combinations. The PK-PD model was successfully (i) evaluated with external data from two clinical S. aureus isolates and further drug combinations and (ii) challenged to predict common clinical PK-PD indices and breakpoints. Finally, clinical trial simulations were performed that revealed that the combination of VAN-MER might be favorable over LZD-MER due to an unfavorable antagonistic interaction between LZD and MER.},
  language  = {en}
}
@article{EdlundGrisicSteenholdtetal.2019,
  author    = {Edlund, Helena and Grisic, Ana-Marija and Steenholdt, Casper and Ainsworth, Mark Andrew and Brynskov, Torn and Huisinga, Wilhelm and Kloft, Charlotte},
  title     = {Absence of Relationship Between Crohn's Disease Activity Index or C-Reactive Protein and Infliximab Exposure Calls for Objective Crohn's Disease Activity Measures for the Evaluation of Treatment Effects at Treatment Failure},
  series = {Therapeutic drug monitoring : official journal of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology},
  volume    = {41},
  journal   = {Therapeutic drug monitoring : official journal of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology},
  number    = {2},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {0163-4356},
  doi       = {10.1097/FTD.0000000000000590},
  pages     = {235 -- 242},
  year      = {2019},
  abstract  = {Background: Circulating infliximab (IFX) concentrations correlate with clinical outcomes, forming the basis of the IFX concentration monitoring in patients with Crohn's disease. This study aims to investigate and refine the exposure-response relationship by linking the disease activity markers "Crohn's disease activity index" (CDAI) and C-reactive protein (CRP) to IFX exposure. In addition, we aim to explore the correlations between different disease markers and exposure metrics. Methods: Data from 47 Crohn's disease patients of a randomized controlled trial were analyzed post hoc. All patients had secondary treatment failure at inclusion and had received intensified IFX of 5 mg/kg every 4 weeks for up to 20 weeks. Graphical analyses were performed to explore exposure-response relationships. Metrics of exposure included area under the concentration-time curve (AUC) and trough concentrations (Cmin). Disease activity was measured by CDAI and CRP values, their change from baseline/last visit, and response/remission outcomes at week 12. Results: Although trends toward lower Cmin and lower AUC in nonresponders were observed, neither CDAI nor CRP showed consistent trends of lower disease activity with higher IFX exposure across the 30 evaluated relationships. As can be expected, Cmin and AUC were strongly correlated with each other. Contrarily, the disease activity markers were only weakly correlated with each other. Conclusions: No significant relationship between disease activity, as evaluated by CDAI or CRP, and IFX exposure was identified. AUC did not add benefit compared with Cmin. These findings support the continued use of Cmin and call for stringent objective disease activity (bio-)markers (eg, endoscopy) to form the basis of personalized IFX therapy for Crohn's disease patients with IFX treatment failure.},
  language  = {en}
}
@article{KnoechelKloftHuisinga2018,
  author    = {Kn{\"o}chel, Jane and Kloft, Charlotte and Huisinga, Wilhelm},
  title     = {Understanding and reducing complex systems pharmacology models based on a novel input-response index},
  series = {Journal of pharmacokinetics and pharmacodynamics},
  volume    = {45},
  journal   = {Journal of pharmacokinetics and pharmacodynamics},
  number    = {1},
  publisher = {Springer Science + Business Media B.V.},
  address   = {New York},
  issn      = {1567-567X},
  doi       = {10.1007/s10928-017-9561-x},
  pages     = {139 -- 157},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@phdthesis{Knoechel2019,
  author    = {Kn{\"o}chel, Jane},
  title     = {Model reduction of mechanism-based pharmacodynamic models and its link to classical drug effect models},
  doi       = {10.25932/publishup-44059},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-440598},
  school      = {Universit{\"a}t Potsdam},
  pages     = {vii, 147},
  year      = {2019},
  abstract  = {Continuous insight into biological processes has led to the development of large-scale, mechanistic systems biology models of pharmacologically relevant networks. While these models are typically designed to study the impact of diverse stimuli or perturbations on multiple system variables, the focus in pharmacological research is often on a specific input, e.g., the dose of a drug, and a specific output related to the drug effect or response in terms of some surrogate marker. To study a chosen input-output pair, the complexity of the interactions as well as the size of the models hinders easy access and understanding of the details of the input-output relationship. The objective of this thesis is the development of a mathematical approach, in specific a model reduction technique, that allows (i) to quantify the importance of the different state variables for a given input-output relationship, and (ii) to reduce the dynamics to its essential features -- allowing for a physiological interpretation of state variables as well as parameter estimation in the statistical analysis of clinical data. We develop a model reduction technique using a control theoretic setting by first defining a novel type of time-limited controllability and observability gramians for nonlinear systems. We then show the superiority of the time-limited generalised gramians for nonlinear systems in the context of balanced truncation for a benchmark system from control theory. The concept of time-limited controllability and observability gramians is subsequently used to introduce a state and time-dependent quantity called the input-response (ir) index that quantifies the importance of state variables for a given input-response relationship at a particular time. We subsequently link our approach to sensitivity analysis, thus, enabling for the first time the use of sensitivity coefficients for state space reduction. The sensitivity based ir-indices are given as a product of two sensitivity coefficients. This allows not only for a computational more efficient calculation but also for a clear distinction of the extent to which the input impacts a state variable and the extent to which a state variable impacts the output. The ir-indices give insight into the coordinated action of specific state variables for a chosen input-response relationship. Our developed model reduction technique results in reduced models that still allow for a mechanistic interpretation in terms of the quantities/state variables of the original system, which is a key requirement in the field of systems pharmacology and systems biology and distinguished the reduced models from so-called empirical drug effect models. The ir-indices are explicitly defined with respect to a reference trajectory and thereby dependent on the initial state (this is an important feature of the measure). This is demonstrated for an example from the field of systems pharmacology, showing that the reduced models are very informative in their ability to detect (genetic) deficiencies in certain physiological entities. Comparing our novel model reduction technique to the already existing techniques shows its superiority. The novel input-response index as a measure of the importance of state variables provides a powerful tool for understanding the complex dynamics of large-scale systems in the context of a specific drug-response relationship. Furthermore, the indices provide a means for a very efficient model order reduction and, thus, an important step towards translating insight from biological processes incorporated in detailed systems pharmacology models into the population analysis of clinical data.},
  language  = {en}
}
@phdthesis{Solms2017,
  author    = {Solms, Alexander Maximilian},
  title     = {Integrating nonlinear mixed effects and physiologically-based modeling approaches for the analysis of repeated measurement studies},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-397070},
  school      = {Universit{\"a}t Potsdam},
  pages     = {x, 141},
  year      = {2017},
  abstract  = {During the drug discovery \& development process, several phases encompassing a number of preclinical and clinical studies have to be successfully passed to demonstrate safety and efficacy of a new drug candidate. As part of these studies, the characterization of the drug's pharmacokinetics (PK) is an important aspect, since the PK is assumed to strongly impact safety and efficacy. To this end, drug concentrations are measured repeatedly over time in a study population. The objectives of such studies are to describe the typical PK time-course and the associated variability between subjects. Furthermore, underlying sources significantly contributing to this variability, e.g. the use of comedication, should be identified. The most commonly used statistical framework to analyse repeated measurement data is the nonlinear mixed effect (NLME) approach. At the same time, ample knowledge about the drug's properties already exists and has been accumulating during the discovery \& development process: Before any drug is tested in humans, detailed knowledge about the PK in different animal species has to be collected. This drug-specific knowledge and general knowledge about the species' physiology is exploited in mechanistic physiological based PK (PBPK) modeling approaches -it is, however, ignored in the classical NLME modeling approach. Mechanistic physiological based models aim to incorporate relevant and known physiological processes which contribute to the overlying process of interest. In comparison to data--driven models they are usually more complex from a mathematical perspective. For example, in many situations, the number of model parameters outrange the number of measurements and thus reliable parameter estimation becomes more complex and partly impossible. As a consequence, the integration of powerful mathematical estimation approaches like the NLME modeling approach -which is widely used in data-driven modeling -and the mechanistic modeling approach is not well established; the observed data is rather used as a confirming instead of a model informing and building input. Another aggravating circumstance of an integrated approach is the inaccessibility to the details of the NLME methodology so that these approaches can be adapted to the specifics and needs of mechanistic modeling. Despite the fact that the NLME modeling approach exists for several decades, details of the mathematical methodology is scattered around a wide range of literature and a comprehensive, rigorous derivation is lacking. Available literature usually only covers selected parts of the mathematical methodology. Sometimes, important steps are not described or are only heuristically motivated, e.g. the iterative algorithm to finally determine the parameter estimates. Thus, in the present thesis the mathematical methodology of NLME modeling is systemically described and complemented to a comprehensive description, comprising the common theme from ideas and motivation to the final parameter estimation. Therein, new insights for the interpretation of different approximation methods used in the context of the NLME modeling approach are given and illustrated; furthermore, similarities and differences between them are outlined. Based on these findings, an expectation-maximization (EM) algorithm to determine estimates of a NLME model is described. Using the EM algorithm and the lumping methodology by Pilari2010, a new approach on how PBPK and NLME modeling can be combined is presented and exemplified for the antibiotic levofloxacin. Therein, the lumping identifies which processes are informed by the available data and the respective model reduction improves the robustness in parameter estimation. Furthermore, it is shown how apriori known factors influencing the variability and apriori known unexplained variability is incorporated to further mechanistically drive the model development. Concludingly, correlation between parameters and between covariates is automatically accounted for due to the mechanistic derivation of the lumping and the covariate relationships. A useful feature of PBPK models compared to classical data-driven PK models is in the possibility to predict drug concentration within all organs and tissue in the body. Thus, the resulting PBPK model for levofloxacin is used to predict drug concentrations and their variability within soft tissues which are the site of action for levofloxacin. These predictions are compared with data of muscle and adipose tissue obtained by microdialysis, which is an invasive technique to measure a proportion of drug in the tissue, allowing to approximate the concentrations in the interstitial fluid of tissues. Because, so far, comparing human in vivo tissue PK and PBPK predictions are not established, a new conceptual framework is derived. The comparison of PBPK model predictions and microdialysis measurements shows an adequate agreement and reveals further strengths of the presented new approach. We demonstrated how mechanistic PBPK models, which are usually developed in the early stage of drug development, can be used as basis for model building in the analysis of later stages, i.e. in clinical studies. As a consequence, the extensively collected and accumulated knowledge about species and drug are utilized and updated with specific volunteer or patient data. The NLME approach combined with mechanistic modeling reveals new insights for the mechanistic model, for example identification and quantification of variability in mechanistic processes. This represents a further contribution to the learn \& confirm paradigm across different stages of drug development. Finally, the applicability of mechanism--driven model development is demonstrated on an example from the field of Quantitative Psycholinguistics to analyse repeated eye movement data. Our approach gives new insight into the interpretation of these experiments and the processes behind.},
  language  = {en}
}
@phdthesis{Gopalakrishnan2016,
  author    = {Gopalakrishnan, Sathej},
  title     = {Mathematical modelling of host-disease-drug interactions in HIV disease},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-100100},
  school      = {Universit{\"a}t Potsdam},
  pages     = {121},
  year      = {2016},
  abstract  = {The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug combination, and exploring potential salvage treatment regimens. Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics. In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors. Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression. Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.},
  language  = {en}
}
@article{StachanowNeumannBlankensteinetal.2022,
  author    = {Stachanow, Viktoria and Neumann, Uta and Blankenstein, Oliver and Bindellini, Davide and Melin, Johanna and Ross, Richard and Whitaker, Martin J. J. and Huisinga, Wilhelm and Michelet, Robin and Kloft, Charlotte},
  title     = {Exploring dried blood spot cortisol concentrations as an alternative for monitoring pediatric adrenal insufficiency patients},
  series = {Frontiers in pharmacology},
  volume    = {13},
  journal   = {Frontiers in pharmacology},
  publisher = {Frontiers Media},
  address   = {Lausanne},
  issn      = {1663-9812},
  doi       = {10.3389/fphar.2022.819590},
  pages     = {8},
  year      = {2022},
  abstract  = {Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling. Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations. In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions. In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.},
  language  = {en}
}
@phdthesis{Schindler2023,
  author    = {Schindler, Daniel},
  title     = {Mathematical modeling and simulation of protrusion-driven cell dynamics},
  doi       = {10.25932/publishup-61327},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-613275},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VI, 161},
  year      = {2023},
  abstract  = {Amoeboid cell motility takes place in a variety of biomedical processes such as cancer metastasis, embryonic morphogenesis, and wound healing. In contrast to other forms of cell motility, it is mainly driven by substantial cell shape changes. Based on the interplay of explorative membrane protrusions at the front and a slower-acting membrane retraction at the rear, the cell moves in a crawling kind of way. Underlying these protrusions and retractions are multiple physiological processes resulting in changes of the cytoskeleton, a meshwork of different multi-functional proteins. The complexity and versatility of amoeboid cell motility raise the need for novel computational models based on a profound theoretical framework to analyze and simulate the dynamics of the cell shape. The objective of this thesis is the development of (i) a mathematical framework to describe contour dynamics in time and space, (ii) a computational model to infer expansion and retraction characteristics of individual cell tracks and to produce realistic contour dynamics, (iii) and a complementing Open Science approach to make the above methods fully accessible and easy to use. In this work, we mainly used single-cell recordings of the model organism Dictyostelium discoideum. Based on stacks of segmented microscopy images, we apply a Bayesian approach to obtain smooth representations of the cell membrane, so-called cell contours. We introduce a one-parameter family of regularized contour flows to track reference points on the contour (virtual markers) in time and space. This way, we define a coordinate system to visualize local geometric and dynamic quantities of individual contour dynamics in so-called kymograph plots. In particular, we introduce the local marker dispersion as a measure to identify membrane protrusions and retractions in a fully automated way. This mathematical framework is the basis of a novel contour dynamics model, which consists of three biophysiologically motivated components: one stochastic term, accounting for membrane protrusions, and two deterministic terms to control the shape and area of the contour, which account for membrane retractions. Our model provides a fully automated approach to infer protrusion and retraction characteristics from experimental cell tracks while being also capable of simulating realistic and qualitatively different contour dynamics. Furthermore, the model is used to classify two different locomotion types: the amoeboid and a so-called fan-shaped type. With the complementing Open Science approach, we ensure a high standard regarding the usability of our methods and the reproducibility of our research. In this context, we introduce our software publication named AmoePy, an open-source Python package to segment, analyze, and simulate amoeboid cell motility. Furthermore, we describe measures to improve its usability and extensibility, e.g., by detailed run instructions and an automatically generated source code documentation, and to ensure its functionality and stability, e.g., by automatic software tests, data validation, and a hierarchical package structure. The mathematical approaches of this work provide substantial improvements regarding the modeling and analysis of amoeboid cell motility. We deem the above methods, due to their generalized nature, to be of greater value for other scientific applications, e.g., varying organisms and experimental setups or the transition from unicellular to multicellular movement. Furthermore, we enable other researchers from different fields, i.e., mathematics, biophysics, and medicine, to apply our mathematical methods. By following Open Science standards, this work is of greater value for the cell migration community and a potential role model for other Open Science contributions.},
  language  = {en}
}
@article{HijaziFreitagLandwehr2023,
  author    = {Hijazi, Saddam and Freitag, Melina A. and Landwehr, Niels},
  title     = {POD-Galerkin reduced order models and physics-informed neural networks for solving inverse problems for the Navier-Stokes equations},
  series = {Advanced modeling and simulation in engineering sciences : AMSES},
  volume    = {10},
  journal   = {Advanced modeling and simulation in engineering sciences : AMSES},
  number    = {1},
  publisher = {SpringerOpen},
  address   = {Berlin},
  issn      = {2213-7467},
  doi       = {10.1186/s40323-023-00242-2},
  pages     = {38},
  year      = {2023},
  abstract  = {We present a Reduced Order Model (ROM) which exploits recent developments in Physics Informed Neural Networks (PINNs) for solving inverse problems for the Navier-Stokes equations (NSE). In the proposed approach, the presence of simulated data for the fluid dynamics fields is assumed. A POD-Galerkin ROM is then constructed by applying POD on the snapshots matrices of the fluid fields and performing a Galerkin projection of the NSE (or the modified equations in case of turbulence modeling) onto the POD reduced basis. A POD-Galerkin PINN ROM is then derived by introducing deep neural networks which approximate the reduced outputs with the input being time and/or parameters of the model. The neural networks incorporate the physical equations (the POD-Galerkin reduced equations) into their structure as part of the loss function. Using this approach, the reduced model is able to approximate unknown parameters such as physical constants or the boundary conditions. A demonstration of the applicability of the proposed ROM is illustrated by three cases which are the steady flow around a backward step, the flow around a circular cylinder and the unsteady turbulent flow around a surface mounted cubic obstacle.},
  language  = {en}
}
@article{MolkenthinDonnerReichetal.2022,
  author    = {Molkenthin, Christian and Donner, Christian and Reich, Sebastian and Z{\"o}ller, Gert and Hainzl, Sebastian and Holschneider, Matthias and Opper, Manfred},
  title     = {GP-ETAS: semiparametric Bayesian inference for the spatio-temporal epidemic type aftershock sequence model},
  series = {Statistics and Computing},
  volume    = {32},
  journal   = {Statistics and Computing},
  number    = {2},
  publisher = {Springer},
  address   = {Dordrecht},
  issn      = {0960-3174},
  doi       = {10.1007/s11222-022-10085-3},
  pages     = {25},
  year      = {2022},
  abstract  = {The spatio-temporal epidemic type aftershock sequence (ETAS) model is widely used to describe the self-exciting nature of earthquake occurrences. While traditional inference methods provide only point estimates of the model parameters, we aim at a fully Bayesian treatment of model inference, allowing naturally to incorporate prior knowledge and uncertainty quantification of the resulting estimates. Therefore, we introduce a highly flexible, non-parametric representation for the spatially varying ETAS background intensity through a Gaussian process (GP) prior. Combined with classical triggering functions this results in a new model formulation, namely the GP-ETAS model. We enable tractable and efficient Gibbs sampling by deriving an augmented form of the GP-ETAS inference problem. This novel sampling approach allows us to assess the posterior model variables conditioned on observed earthquake catalogues, i.e., the spatial background intensity and the parameters of the triggering function. Empirical results on two synthetic data sets indicate that GP-ETAS outperforms standard models and thus demonstrate the predictive power for observed earthquake catalogues including uncertainty quantification for the estimated parameters. Finally, a case study for the l'Aquila region, Italy, with the devastating event on 6 April 2009, is presented.},
  language  = {en}
}
@article{KucharskiErgintavAhmadetal.2019,
  author    = {Kucharski, Maciej and Ergintav, Arzu and Ahmad, Wael Abdullah and Krstić, Miloš and Ng, Herman Jalli and Kissinger, Dietmar},
  title     = {A Scalable 79-GHz Radar Platform Based on Single-Channel Transceivers},
  series = {IEEE Transactions on Microwave Theory and Techniques},
  volume    = {67},
  journal   = {IEEE Transactions on Microwave Theory and Techniques},
  number    = {9},
  publisher = {Inst. of Electr. and Electronics Engineers},
  address   = {Piscataway},
  issn      = {0018-9480},
  doi       = {10.1109/TMTT.2019.2914104},
  pages     = {3882 -- 3896},
  year      = {2019},
  abstract  = {This paper presents a scalable E-band radar platform based on single-channel fully integrated transceivers (TRX) manufactured using 130-nm silicon-germanium (SiGe) BiCMOS technology. The TRX is suitable for flexible radar systems exploiting massive multiple-input-multipleoutput (MIMO) techniques for multidimensional sensing. A fully integrated fractional-N phase-locked loop (PLL) comprising a 39.5-GHz voltage-controlled oscillator is used to generate wideband frequency-modulated continuous-wave (FMCW) chirp for E-band radar front ends. The TRX is equipped with a vector modulator (VM) for high-speed carrier modulation and beam-forming techniques. A single TRX achieves 19.2-dBm maximum output power and 27.5-dB total conversion gain with input-referred 1-dB compression point of -10 dBm. It consumes 220 mA from 3.3-V supply and occupies 3.96 mm(2) silicon area. A two-channel radar platform based on full-custom TRXs and PLL was fabricated to demonstrate high-precision and high-resolution FMCW sensing. The radar enables up to 10-GHz frequency ramp generation in 74-84-GHz range, which results in 1.5-cm spatial resolution. Due to high output power, thus high signal-to-noise ratio (SNR), a ranging precision of 7.5 mu m for a target at 2 m was achieved. The proposed architecture supports scalable multichannel applications for automotive FMCW using a single local oscillator (LO).},
  language  = {en}
}
@article{SharmaHainzlZoelleretal.2020,
  author    = {Sharma, Shubham and Hainzl, Sebastian and Z{\"o}ller, Gert and Holschneider, Matthias},
  title     = {Is Coulomb stress the best choice for aftershock forecasting?},
  series = {Journal of geophysical research : Solid earth},
  volume    = {125},
  journal   = {Journal of geophysical research : Solid earth},
  number    = {9},
  publisher = {American Geophysical Union},
  address   = {Washington},
  issn      = {2169-9313},
  doi       = {10.1029/2020JB019553},
  pages     = {12},
  year      = {2020},
  abstract  = {The Coulomb failure stress (CFS) criterion is the most commonly used method for predicting spatial distributions of aftershocks following large earthquakes. However, large uncertainties are always associated with the calculation of Coulomb stress change. The uncertainties mainly arise due to nonunique slip inversions and unknown receiver faults; especially for the latter, results are highly dependent on the choice of the assumed receiver mechanism. Based on binary tests (aftershocks yes/no), recent studies suggest that alternative stress quantities, a distance-slip probabilistic model as well as deep neural network (DNN) approaches, all are superior to CFS with predefined receiver mechanism. To challenge this conclusion, which might have large implications, we use 289 slip inversions from SRCMOD database to calculate more realistic CFS values for a layered half-space and variable receiver mechanisms. We also analyze the effect of the magnitude cutoff, grid size variation, and aftershock duration to verify the use of receiver operating characteristic (ROC) analysis for the ranking of stress metrics. The observations suggest that introducing a layered half-space does not improve the stress maps and ROC curves. However, results significantly improve for larger aftershocks and shorter time periods but without changing the ranking. We also go beyond binary testing and apply alternative statistics to test the ability to estimate aftershock numbers, which confirm that simple stress metrics perform better than the classic Coulomb failure stress calculations and are also better than the distance-slip probabilistic model.},
  language  = {en}
}