@article{PilariPreusseHuisinga2011,
  author    = {Pilari, Sabine and Preusse, Cornelia and Huisinga, Wilhelm},
  title     = {Gestational influences on the pharmacokinetics of gestagenic drugs a combined in silico, in vitro and in vivo analysis},
  series = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, EUFEPS},
  volume    = {42},
  journal   = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, EUFEPS},
  number    = {4},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0928-0987},
  doi       = {10.1016/j.ejps.2010.12.003},
  pages     = {318 -- 331},
  year      = {2011},
  abstract  = {During preclinical development of a gestagenic drug, a significant increase of the total plasma concentration was observed after multiple dosing in pregnant rabbits, but not in (non-pregnant) rats or monkeys. We used a PBPK modeling approach in combination with in vitro and in vivo data to address the question to what extent the pharmacologically active free drug concentration is affected by pregnancy induced processes. In human, a significant increase in sex hormone binding globulin (SHBG), and an induction of hepatic CYP3A4 as well as plasma esterases is observed during pregnancy. We find that the observed increase in total plasma trough levels in rabbits can be explained as a combined result of (i) drug accumulation due to multiple dosing, (ii) increase of the binding protein SHBG, and (iii) clearance induction. For human, we predict that free drug concentrations in plasma would not increase during pregnancy above the steady state trough level for non-pregnant women.},
  language  = {en}
}
@article{vonKleistMenzStockeretal.2011,
  author    = {von Kleist, Max and Menz, Stephan and Stocker, Hartmut and Arasteh, Keikawus and Schuette, Christof and Huisinga, Wilhelm},
  title     = {HIV quasispecies dynamics during pro-active treatment switching impact on multi-drug resistance and resistance archiving in latent reservoirs},
  series = {PLoS one},
  volume    = {6},
  journal   = {PLoS one},
  number    = {3},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0018204},
  pages     = {12},
  year      = {2011},
  abstract  = {The human immunodeficiency virus (HIV) can be suppressed by highly active anti-retroviral therapy (HAART) in the majority of infected patients. Nevertheless, treatment interruptions inevitably result in viral rebounds from persistent, latently infected cells, necessitating lifelong treatment. Virological failure due to resistance development is a frequent event and the major threat to treatment success. Currently, it is recommended to change treatment after the confirmation of virological failure. However, at the moment virological failure is detected, drug resistant mutants already replicate in great numbers. They infect numerous cells, many of which will turn into latently infected cells. This pool of cells represents an archive of resistance, which has the potential of limiting future treatment options. The objective of this study was to design a treatment strategy for treatment-naive patients that decreases the likelihood of early treatment failure and preserves future treatment options. We propose to apply a single, pro-active treatment switch, following a period of treatment with an induction regimen. The main goal of the induction regimen is to decrease the abundance of randomly generated mutants that confer resistance to the maintenance regimen, thereby increasing subsequent treatment success. Treatment is switched before the overgrowth and archiving of mutant strains that carry resistance against the induction regimen and would limit its future re-use. In silico modelling shows that an optimal trade-off is achieved by switching treatment at \& 80 days after the initiation of antiviral therapy. Evaluation of the proposed treatment strategy demonstrated significant improvements in terms of resistance archiving and virological response, as compared to conventional HAART. While continuous pro-active treatment alternation improved the clinical outcome in a randomized trial, our results indicate that a similar improvement might also be reached after a single pro-active treatment switch. The clinical validity of this finding, however, remains to be shown by a corresponding trial.},
  language  = {en}
}
@inproceedings{SteenholdtEdlundAinsworthetal.2015,
  author    = {Steenholdt, Casper and Edlund, Helena and Ainsworth, Mark A. and Brynskov, Jorn and Thomsen, Ole Ostergaard and Huisinga, Wilhelm and Kloft, Charlotte},
  title     = {Relationship between measures of infliximab exposure and clinical outcome of infliximab intensification at therapeutic failure in Crohn's disease},
  series = {JOURNAL OF CROHNS \& COLITIS},
  volume    = {9},
  booktitle = {JOURNAL OF CROHNS \& COLITIS},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1873-9946},
  pages     = {S330 -- S330},
  year      = {2015},
  language  = {en}
}
@article{MenzLatorreSchuetteetal.2012,
  author    = {Menz, Stephan and Latorre, Juan C. and Sch{\"u}tte, Christof and Huisinga, Wilhelm},
  title     = {Hybrid stochastic-deterministic solution of the chemical master equation},
  series = {Multiscale modeling \& simulation : a SIAM interdisciplinary journal},
  volume    = {10},
  journal   = {Multiscale modeling \& simulation : a SIAM interdisciplinary journal},
  number    = {4},
  publisher = {Society for Industrial and Applied Mathematics},
  address   = {Philadelphia},
  issn      = {1540-3459},
  doi       = {10.1137/110825716},
  pages     = {1232 -- 1262},
  year      = {2012},
  abstract  = {The chemical master equation (CME) is the fundamental evolution equation of the stochastic description of biochemical reaction kinetics. In most applications it is impossible to solve the CME directly due to its high dimensionality. Instead, indirect approaches based on realizations of the underlying Markov jump process are used, such as the stochastic simulation algorithm (SSA). In the SSA, however, every reaction event has to be resolved explicitly such that it becomes numerically inefficient when the system's dynamics include fast reaction processes or species with high population levels. In many hybrid approaches, such fast reactions are approximated as continuous processes or replaced by quasi-stationary distributions in either a stochastic or a deterministic context. Current hybrid approaches, however, almost exclusively rely on the computation of ensembles of stochastic realizations. We present a novel hybrid stochastic-deterministic approach to solve the CME directly. Our starting point is a partitioning of the molecular species into discrete and continuous species that induces a partitioning of the reactions into discrete-stochastic and continuous-deterministic processes. The approach is based on a WKB (Wentzel-Kramers-Brillouin) ansatz for the conditional probability distribution function (PDF) of the continuous species (given a discrete state) in combination with Laplace's method of integral approximation. The resulting hybrid stochastic-deterministic evolution equations comprise a CME with averaged propensities for the PDF of the discrete species that is coupled to an evolution equation of the related expected levels of the continuous species for each discrete state. In contrast to indirect hybrid methods, the impact of the evolution of discrete species on the dynamics of the continuous species has to be taken into account explicitly. The proposed approach is efficient whenever the number of discrete molecular species is small. We illustrate the performance of the new hybrid stochastic-deterministic approach in an application to model systems of biological interest.},
  language  = {en}
}
@inproceedings{AnderssonKeuneckeEseretal.2014,
  author    = {Andersson, H. and Keunecke, A. and Eser, A. and Huisinga, Wilhelm and Reinisch, W. and Kloft, Charlotte},
  title     = {Pharmacokinetic considerations for optimising dosing regimens of a potsdam univ infliximab in patients with Crohn's disease},
  series = {JOURNAL OF CROHNS \& COLITIS},
  volume    = {8},
  booktitle = {JOURNAL OF CROHNS \& COLITIS},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1873-9946},
  doi       = {10.1016/S1873-9946(14)60086-6},
  pages     = {S44 -- S44},
  year      = {2014},
  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}
}
@article{GerlachGlueckKunze2023,
  author    = {Gerlach, Moritz and Gl{\"u}ck, Jochen and Kunze, Markus},
  title     = {Stability of transition semigroups and applications to parabolic equations},
  series = {Transactions of the American Mathematical Society},
  volume    = {376},
  journal   = {Transactions of the American Mathematical Society},
  number    = {1},
  publisher = {American Mathematical Soc.},
  address   = {Providence},
  issn      = {0002-9947},
  doi       = {10.1090/tran/8620},
  pages     = {153 -- 180},
  year      = {2023},
  abstract  = {This paper deals with the long-term behavior of positive operator semigroups on spaces of bounded functions and of signed measures, which have applications to parabolic equations with unbounded coefficients and to stochas-tic analysis. The main results are a Tauberian type theorem characterizing the convergence to equilibrium of strongly Feller semigroups and a generalization of a classical convergence theorem of Doob. None of these results requires any kind of time regularity of the semigroup.},
  language  = {en}
}
@article{DimitrovaKoppitz2022,
  author    = {Dimitrova, Ilinka and Koppitz, J{\"o}rg},
  title     = {On relative ranks of the semigroup of orientation-preserving transformations on infinite chain with restricted range},
  series = {Communications in algebra},
  volume    = {50},
  journal   = {Communications in algebra},
  number    = {5},
  publisher = {Taylor \& Francis Group},
  address   = {Philadelphia},
  issn      = {0092-7872},
  doi       = {10.1080/00927872.2021.2000998},
  pages     = {2157 -- 2168},
  year      = {2022},
  abstract  = {Let X be an infinite linearly ordered set and let Y be a nonempty subset of X. We calculate the relative rank of the semigroup OP(X,Y) of all orientation-preserving transformations on X with restricted range Y modulo the semigroup O(X,Y) of all order-preserving transformations on X with restricted range Y. For Y = X, we characterize the relative generating sets of minimal size.},
  language  = {en}
}
@article{DimitrovaKoppitz2020,
  author    = {Dimitrova, Ilinka and Koppitz, J{\"o}rg},
  title     = {On relative ranks of the semigroup of orientation-preserving transformations on infinite chains},
  series = {Asian-European journal of mathematics},
  volume    = {14},
  journal   = {Asian-European journal of mathematics},
  number    = {08},
  publisher = {World Scientific},
  address   = {Singapore},
  issn      = {1793-5571},
  doi       = {10.1142/S1793557121501461},
  pages     = {15},
  year      = {2020},
  abstract  = {In this paper, we determine the relative rank of the semigroup OP(X) of all orientation-preserving transformations on infinite chains modulo the semigroup O(X) of all order-preserving transformations.},
  language  = {en}
}
@article{KaminskiSchlagenhaufRappetal.2018,
  author    = {Kaminski, Jakob A. and Schlagenhauf, Florian and Rapp, Michael A. and Awasthi, Swapnil and Ruggeri, Barbara and Deserno, Lorenz and Banaschewski, Tobias and Bokde, Arun L. W. and Bromberg, Uli and B{\"u}chel, Christian and Quinlan, Erin Burke and Desrivieres, Sylvane and Flor, Herta and Frouin, Vincent and Garavan, Hugh and Gowland, Penny and Ittermann, Bernd and Martinot, Jean-Luc and Martinot, Marie-Laure Paillere and Nees, Frauke and Orfanos, Dimitri Papadopoulos and Paus, Tomas and Poustka, Luise and Smolka, Michael N. and Fr{\"o}hner, Juliane H. and Walter, Henrik and Whelan, Robert and Ripke, Stephan and Schumann, Gunter and Heinz, Andreas},
  title     = {Epigenetic variance in dopamine D2 receptor},
  series = {Translational Psychiatry},
  volume    = {8},
  journal   = {Translational Psychiatry},
  publisher = {Nature Publ. Group},
  address   = {New York},
  organization    = {IMAGEN Consortium},
  issn      = {2158-3188},
  doi       = {10.1038/s41398-018-0222-7},
  pages     = {11},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}