TY - GEN A1 - Boer, H. Marike T. A1 - Stötzel, Claudia A1 - Röblitz, Susanna A1 - Deuflhard, Peter A1 - Veerkamp, Roel F. A1 - Woelders, Henri T1 - A simple mathematical model of the bovine estrous cycle: follicle development and endocrine interactions N2 - Bovine fertility is the subject of extensive research in animal sciences, especially because fertility of dairy cows has declined during the last decades. The regulation of estrus is controlled by the complex interplay of various organs and hormones. Mathematical modeling of the bovine estrous cycle could help in understanding the dynamics of this complex biological system. In this paper we present a mathematical model of the bovine estrous cycle that includes the processes of follicle and corpus luteum development and the key hormones that interact to control these processes. Focus in this paper is on development of the model, but also some simulation results are presented, showing that a set of equations and parameters is obtained that describes the system consistent with empirical knowledge. Even though the majority of the mechanisms that are included are only known qualitatively as stimulatory or inhibitory effects, the model surprisingly well features quantitative observations made in reality. This model of the bovine estrous cycle could be used as a basis for more elaborate models with the ability to study effects of external manipulations and genetic differences. T3 - ZIB-Report - 10-06 KW - cow KW - reproduction KW - hormone patterns KW - ordinary differential equations KW - systems biology Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-11682 SN - 1438-0064 ER - TY - GEN A1 - Röblitz, Susanna A1 - Stötzel, Claudia A1 - Deuflhard, Peter A1 - Jones, Hannah M. A1 - Azulay, David-Olivier A1 - van der Graaf, Piet A1 - Martin, Steven T1 - A mathematical model of the human menstrual cycle for the administration of GnRH analogues N2 - This study presents a differential equation model for the feedback mechanisms between Gonadotropin-releasing Hormone (GnRH), Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), development of follicles and corpus luteum, and the production of estradiol (E2), progesterone (P4), inhibin A (IhA), and inhibin B (IhB) during the female menstrual cycle. In contrast to other models, this model does not involve delay differential equations and is based on deterministic modelling of the GnRH pulse pattern, which allows for faster simulation times and efficient parameter identification. These steps were essential to tackle the task of developing a mathematical model for the administration of GnRH analogues. The focus of this paper is on model development for GnRH receptor binding and the integration of a pharmacokinetic/pharmacodynamic model for the GnRH agonist Nafarelin and the GnRH antagonist Cetrorelix into the menstrual cycle model. The final mathematical model describes the hormone profiles (LH, FSH, P4, E2) throughout the menstrual cycle in 12 healthy women. Moreover, it correctly predicts the changes in the cycle following single and multiple dose administration of Nafarelin or Cetrorelix at different stages in the cycle. T3 - ZIB-Report - 11-16 KW - human menstrual cycle KW - systems biology KW - mathematical modelling KW - GnRH analogues KW - differential equations Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-12732 ER - TY - GEN A1 - Dierkes, Thomas A1 - Wade, Moritz A1 - Nowak, Ulrich A1 - Röblitz, Susanna T1 - BioPARKIN - Biology-related Parameter Identification in Large Kinetic Networks N2 - Modelling, parameter identification, and simulation play an important rôle in Systems Biology. In recent years, various software packages have been established for scientific use in both licencing types, open source as well as commercial. Many of these codes are based on inefficient and mathematically outdated algorithms. By introducing the package BioPARKIN recently developed at ZIB, we want to improve this situation significantly. The development of the software BioPARKIN involves long standing mathematical ideas that, however, have not yet entered the field of Systems Biology, as well as new ideas and tools that are particularly important for the analysis of the dynamics of biological networks. BioPARKIN originates from the package PARKIN, written by P.Deuflhard and U.Nowak, that has been applied successfully for parameter identification in physical chemistry for many years. T3 - ZIB-Report - 11-15 KW - systems biology KW - ordinary differential equations KW - sensitivity analysis KW - parameter identification KW - affine invariant Gauss-Newton algorithm KW - numerical library KW - graphical user interface Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-12706 ER -