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91 Publications visible to you, out of a total of 91
Primary and Recurrent Repair of Incisional Hernia Based on Biomechanical Considerations to Avoid Mesh-Related Complications

Abstract

Not specified

Authors: Regine Nessel, Thorsten Löffler, Johannes Rinn, Philipp Lösel, Samuel Voss, Vincent Heuveline, Matthias Vollmer, Johannes Görich, Yannique-Maximilian Ludwig, Luai Al-Hileh, Friedrich Kallinowski

Date Published: 15th Dec 2021

Publication Type: Journal

Biomechanical Influences on Mesh-Related Complications in Incisional Hernia Repair

Abstract

Not specified

Authors: Friedrich Kallinowski, Yannique Ludwig, Dominik Gutjahr, Christian Gerhard, Hannah Schulte-Hörmann, Lena Krimmel, Carolin Lesch, Katharina Uhr, Philipp Lösel, Samuel Voß, Vincent Heuveline, Matthias Vollmer, Johannes Görich, Regine Nessel

Date Published: 29th Oct 2021

Publication Type: Journal

A computational model for investigating the evolution of colonic crypts during Lynch syndrome carcinogenesis

Abstract (Expand)

Abstract Lynch syndrome (LS), the most common inherited colorectal cancer (CRC) syndrome, increases the cancer risk in affected individuals. LS is caused by pathogenic germline variants in one of the … DNA mismatch repair (MMR) genes, complete inactivation of which causes numerous mutations in affected cells. As CRC is believed to originate in colonic crypts, understanding the intra-crypt dynamics caused by mutational processes is essential for a complete picture of LS CRC and may have significant implications for cancer prevention. We propose a computational model describing the evolution of colonic crypts during LS carcinogenesis. Extending existing modeling approaches for the non-Lynch scenario, we incorporated MMR deficiency and implemented recent experimental data demonstrating that somatic CTNNB1 mutations are common drivers of LS-associated CRCs, if affecting both alleles of the gene. Further, we simulated the effect of different mutations on the entire crypt, distinguishing non-transforming and transforming mutations. As an example, we analyzed the spread of mutations in the genes APC and CTNNB1, which are frequently mutated in LS tumors, as well as of MMR deficiency itself. We quantified each mutation's potential for monoclonal conversion and investigated the influence of the cell location and of stem cell dynamics on mutation spread. The in silico experiments underline the importance of stem cell dynamics for the overall crypt evolution. Further, simulating different mutational processes is essential in LS since mutations without survival advantages (the MMR deficiency-inducing second hit) play a key role. The effect of other mutations can be simulated with the proposed model. Our results provide first mathematical clues towards more effective surveillance protocols for LS carriers.

Authors: Saskia Haupt, Nils Gleim, Aysel Ahadova, Hendrik Bläker, Magnus von Knebel Doeberitz, Matthias Kloor, Vincent Heuveline

Date Published: 4th Jul 2021

Publication Type: Journal

Spatial Effect on Separatrix of Two-Cell System and Parameter Sensitivity Analysis

Abstract

Not specified

Authors: Chen Song, Jonas Roller, Ana Victoria Ponce-Bobadilla, Nicolas Palacio-Escat, Julio Saez-Rodriguez, Vincent Heuveline

Date Published: 11th May 2021

Publication Type: Unpublished

Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure

Abstract (Expand)

Like many other types of cancer, colorectal cancer (CRC) develops through multiple pathways of carcinogenesis. This is also true for colorectal carcinogenesis in Lynch syndrome (LS), the most common … inherited CRC syndrome. However, a comprehensive understanding of the distribution of these pathways of carcinogenesis, which allows for tailored clinical treatment and even prevention, is still lacking. We suggest a linear dynamical system modeling the evolution of different pathways of colorectal carcinogenesis based on the involved driver mutations. The model consists of different components accounting for independent and dependent mutational processes. We define the driver gene mutation graphs and combine them using the Cartesian graph product. This leads to matrix components built by the Kronecker sum and product of the adjacency matrices of the gene mutation graphs enabling a thorough mathematical analysis and medical interpretation. Using the Kronecker structure, we developed a mathematical model which we applied exemplarily to the three pathways of colorectal carcinogenesis in LS. Beside a pathogenic germline variant in one of the DNA mismatch repair (MMR) genes, driver mutations in APC, CTNNB1, KRAS and TP53 are considered. We exemplarily incorporate mutational dependencies, such as increased point mutation rates after MMR deficiency, and based on recent experimental data, biallelic somatic CTNNB1 mutations as common drivers of LS-associated CRCs. With the model and parameter choice, we obtained simulation results that are in concordance with clinical observations. These include the evolution of MMR-deficient crypts as early precursors in LS carcinogenesis and the influence of variants in MMR genes thereon. The proportions of MMR-deficient and MMR-proficient APC-inactivated crypts as first measure for the distribution among the pathways in LS-associated colorectal carcinogenesis are compatible with clinical observations. The approach provides a modular framework for modeling multiple pathways of carcinogenesis yielding promising results in concordance with clinical observations in LS CRCs.

Authors: Saskia Haupt, Alexander Zeilmann, Aysel Ahadova, Hendrik Bläker, Magnus von Knebel Doeberitz, Matthias Kloor, Vincent Heuveline

Date Published: 1st May 2021

Publication Type: Journal

Biomechanics applied to incisional hernia repair – Considering the critical and the gained resistance towards impacts related to pressure

Abstract

Not specified

Authors: F. Kallinowski, Y. Ludwig, T. Löffler, M. Vollmer, P.D. Lösel, S. Voß, J. Görich, V. Heuveline, R. Nessel

Date Published: 1st Feb 2021

Publication Type: Journal

A Simple Model for Portable and Fast Prediction of Execution Time and Power Consumption of GPU Kernels

Abstract

Not specified

Authors: Lorenz Braun, Sotirios Nikas, Chen Song, Vincent Heuveline, Holger Fröning

Date Published: 21st Jan 2021

Publication Type: Journal

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