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Full-Text Articles in Medicine and Health Sciences
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Biomedical Sciences ETDs
This dissertation explores the effects of heterogeneity across different biological scales in cancer as well as normal cells. At the tissue scale, we investigated the variability present in the tumor microenvironment and its effect on patient chemotherapeutic outcomes using a mathematical model of drug transport. We found that parameters such as tumor blood perfusion and radius of blood vessel had an impact on the tumor cytotoxicity. This indicated that the physical microenvironment of the tumor is an important regulator of the tumor response to chemotherapy. At the cellular scale, we investigated the heterogeneity present on the membrane landscape of ErbB2 …
A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner
A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner
Biomedical Engineering ETDs
Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …
Cd82 Membrane Scaffolding Regulates Hematopoietic Cell Functions, Christina M. Termini
Cd82 Membrane Scaffolding Regulates Hematopoietic Cell Functions, Christina M. Termini
Biomedical Sciences ETDs
Through their ability to self-renew and differentiate, hematopoietic stem/progenitor cells (HSPCs) maintain the adult blood and immune systems. The microenvironment, or niche, in which HSPCs reside, serves as a critical regulator of HSPC functions. As previous work has identified the tetraspanin CD82 as a mediator of HSPC-niche interactions, we aimed to determine the mechanism by which this occurs. Our data demonstrate that CD82 expression and scaffolding regulate HSPC interactions with niche components by organizing the α4 integrin subunit into tightly packed nanoclusters. The HSPC niche can also protect acute myeloid leukemia (AML) cells from therapeutics. Therefore, we next examined how …