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Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older ('immortal') DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells. Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate(More)
Recent experiments show that vascular endothelial growth factor (VEGF) is the crucial mediator of downstream events that ultimately lead to enhanced endothelial cell survival and increased vascular density within many tumors. The newly discovered pathway involves up-regulation of the anti-apoptotic protein Bcl-2, which in turn leads to increased production(More)
This work describes the first cell-based model of tumor-induced angiogenesis. At the extracellular level, the model describes diffusion, uptake, and decay of tumor-secreted pro-angiogenic factor. At the cellular level, the model uses the cellular Potts model based on system-energy reduction to describe endothelial cell migration, growth, division, cellular(More)
Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and(More)
A mathematical model is developed that describes the reduction in volume of a vascular tumor in response to specific chemotherapeutic administration strategies. The model consists of a system of partial differential equations governing intratumoral drug concentration and cancer cell density. In the model the tumor is treated as a continuum of two types of(More)
In this paper, a mathematical modeling framework is presented which describes the growth, encapsulation, and transcapsular spread of solid tumors. The model is based on the physical forces and cellular interactions involved in tumorigenesis and is used to test and compare the active (foreign body hypothesis) and passive (expansive growth hypothesis)(More)
There is increasing evidence for the "cancer stem cell hypothesis" which holds that cancers originate in tissue stem cells or progenitor cells. As a result of this, cancers are driven by a cellular subcomponent that retains stem cell properties. Among these properties are self-renewal and multi-lineage differentiation. The biological processes which account(More)
Cancer invasion and metastasis depend on tumor-induced angiogenesis, the means by which cancer cells attract and maintain a blood supply. During angiogenesis, cellular processes are tightly coordinated by signaling molecules and their receptors. Understanding how endothelial cells synthesize multiple biochemical signals can catalyze the development of novel(More)
The bacterial pathogen Klebsiella pneumoniae is a cause of community- and hospital-acquired lung, urinary tract and blood stream infections. It is a common contaminant of indwelling catheters and it is theorized in that context that systemic infection follows shedding of aggregates off of surface-adherent biofilm colonies. In an effort to better understand(More)
The scientific importance of understanding programmed cell death is undeniable; however, the complexity of death signal propagation and the formerly incomplete knowledge of apoptotic pathways has left this topic virtually untouched by mathematical modeling. In this paper, we use a mechanistic approach to frame the current understanding of receptor-mediated(More)