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The division tracking dye, carboxyfluorescin diacetate succinimidyl ester (CFSE) is currently the most informative labeling technique for characterizing the division history of cells in the immune system. Gett and Hodgkin [Nat. Immunol. 1:239–244, 2000] have pioneered the quantitative analysis of CFSE data. We confirm and extend their data analysis approach using simple mathematical models. We employ the extended Gett and Hodgkin [Nat. Immunol. 1:239–244, 2000] method to estimate the time to first division, the fraction of cells recruited into division, the cell cycle time, and the average death rate from CFSE data on T cells stimulated under different concentrations of IL-2. The same data is also fitted with a simple mathematical model that we derived by reformulating the numerical model of Deenick et al. [J. Immunol. 170:4963–4972, 2...
Type 1 diabetes is an autoimmune disease resulting in the selective destruction of the insulin producing β-cells in the pancreas. Pro-inflammatory cytokines and the free radical nitric oxide (NO) have been implicated in mediating the destruction of β-cells, possibly through activation of the mitogen activated protein kinases (MAPKs) JNK, ERK and p38. In addition to MAPKs, cytokine signaling also results in activation of the transcription factor nuclear factor-kappaB (NF-κB). The upstream signaling events leading to MAPK and NF-κB activation in β-cells are not well known. The work presented in this thesis therefore aims at characterizing the regulation of MAPKs and NF-κB in human islets, with emphasis on the role of the MAPK activator MAP/ERK kinase kinase-1 (MEKK-1) in islet cell death. It was found that MEKK-1 was phosphorylated in re...
This paper analyzes the effects of macro-economic conditions throughout life on the individual mortality rate. We estimate flexible duration models where the individual?s mortality rate depends on current conditions, conditions earlier in life (notably during childhood), calendar time, age, individual characteristics, including individual socio-economic indicators, and interaction terms. We use individual data records from Dutch registers of birth, marriage, and death certificates, covering an observation window of unprecedented size (1812-1999). These are merged with historical data on macro-economic and health indicators. The results indicate a strong effect of macro-economic conditions during childhood on mortality at all ages. Those who are born in bad times on average have a high mortality rate throughout life, in particular durin...
In this paper, generalized nonlinear models are proposed in order to incorporate the following considerations in modeling an epidemic disease outbreak statistically. (1) The dependence of the data is handled with a nonhomogeneous death or a nonhomogeneous birth process. (2) The first stage of the outbreak is described with an epidemic susceptibles-infectives-removed (SIR) model. Soon the control measures taken will dominate the process. These measures are in addition to the natural epidemic removal process. The prevalence is related to the censored infection times in such a way that the distribution function and thus the survival function satisfy approximately the first equation of the SIR model. This leads in a natural way to the Burr family of distributions. (3) The nonhomogeneous birth process handles the fact that in practice, with...
Published January 1989. Please look for up-to-date information in the OSU Extension Catalog: http://extension.oregonstate.edu/catalog
The purpose of this note is to point out that Karlin and McGregor's integral representation for the transition probabilities of a birth-death process on a semi-infinite lattice with an absorbing bottom state remains valid if one allows the possibility of absorption into the bottom state from any other state. Conditions for uniqueness of the minimal transition function are also given.
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