The most significant outcome of our studies conducted under the auspices of NIH/NINDS Grant RO1 NS39511 is a stochastic model of in vitro development of oligodendrocytes, which has been tested against several sets of experimental data. New estimation techniques built on this model allow analysis of the underlying processes in terms of biologically meaningful parameters. These results provide a solid groundwork for designing inferential procedures that are very much needed to analyze relevant in vivo studies. The general objective of the proposed research is to evolve such procedures with a special focus on embryonic development of the spinal cord. The major challenge here is that the dynamics of oligodendrocyte precursors in the developing spinal cord are highly non-stationary. A combination of analytical and simulation techniques is proposed as a constructive solution to this problem. Our recent analytical results make the problem approachable. The proposed stochastic model is sufficiently flexible to describe the complex patterns of cell dynamics in the experimental system under study. Biological experiments will be specially designed to fully utilize the power of the proposed modeling techniques and computational algorithms. This approach will provide a detailed understanding of cell development in the normal spinal cord, and in the pathological condition of iron deficiency.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039511-09
Application #
7794959
Study Section
Special Emphasis Panel (ZRG1-MDCN-N (02))
Program Officer
Owens, David F
Project Start
1999-12-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$333,507
Indirect Cost
Name
University of Rochester
Department
Biostatistics & Other Math Sci
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Hyrien, Ollivier; Baran, Andrea (2016) Fast Nonparametric Density-Based Clustering of Large Data Sets Using a Stochastic Approximation Mean-Shift Algorithm. J Comput Graph Stat 25:899-916
Greminger, Allison R; Mayer-Pröschel, Margot (2015) Identifying the threshold of iron deficiency in the central nervous system of the rat by the auditory brainstem response. ASN Neuro 7:
Hyrien, Ollivier; Yanev, Nikolay M; Jordan, Craig T (2015) A test of homogeneity for age-dependent branching processes with immigration. Electron J Stat 9:898-925
Hyrien, O; Peslak, S A; Yanev, N M et al. (2015) Stochastic modeling of stress erythropoiesis using a two-type age-dependent branching process with immigration. J Math Biol 70:1485-521
Greminger, Allison R; Lee, Dawn L; Shrager, Peter et al. (2014) Gestational iron deficiency differentially alters the structure and function of white and gray matter brain regions of developing rats. J Nutr 144:1058-66
Chen, Rui; Hyrien, Ollivier (2014) ON CLASSES OF EQUIVALENCE AND IDENTIFIABILITY OF AGE-DEPENDENT BRANCHING PROCESSES. Adv Appl Probab 46:704-718
Hyrien, Ollivier; Yanev, Nikolay M (2012) Asymptotic behavior of cell populations described by two-type reducible age-dependent branching processes with non-homogeneous immigration(). Math Popul Stud 19:164-176
Lee, Dawn L; Strathmann, Frederick G; Gelein, Robert et al. (2012) Iron deficiency disrupts axon maturation of the developing auditory nerve. J Neurosci 32:5010-5
Mihaila, Camelia; Schramm, Jordan; Strathmann, Frederick G et al. (2011) Identifying a window of vulnerability during fetal development in a maternal iron restriction model. PLoS One 6:e17483
Chen, Rui; Hyrien, Ollivier; Noble, Mark et al. (2011) A composite likelihood approach to the analysis of longitudinal clonal data on multitype cellular systems under an age-dependent branching process. Biostatistics 12:173-91

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