Thomas B. Kepler

Works (19)

Updated: February 10th, 2025 16:10

2001 journal article

A linear two-state model with complex dynamics

PHYSICS LETTERS A, 280(4), 204–208.

By: T. Elston n & T. Kepler*

Source: Web Of Science
Added: August 6, 2018

2001 journal article

Improved inference of mutation rates - II. Generalization of the Luria-Delbruck distribution for realistic cell-cycle time distributions

THEORETICAL POPULATION BIOLOGY, 59(1), 49–59.

By: M. Oprea* & T. Kepler n

MeSH headings : Algorithms; Bias; Cell Cycle / genetics; Confidence Intervals; Data Interpretation, Statistical; Genetics, Population; Models, Genetic; Mutation / genetics; Phenotype; Phylogeny; Population Density; Statistical Distributions; Time Factors
TL;DR: This paper introduces a two-parameter generalization of the continuum Luria-Delbrück distribution for two of the more commonly used cell-cycle time distributions: gamma and shifted exponential and obtains the generalized distribution by defining a map from the actual parameters to "effective" parameters. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2001 journal article

Stochasticity in transcriptional regulation: Origins, consequences, and mathematical representations

BIOPHYSICAL JOURNAL, 81(6), 3116–3136.

By: T. Kepler n & T. Elston n

MeSH headings : Feedback, Physiological; Gene Expression Regulation; Models, Theoretical; Monte Carlo Method; Promoter Regions, Genetic; Stochastic Processes; Time Factors; Transcription, Genetic
TL;DR: Stochastic bistability where the deterministic equations predict monostability and vice-versa is found; among them, bifurcations driven solely by changing the rate of operator fluctuations even as the underlying deterministic system remains unchanged are found. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2001 journal article

Waiting times to appearance and dominance of advantageous mutants: estimation based on the likelihood

Mathematical Biosciences, 170(1), 59–77.

By: M. Radmacher & T. Kepler

Source: NC State University Libraries
Added: August 6, 2018

2000 journal article

Quantitative evaluation of alternative mechanisms of blood disposition of di(n-butyl) phthalate and mono(n-butyl) phthalate in rats

TOXICOLOGICAL SCIENCES, 53(2), 173–184.

By: D. Keys n, D. Wallace, T. Kepler & R. Conolly

author keywords: phthalates; DBP; MBP; PBPK; model; flow-limited; diffusion-limited; pH trapping; enterohepatic circulation; log-likelihood ratio test
MeSH headings : Administration, Oral; Animals; Dibutyl Phthalate / analysis; Dibutyl Phthalate / pharmacokinetics; Environmental Pollutants / blood; Environmental Pollutants / pharmacokinetics; Injections, Intravenous; Male; Models, Biological; Phthalic Acids / blood; Phthalic Acids / pharmacokinetics; Rats; Rats, Sprague-Dawley; Rats, Wistar
TL;DR: The application of the pH trapping model is a step toward developing a generic model structure for all phthalate esters, though more work is required before a generic structure can be identified with confidence. (via Semantic Scholar)
Source: Web Of Science
Added: August 6, 2018

2000 journal article

The nucleotide-replacement spectrum under somatic hypermutation exhibits microsequence dependence that is strand-symmetric and distinct from that under germline mutation

JOURNAL OF IMMUNOLOGY, 164(4), 1971–1976.

By: L. Cowell  n & T. Kepler n

MeSH headings : Adenine / immunology; Animals; Base Composition; Base Sequence; DNA Mutational Analysis / methods; DNA Mutational Analysis / statistics & numerical data; Gene Rearrangement; Germ-Line Mutation / immunology; Humans; Immunoglobulin Variable Region / genetics; Mice; Nucleotides / genetics; Nucleotides / immunology; Pseudogenes / immunology; Thymine / immunology
TL;DR: The findings suggest that the mechanism of somatic hypermutation is complex, involving two or more stages: introduction of mis-pairs and their subsequent resolution, each with distinct sequence specificity and strand bias. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1999 journal article

Enhanced evolvability in immunoglobulin V genes under somatic hypermutation

JOURNAL OF MOLECULAR EVOLUTION, 49(1), 23–26.

By: L. Cowell  n, H. Kim*, T. Humaljoki*, C. Berek* & T. Kepler n

author keywords: genome evolution; adaptability; somatic hypermutation; affinity maturation
MeSH headings : Arthritis / genetics; Arthritis / immunology; Arthritis, Rheumatoid / genetics; Arthritis, Rheumatoid / immunology; DNA, Complementary / genetics; Evolution, Molecular; Gene Frequency; Genes, Immunoglobulin; Humans; Immunoglobulin Variable Region / genetics; Mutation; Selection, Genetic; Serine / genetics
TL;DR: Using a χ2 test, it is shown that the number of mutations in the CDRs is significantly higher than the numberof mutations found in the FRs, providing direct evidence for the hypothesis that mutations are preferentially targeted into the CDR. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1999 journal article

Genetic plasticity of V genes under somatic hypermutation: Statistical analyses using a new resampling-based methodology

GENOME RESEARCH, 9(12), 1294–1304.

By: M. Oprea* & T. Kepler n

MeSH headings : Base Sequence; Codon; Computational Biology; Genes, T-Cell Receptor / genetics; Humans; Immunoglobulin Variable Region / genetics; Molecular Sequence Data; Mutation; Phylogeny; Sequence Analysis, DNA
TL;DR: The findings provide support to the hypothesis that somatic hypermutation appeared very early in the phylogeny of immune systems, that it is, to a large extent, shared between species, and that it makes an essential contribution to the generation of the antibody repertoire. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1999 journal article

Human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity is inversely correlated with HIV type 1 viral load in HIV type 1-infected long-term survivors

AIDS RESEARCH AND HUMAN RETROVIRUSES, 15(13), 1219–1228.

By: M. Betts *, J. Krowka*, T. Kepler n, M. Davidian n , C. Christopherson*, S. Kwok *, L. Louie*, J. Eron*, H. Sheppard*, J. Frelinger *

MeSH headings : CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes / immunology; Cross-Sectional Studies; Cytotoxicity Tests, Immunologic; Gene Products, pol / genetics; Gene Products, pol / metabolism; HIV Infections / immunology; HIV Infections / virology; HIV Long-Term Survivors; HIV-1 / immunology; HIV-1 / physiology; Histocompatibility Antigens Class I / classification; Histocompatibility Antigens Class I / genetics; Histocompatibility Antigens Class I / immunology; Humans; Longitudinal Studies; Male; Receptors, CCR5 / genetics; T-Lymphocytes, Cytotoxic / immunology; Viral Load
TL;DR: The data suggest that the presence of HIV- 1-specific CTL activity in HIV-1-infected long-term survivors is an important component in the effective control of HIV -1 replication. (via Semantic Scholar)
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3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: Web Of Science, NC State University Libraries
Added: August 6, 2018

1999 journal article

Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination

JOURNAL OF CLINICAL INVESTIGATION, 103(6), 833–841.

By: L. Gangi-Peterson, D. Sorscher*, J. Reynolds*, T. Kepler n & B. Mitchell

MeSH headings : Adenosine Deaminase / deficiency; Adenosine Deaminase Inhibitors; Adenosine Triphosphate / metabolism; Cells, Cultured; DNA Nucleotidylexotransferase / metabolism; Deoxyadenosines / pharmacology; Deoxyguanine Nucleotides / metabolism; Deoxyribonucleotides / metabolism; Gene Rearrangement, B-Lymphocyte; Humans; Immunoglobulin M / genetics; Purine-Pyrimidine Metabolism, Inborn Errors / enzymology; Recombination, Genetic; Sequence Analysis, DNA
TL;DR: It is concluded that the frequency of V(D)J recombination and the composition of N-insertions are influenced by increases in dATP levels, potentially leading to alterations in antigen receptors and aberrant lymphoid development. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1999 journal article

Quantitative evaluation of alternative mechanisms of blood and testes disposition of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in rats

TOXICOLOGICAL SCIENCES, 49(2), 172–185.

By: D. Keys n, D. Wallace, T. Kepler & R. Conolly

author keywords: phthalates; DEHP; MEHP; PBPK; model; flow-limited; diffusion-limited; pH trapping; enterohepatic circulation; log-likelihood ratio test
MeSH headings : Animals; Diffusion; Enterohepatic Circulation / physiology; Hydrogen-Ion Concentration; Male; Models, Biological; Phthalic Acids / blood; Phthalic Acids / pharmacokinetics; Plasticizers / metabolism; Rats; Rats, Sprague-Dawley; Solubility; Testis / metabolism
TL;DR: To quantify the testes dose of MEHP with various routes of exposure and dose levels, a physiologically based pharmacokinetic (PBPK) model was developed and the pH-trapping model gave the best predictions with the largest value of the log likelihood function. (via Semantic Scholar)
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6. Clean Water and Sanitation (OpenAlex)
Source: Web Of Science
Added: August 6, 2018

1998 journal article

Density-dependent prenatal androgen exposure as an endogenous mechanism for the generation of cycles in small mammal populations

JOURNAL OF THEORETICAL BIOLOGY, 190(1), 93–106.

By: L. Cowell  n, L. Crowder* & T. Kepler n

TL;DR: A mathematical model is developed and analysed to investigate the possible role of prenatal androgen exposure in the generation of limit cycles and shows that limit cycles depend on three parameters: the delay between birth and sexual maturation, the slope of the function that relates average prenatal androgens exposure to total population density, and the difference between the maximum birth rates of the low- and high-androgen exposed females. (via Semantic Scholar)
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5. Gender Equality (Web of Science)
Source: Web Of Science
Added: August 6, 2018

1998 journal article

Drug concentration heterogeneity facilitates the evolution of drug resistance

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 95(20), 11514–11519.

By: T. Kepler n & A. Perelson  n

author keywords: sanctuary sites; HIV
MeSH headings : Anti-HIV Agents / administration & dosage; Anti-HIV Agents / pharmacokinetics; Anti-HIV Agents / pharmacology; Biological Evolution; Drug Resistance, Microbial / genetics; HIV Infections / drug therapy; HIV Infections / metabolism; HIV Infections / virology; HIV-1 / drug effects; HIV-1 / genetics; HIV-1 / physiology; Humans; Mathematics; Models, Biological; Mutation; Virus Replication
TL;DR: It is argued that a quantitative understanding of the role played by heterogeneity in drug levels and pathogen transport is crucial for attempts to control re-emergent infectious disease. (via Semantic Scholar)
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3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018

1998 chapter

Plasticity under somatic mutation in antigen receptors

In G. Kelsoe & M. F. Flajnik (Eds.), Somatic diversification of immune responses (Current topics in microbiology and immunology ; 229) (Vol. 229, pp. 149–162). Berlin; New York: Springer.

By: T. Kepler & S. Bartl

Ed(s): . G. Kelsoe & M. Flajnik

Source: NC State University Libraries
Added: August 6, 2018

1998 journal article

Predicted and inferred waiting times for key mutations in the germinal centre reaction: Evidence for stochasticity in selection

IMMUNOLOGY AND CELL BIOLOGY, 76(4), 373–381.

By: M. Radmacher n, G. Kelsoe * & T. Kepler n

author keywords: b-lymphocytes; germinal centre; immunoglobulins; maximum likelihood estimates; statistical models
MeSH headings : Animals; Cell Differentiation; Germinal Center; Humans; Mutation; Stochastic Processes; Time Factors
TL;DR: It is proposed that the remaining disparity is attributable to some further stochastic process in the GCR: many early key mutations arise but fail to ‘take root’ within the GC, either due to emigration or failure of cognate T cell/B cell interaction. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1998 journal article

The distribution of variation in regulatory gene segments, as present in MHC class II promoters

GENOME RESEARCH, 8(2), 124–134.

By: L. Cowell *, T. Kepler n, M. Janitz *, R. Lauster* & N. Mitchison*

MeSH headings : Animals; Binding Sites / genetics; Binding Sites / immunology; Chickens; Genes, MHC Class II; Genetic Variation / genetics; Genetic Variation / immunology; Humans; Mice; Mole Rats; Promoter Regions, Genetic / immunology; Regulatory Sequences, Nucleic Acid / immunology; Selection, Genetic; Sequence Analysis, DNA; Species Specificity; Zebrafish
TL;DR: A high level of intraspecies variability in MHC class II gene promoters in man and mouse is observed, which in mouse but not in man is localized to a significant extent near the binding sites of transcription factors-sites that are conserved over longer evolutionary distances. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1997 journal article

Codon bias and plasticity in immunoglobulins

MOLECULAR BIOLOGY AND EVOLUTION, 14(6), 637–643.

By: T. Kepler n

author keywords: codon bias; immunoglobulin; somatic mutation; hypermutation; immunity
MeSH headings : Amino Acids / genetics; Binding Sites; Codon; Genetic Variation; Humans; Immunoglobulin Variable Region / genetics; Immunoglobulins / physiology; Linear Models; Models, Genetic; Molecular Sequence Data; Mutation; Selection, Genetic; Sequence Alignment
TL;DR: Two statistical tests strongly suggest that evolution has acted to enhance the plasticity of immunoglobulin genes under somatic hypermutation. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

1996 journal article

Interdependence of N nucleotide addition and recombination site choice in V(D)J rearrangement

Journal of Immunology, 157(10), 4451.

By: T. Kepler, M. Borrero, B. Rugerio, S. McCray & S. Clarke

Source: NC State University Libraries
Added: August 6, 2018

1995 journal article

Cellular interaction in germinal-centers - roles of cd40 ligand and b7-2 in established germinal-centers

Journal of Immunology, 155(2), 556–567.

By: S. Han, K. Hathcock, B. Zheng, T. Kepler, R. Hodes & G. Kelsoe

Source: NC State University Libraries
Added: August 6, 2018

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