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Linear-in-flux-expression (LIFE) approach to dynamic biological networks

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TitleInfo
Title
Linear-in-flux-expression (LIFE) approach to dynamic biological networks
Name (type = personal)
NamePart (type = family)
Merrill
NamePart (type = given)
Nathaniel J.
NamePart (type = date)
1992-
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Nathaniel J. Merrill
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author
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Piccoli
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Benedetto
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Benedetto Piccoli
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Advisory Committee
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chair
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Lee
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Kwangwon
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Kwangwon Lee
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Advisory Committee
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internal member
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Gonzalez
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Angelica
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Angelica Gonzalez
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Advisory Committee
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internal member
Name (type = personal)
NamePart (type = family)
Chyba
NamePart (type = given)
Monique
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Monique Chyba
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Advisory Committee
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outside member
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Camden Graduate School
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school
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Text
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theses
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2020
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2020-05
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English
Abstract (type = abstract)
This work analyzes the dynamics of three distinct classes of biological systems. The first is metabolic networks. The methodology named LIFE (Linear-in-Flux-Expression) was developed with the purpose of studying and analyzing large metabolic systems. With LIFE, the number of model parameters is reduced by accounting for correlations among the components of the system. These systems can be associated to graphs. General results on the stability of LIFE systems are discussed, particularly we formulate necessary conditions on the graph's structure to ensure the stability of the dynamics. Moreover, stability analysis from related fields, such as Markov chains, network flows, and compartmental systems, can also be applied. Control of LIFE systems through the addition of drugs as well as modifying intakes is discussed. A generalized graph object which incorporates hyperedges and uberedges is used to apply LIFE to metabolic networks, in particular to Mycobacterium tuberculosis (MTB). Results from LIFE simulations on MTB carbon metabolism are presented via simulations. Finally, the method allows us to rank 4-drug combinations in terms of their effectiveness in destabilizing MTB metabolic networks, thus killing the bacterium.

The second class of systems is models for circadian rhythm. One of the essential characteristics of an authentic circadian clock is that the free-running period sustains an approximately24-hour cycle. The dynamics of the circadian clock is modified by an external stimulus, called a zeitgeber. This modification process is known as entrainment and operates to reset the phase and period of the circadian clock. When analyzing the phase of entrainment of many individuals, it is often assumed that an organism with a short period will have a phase advance, and a prolonged period will have a phase delay; however, this does not explain all known experimental data, so a Two-Step Entrainment model was developed. This work analyzes how parameters of the model affect the dynamics and presents results fitting the Two-Step Entrainment model to human data.

The third class of systems consists of ecological networks. The interactions of species are often described via a network. Construction of networks in paleoecology is challenging due to the lack of observations of interactions, as well as biases in the preservation of species. The links of species in these networks must be inferred based on properties such as body size, similarities to living species, genetic information (when possible), and other known characteristics. Studying how paleo-networks have changed and adapted through time could assist in predicting how current ecological communities might react to environmental stressors. This work reconstructs networks from arthropod data found in rodent middens. The dynamics of these networks over 20,000 years is analyzed, and network metrics such as connectance are compared to modern networks.
Subject (authority = local)
Topic
Metabolic networks
Subject (authority = RUETD)
Topic
Computational and Integrative Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_10964
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application/pdf
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text/xml
Extent
1 online resource (viii, 207 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
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Title
Camden Graduate School Electronic Theses and Dissertations
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rucore10005600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-k49a-yr31
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Merrill
GivenName
Nathaniel
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-05-15 14:43:33
AssociatedEntity
Name
Nathaniel Merrill
Role
Copyright holder
Affiliation
Rutgers University. Camden Graduate School
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2020-05-21T10:46:13
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2020-05-21T10:46:13
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