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A multiscale model for the assessment of autonomic dysfunction in human endotoxemia

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
A multiscale model for the assessment of autonomic dysfunction in human endotoxemia
Identifier
ETD_2611
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000053028
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Biomedical Engineering
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Endotoxemia
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Inflammation--Mathematical models
Abstract (type = abstract)
The overall goal of this dissertation is the development of a semi-mechanistic, physiology-based, multiscale model of human endotoxemia, as a prototype model of acute inflammation in humans that integrates essential regulatory processes across the host from the cellular to the systemic level. The complex and multiplex characteristics of the acute inflammatory response and its complications have been thought to be a leading potential reason for the inability to propose effective clinical intervention strategies. The nature of the response has led researchers to the realization that mathematical models of inflammation offer the opportunity to study the dynamics of interacting components and establish a causal inference relationship through the manipulation of the corresponding dynamic elements. Driven by the premise to develop in silico methodologies that will enable translational research to elucidate mechanisms by which macroscopic responses, at the physiome level, emerge as the result of propagating information across an intricate web of interacting modules, a systems-level modeling approach is developed that addresses the following unique aspects: (i) identification of the essential components characterizing cellular transcriptional dynamics in response to an external perturbation; (ii) reverse engineering of quantifiable representations of these elements exploring the concept of physicochemical and indirect response modeling that connect extracellular signals and intracellular signaling cascades leading to the emergent transcriptional dynamics; and finally (iii) multiscale, physiology-based modeling that quantifies critical aspects of the complex neuro-immune crosstalk while clinical observables are explicitly incorporated to assess systemic abnormalities indicative of the severity of the host. It is therefore the purpose of this research to demonstrate the feasibility of a relevant human inflammation model that bridges the initiating signal and phenotypic expressions through semi-mechanistic based host response models that include transcriptional dynamics, signaling cascades and physiological components; and to define a notional template for multiscale modeling extendable to a wide range of clinically important conditions. The ultimate deliverable of the proposed research is the multiscale human inflammation model that would allow us to clarify the clinical contexts in which inflammatory dysregulation contributes to morbidity and mortality in acutely stressed patients; thereby advancing the translational potential of systems modeling in clinical research.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
xxiii, 235 p. : ill.
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application/pdf
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text/xml
Note (type = degree)
Ph.D.
Note
Includes abstract
Note
Vita
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Panagiota Theodoros Foteinou
Name (ID = NAME-1); (type = personal)
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Foteinou
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Panagiota
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1981-
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author
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Panagiota Foteinou
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Androulakis
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Ioannis P
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chair
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Advisory Committee
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Ioannis P Androulakis
Name (ID = NAME-3); (type = personal)
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Yarmush
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Martin l
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internal member
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Advisory Committee
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Martin l Yarmush
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Moghe
NamePart (type = given)
Prabhas V
Role
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internal member
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Advisory Committee
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Prabhas V Moghe
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Calvano
NamePart (type = given)
Steven E
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outside member
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Advisory Committee
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Steven E Calvano
Name (ID = NAME-6); (type = personal)
NamePart (type = family)
Lowry
NamePart (type = given)
Stephen F
Role
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outside member
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Advisory Committee
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Stephen F Lowry
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
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degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010
Place
PlaceTerm (type = code)
xx
Location
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NjNbRU
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Identifier (type = doi)
doi:10.7282/T34749ZJ
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Foteinou
GivenName
Panagiota
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-04-14 22:02:33
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Panagiota Foteinou
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
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.
RightsEvent (ID = RE-2); (AUTHORITY = rulib)
Type
Embargo
DateTime
2010-05-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2010.
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