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Time-dependent models of signal transduction networks

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Signaling cascades transduce signals received on the cell membrane to the nucleus. While noise filtering, ultra-sensitive switches, and signal amplification have all been shown to be features of such signaling cascades, it is not understood why cascades typically show three

Signaling cascades transduce signals received on the cell membrane to the nucleus. While noise filtering, ultra-sensitive switches, and signal amplification have all been shown to be features of such signaling cascades, it is not understood why cascades typically show three or four layers. Using singular perturbation theory, Michaelis-Menten type equations are derived for open enzymatic systems. When these equations are organized into a cascade, it is demonstrated that the output signal as a function of time becomes sigmoidal with the addition of more layers. Furthermore, it is shown that the activation time will speed up to a point, after which more layers become superfluous. It is shown that three layers create a reliable sigmoidal response progress curve from a wide variety of time-dependent signaling inputs arriving at the cell membrane, suggesting that natural selection may have favored signaling cascades as a parsimonious solution to the problem of generating switch-like behavior in a noisy environment.

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Date Created
2013

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Wada basins of attraction in diffeomorphic maps

Description

Dividing the plane in half leaves every border point of one region a border point of both regions. Can we divide up the plane into three or more regions such that any point on the boundary of at least one

Dividing the plane in half leaves every border point of one region a border point of both regions. Can we divide up the plane into three or more regions such that any point on the boundary of at least one region is on the border of all the regions? In fact, it is possible to design a dynamical system for which the basins of attractions have this Wada property. In certain circumstances, both the Hénon map, a simple system, and the forced damped pendulum, a physical model, produce Wada basins.

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2013-05

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A chemostat model of bacteriophage-bacteria interaction with infinite distributed delays

Description

Bacteriophage (phage) are viruses that infect bacteria. Typical laboratory experiments show that in a chemostat containing phage and susceptible bacteria species, a mutant bacteria species will evolve. This mutant species is usually resistant to the phage infection and less competitive

Bacteriophage (phage) are viruses that infect bacteria. Typical laboratory experiments show that in a chemostat containing phage and susceptible bacteria species, a mutant bacteria species will evolve. This mutant species is usually resistant to the phage infection and less competitive compared to the susceptible bacteria species. In some experiments, both susceptible and resistant bacteria species, as well as phage, can coexist at an equilibrium for hundreds of hours. The current research is inspired by these observations, and the goal is to establish a mathematical model and explore sufficient and necessary conditions for the coexistence. In this dissertation a model with infinite distributed delay terms based on some existing work is established. A rigorous analysis of the well-posedness of this model is provided, and it is proved that the susceptible bacteria persist. To study the persistence of phage species, a "Phage Reproduction Number" (PRN) is defined. The mathematical analysis shows phage persist if PRN > 1 and vanish if PRN < 1. A sufficient condition and a necessary condition for persistence of resistant bacteria are given. The persistence of the phage is essential for the persistence of resistant bacteria. Also, the resistant bacteria persist if its fitness is the same as the susceptible bacteria and if PRN > 1. A special case of the general model leads to a system of ordinary differential equations, for which numerical simulation results are presented.

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Date Created
2012

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Merging prospect theory with the analytic hierarchy process: applications to technology markets

Description

This thesis presents a model for the buying behavior of consumers in a technology market. In this model, a potential consumer is not perfectly rational, but exhibits bounded rationality following the axioms of prospect theory: reference dependence, diminishing returns and

This thesis presents a model for the buying behavior of consumers in a technology market. In this model, a potential consumer is not perfectly rational, but exhibits bounded rationality following the axioms of prospect theory: reference dependence, diminishing returns and loss sensitivity. To evaluate the products on different criteria, the analytic hierarchy process is used, which allows for relative comparisons. The analytic hierarchy process proposes that when making a choice between several alternatives, one should measure the products by comparing them relative to each other. This allows the user to put numbers to subjective criteria. Additionally, evidence suggests that a consumer will often consider not only their own evaluation of a product, but also the choices of other consumers. Thus, the model in this paper applies prospect theory to products with multiple attributes using word of mouth as a criteria in the evaluation.

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Date Created
2014

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Mathematical and statistical insights in evaluating state dependent effectiveness of HIV prevention interventions

Description

Pre-Exposure Prophylaxis (PrEP) is any medical or public health procedure used before exposure to the disease causing agent, its purpose is to prevent, rather than treat or cure a disease. Most commonly, PrEP refers to an experimental HIV-prevention strategy that

Pre-Exposure Prophylaxis (PrEP) is any medical or public health procedure used before exposure to the disease causing agent, its purpose is to prevent, rather than treat or cure a disease. Most commonly, PrEP refers to an experimental HIV-prevention strategy that would use antiretrovirals to protect HIV-negative people from HIV infection. A deterministic mathematical model of HIV transmission is developed to evaluate the public-health impact of oral PrEP interventions, and to compare PrEP effectiveness with respect to different evaluation methods. The effects of demographic, behavioral, and epidemic parameters on the PrEP impact are studied in a multivariate sensitivity analysis. Most of the published models on HIV intervention impact assume that the number of individuals joining the sexually active population per year is constant or proportional to the total population. In the second part of this study, three models are presented and analyzed to study the PrEP intervention, with constant, linear, and logistic recruitment rates. How different demographic assumptions can affect the evaluation of PrEP is studied. When provided with data, often least square fitting or similar approaches can be used to determine a single set of approximated parameter values that make the model fit the data best. However, least square fitting only provides point estimates and does not provide information on how strongly the data supports these particular estimates. Therefore, in the third part of this study, Bayesian parameter estimation is applied on fitting ODE model to the related HIV data. Starting with a set of prior distributions for the parameters as initial guess, Bayes' formula can be applied to obtain a set of posterior distributions for the parameters which makes the model fit the observed data best. Evaluating the posterior distribution often requires the integration of high-dimensional functions, which is usually difficult to calculate numerically. Therefore, the Markov chain Monte Carlo (MCMC) method is used to approximate the posterior distribution.

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Date Created
2014

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An aggregate second order continuum model for transient production planning

Description

Factory production is stochastic in nature with time varying input and output processes that are non-stationary stochastic processes. Hence, the principle quantities of interest are random variables. Typical modeling of such behavior involves numerical simulation and statistical

Factory production is stochastic in nature with time varying input and output processes that are non-stationary stochastic processes. Hence, the principle quantities of interest are random variables. Typical modeling of such behavior involves numerical simulation and statistical analysis. A deterministic closure model leading to a second order model for the product density and product speed has previously been proposed. The resulting partial differential equations (PDE) are compared to discrete event simulations (DES) that simulate factory production as a time dependent M/M/1 queuing system. Three fundamental scenarios for the time dependent influx are studied: An instant step up/down of the mean arrival rate; an exponential step up/down of the mean arrival rate; and periodic variation of the mean arrival rate. It is shown that the second order model, in general, yields significant improvement over current first order models. Specifically, the agreement between the DES and the PDE for the step up and for periodic forcing that is not too rapid is very good. Adding diffusion to the PDE further improves the agreement. The analysis also points to fundamental open issues regarding the deterministic modeling of low signal-to-noise ratio for some stochastic processes and the possibility of resonance in deterministic models that is not present in the original stochastic process.

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Date Created
2015

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The economics of need-based transfers

Description

Need-based transfers (NBTs) are a form of risk-pooling in which binary welfare exchanges

occur to preserve the viable participation of individuals in an economy, e.g. reciprocal gifting

of cattle among East African herders or food sharing among vampire bats. With the

broad goal

Need-based transfers (NBTs) are a form of risk-pooling in which binary welfare exchanges

occur to preserve the viable participation of individuals in an economy, e.g. reciprocal gifting

of cattle among East African herders or food sharing among vampire bats. With the

broad goal of better understanding the mathematics of such binary welfare and risk pooling,

agent-based simulations are conducted to explore socially optimal transfer policies

and sharing network structures, kinetic exchange models that utilize tools from the kinetic

theory of gas dynamics are utilized to characterize the wealth distribution of an NBT economy,

and a variant of repeated prisoner’s dilemma is analyzed to determine whether and

why individuals would participate in such a system of reciprocal altruism.

From agent-based simulation and kinetic exchange models, it is found that regressive

NBT wealth redistribution acts as a cutting stock optimization heuristic that most efficiently

matches deficits to surpluses to improve short-term survival; however, progressive

redistribution leads to a wealth distribution that is more stable in volatile environments and

therefore is optimal for long-term survival. Homogeneous sharing networks with low variance

in degree are found to be ideal for maintaining community viability as the burden and

benefit of NBTs is equally shared. Also, phrasing NBTs as a survivor’s dilemma reveals

parameter regions where the repeated game becomes equivalent to a stag hunt or harmony

game, and thus where cooperation is evolutionarily stable.

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Agent

Created

Date Created
2018

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Network Based Models of Opinion Formation: Consensus and Beyond

Description

Understanding the evolution of opinions is a delicate task as the dynamics of how one changes their opinion based on their interactions with others are unclear.

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Created

Date Created
2021

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Observability methods in sensor scheduling

Description

Modern measurement schemes for linear dynamical systems are typically designed so that different sensors can be scheduled to be used at each time step. To determine which sensors to use, various metrics have been suggested. One possible such metric is

Modern measurement schemes for linear dynamical systems are typically designed so that different sensors can be scheduled to be used at each time step. To determine which sensors to use, various metrics have been suggested. One possible such metric is the observability of the system. Observability is a binary condition determining whether a finite number of measurements suffice to recover the initial state. However to employ observability for sensor scheduling, the binary definition needs to be expanded so that one can measure how observable a system is with a particular measurement scheme, i.e. one needs a metric of observability. Most methods utilizing an observability metric are about sensor selection and not for sensor scheduling. In this dissertation we present a new approach to utilize the observability for sensor scheduling by employing the condition number of the observability matrix as the metric and using column subset selection to create an algorithm to choose which sensors to use at each time step. To this end we use a rank revealing QR factorization algorithm to select sensors. Several numerical experiments are used to demonstrate the performance of the proposed scheme.

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Created

Date Created
2015

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Critical coupling and synchronized clusters in arbitrary networks of Kuramoto oscillators

Description

The Kuramoto model is an archetypal model for studying synchronization in groups

of nonidentical oscillators where oscillators are imbued with their own frequency and

coupled with other oscillators though a network of interactions. As the coupling

strength increases, there is a bifurcation to

The Kuramoto model is an archetypal model for studying synchronization in groups

of nonidentical oscillators where oscillators are imbued with their own frequency and

coupled with other oscillators though a network of interactions. As the coupling

strength increases, there is a bifurcation to complete synchronization where all oscillators

move with the same frequency and show a collective rhythm. Kuramoto-like

dynamics are considered a relevant model for instabilities of the AC-power grid which

operates in synchrony under standard conditions but exhibits, in a state of failure,

segmentation of the grid into desynchronized clusters.

In this dissertation the minimum coupling strength required to ensure total frequency

synchronization in a Kuramoto system, called the critical coupling, is investigated.

For coupling strength below the critical coupling, clusters of oscillators form

where oscillators within a cluster are on average oscillating with the same long-term

frequency. A unified order parameter based approach is developed to create approximations

of the critical coupling. Some of the new approximations provide strict lower

bounds for the critical coupling. In addition, these approximations allow for predictions

of the partially synchronized clusters that emerge in the bifurcation from the

synchronized state.

Merging the order parameter approach with graph theoretical concepts leads to a

characterization of this bifurcation as a weighted graph partitioning problem on an

arbitrary networks which then leads to an optimization problem that can efficiently

estimate the partially synchronized clusters. Numerical experiments on random Kuramoto

systems show the high accuracy of these methods. An interpretation of the

methods in the context of power systems is provided.

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Date Created
2018