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Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.

ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Action language C+ is a formalism for describing properties of actions, which is based on nonmonotonic causal logic. The definite fragment of C+ is implemented in the Causal Calculator (CCalc), which is based on the reduction of nonmonotonic causal logic to propositional logic. This thesis describes the language

Action language C+ is a formalism for describing properties of actions, which is based on nonmonotonic causal logic. The definite fragment of C+ is implemented in the Causal Calculator (CCalc), which is based on the reduction of nonmonotonic causal logic to propositional logic. This thesis describes the language of CCalc in terms of answer set programming (ASP), based on the translation of nonmonotonic causal logic to formulas under the stable model semantics. I designed a standard library which describes the constructs of the input language of CCalc in terms of ASP, allowing a simple modular method to represent CCalc input programs in the language of ASP. Using the combination of system F2LP and answer set solvers, this method achieves functionality close to that of CCalc while taking advantage of answer set solvers to yield efficient computation that is orders of magnitude faster than CCalc for many benchmark examples. In support of this, I created an automated translation system Cplus2ASP that implements the translation and encoding method and automatically invokes the necessary software to solve the translated input programs.
ContributorsCasolary, Michael (Author) / Lee, Joohyung (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Baral, Chitta (Committee member) / Arizona State University (Publisher)
Created2011
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Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to its modeling

Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to its modeling language in order to enhance expressivity, such as incorporating aggregates and interfaces with ontologies. Also, in order to overcome the grounding bottleneck of computation in ASP, there are increasing interests in integrating ASP with other computing paradigms, such as Constraint Programming (CP) and Satisfiability Modulo Theories (SMT). Due to the non-monotonic nature of the ASP semantics, such enhancements turned out to be non-trivial and the existing extensions are not fully satisfactory. We observe that one main reason for the difficulties rooted in the propositional semantics of ASP, which is limited in handling first-order constructs (such as aggregates and ontologies) and functions (such as constraint variables in CP and SMT) in natural ways. This dissertation presents a unifying view on these extensions by viewing them as instances of formulas with generalized quantifiers and intensional functions. We extend the first-order stable model semantics by by Ferraris, Lee, and Lifschitz to allow generalized quantifiers, which cover aggregate, DL-atoms, constraints and SMT theory atoms as special cases. Using this unifying framework, we study and relate different extensions of ASP. We also present a tight integration of ASP with SMT, based on which we enhance action language C+ to handle reasoning about continuous changes. Our framework yields a systematic approach to study and extend non-monotonic languages.
ContributorsMeng, Yunsong (Author) / Lee, Joohyung (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Baral, Chitta (Committee member) / Fainekos, Georgios (Committee member) / Lifschitz, Vladimir (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Biological organisms are made up of cells containing numerous interconnected biochemical processes. Diseases occur when normal functionality of these processes is disrupted, manifesting as disease symptoms. Thus, understanding these biochemical processes and their interrelationships is a primary task in biomedical research and a prerequisite for activities including diagnosing diseases and

Biological organisms are made up of cells containing numerous interconnected biochemical processes. Diseases occur when normal functionality of these processes is disrupted, manifesting as disease symptoms. Thus, understanding these biochemical processes and their interrelationships is a primary task in biomedical research and a prerequisite for activities including diagnosing diseases and drug development. Scientists studying these interconnected processes have identified various pathways involved in drug metabolism, diseases, and signal transduction, etc. High-throughput technologies, new algorithms and speed improvements over the last decade have resulted in deeper knowledge about biological systems, leading to more refined pathways. Such pathways tend to be large and complex, making it difficult for an individual to remember all aspects. Thus, computer models are needed to represent and analyze them. The refinement activity itself requires reasoning with a pathway model by posing queries against it and comparing the results against the real biological system. Many existing models focus on structural and/or factoid questions, relying on surface-level information. These are generally not the kind of questions that a biologist may ask someone to test their understanding of biological processes. Examples of questions requiring understanding of biological processes are available in introductory college level biology text books. Such questions serve as a model for the question answering system developed in this thesis. Thus, the main goal of this thesis is to develop a system that allows the encoding of knowledge about biological pathways to answer questions demonstrating understanding of the pathways. To that end, a language is developed to specify a pathway and pose questions against it. Some existing tools are modified and used to accomplish this goal. The utility of the framework developed in this thesis is illustrated with applications in the biological domain. Finally, the question answering system is used in real world applications by extracting pathway knowledge from text and answering questions related to drug development.
ContributorsAnwar, Saadat (Author) / Baral, Chitta (Thesis advisor) / Inoue, Katsumi (Committee member) / Chen, Yi (Committee member) / Davulcu, Hasan (Committee member) / Lee, Joohyung (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Different logic-based knowledge representation formalisms have different limitations either with respect to expressivity or with respect to computational efficiency. First-order logic, which is the basis of Description Logics (DLs), is not suitable for defeasible reasoning due to its monotonic nature. The nonmonotonic formalisms that extend first-order logic, such as circumscription

Different logic-based knowledge representation formalisms have different limitations either with respect to expressivity or with respect to computational efficiency. First-order logic, which is the basis of Description Logics (DLs), is not suitable for defeasible reasoning due to its monotonic nature. The nonmonotonic formalisms that extend first-order logic, such as circumscription and default logic, are expressive but lack efficient implementations. The nonmonotonic formalisms that are based on the declarative logic programming approach, such as Answer Set Programming (ASP), have efficient implementations but are not expressive enough for representing and reasoning with open domains. This dissertation uses the first-order stable model semantics, which extends both first-order logic and ASP, to relate circumscription to ASP, and to integrate DLs and ASP, thereby partially overcoming the limitations of the formalisms. By exploiting the relationship between circumscription and ASP, well-known action formalisms, such as the situation calculus, the event calculus, and Temporal Action Logics, are reformulated in ASP. The advantages of these reformulations are shown with respect to the generality of the reasoning tasks that can be handled and with respect to the computational efficiency. The integration of DLs and ASP presented in this dissertation provides a framework for integrating rules and ontologies for the semantic web. This framework enables us to perform nonmonotonic reasoning with DL knowledge bases. Observing the need to integrate action theories and ontologies, the above results are used to reformulate the problem of integrating action theories and ontologies as a problem of integrating rules and ontologies, thus enabling us to use the computational tools developed in the context of the latter for the former.
ContributorsPalla, Ravi (Author) / Lee, Joohyung (Thesis advisor) / Baral, Chitta (Committee member) / Kambhampati, Subbarao (Committee member) / Lifschitz, Vladimir (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the

Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the cells of multicellular organisms which arises when the cell is subjected to an unusual amount of stress. Since this default phenotype is similar across cell types and even organisms, it seems it must be an evolutionarily ancestral phenotype. We take a phylostratigraphical approach, but systematically add species divergence time data to estimate gene ages numerically and use these ages to investigate the ages of genes involved in cancer. We find that ancient disease-recessive cancer genes are significantly enriched for DNA repair and SOS activity, which seems to imply that a core component of cancer development is not the regulation of growth, but the regulation of mutation. Verification of this finding could drastically improve cancer treatment and prevention.
ContributorsOrr, Adam James (Author) / Davies, Paul (Thesis director) / Bussey, Kimberly (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Natural Language Processing is a subject that combines computer science and linguistics, aiming to provide computers with the ability to understand natural language and to develop a more intuitive human-computer interaction. The research community has developed ways to translate natural language to mathematical formalisms. It has not yet been shown,

Natural Language Processing is a subject that combines computer science and linguistics, aiming to provide computers with the ability to understand natural language and to develop a more intuitive human-computer interaction. The research community has developed ways to translate natural language to mathematical formalisms. It has not yet been shown, however, how to automatically translate different kinds of knowledge in English to distinct formal languages. Most of the recent work presents the problem that the translation method aims to a specific formal language or is hard to generalize. In this research, I take a first step to overcome this difficulty and present two algorithms which take as input two lambda-calculus expressions G and H and compute a lambda-calculus expression F. The expression F returned by the first algorithm satisfies F@G=H and, in the case of the second algorithm, we obtain G@F=H. The lambda expressions represent the meanings of words and sentences. For each formal language that one desires to use with the algorithms, the language must be defined in terms of lambda calculus. Also, some additional concepts must be included. After doing this, given a sentence, its representation and knowing the representation of several words in the sentence, the algorithms can be used to obtain the representation of the other words in that sentence. In this work, I define two languages and show examples of their use with the algorithms. The algorithms are illustrated along with soundness and completeness proofs, the latter with respect to typed lambda-calculus formulas up to the second order. These algorithms are a core part of a natural language semantics system that translates sentences from English to formulas in different formal languages.
ContributorsAlvarez Gonzalez, Marcos (Author) / Baral, Chitta (Thesis advisor) / Lee, Joohyung (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2010
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Description

Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT,

Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT, is an alternative to continuous ADT that improves the patient’s quality of life while testosterone levels recover between cycles. In this paper,we explore the response of intermittent ADT to metastasized prostate cancer by employing a previously clinical data validated mathematical model to new clinical data from patients undergoing Abiraterone therapy. This cell quota model, a system of ordinary differential equations constructed using Droop’s nutrient limiting theory, assumes the tumor comprises of castration-sensitive (CS) and castration-resistant (CR)cancer sub-populations. The two sub-populations rely on varying levels of intracellular androgen for growth, death and transformation. Due to the complexity of the model,we carry out sensitivity analyses to study the effect of certain parameters on their outputs, and to increase the identifiability of each patient’s unique parameter set. The model’s forecasting results show consistent accuracy for patients with sufficient data,which means the model could give useful information in practice, especially to decide whether an additional round of treatment would be effective.

ContributorsBennett, Justin Klark (Author) / Kuang, Yang (Thesis director) / Kostelich, Eric (Committee member) / Phan, Tin (Committee member) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
AARP estimates that 90% of seniors wish to remain in their homes during retirement. Seniors need assistance as they age, historically they have received assistance from either family members, nursing homes, or Continuing Care Retirement Communities. For seniors not wanting any of these options, there has been very few alternatives.

AARP estimates that 90% of seniors wish to remain in their homes during retirement. Seniors need assistance as they age, historically they have received assistance from either family members, nursing homes, or Continuing Care Retirement Communities. For seniors not wanting any of these options, there has been very few alternatives. Now, the emergence of the continuing care at home program is providing hope for a different method of elder care moving forward. CCaH programs offer services such as: skilled nursing care, care coordination, emergency response systems, aid with personal and health care, and transportation. Such services allow seniors to continue to live in their own home with assistance as their health deteriorates over time. Currently, only 30 CCaH programs exist. With the growth of the elderly population in the coming years, this model seems poised for growth.
ContributorsSturm, Brendan (Author) / Milovanovic, Jelena (Thesis director) / Hassett, Matthew (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05