VictorJuiz/thesis huggingface dataset:
Comparative Approaches to Characterization of Lymphatic Endothelial Cells as Phenotypically Distinct from Blood Endothelial Cells

The lymphatic system complements the blood circulatory system in absorption and transport of nutrients, and in the maintenance of homeostasis. Historically, the angiogenesis field has advanced faster and farther than the field of lymphangiogenesis. The discovery of lymphatic markers and the emerging evidence implicating the lymphatic system as a central player in a variety of pathological conditions has attracted research interest and driven the field forward. Research efforts have produced the observation that regulators of the blood endothelium are frequently members of the same protein families of regulators of the lymphatic endothelium. More importantly, these regulators do not act discretely, restricting their regulatory activities to one endothelial cell (EC) type. Two examples of regulators that behave in this manner are the VEGF and the Angiopoietin families of proteins, which have cell-type-dependent effects on EC processes such as migration, proliferation and survival. The study of these regulators therefore requires an in vitro EC system capable of accommodating the simultaneous characterization of the signaling pathways downstream of these shared molecular regulators in venous, arterial and lymphatic endotheliums. To build such an in vitro system, I isolated and validated lymphatic, venous, and arterial ECs derived from vessels of bovine mesentery. The proteomes of the three cell types were comparatively studied using two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometric identification. The three cell types were used in a subtractive immunization scheme for the production of a monoclonal antibody selectively reactive to a potentially novel surface protein marker of lymphatic ECs. The studies recorded herein all share the common goal of identifying and characterizing unique molecular signatures that distinguish lymphatic ECs from blood ECs, and that may underline the cellular biology of the lymphatic endothelium as distinct from the blood endothelium.

Keywords: Lymphatic endothelium
endothelial cells
Advisor: Dumont, Daniel Joseph
Biomarker and Therapeutic Studies of Antibodies and Small Molecules that Target EGFR

The field of targeted cancer therapy has progressed in recent years with the approval of new oncology drugs. Coupled with the benefits that these agents provide, has come an appreciation for challenges that occur when attempting to translate successful experiments from the laboratory into effective clinical trials. One such challenge has been predicting the optimal dose and schedule to take into clinical evaluation, given the possibility that certain targeted therapeutics may exhibit maximal anti-tumour efficacy well below maximum tolerated doses. Recent work with a targeted antibody to the mouse vascular endothelial growth factor receptor-2 demonstrated that detection of increased levels of its endogenous ligand in the plasma, namely VEGF, could address this issue, as maximal increases in VEGF paralleled optimal drug activity. The VEGF result has become recognized as a potential class effect for this family of inhibitors. This thesis summarizes experiments designed to build upon this discovery by investigating whether the utility of ligand measurement might also apply to drugs that inhibit the epidermal growth factor receptor (EGFR), which have also received recent regulatory approval, and inhibit angiogenesis as one of their mechanisms of action. In addition, we investigated the potential application of EGFR inhibitors to influence other markers of tumour angiogenesis, specifically their effects on levels of circulating endothelial progenitor cells (CEPs). Finally, we evaluated combination treatment of EGFR inhibition with anti-angiogenic scheduling of chemotherapy. The EGFR ligand TGF-alpha increased in a dose dependent fashion following treatment with cetuximab, and levels in the circulation paralleled anti-tumour activity. This was a host-dependent effect that was not observed with the lower affinity antibody nimotuzumab. Inhibition of host EGFR also reduced plasma CEPs, but at higher doses these drugs increased off target growth factors VEGF and G-CSF, as well as CEPs. In a model of advanced triple negative breast cancer, the combination of nimotuzumab and metronomic cyclophosphamide was efficacious and well tolerated, leading to a potential new treatment strategy for this aggressive disease. Taken together, these studies identify new and useful applications for EGFR-targeted antibodies, and shed further light on their contributions within the field of tumour angiogenesis and antiangiogenic therapy.

Keywords: EGFR
experimental therapeutics
biomarkers
Advisor: Kerbel, Robert S.
Modulation of Intracrine Estrogen in Menopausal Women: Implications for Women’s Reproductive Health and Breast Cancer Risk

Extensive research and clinical observations in the past 20 years confirmed that the cessation of ovarian function at menopause does not stop the process of sex steroid hormone synthesis in females. Indeed, multiple extra-ovarian tissues contain the same enzymatic machinery the ovary uses which can maintain a significant rate of local hormonal synthesis sufficient to cause pathological outcomes. This is commonly termed “intracrine”. However, two obstacles face intracrinology. Firstly, wide clinical appreciation of this mechanism in causing disease and in targeting it with therapy does not currently exist. Secondly, blood hormonal assays are used in the clinic to diagnose and manage intracrine based disorders. This could be entirely misleading, since hormonal synthesis, action and metabolism occur within the tissue and, therefore, measuring blood levels is not reflective of the actual disease environment. This thesis presents evidence of significant intracrine based disorders in menopausal women that could be effectively managed by tackling the core intracrine mechanism. Three protocols are investigated emphasizing the usefulness of menopausal intracrine estrogen inhibition. The first presents a joint objective of treating menopausal symptoms using estrogenic replacement therapy while reducing breast cancer risk using long-term aromatase inhibitors. Aromatase inhibition is used to suppress the local estrogen synthesis in the breast. The second protocol is a new method of acute inhibition of breast estrogens to improve the accuracy of breast imaging techniques. This method showed a benefit in reducing the benign parenchymal enhancement during breast MRI indicating a potential improvement in specificity. The third protocol involves using aromatase inhibitors in the treatment of severe endometriosis that did not respond to oophorectomy. The pathogenesis of breast cancer, endometriosis and fibroids are believed to involve intracrine estrogen activity. Another significant contribution presented in this thesis is the development of a new technique that enables minimally invasive tissue assays of hormones in their genuine site of synthesis rather than indirectly in the blood. The new assay requires only microliter volumes of sample and employs a novel digital microfluidics technology. Estrogen and other sex steroids were extracted from droplet-scale breast tissue and blood samples.

Keywords: Menopause
Estrogen
Intracrinology
Breast
Reproductive Health
Aromatase Inhibitors
Advisor: Casper, Robert
Grassmann Dynamics

The present work is divided in two parts. The first is concerned with the dynamics on the Grassmann manifold of k-dimensional subvector spaces of an n dimensional real or complex vector space induced by a linear invertible transformation A of the vector space into itself. The Grassmann map GA sends p to Ap, and one asks, what are the dynamics of GA? In the second part, I consider dynamics induced by a linear cocycle covering a diffeomorphism of a compact manifold, acting on the Grassmann bundle of k-dimensional linear subspaces of TN. I prove a Kupka-Smale theorem for the space of cocycles covering diffeomorphisms of a compact manifold. The proof of this theorem implies the same type of results for derived cocycles parametrized in the space of diffeomorphisms. The results of the second part can be generalized without effort to cocycles covering endomorphisms of N.

Keywords: Real Dynamical Systems
Grassmannian
Advisor: Shub, Michael
Pugh, Charles Chapman
"Living Cadavers" in Bangladesh: Ethics of the Human Organ Bazaar

The “miracle” success of transplant technology, alongside the commercialization of health care, and the increasing polarization between rich and poor have created the conditions for an illegal but thriving trade in human body parts. Based on 15 months of challenging fieldwork, my research examines the ethics of the organ bazaar, particularly the experiences of 33 kidney sellers living in Bangladesh. On the underground bazaar, not only human kidneys but also livers and corneas are advertised for sale. Recipients, sellers, and brokers regularly post newspaper advertisements to buy and sell organs. The average price for a kidney is US $1,500 in Bangladesh, a country where 78% of people live on less than $2 a day. My research examines serious ethical questions, such as these: Is it right to purchase an organ, even if the organ sought provides longevity? Is the sale of one’s organ a justifiable means of fighting poverty? These questions allow me to examine the ethics of harvesting organs, particularly from the bodies of impoverished people. Narrating the victims’ deeply moving testimonies, my ethnography reveals how organ buyers (both recipients and brokers) tricked and pressured Bangladeshi poor into selling their kidneys. In the end, these sellers were brutally deprived and deceived, and their suffering was extreme. In the post-vending period, sellers’ health, economic, and social conditions significantly deteriorated, yet none of them received the promised post-operative care—not even one appointment. My research therefore concludes that organ commodification is serious structural violence against the poor, at the terrible cost of harm and suffering to them. Examining the organ market proposition, I argue that the resulting violence and injustice against the poor provide a hefty reason to rebut this trade. Bangladeshi kidney sellers also stood up against organ commodification, speaking out about their suffering, and about various detrimental and unethical outcomes incurred in this deal. My research aims to offer insights to bioethics and to broaden the debate on human rights by exposing how technological advancement, structural violence, and grinding poverty intersect in the violation of justice to the poor, turning them into “living cadavers.”

Keywords: Organ Trafficking
Kidney Seller
Ethics of Kidney Trade
Medical Tourism
Medical Anthropology
Bangladesh
Advisor: Cunningham, Hilary
Mental Health Issues and Work: Institutional Practices of Silence in a Mental Healthcare Organization

Over the past decade, mental illness in the workplace has become a key issue in the health and business communities, fueled in part by recognition of the high prevalence rates and significant costs for individuals and organizations. Although research in the field is starting to emerge, there are significant gaps in what is known, particularly with respect to the workplace context and its impact on workers. The overall objective of this study was to characterize, from a sociological perspective, the experiences of healthcare workers with mental health issues, and to account for how their experiences were shaped by the social relations of work. A qualitative approach, based on principles of institutional ethnography, guided exploration of the interactional, structural and discursive dimensions of work within a large mental health and addictions treatment facility. Data collection included in-depth interviews with twenty employees regarding their personal experiences with mental health issues, interviews with twelve workplace stakeholders regarding their interactions with workers, and a review of organizational texts related to health, illness and productivity. Analysis of the transcripts and texts was based on an institutional ethnography approach to mapping social processes; examining connections between local sites of experience and the social organization of work. The study findings revealed a critical disjuncture between the public mandate of advocacy, open dialogue, and support regarding mental health issues, and the private experience of workers which was characterized by silence, secrecy and inaction. Practices of silence were adopted by workers and workplace stakeholders across the organization, and were shaped by discursive forces related to stigma, staff-client boundaries, and responsibility to act. The silence had both positive and negative implications for the mental health of workers, as well as for relationships and productivity in the workplace. In accounting for the practices and production of silence, I argue that silence is complex, multi-dimensional, and embedded within the social relations of healthcare work. It serves to maintain institutional order. This conceptualization of silence challenges current beliefs and practices related to stigma, disclosure, early identification, support, and return to work for employees with mental health issues.

Keywords: Mental health
Employment
Healthcare
Institutional ethnography
Qualitative research
Advisor: Eakin, Joan
Characterization of the Cu-Si System and Utilization of Metallurgical Techniques in Silicon Refining for Solar Cell Applications

Two methods for refining metallurgical grade silicon to solar grade silicon have been investigated. The first method involved the reduction of impurities from metallurgical grade silicon by high temperature vacuum refining. The concentrations of analyzed elements were reduced several times. The main steps in the second refining method include alloying with copper, solidification, grinding and heavy media separation. A metallographic study of the Si-Cu alloy showed the presence of only two microconstituents, mainly pure silicon dendrites and the Cu3Si intermetallic. SEM analysis showed a distinct boundary between the silicon and the Cu3Si phases, with a large concentration of microcracks along the boundary, which allowed for efficient separation. After alloying and grinding, a heavy media liquid was used to separate the light silicon phase from the heavier Cu3Si phase. Cu3Si residues together with the remaining impurities were found to be located at the surface of the pure silicon particles, and should be efficiently removed by acid leaching. Thirty elements were analyzed by the Inductively Coupled Plasma Mass Spectrometry (ICP) chemical analysis technique. ICP revealed a several times higher impurity level in the Cu3Si intermetallic than in the pure silicon; furthermore, the amounts of 22 elements in the refined silicon were reduced below the detection limit where the concentrations of 7 elements were below 1ppmw and 6 elements were below 2ppmw. The results showed that the suggested method is efficient in removing impurities from metallurgical grade silicon with great potential for further development.

Keywords: Silicon
Refining
Impurity removal
Solar Si
Cu-Si alloy
Advisor: Torstein, Utigard
Machine Learning Approaches to Biological Sequence and Phenotype Data Analysis

To understand biology at a system level, I presented novel machine learning algorithms to reveal the underlying mechanisms of how genes and their products function in different biological levels in this thesis. Specifically, at sequence level, based on Kernel Support Vector Machines (SVMs), I proposed learned random-walk kernel and learned empirical-map kernel to identify protein remote homology solely based on sequence data, and I proposed a discriminative motif discovery algorithm to identify sequence motifs that characterize protein sequences' remote homology membership. The proposed approaches significantly outperform previous methods, especially on some challenging protein families. At expression and protein level, using hierarchical Bayesian graphical models, I developed the first high-throughput computational predictive model to filter sequence-based predictions of microRNA targets by incorporating the proteomic data of putative microRNA target genes, and I proposed another probabilistic model to explore the underlying mechanisms of microRNA regulation by combining the expression profile data of messenger RNAs and microRNAs. At cellular level, I further investigated how yeast genes manifest their functions in cell morphology by performing gene function prediction from the morphology data of yeast temperature-sensitive alleles. The developed prediction models enable biologists to choose some interesting yeast essential genes and study their predicted novel functions.

Keywords: Machine Learning
Bioinformatics
Computational Biology
Advisor: Bonner, Anthony
Zhang, Zhaolei
Liberalitas in Late Republican and Early Augustan Roman Poetry

Liberalitas forms one of the central frameworks for defining social bonds within Roman society, and was part of how Roman poets constructed the world. This is most explicitly evident in the poets’ references to “patrons” and benefactors, but it extends much further. The poets worked within a broad framework of social conventions and expectations which must be understood in order to see how their poetry uses and responds to the concepts associated with liberalitas. Cicero’s de officiis and Seneca’s de beneficiis are therefore useful, as they offer idealised, prescriptive views of liberalitas in Roman society. Many scholars have investigated the relationships between poets and their patrons, including Peter White, Barbara Gold, James Zetzel, and Phebe Lowell Bowditch. I argue that any true understanding of the role of liberalitas in Roman poetry must also comprehend its importance in other areas. This dissertation focuses on the poetry of Catullus, Horace, Propertius, Tibullus, and Virgil in the Eclogues. The introduction addresses traditional liberalitas as defined by Cicero and Seneca in their works on benefits and duties. Chapter one illustrates how Catullus, Horace, and Tibullus display ideals similar to those of Cicero and Seneca and use the conventions of liberalitas for praising and blaming members of their social groups. Chapter two addresses the problems of status raised by liberalitas and investigates the strategies used by Catullus, Horace, Propertius, and Tibullus to mitigate these problems and further their social, literary, and aesthetic aims. Chapter three demonstrates how the love poets used and redefined the terminology and ideology of liberalitas to construct an obligation on the part of their beloveds to reciprocate the gifts given by the poets but reject the gifts given by rival lovers. Finally, Chapter four examines the role of liberalitas in formulating and expressing a poetic program in Virgil’s Eclogues, which points to its function in mediating the connection between ‘real-life’ political and social concerns and the literary preoccupations of Roman poets. The various applications of this concept demonstrated in these four chapters present the study of liberalitas as a useful and productive tool in the investigation of the poetry of this period.

Keywords: Latin
Poetry
Catullus
Virgil
Horace
Tibullus
Propertius
Gift Exchange
Advisor: Dewar, Michael
Non-Abelian Localization and U(1) Chern-Simons Theory

This thesis studies U(1) Chern-Simons theory and its relation to the results of Chris Beasley and Edward Witten (2005). Using the partition function formalism, we are led to compare U(1) Chern-Simons theory as constructed by Manoliu (1998) to the results of Beasley and Witten (2005). This leads to an explicit calculation of the U(1) Chern Simons partition function on a closed Sasakian three-manifold and opens the door to studying rigorous extensions of this theory to more general gauge groups and three-manifold geometries.

Keywords: Chern-Simons Gauge Theory
Sasakian Geometry
Quantum Field Theory
Symplectic Geometry
Advisor: Jeffrey, Lisa
Secure Wavelet-based Coding of Images, and Application to Privacy Protected Video Surveillance

The protection of digital images and video from unauthorized access is important for a number of applications, including privacy protection in video surveillance and digital rights management for consumer applications. However, traditional cryptographic methods are not well suited to digital visual content. Applying standard encryption approaches to the entire content can require significant computational resources due to the large size of the data. Furthermore, digital images and video often need to be manipulated,such as by resizing or transcoding, which traditional encryption would hinder. A number of image and video-specific encryption approaches have been proposed in the literature, but many of the them have significant negative impact on the ability to compress the data, which is a necessary requirement of most imaging systems. In this work, a secure image coder, called Secure Set Partitioning in Hierarchical Trees (SecSPIHT), is proposed. It combines wavelet-based image coding (compression) with efficient encryption. The encryption is applied to a small number of selected bits in the code domain, to achieve complete confidentiality of all the content while having no negative impact on compression performance. The output of the system is a secure code that cannot be decrypted and decoded without the provision of a secret key. It has superior rate-distortion performance compared to JPEG and JPEG2000, and the bit-rate can be easily scaled via a simple truncation operation. The computational overhead of the encryption operation is very low, typically requiring less than 1% of the coded image data to be encrypted. A related secure object-based coding approach is also presented. Called Secure Shape and Texture Set Partitioning in Hierarchical Trees (SecST-SPIHT), it codes and encrypts arbitrarily-shaped visual objects. A privacy protection system for video surveillance is proposed, using SecST-SPIHT to protect private data, such as face and body images appearing in surveillance footage. During normal operation of the system, the private data objects are protected via SecST-SPIHT. If an incident occurs that requires access to the data (e.g., for investigation), a designated authority must release the key. This is superior to other methods of privacy protection which irreversibly blur or mask the private data.

Keywords: wavelet
image coding
encryption
security
privacy
video coding
secure image coding
secure object coding
Advisor: Plataniotis, Konstantinos N.