VictorJuiz/thesis huggingface dataset:
De Rham Theory and Semialgebraic Geometry

This thesis consists of six chapters and deals with four topics related to De Rham Theory on semialgebraic sets. The first topic deals with L-infinity cohomology on semialgebraic sets. We introduce smooth L-infinity differential forms on a singular (semialgebraic) space X in Rn. Roughly speaking, a smooth L-infinity differential form is a collection of smooth forms on disjoint smooth subsets (stratification) of X with matching tangential components on the adjacent strata and of bounded size (in the metric induced from Rn). We identify the singular homology of X as the homology of the chain complex generated by semialgebraic singular simplices, i.e. continuous semialgebraic maps from the standard simplex into X. Singular cohomology of X is defined as the homology of the Hom dual to the chain complex of the singular chains. Finally, we prove a De Rham type theorem establishing a natural isomorphism between the singular cohomology and the cohomology of smooth L-infinity forms. The second topic is a construction of a Lipschitz deformation retraction on a neighborhood of a point in a semialgebraic set with estimates on its derivatives. Such a deformation retraction is the key to the results of the first and the third topics. The third topic is related to Poincare inequality on a semialgebraic set. We study Poincare type Lp inequality for differential forms on a compact semialgebraic subset of Rn for p >> 1. First we derive a local inequality by using a Lipschitz deformation retraction with estimates on its derivatives from the second topic and then we extend it to a global inequality by employing a technique developed in the appendix. As a consequence we obtain an isomorphism between Lp cohomology and singular cohomology of a normal compact semialgebraic set. The final topic is in the appendix. It deals with an explicit proof of Poincare type inequality for differential forms on compact manifolds. We prove the latter inequality by means of a constructive 'globalization' method of a local Poincare inequality on convex sets. The appendix serves as a model case for the results of the third topic in Chapter 5.

Keywords: Semialgebraic geometry
metric invariants
L^p cohomology
Poincare inequality for differential forms
Advisor: Milman, Pierre
A Global Kinase and Phosphatase Interaction Network in the Budding Yeast Reveals Novel Effectors of the Target of Rapamycin (TOR) Pathway

In the budding yeast Saccharomyces cerevisiae, the evolutionarily conserved Target of Rapamycin (TOR) signaling network regulates cell growth in accordance with nutrient and stress conditions. In this work, I present evidence that the TOR complex 1 (TORC1)-interacting proteins Nnk1, Fmp48, Mks1, and Sch9 link TOR to various facets of nitrogen metabolism and mitochondrial function. The Nnk1 kinase controlled nitrogen catabolite repression-sensitive gene expression via Ure2 and Gln3, and physically interacted with the NAD+-linked glutamate dehydrogenase Gdh2 that catalyzes deamination of glutamate to alpha-ketoglutarate and ammonia. In turn, Gdh2 modulated rapamycin sensitivity, was phosphorylated in Nnk1 immune complexes in vitro, and was relocalized to a discrete cytoplasmic focus in response to NNK1 overexpression or respiratory growth. The Fmp48 kinase regulated respiratory function and mitochondrial morphology, while Mks1 linked TORC1 to the mitochondria-to-nucleus retrograde signaling pathway. The Sch9 kinase appeared to act as both an upstream regulator and downstream sensor of mitochondrial function. Loss of Sch9 conferred a respiratory growth defect, a defect in mitochondrial DNA transmission, lower mitochondrial membrane potential, and decreased levels of reactive oxygen species. Conversely, loss of mitochondrial DNA caused loss of Sch9 enrichment at the vacuolar membrane, loss of Sch9 phospho-isoforms, and small cell size suggestive of reduced Sch9 activity. Sch9 also exhibited dynamic relocalization in response to stress, including enrichment at mitochondria under conditions that have previously been shown to induce apoptosis in yeast. Taken together, this work reveals intimate connections between TORC1, nitrogen metabolism, and mitochondrial function, and has implications for the role of TOR in regulating aging, cancer, and other human diseases.

Keywords: Target of Rapamycin
budding yeast
Saccharomyces cerevisiae
yeast
kinase
phosphatase
protein-protein interactions
TOR
nutrients
growth
rapamycin
signaling
network
metabolism
nitrogen catabolite repression
retrograde response
glutamate dehydrogenase
glutamine
glutamate
alpha-ketoglutarate
cell size
aging
lifespan
mitochondria
uncoupled respiration
petite
reactive oxygen species
free radical theory of aging
apoptosis
cancer
glutaminolysis
TORC1
Nnk1
Fmp48
Mks1
Sch9
Gdh2
Ure2
ribosomal protein S6 kinase
S6K
cell biology
molecular biology
Advisor: Tyers, Michael D.
On the Squeezing and Over-squeezing of Photons

Quantum mechanics allows us to use nonclassical states of light to make measurements with a greater precision than comparable classical states. Here an experiment is presented that squeezes the polarization state of three photons. We demonstrate the deep connection that exists between squeezing and entanglement, unifying the squeezed state and multi-photon entangled state approaches to quantum metrology. For the first time we observe the phenomenon of over-squeezing where a system is squeezed to the point that further squeezing leads to a counter-intuitive increase in measurement uncertainty. Quasi-probability distributions on the surface of a Poincaré sphere are the most natural way to represent the topology of our polarization states. Using this representation it is easy to observe the squeezing and over-squeezing behaviour of our photon states. Work is also presented on two different technologies for generating nonclassical states of light. The first is based on the nonlinear process of spontaneous parametric downconversion to produce pairs of photons. With this source up to 200,000 pairs of photons/s have been collected into single-mode fibre, and over 100 double pairs/s have been detected. This downconversion source is suitable for use in a wide variety of multi-qubit quantum information applications. The second source presented is a single-photon source based on semiconductor quantum dots. The single-photon character of the source is verified using a Hanbury Brown-Twiss interferometer.

Keywords: Quantum Optics
Entanglement
Quantum Information
Squeezing
single photon
Metrology
Advisor: Steinberg, Aephraim
Identification of Genes and Pathways Involved in Familial Ovarian Cancer

One of the most important risk factors in ovarian cancer is family history, and two well-studied tumour suppressor genes BRCA1 and BRCA2 have already been identified in “high-risk” families. However, alterations of other genes may also be important for ovarian cancer pathogenesis in individuals with family history of breast/ovarian cancer. In this thesis, I compared the gene expression profiles of tumours from patients with strong and weak family history of breast and/or ovarian cancer to identify genes that may be significant in the subset of patients with ovarian cancer predisposition. Based on this comparison, two genes of interest were selected for further investigations: hCDC4/FBXW7 (F-box and WD repeat domain containing 7) and PRKCZ (protein kinase C zeta). Through mutational analyses I identified one nucleotide alteration within exon 7 of hCDC4; however, overall I found that hCDC4 mutation is a rare event in ovarian tumours. Additional epigenetics analyses revealed that promoter methylation is not a significant mechanism responsible for repression of hCDC4 expression in ovarian cancer. Nevertheless, the variable expression of hCDC4 proteins observed in ovarian tumour tissues by immunohistochemical staining of tissue microarrays suggests that hCDC4 deregulation may potentially be important in a subset of ovarian cancers. Additionally, I observed that expression levels of PRKCZ are higher in ovarian tumours from patients with strong family history compared to patients with weak family history. PRKCZ has previously been shown to be involved in a variety of cellular processes; however its role in ovarian cancer remained elusive. To further understand the role of PRKCZ in ovarian tumourigenesis, including cell viability, cell migration, as well as relevant downstream signaling pathways, I performed functional assays using an in vitro ovarian cancer model. I observed that PRKCZ increases proliferation of the SKOV3 ovarian cancer cell line and participates in EGF-induced chemotaxis. Furthermore, I identified IGF1R (insulin-like growth factor 1 receptor) and ITGB3 (integrin beta 3) as downstream effectors of PRKCZ as expression of these genes is significantly altered when PRKCZ is over-expressed. Given their previously identified associations with familial ovarian cancer, the IGF1 and ITGB3 signaling pathways may therefore represent a possible link between PRKCZ and this disease.

Keywords: ovarian cancer
genetics
Advisor: Andrulis, Irene
Design and Evaluation of a Mobile Phone-based Remote Patient Monitoring System for Heart Failure Management: A Focus on Self-care

Methods to improve self-care and clinical management of heart failure are required, especially in light of the anticipated increase in heart failure prevalence and associated high costs. Remote patient monitoring (RPM) has been shown to improve heart failure outcomes, but the feasibility and efficacy of mobile phone-based RPM systems are still unknown. The main objectives of this research were to investigate the optimal design of a mobile phone-based RPM system, and to determine the effects of the system on self-care, clinical management, and health outcomes. A mobile phone-based RPM system was first developed using a user-centric design process. It was then evaluated with a six-month randomized controlled trial consisting of 100 patients attending a heart function clinic. The quality of life improved only for the intervention group, but both intervention and control groups improved with respect to self-care, heart function, and heart failure prognosis. The clinic was determined to be a confounder. Patients who were enrolled into the clinic for less than six months showed significantly greater improvements (six months is required for patients to stabilize from medication optimization). Therefore, a subgroup analysis using data from the 63 patients who were enrolled into the clinic for over six months at time of recruitment was performed. The results from the subgroup analysis indicated that the RPM system improved self-care, heart function, and heart failure prognosis at statistically significant and clinically meaningful levels. These improvements were found to be a result of enhanced self-care knowledge and practices, as well as enhanced clinical management enabled by the system. No differences in mortality or hospital admissions were found between groups, but the trial was underpowered to detect changes in these outcome measures. In summary, mobile phone-based RPM was found to be a feasible and effective tool to help improve heart failure management and outcomes.

Keywords: patient monitoring
self-care
mobile phone
heart failure
Advisor: Leonard, Kevin
Old Comedy and its Performative Rivals of the Fifth Century

This dissertation analyzes Old Comedy’s generic interaction with its primary performative rivals of the fifth century, tragedy and satyr play. While previous scholarship on this subject is concerned almost exclusively with paratragedy, I examine issues such as Old Comedy’s engagement with satyr play and the frequently unacknowledged evidence for generic interaction in the comic iconography of Attic and South Italian vase-painting. Chapter One analyzes the earliest known intergeneric, comic experiment for which any considerable evidence survives, Cratinus’ fragmentary (and parasatyric) Dionysalexandros. Chapter Two departs briefly from textual evidence and examines the visual record for strategies of intergeneric engagement in the comic iconography of Attic and South Italian vase-painting. Chapter Three signals the beginning of the study’s play-based core and examines the best surviving evidence for cross-generic play in three productions of the Aristophanic corpus. This chapter’s study of Peace (421 BCE) is followed by chapters on Thesmophoriazusae (411 BCE) and Frogs (405 BCE), respectively. My approach, which considers both verbal and visual evidence for comic appropriation, allows for a more comprehensive understanding of the parody of tragedy and satyr play by comic playwrights, whose aggressive adaptation of performative rivals can be seen as central to an ongoing project of defining comedy as an essential polis institution in the latter half of the fifth century.

Keywords: Aristophanes
Greek Comedy
Advisor: Revermann, Martin
Part-based Representation and Editing of 3D Surface Models

The idea that a complex object can be decomposed into simpler parts is fundamental to 3D design, so it is clearly desirable that digital representations of 3D shapes incorporate this part information. While solid modeling techniques based on set-theoretic volumetric composition intrinsically support hierarchical part-based shape descriptions, organic objects such as a human vertebra are more efficiently represented by surface modeling techniques. And although a human observer will easily identify part decompositions in surface models, the homogenous graphs of connected points and edges used in surface representations do not readily support explicit part decompositions. In this thesis, I will develop a part-based representation for 3D surface models. In abstract mathematics, a surface part can be represented as a deformation of a Riemannian manifold. To create a practical implementation, it is necessary to define representations of the 3D part shape and the region on the target surface where the part is to be placed. To represent the part region I will develop the Discrete Exponential Map (DEM), an algorithm which approximates the intrinsic normal coordinates on manifolds. To support arbitrary part shapes I will develop the COILS surface deformation, a robust geometric differential representation of point-sampled surfaces. Based on this part definition, I will then propose the Surface Tree, which makes possible the representation of complex shapes via a procedural, hierarchical composition of surface parts, analogous to the trees used in solid modeling. A major theme throughout the thesis is that part-based approaches have the potential to make surface design interfaces significantly more efficient and expressive. To explore this question and demonstrate the utility of my technical contributions, I present three novel modeling tools: an interactive texture design interface, a drag-and-drop mesh composition tool, and a sketch-based Surface Tree modeling environment. In addition to comparative algorithmic evaluations, and a consideration of representational capabilities, I have evaluated this body of work by publicly distributing my modeling tools. I will close the thesis with a discussion of the extensive feedback provided by users of my drag-and-drop mesh composition tool, called meshmixer. This feedback suggests that part-based approaches have significant benefits for surface modeling.

Keywords: shape modeling
interaction
procedural modeling
3D design
Advisor: Singh, Karan
Moving Patients across Organizations: Exploring the Antecedents of Effective and Efficient Referral Processes

The purpose of this study was to explore what makes the interorganizational referral process effective and efficient from the perspectives of acute care referral senders and post acute care referral receivers. The referral process was conceptualized as the classic communication model involving a sender, receiver, information, a communication channel and contextual factors such as formalization and relationships. The hypotheses proposed that the relationships between each of the variables information usefulness, communication channel richness, and degree of formalization affected each of perceived referral process effectiveness and efficiency through the variable ‘relational coordination’. Key informants who either sent referrals from acute care settings or who received them in post acute care inpatient settings were asked to discuss each variable. These results were combined with those of a literature review to develop questionnaires containing a scale with acceptable Chronbach alpha for each. Surveys were disseminated through networks and associations involved in acute and post acute stroke and hip fracture care and in discharge planning and Long Term Care. Useable responses included 114 surveys from referral senders and 171 from referral recipients. Baron and Kenny’s four step test for mediation was used to test the hypotheses. For senders, each of channel richness (adjR2 = 10% p= 0.001), information usefulness (adjR2 = 16% p= 0.000), and formalization (adjR2 = 10% p= 0.000) were significantly related to perceived effectiveness. For channel richness, the relationship with perceived effectiveness was partially mediated by relational coordination (adjR2 = 19% p= 0.001). This was also the case for the relationship between information usefulness and perceived effectiveness (adjR2 = 0.20; p=000). For receivers, channel richness is related to perceived effectiveness through relational coordination (adjR2 = 12% p= 0.003). This was also the case for information usefulness (adjR2 = 13% p= 0.000). In neither group were any of the variables significantly related to efficiency. We may conclude that in the referral process, channel richness and information usefulness are related to perceived effectiveness for both senders and receivers. These may provide an important return on investment if chosen as an areas for referral process improvement, if accompanied by concurrent investments in relational coordination.

Keywords: Communication
Referral process
Interorganizational
Coordination
Information
Relational coordination
Transitions
Continuum of care
Long term care
Acute care
Post acute care
Referral
Decision making
Organizations
Effectiveness
Performance
Advisor: Lemieux-Charles, Louise
Querying, Exploring and Mining the Extended Document

The evolution of the Web into an interactive medium that encourages active user engagement has ignited a huge increase in the amount, complexity and diversity of available textual data. This evolution forces us to re-evaluate our view of documents as simple pieces of text and of document collections as immutable and isolated. Extended documents published in the context of blogs, micro-blogs, on-line social networks, customer feedback portals, can be associated with a wealth of meta-data in addition to their textual component: tags, links, sentiment, entities mentioned in text, etc. Collections of user-generated documents grow, evolve, co-exist and interact: they are dynamic and integrated. These unique characteristics of modern documents and document collections present us with exciting opportunities for improving the way we interact with them. At the same time, this additional complexity combined with the vast amounts of available textual data present us with formidable computational challenges. In this context, we introduce, study and extensively evaluate an array of effective and efficient solutions for querying, exploring and mining extended documents, dynamic and integrated document collections. For collections of socially annotated extended documents, we present an improved probabilistic search and ranking approach based on our growing understanding of the dynamics of the social annotation process. For extended documents, such as blog posts, associated with entities extracted from text and categorical attributes, we enable their interactive exploration through the efficient computation of strong entity associations. Associated entities are computed for all possible attribute value restrictions of the document collection. For extended documents, such as user reviews, annotated with a numerical rating, we introduce a keyword-query refinement approach. The solution enables the interactive navigation and exploration of large result sets. We extend the skyline query to document streams, such as news articles, associated with categorical attributes and partially ordered domains. The technique incrementally maintains a small set of recent, uniquely interesting extended documents from the stream.Finally, we introduce a solution for the scalable integration of structured data sources into Web search. Queries are analysed in order to determine what structured data, if any, should be used to augment Web search results.

Keywords: textual data
data management
Advisor: Koudas, Nick
Use of Modified U1snRNAs to Inhibit HIV-1 Replication

The rapid evolutionary rate of HIV-1 has lead to the emergence of multi-drug resistant variants, emphasizing the need for novel inhibitory methods. One such method could be based upon inhibiting viral gene expression through disruption of HIV-1 RNA processing. A means of accomplishing this goal is through use of modified U1snRNA variants that target highly conserved regions of HIV-1 at its terminal exon and prevent 3’ end formation. The modification consists of a 10-nucleotide substitution at the 5’ end complementary to the conserved HIV-1 regions. When modified U1snRNA targeted to HIV-1 were cotransfected with replication deficient HIV-1 proviruses, western blot indicated a specific and significant reduction in the level of viral protein production (p24 and gp120), while U1 constructs that lacked complementary sequences had no effect on HIV-1 protein expression. To further investigate targeted U1snRNA inhibitory effects on HIV-1, efforts are currently underway to determine if this approach has the ability to suppress protein expression in a gene therapeutic model. To date, suppression of viral protein production has reached 50% when tested with a moderately inhibitory U1snRNA. If shown to be effective, such an inhibition would be increased with the use of combinatory modified U1snRNA constructs producing a synergistic effect.

Keywords: HIV-1 inhibition
U1snRNA
mRNA maturation
Advisor: Cochrane, Alan