VictorJuiz/thesis huggingface dataset:
Molecular Mechanisms Regulating Fate Determination of Cerebral Cortex Precursors

During development of the mammalian nervous system, neural stem cells generate neurons first and glia second, thereby allowing the initial establishment of neuronal circuitry, and subsequent matching of glial numbers and position to that circuitry. Multiple molecular mechanisms act in concert to control neural precursor expansion prior to neurogenesis, and to allow for an exponential generation of neurons while ensuring the maintenance of sufficient precursors to produce later-born neurons, glial cells and adult neural stem cells. Throughout cortical development, these processes are regulated in part by the precursors’ environment as well as intrinsic changes in precursors and their modes of division, which regulate the fate of daughter cells and the balance between self-renewal and differentiation. In the first part of this thesis, the protein tyrosine phosphatase SHP-2 was identified as a novel signaling protein that regulates the neurogenic to gliogenic switch by potentiating neurogenic signals and suppressing gliogenic signals until the appropriate developmental time point for astrogenesis, providing one mechanism whereby precursors integrate conflicting environmental cues. A Noonan Syndrome (NS)-associated activated SHP-2 mutation causes perturbations in neural cell genesis, which may contribute to the mild mental retardation and learning disabilities observed in NS patients. In the second part of this thesis, a novel Rho-regulatory pathway which includes the Rho-GEF Lfc and its negative regulator Tctex-1 were also found to regulate neurogenesis, potentially by directing mitotic spindle orientation during precursor divisions, thereby regulating the symmetric and asymmetric nature of radial precursor divisions.

Keywords: neural stem cells
SHP-2
Lfc
Tctex-1
neurogenesis
gliogenesis
symmetric divisions
asymmetric divisions
Advisor: Miller, Freda
Kaplan, David
D-brane Chan-Paton Factors and Orientifolds

In this thesis, we mainly study the structure of D 9-brane Chan-Paton factors in Type II orientifold [special characters omitted] theories. An explicit structure is found through a thorough and systematic derivation. For this purpose, we give a complete analysis of the worldsheet parity square action for all p-q open strings (i.e., the strings starting from Dp-branes and ending on Dq-branes), which is an extension of Gimon-Polchinski's work on the parity square action for p-q strings with p - q even. We also formulate the rules for computing the scattering amplitudes of open strings ending on D-branes. These are important to build phenomenological models in string theory. As an application to the mathematical aspects of string theory, we confirm the proposal that the D-brane charges in Type II orientifolds are classified by the KR-theory groups. All these results will appear in our paper [1]. We also show some preliminary results on the B-type D-branes in the orientifolds of linear sigma models. A typical linear sigma model has both a geometric phase and a Landau-Ginzberg phase over its K¨ahler moduli space. The B-type D-branes are described by suitable categories in a linear sigma model and its phases. The orientifold projection induces parity mappings on the various categories. By looking at the transportation of invariant branes in the moduli space, we find the relations among the parity mappings of different phases in the quintic model.

Keywords: D-brane
Orientifold
Advisor: Hori, Kentaro
Monitoring the Generation and Execution of Optimal Plans

In dynamic domains, the state of the world may change in unexpected ways during the generation or execution of plans. Regardless of the cause of such changes, they raise the question of whether they interfere with ongoing planning efforts. Unexpected changes during plan generation may invalidate the current planning effort, while discrepancies between expected and actual state of the world during execution may render the executing plan invalid or sub-optimal, with respect to previously identified planning objectives. In this thesis we develop a general monitoring technique that can be used during both plan generation and plan execution to determine the relevance of unexpected changes and which supports recovery. This way, time intensive replanning from scratch in the new and unexpected state can often be avoided. The technique can be applied to a variety of objectives, including monitoring the optimality of plans, rather then just their validity. Intuitively, the technique operates in two steps: during planning the plan is annotated with additional information that is relevant to the achievement of the objective; then, when an unexpected change occurs, this information is used to determine the relevance of the discrepancy with respect to the objective. We substantiate the claim of broad applicability of this relevance-based technique by developing four concrete applications: generating optimal plans despite frequent, unexpected changes to the initial state of the world, monitoring plan optimality during execution, monitoring the execution of near-optimal policies in stochastic domains, and monitoring the generation and execution of plans with procedural hard constraints. In all cases, we use the formal notion of regression to identify what is relevant for achieving the objective. We prove the soundness of these concrete approaches and present empirical results demonstrating that in some contexts orders of magnitude speed-ups can be gained by our technique compared to replanning from scratch.

Keywords: artificial intelligence
automated planning
monitoring
execution
Advisor: McIlraith, Sheila Ann
Sonorant Relationships in Two Varieties of Sardinian

Phonological interactions among sonorant sounds, and between sonorants and obstruents, are widespread in Romance languages. In this dissertation, I examine in detail such interactions in two dialects of Sardinian (Italo-Romance), Campidanese and Nuorese, showing that sonorant relationships differentiate the synchronic grammars of these dialects. The synchronic patterning of nasals and liquids, and how these two sonorant subclasses interact with obstruents, is significantly different between the two dialects. In particular, nasals trigger phonological nasalization of vowels and of the rhotic in Campidanese but not in Nuorese. The arguments for a phonological analysis of vowel nasalization in Campidanese are reviewed, expanded, and tested against an acoustic study. The historical traces of interaction between /n/ and /r/ in this dialect are linked to the synchronic rhotic nasalization process highlighted by an acoustic study of fieldwork data. In Nuorese, on the other hand, /n/ does not initiate phonological nasalization either of vowels or of the rhotic, and it is the target of total assimilation when followed by any segments but an oral stop. Nasals in the two dialects thus pattern in two very different ways phonologically: nasals are process triggers in Campidanese and process targets in Nuorese. The rhotic also shows distinct patterns in the two dialects, interacting with /n/ in Campidanese and with /s/ in Nuorese. The two dialects, with those asymmetries, thus display complementary sonorant patterns. I argue that a model able to capture such complementarity of patterns is the theory of the contrastive hierarchy (Dresher 2008). The Campidanese and Nuorese sonorant patterns, so radically different, lead one to question whether sonorants form a homogeneous phonological class cross-linguistically. Campidanese and Nuorese show that the make-up of such a class appears to be language-specific. Since the sonorant class is a universal class of sounds, its heterogeneity, in turn, questions the notion of phonological classhood at large. The data and the analysis presented in this dissertation thus feed the debate around phonological classhood. According to the theoretical model adopted in the present dissertation, the language-specific make-up of a class of sounds is all that can be labeled a ‘phonological’ class. Classes of sounds can be described in phonetic terms, but classes phonetically defined do not necessarily amount to phonological classes.

Keywords: Phonology
Phonetics
Sonorants
Nasalization
Romance
Sardinian
Advisor: Rice, Keren
A Functional Role for Doscoidin Domain Receptor 1 (Ddr1) in the Regulation of Inflmmation and Fibrosis During Atherosclerotic Plaque Development

Collagens are abundant components of the extracellular matrix in the atherosclerotic plaque. In addition to contributing to lesion volume and mechanical stability, collagens can influence the behavior of macrophages and smooth muscle cells (SMCs) and have profound effects on both inflammation and fibrosis during lesion development. The aim of this thesis was to define a functional role for the discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine kinase, in murine models of atherogenesis. In our first study, using Ddr1+/+;Ldlr-/- and Ddr1-/-;Ldlr-/- mice fed a high fat diet, we identified DDR1 as a novel positive regulator of atherogenesis. Targeted deletion of DDR1 attenuated atherosclerotic plaque development by limiting inflammation and accelerating matrix accumulation and resulted in the formation of macrophage poor, matrix rich lesions. In the second study, we used bone marrow transplantation to generate chimeric mice with a deficiency of DDR1 in bone marrow derived cells and reveal a central role for macrophage DDR1 in atherogenesis. Deficiency of DDR1 in bone marrow derived cells reduced lesion size by limiting macrophage accumulation in the developing plaque. Moreover using BrdU pulse labeling, we demonstrated reduced monocyte recruitment into the early fatty streak lesions of Ddr1-/-;Ldlr-/- mice. In our third study, we again utilized bone marrow transplantation to generate mice with deficiency of DDR1 in the host derived tissues such as the vessel wall and uncovered a distinct role for DDR1 expressed on resident vessel wall smooth muscle cells in the regulation of matrix accumulation and fibrous cap formation during atherogenesis. Deficiency of DDR1 in vessel wall cells resulted in robust accumulation of collagen and elastin and resulted in the formation of larger atherosclerotic plaques, with thick fibrous caps. Taken together, these studies support a critical role for DDR1 in the development of the atherosclerotic plaque. We demonstrate that DDR1 exerts distinct and opposing effects on lesion size by regulating both monocyte recruitment and matrix accumulation. These studies underscore the importance of collagen signaling during atherogenesis, and identify DDR1 as a key transducer; providing signals that regulate both inflammation and fibrosis during atherogenesis.

Keywords: atherosclerosis
collagen
macrophages
vascular smooth muscle cells
discoidin domain receptor
vascular biology
Advisor: Bendeck, Michelle
Application and Manipulation of Bipartite and Multipartite Entangled States

The phenomenon of quantum entanglement is a fundamental feature of quantum mechanics which, as a counterintuitive and inherently ”quantum” phenomenon (with no classical analogue) has been the subject of much study, especially in quantum information theory. One fruitful approach to the description of entanglement has been in its operational description - that is, in the consideration of what can be achieved using entangled states under certain restrictions, typically the regime of local operations and classical communications. We present results here related to the operational characterisation of entanglement in the resource model, in both bipartite and multipartite cases. First, we consider the conversion between pure bipartite entangled states in terms of an often-ignored resource - the classical communication cost. Using prior results for more specific conversions, we derive lower bounds on this cost (and the related quantity of the conversion inefficiency) for general bipartite pure states. We also consider pure-state conversions of multipartite entanglement, in particular the class of protocols in which multipartite states are converted to states shared between fewer parties. We have found a previously-unconsidered variety of such conversions, in which the target state of the conversion is a state shared between a random subset of the parties. We find that when such post-selection of parties in the protocol is permitted allows for a wider variety of achievable target states; certain states which can not be reliably obtained between predetermined parties (even some where the probability of doing so is arbitrarily small) can be obtained between random parties. We consider a variety of states in which this phenomenon occurs, as well as bounds on such protocols can achieve. Finally we consider a practical use of entanglement as a resource, in an experimental implementation of a multipartite QKD protocol. This is based on the tripartite GHZ entangled state, but can be implemented using only bipartite entanglement. We adapt existing QKD results for both the bipartite and multipartite case to derive a secure key rate for this implementation, taking into account the ways in which it differs from the idealised theoretical case.

Keywords: Quantum Information
Entanglement
Advisor: Lo, Hoi-Kwong
Extensible Networked-storage Virtualization with Metadata Management at the Block Level

Increased scaling costs and lack of desired features is leading to the evolution of high-performance storage systems from centralized architectures and specialized hardware to decentralized, commodity storage clusters. Existing systems try to address storage cost and management issues at the filesystem level. Besides dictating the use of a specific filesystem, however, this approach leads to increased complexity and load imbalance towards the file-server side, which in turn increase costs to scale. In this thesis, we examine these problems at the block-level. This approach has several advantages, such as transparency, cost-efficiency, better resource utilization, simplicity and easier management. First of all, we explore the mechanisms, the merits, and the overheads associated with advanced metadata-intensive functionality at the block level, by providing versioning at the block level. We find that block-level versioning has low overhead and offers transparency and simplicity advantages over filesystem-based approaches. Secondly, we study the problem of providing extensibility required by diverse and changing application needs that may use a single storage system. We provide support for (i)adding desired functions as block-level extensions, and (ii)flexibly combining them to create modular I/O hierarchies. In this direction, we design, implement and evaluate an extensible block-level storage virtualization framework, Violin, with support for metadata-intensive functions. Extending Violin we build Orchestra, an extensible framework for cluster storage virtualization and scalable storage sharing at the block-level. We show that Orchestra's enhanced block interface can substantially simplify the design of higher-level storage services, such as cluster filesystems, while being scalable. Finally, we consider the problem of consistency and availability in decentralized commodity clusters. We propose RIBD, a novel storage system that provides support for handling both data and metadata consistency issues at the block layer. RIBD uses the notion of consistency intervals (CIs) to provide fine-grain consistency semantics on sequences of block level operations by means of a lightweight transactional mechanism. RIBD relies on Orchestra's virtualization mechanisms and uses a roll-back recovery mechanism based on low-overhead block-level versioning. We evaluate RIBD on a cluster of 24 nodes, and find that it performs comparably to two popular cluster filesystems, PVFS and GFS, while offering stronger consistency guarantees.

Keywords: Operating Systems
Computer Systems
Distributed Systems
File Systems
Cluster Storage
Block-level Versioning
Storage Virtualization
Commodity Clusters
Block-level Storage
Disk Storage
Shared Virtual Disk
Extensible Virtual Storage
Consistency
Availability
Advisor: Bilas, Angelos
Ptolemy in Philosophical Context: A Study of the Relationships Between Physics, Mathematics, and Theology

This study situates Ptolemy’s philosophy within the second-century milieu of Middle Platonism and the nascent Aristotelian commentary tradition. It focuses on Ptolemy’s adaptation and application of Aristotle’s tripartite division of theoretical philosophy into the physical, mathematical, and theological. In Almagest 1.1, Ptolemy defines these three sciences, describes their relations and objects of study, and addresses their epistemic success. According to Ptolemy, physics and theology are conjectural, and mathematics alone yields knowledge. This claim is unprecedented in the history of ancient Greek philosophy. Ptolemy substantiates this claim by constructing and employing a scientific method consistent with it. In Almagest 1.1, after defining the theoretical sciences, Ptolemy adds that, while theology and physics are conjectural, mathematics can make a good guess at the nature of theological objects and contribute significantly to the study of physics. He puts this claim into practice in the remainder of his corpus by applying mathematics to theology and physics in order to produce results in these fields. After the introductory chapter, I present Ptolemy’s philosophy and practice of the three theoretical sciences. In Chapter 2, I examine how and why Ptolemy defines the sciences in Almagest 1.1. In Chapter 3, I further analyze how Ptolemy defines mathematical objects, how he describes the relationships between the tools and branches of mathematics, and whether he demonstrates in the Harmonics and Almagest that he believed mathematics yields sure and incontrovertible knowledge, as he claims in Almagest 1.1. In Chapter 4, I present Ptolemy’s natural philosophy. While in Chapter 2 I discuss his element theory, in Chapter 4 I focus on his physics of composite bodies: astrology, psychology, and cosmology as conveyed in the Tetrabiblos, On the Kritêrion, Harmonics, and Planetary Hypotheses. I do not devote a chapter to theology, as Ptolemy refers to this science only once in his corpus. Therefore, I limit my analysis of his definition and practice of theology to Chapter 2. In the concluding chapter, I discuss Ptolemy’s ethical motivation for studying mathematics. What emerges from this dissertation is a portrait of Ptolemy’s philosophy of science and the scientific method he employs consistently in his texts.

Keywords: History of Science
Ptolemy
Ancient Science
Ancient Philosophy
Advisor: Jones, Alexander
Identification and Functional Characterization of a Novel Activation Cascade of the KLK Family in Seminal Plasma

Proteolytic processes are often mediated by highly orchestrated cascades, through which protease enzymes function coordinately to ensure a stepwise activation. This thesis presents experimental data which supports and complements the previously postulated mechanism of KLK (kallikrein-related protease) activation through proteolytic cascades. Further examination of the seminal KLK cascade has revealed several of its key (patho) physiological roles in human reproductive system. Multiple members of the seminal KLK cascade, in particular KLK14, were shown to play a pivotal role in regulating semen liquefaction. The cascade was further shown to be tightly regulated through a series of highly orchestrated feedback loops, to prevent deleterious effects due to aberrant protease activation. Accordingly, a strong association was observed between the expression level of several seminal KLKs, delayed liquefaction, and other markers of semen quality, including semen hyperviscosity. Furthermore, a strong association was found between delayed liquefaction and abnormal sperm motility. Therefore, dysregulated KLK expressions and/or activities were proposed as an underlying cause of male subfertility. Finally, this thesis has provided initial insights into a novel potential function of multiple members of the seminal KLK cascade in activation of the key immune-deviating agent, TGFβ1, in seminal plasma. TGFβ1 activation is postulated to be mediated directly through complete fragmentation or indirectly through partial cleavage and conformational changes of the LAP propeptide motif of the latent TGFβ1. KLK- mediate proteolytic cleavage of the TGFβ1 binding protein, LTBP1, is also suggested as a potential physiological mechanism for release of the membrane-bound latent TGFβ1. Overall, the data provided here may suggest a common regulatory mechanism, involved co-temporally in the two key processes of semen liquefaction and immune-suppression. This might be critical in protecting motile sperms following their release from semen coagulum. Understanding KLK-mediated proteolytic events in seminal plasma can shed light not only on the physiological role of this family of enzymes, but also on some of causes of male subfertility. Accordingly, therapeutic induction of this cascade may be utilized to supplement the current clinical treatment of male subfertility. Conversely, targeted inhibition of key components of the cascade may have potential pharmaceutical utility as a novel topical contraceptive strategy.

Keywords: Proteolytic Cascade
kallikrein-related peptidases
Advisor: Diamandis, Eleftherios P.
Influencing Factors on Methadone Pharmacology: Impact on Satisfaction with Methadone Maintenance Treatment

The methadone maintenance treatment population suffers from high rates of comorbid psychiatric and substance use disorders. Despite a more than 40-year treatment history, not all patients are satisfied with methadone treatment and more than half of the patients complain of significant inter-dose withdrawal at least some of the time. The objectives of this research were to investigate the pharmacological response to methadone under the influence of comorbid major depressive disorder and smoking; and to identify factors other than physical withdrawal symptoms that can differentiate patients based on their complaints of dissatisfaction with treatment. In Study 1, seven depressed methadone maintenance patients experienced more opioid withdrawal symptomatology over a 24-hour methadone-dosing interval than 10 nondepressed methadone patients. Depression severity was significantly correlated with trough opioid withdrawal severity. This suggests that depression or depressive symptoms are related to reported opioid withdrawal. In Study 2, many factors other than physical opioid withdrawal symptoms were able to differentiate patients who were satisfied with treatment (holders, n=25), partially satisfied with treatment (partial holders, n=35), and not satisfied with treatment(nonholders, n=30). Results suggested that these patient satisfaction groups cluster differently depending on physical opioid withdrawal, mood, psychological distress, and personality. Nonholders experienced more physical withdrawal symptoms, craving for opioids, and negative drug effects. Holders had less psychological distress and experienced less negative mood states than the other groups. Partial holders had less agreeable personalities compared to patients in the other groups. In Study 3, opioid and nicotine withdrawal symptoms and effects were measured in 40 methadone-maintained patients who were current smokers during trough and peak methadone effects, both pre and post-nicotine administration. Cigarette smoking enhanced opioid withdrawal suppression during the peak methadone condition, methadone attenuated nicotine withdrawal, and methadone and nicotine shared many of the same main effects, suggesting that smoking and methadone effects may be inseparable dimensions. In summary, the results of these studies suggest that in addition to physical symptoms, mood related factors are important to opioid withdrawal perception and that the mood factors and drug interactions can impact on a patient’s perception of satisfaction with methadone treatment.

Keywords: Methadone Maintenance Treatment
Depression
Methadone-Nicotine Interaction
Opioid Withdrawal
Advisor: Sproule, Beth