VictorJuiz/thesis huggingface dataset:
Novel Mechanisms of Transcriptional Repression by the Paired-like Homeodomain Transcription Factor Goosecoid

Gastrulation is the process by which the three germ layers are generated during vertebrate development. Nodal ligands, which form a subgroup of the Transforming Growth Factor β (TGFβ) superfamily, regulate the expression several transcription factors implicated in gastrulation. Among these are the paired-like homeodomain transcription factors Goosecoid (Gsc) and Mixl1. At the molecular level, Gsc has been described to function as a transcriptional repressor by directly binding to paired homedomain binding sites on target promoters. Here, I describe a novel mechanism of transcriptional repression by Gsc. Using a molecular and embryological approach, I demonstrate that the forkhead transcription factor Foxh1, a major transducer of Nodal signaling, associates with Gsc which in turn recruits histone deacetylases to negatively regulate Mixl1 expression during early mouse development. Post-translational modification of transcription factors by SUMO proteins represents an important mechanism through which their activity is controlled. Here, I also demonstrate that Gsc is sumoylated in mammalian cells by members of the PIAS family of proteins and this modification potentiates the repressive activity of Gsc on direct targets such as the Xbra and Gsc promoters, but not on indirect targets such as Mixl1. Taken together, work presented in this thesis describes two novel mechanisms of transcriptional repression by Gsc.

Keywords: Foxh1
Goosecoid
Sumoylation
Transcription
Mixl1
Smads
TGF-beta
Advisor: Attisano, Liliana
Planar Lightwave Circuits Employing Coupled Waveguides in Aluminum Gallium Arsenide

This dissertation addresses three research challenges in planar lightwave circuit (PLC) optical signal processing. 1. Dynamic localization, a relatively new class of quantum phenomena, has not been demonstrated in any system to date. To address this challenge, the quantum system was mapped to the optical domain using a set of curved, coupled PLC waveguides in aluminum gallium arsenide (AlGaAs). The devices demonstrated, for the first time, exact dynamic localization in any system. These experiments motivate further mappings of quantum phenomena in the optical domain, leading toward the design of novel optical signal processing devices using these quantum-analog effects. 2. The PLC microresonator promises to reduce PLC device size and increase optical signal processing functionality. Microresonators in a parallel cascaded configuration, called "side coupled integrated spaced sequence of resonators" (SCISSORs), could offer very interesting dispersion compensation abilities, if a sufficient number of rings is present to produce fully formed "Bragg" gaps. To date, a SCISSOR with only three rings has been reported in a high-index material system. In this work, one, two, four and eight-ring SCISSORs were fabricated in AlGaAs. The eight-ring SCISSOR succeeded in producing fully formed Bragg peaks, and offers a platform to study interesting linear and nonlinear phenomena such as dispersion compensators and gap solitons. 3. PLCs are ideal candidates to satisfy the projected performance requirements of future microchip interconnects. In addition to data routing, these PLCs must provide over 100-bit switchable delays operating at ~ 1 Tbit/s. To date, no low loss optical device has met these requirements. To address this challenge, an ultrafast, low loss, switchable optically controllable delay line was fabricated in AlGaAs, capable of delaying 126 bits, with a bit-period of 1.5 ps. This successful demonstrator offers a practical solution for the incorporation of optics with microelectronics systems. The three aforementioned projects all employ, in their unique way, the coupling of light between PLC waveguides in AlGaAs. This central theme is explored in this dissertation in both its two- and multi-waveguide embodiments.

Keywords: Planar Lightwave Circuits
optical waveguides
optical switching
microresonators
dynamic localization
optical delay
Advisor: Aitchison, J. Stewart
Precoder Designs for Receivers with Channel Estimators in Fading Channels

Diversity transmission is an effective technique to combat fading channels and this thesis introduces two main ideas. Firstly, a novel precoding technique is proposed to achieve diversity transmission and improve bit error rate (BER) performance over the existing linear constellation precoding (LCP) techniques. Experimental and theoretical results are presented to show that the proposed precoding schemes can outperform the existing LCP schemes in various fading channels and additive white Gaussian noise channels. Secondly, an interleaving technique to further improve the BER performance is proposed. The proposed diversity transmission techniques are implemented for both single-carrier and orthogonal frequency division multiplexing (OFDM) systems. The second part of the thesis focuses on the pairwise error probability analysis of the proposed and LCP schemes when receivers have imperfect channel state information (CSI). The BER performance of the proposed precoding and interleaver scheme are investigated in OFDM systems with minimum mean square error channel estimators and single-carrier systems with basis expansion model based channel estimators. It is demonstrated that while precoding schemes designed for receivers with perfect CSI yield near-optimum BER performance in the former system, the proposed phase-shift keying based precoding schemes perform well in the latter system. In both cases, the proposed precoding scheme, combined with the novel interleaving technique, outperforms the existing LCP schemes.

Keywords: orthogonal frequency division multiplexing
block precoder design
interleaver design
fading channel estimation
Advisor: Pasupathy, Subbarayan
Plataniotis, Konstantinos N.
Examination of the Role of Dopamine D3 Receptors in Behavioural Sensitization to Ethanol

Dopamine D3 receptors (D3Rs) have been implicated in mediating behavioural sensitization to various drugs of abuse, but their role in ethanol (EtOH) sensitization has not been directly examined. Neil Richtand proposed a role for D3Rs in the modulation of sensitization by acting as an inhibitor of D1/D2 receptor-mediated behaviours, and several reports suggest D3Rs up-regulate in response to chronic drugs of abuse. In separate experiments, we examined EtOH sensitization in D3R knockout (KO) as well as in D1R and D2R KO mice. We also examined amphetamine sensitization in D3R KOs compared to wild type mice. We challenged C57Bl/6 and DBA/2 mice with a D3R agonist (PD128907) and antagonist (U99194A) to examine how acute and chronic D3R activation and inactivation may affect the induction and expression of EtOH sensitization. We investigated D1/D3R interactions in sensitized and control mice and examined whether EtOH sensitization leads to changes in D3R binding using [125I]-7-OH-PIPAT autoradiography. Results showed that D3R KOs, were resistant to EtOH but not to amphetamine sensitization. Chronic but not acute D3R blockade with U99194A inhibited the induction, whereas acute D3R activation with PD128907 attenuated the expression of EtOH sensitization. In our D1/D3R interaction study we observed that although PD128907 attenuated D1 agonist-induced hyperactivity with SKF81297, this effect was the same in sensitized and control animals, even though sensitized mice were more responsive to PD128907 than controls. This enhanced response, which suggests a functional up-regulation of D3Rs, was not accompanied by changes in D3R binding as indicated by autoradiography, and could mean that functional changes in the D3R associated with EtOH sensitization occur elsewhere than at the level of the membrane-bound receptor. Taken together, these results suggest a modulatory role for the D3R in EtOH but not amphetamine sensitization, where D3R activation attenuates the expression and D3R blockade prevents the induction of EtOH sensitization. These results are important because a better understanding of the role of the D3R in EtOH sensitization may help not only to identify some of the underlying neural mechanisms of sensitization, but also help in the identification of treatment strategies for patients that may be susceptible to alcohol abuse.

Keywords: Behavioural Neuroscience
Neuropharmacology
Dopamine D3 Receptors
Behavioural Sensitization
Ethanol
Dopamine Receptor Knockout Mice
Advisor: Nobrega, José
The Physico-chemical Nature of the Chemical Bond: Valence Bonding and the Path of Physico-chemical Emergence

Through the development of physical chemistry and chemical physics over the late-nineteenth and early-twentieth centuries, the relationship between physics and chemistry changed to create a broad interdisciplinary framework in which chemists and physicists could make contributions to problems of common value. It is here argued that evolving disciplinary factors such as physical and chemical responses to the atomic hypothesis, the nature of disciplinary formation in Germany and the United States, the reception of quantum mechanics within physics and chemistry, and the application of quantum mechanics to the problem of chemical bonding by physicists and chemists, formed the chemical bond into a physico-chemical theory. In the late nineteenth-century context of early physical chemistry, the chemical bond was known as a physical link between atoms, which could not be studied by chemical means because of the lack of an adequate atomistic framework. Both chemists and physicists broadly accepted the atomistic hypothesis following the discovery of the electron at the turn of the twentieth century, which afforded theoretical study of chemical bonding. Between 1916 and 1919, Gilbert N. Lewis and Irving Langmuir proposed the valence bond to be a pair of electrons shared between two atoms, within the context of a cubic model of the atom. However, the lack of a physical mechanism for the shared electron pair prevented the formation of a fully physico-chemical view of bonding. In 1927, physicists Walter Heitler and Fritz London showed the stability of the valence bond was caused by the wave mechanical phenomenon of resonance. Chemist Linus Pauling extended their treatment of the valence bond to a theory of structural chemistry in The Nature of the Chemical Bond. His synthesis of the physical and chemical views, his value as a physico-chemical researcher during the 1930s, and the research of his contemporaries John Slater and Robert Mulliken show that a true physico-chemical blend was only realized within the amorphous discipline of chemical physics. Finally, it is seen that this interdisciplinarity of chemical bonding and its supporting framework force a reevaluation of the reductionist criteria, and a re-definition of the chemical bond as a physico-chemical work.

Keywords: History of Science
History of Chemistry
Chemical Bond
Valence Bond
Linus Pauling
Reductionism
Interdisciplinarity
quantum chemistry
physical chemistry
chemical physics
Advisor: Levere, Trevor
The Cellular and Molecular Properties of Flavinoids in Prostate Cancer Chemoprevention

Flavonoids are a large class of dietary polyphenols that have emerged as candidate agents for chemoprevention in prostate cancer. Despite the large number of known flavonoids (over 9000), only a few have been studied in prostate cancer to date. The work presented in this thesis describes the identification of novel anti-proliferative flavonoids, their molecular effects on cell cycle and related proliferation and survival pathways, and their chemopreventive properties in a murine model of prostate carcinogenesis. We identified several novel flavonoids with potent anti-proliferative effects in human prostate cancer cells in vitro. Non-prostate cell lines were generally resistant to the effect of these flavonoids. Two of the most potent flavonoids identified, 2,2-dihydroxychalcone (DHC) and fisetin, induced S and G2 phase cell cycle arrest in LNCaP and PC3 prostate cancer cells. Gene expression studies employing oligonucleotide microarray demonstrated profound down-regulation in gene expression of 75 key cell cycle (predominantly G2 and M phase) genes by DHC and fisetin, and the enhanced expression of 50 stress-response genes with important roles in cell proliferation and survival. DHC and fisetin induced apoptosis, but not accelerated senescence, in prostate cancer cells. The chemopreventive effect of 4 flavonoids identified from the in vitro studies was examined in an autochthonous murine model of prostate cancer (TRAMP). Mice were administered diets supplemented with 1% DHC, 1% fisetin or a combination of flavonoids (0.25% DHC, 0.25% fisetin, 0.25% quercetin, 0.25% luteolin) for 32 weeks. We demonstrated a significant reduction in genitourinary weight, and a reduction in prostate cancer grade in mice administered 1% DHC and combination diets. Flavonoid supplementation was, however, associated with gastrointestinal toxicity in some mice. Liquid chromatography-mass spectrometry demonstrated the accumulation of high levels of flavonoid in the prostates of TRAMP mice. These findings lay the foundation for further studies of flavonoids in clinical chemoprevention trials.

Keywords: Flavonoids
Prostate Cancer
Cell cycle
Apoptosis
Senescence
TRAMP
Microarray
Diet
Advisor: Klotz, Laurence
Propagation of Shear Waves Generated by a Finite-amplitude Ultrasound Radiation Force in a Viscoelastic Medium

A primary purpose of elasticity imaging, commonly known as elastography, is to extract the viscoelastic properties of a medium (including soft tissue) from the displacement caused by a stress field. Dynamic elastography methods that use the acoustic radiation force of ultrasound have several advantages, such as, non-invasiveness, low cost, and ability to produce a highly localized force field. A method for remotely generating localized low frequency shear waves in soft tissue is investigated, by using the modulated radiation force resulting from two intersecting quasi-CW confocal ultrasound beams of slightly different frequencies. In contrast to most radiation force-based methods previously presented, such shear waves are narrowband rather than broadband. As they propagate within a viscoelastic medium, different frequency-dependent effects will not significantly affect their spectrum, thereby providing a means for measuring the shear attenuation and speed as a function of frequency. Furthermore, to improve the detection signal-to-noise-ratio (SNR), increased acoustic pressure conditions may be needed, causing higher harmonics to be generated due to nonlinear propagation effects. Shear-wave propagation at harmonic modulation frequencies does not appear to have been previously discussed in the elastography literature. The properties of the narrowband shear wave propagation in soft tissue are studied by using the Voigt viscoelastic model and Green’s functions. In particular, the manner in which the characteristics of the viscoelastic medium affect their evolution under both low-amplitude (linear) and high-amplitude (nonlinear) source excitation and conditions that conform to human safety standards. It is shown that an exact solution of the viscoelastic Green’s function is needed to properly represent the propagation in higher-viscosity media, such as soft tissue, at frequencies much beyond a few hundred hertz. Methods for estimating the shear modulus and viscosity in viscoelastic media are developed based on both the fundamental and harmonic shear components.

Keywords: elastography
radiation force
harmonic shear waves
modulation frequency
Advisor: Cobbold, Richard
Architecture Alternatives for Time-interleaved and Input-feedforward Delta-Sigma Modulators

This thesis strives to enhance the performance of delta-sigma modulators in two areas: increasing their speed and enabling their operation in a low voltage environment. Parallelism based on time-interleaving can be used to increase the speed of delta-sigma modulators. A novel single-path time-interleaved architecture is derived and analyzed. Finite opamp gain and bandwidth result in a mismatch between the noise transfer functions of the internal quantizers which degrades the performance of the new modulator. Two techniques are presented to mitigate the mismatch problem: a hybrid topology where the first stage uses multiple integrators while the rest of the modulator uses a single path of integrators and a digital calibration method. The input-feedforward technique removes the input-signal component from the internal nodes of delta-sigma modulators. The removal of the signal component reduces the signal swing and distortion requirements for the opamps. These characteristics enable the reliable implementation of delta-sigma modulators in modern CMOS technology. Two implementation issues for modulators with input-feedforward are considered. First, the drawback of the analog adder at the quantizer input is identified and the capacitive input feedforward technique is introduced to eliminate the adder. Second, the double sampled input technique is proposed to remove the critical path generate by the input feedforward path. Novel input-feedforward delta-sigma architecture is proposed. The new digital input feedforward (DIFF) modulator maintains the low swing and low distortion requirements of the input feedforward technique, it eliminates the analog adder at the quantizer input, and it improves the achievable resolution. To demonstrate these advantages, a configurable delta-sigma modulator which can operate as a feedback topology or in DIFF mode is implemented in 0.18μm CMOS technology. Both modulators operate at 20MHz clock with an oversampling ratio of 8. The power consumption in the DIFF mode is 22mW and in feedback mode is 19mW. However, the DIFF mode achieves a peak SNDR of 73.7dB (77.1dB peak SNR) while the feedback mode achieves a peak SNDR of 64.3dB (65.9dB peak SNR). Therefore, the energy required per conversion step for the DIFF architecture (2.2 pJ/step) is less than half of that required by the feedback architecture (5.7 pJ/step).

Keywords: Delta-Sigma
Sigma-Delta
oversampling
ADC
data converters
analog-to-digital
Input-Feedforward
Time-Interleaved
Advisor: Johns, David A.
Spin-c Quantization, Prequantization and Cutting

In this thesis we extend Lerman’s cutting construction to spin-c structures. Every spin-c structure on an even-dimensional Riemannian manifold gives rise to a Dirac operator D+ acting on sections of the associated spinor bundle. The spin-c quantization of a spin-c manifold is defined to be ker(D+)−coker(D+). It is a virtual vector space, and in the presence of a Lie group action, it is a virtual representation. In 2004, Guillemin et al defined signature quantization and showed that it is additive under cutting. We prove that the spin-c quantization of an S^1-manifold is also additive under cutting. Our proof uses the method of localization, i.e., we express the spin-c quantization of a manifold in terms of local data near connected components of the fixed point set. For a symplectic manifold (M,ω), a spin-c prequantization is a spin-c structure together with a connection compatible with ω. We explain how one can cut a spin-c prequantization and show that the choice of a spin-c structure on the complex plane (which is part of the cutting process) must be compatible with the moment level set along which the cutting is performed. Finally, we prove that the spin-c and metaplectic-c groups satisfy a universal property: Every structure that makes the construction of a spinor bundle possible must factor uniquely through a spin-c structure in the Riemannian case, or through a metaplectic-c structure in the symplectic case.

Keywords: Quantization
Spinors
Symplectic Geometry
Cutting
Advisor: Karshon, Yael
Jamaica's Higher Education Committment under the GATS

This research seeks to answer two questions: why did Jamaica include its higher education (HE) sector in its General Agreement on Trade in Services (GATS) ‘Schedule of Commitments’; and, how do the politicians and policy makers view the impact of this decision? For answers, I looked at arguments linking the GATS with national development and with HE. The thesis explores Jamaica’s HE policy strategies, how they are formed, how well, even after the fact, the decision-makers understand the implications of the regulatory framework of the GATS and the loss of control implicit in some of its tenets. This study is anchored in research findings by UNESCO and the World Bank, among others, which show that HE systems serve as the foundation for nations’ social and economic development, in providing the required knowledge and high levels of trained manpower to build their human capital. However, suggestions have been made that inequities in the global trading system constrain small developing countries in implementing policies that serve these objectives. Therefore, the emergence of the GATS as a new regulatory structure for trade in educational services raises concerns about the ability of countries like Jamaica, to promote an HE system likely to meet their needs. iii Twenty senior policy actors within Jamaican society were interviewed to elicit their views on national priorities for HE and, the opportunities or threats to their fulfilment presented by the GATS Commitment. Of particular interest is the growth in cross-border HE services found in Jamaica. The research found that notwithstanding the inequities of the global trading system, Jamaica embraces the concepts of liberalisation and free trade, and its negotiators, in formulating the Commitment, were seized with GATS’ potential for rapidly expanding access to HE. However, the evidence of this research suggests they were ill-prepared to make this decision, and clearly there is need for a better understanding of the role of HE in Jamaica’s development.

Keywords: Jamaica
Caribbean
Education
Higher Education
Education Policy
Higher Education Policy
Advisor: Mundy, Karen