VictorJuiz/thesis huggingface dataset:
Revisiting Cognitive and Neuropsychological Novelty Effects
Keywords: novelty
familiarity
long-term memory
episodic memory
memory encoding
medial temporal lobe
hippocampus
subsequent memory effect
functional connectivity
fMRI

Recent proposals have attributed a key role to novelty in the formation of new episodic memories. These proposals are based on evidence of enhanced memory and greater metabolic activity in the hippocampus in response to novel relative to familiar materials. However, such novelty effects are incongruous with long-standing observations that familiar items and lists are associated with better memory than novel ones. In four experiments, I explored possible reasons for this apparent discrepancy. In Experiment 1, I directly tested whether previously observed novelty effects were the result of novelty, discrimination demands, or both. I used linguistic materials (proverbs) to replicate the novelty effect but found it occurred only when familiar items were subject to source confusion. In Experiment 2, to examine better how novelty influences episodic memory, I used experimentally familiar, pre-experimentally familiar, and novel proverbs in a paradigm designed to overcome discrimination demand confounds. Memory was better for both types of familiar proverbs. These cognitive results indicate that familiarity, not novelty, leads to better episodic memory for studied items, regardless of whether familiarity is experimentally induced or based on prior knowledge. I also conducted two fMRI experiments to evaluate the neural correlates of the encoding of novel and familiar forms of information. In Experiment 3, I compared the neural encoding correlates of source memory for novel and familiar visual scenes using fMRI. Replicating previous neuroimaging studies, I observed an anterior novelty-sensitive region of the hippocampus specialized in novelty encoding. Unlike past studies, I also probed for familiarity-encoding regions and identified such regions in the posterior hippocampus. I replicated this pattern in Experiment 4 using proverbs as stimuli. As in Experiment 2, I found the effect held whether familiarity was based on prior knowledge or experimental induction. In both fMRI experiments, anterior and posterior hippocampal regions were functionally connected with different large-scale networks, helping to explain local variation in hippocampal functional specialization in terms of different neural contexts. Together, these experiments show that stimulus familiarity enhances episodic memory for materials, and that novelty is processed differently, not preferentially, in the hippocampus. A new model of hippocampal novelty processing is proposed.
Coordinating Cell Cycle Exit and Differentiation in the Mammalian Retina and its Dependence on Rb
Keywords: Retina
Retinoblastoma cell of origin
Cell cycle exit control

Cell cycle exit (“birth”) of retinal progenitor cells (RPCs) is considered a watershed that is preceded by changing levels of cell cycle regulators, and followed rapidly by induction of a post M-phase differentiation cascade. Yet the actual dynamics of these events are largely unclear, thus whether mitosis separates pre- and post- birth differentiation cascades is unproven. We characterized the regulation of many division and differentiation markers relative to each other and final mitosis. Unexpectedly, classic “cell cycle” markers were present well beyond exit (e.g. Ki67, Pcna), early embryonic RPCs expressed “differentiation” markers that later labeled post-mitotic neurons exclusively (e.g. Brn3b, Tubb3, Ptf1a), and factors detected just after cell birth in the embryo were induced well beyond M-phase post-natally (e.g. Nrl, Crx). Thus, the dynamics of birth-associated events shift dramatically during development, even to either side of mitosis. Instead of mitosis behaving as a cog that activates post-exit differentation events we suggest that a common trigger induces both the exit and differentiation programs in RPCs, precisely coordinating their startpoints, but that each subsequent cascade unfolds independently. This model explains the convergence of birth and differentiation but also their temporal maliability. This view fits with our observation that in the absence of the Rb tumor suppressor, differentiation still initiates even without cell cycle exit. Finally, neoplastic transformation in the mouse retina requires loss of Rb and its relative p107, and emerging tumor features suggest an amacrine cell-of-origin. We studied Rb/p107 null clones, and noted two striking features. First, despite initial expansion of aberrantly dividing differentiating cells, apoptosis pruned clones precisely to wild type sizes. “Cell competition” maintains tissue size by selecting fitter over weaker progenitors; our data provide a unique example of competition among differentiating cells. Second, despite normal numbers of amacrine cells per Rb/p107 null clone, more clones contained amacrine cells and fewer had bipolar cells. Both this effect and ectopic division were E2f1-dependent. Thus, the oncogenic initiation event in mouse retinoblastoma triggers a very early fate switch, even before neoplastic transformation, broadening the possibilities for the cell-of-origin of retinoblastoma, and arguing that even very early stage tumors cannot be used to define cancer origin.
Development of Novel Antiangiogenic Biologics
Keywords: angiogenesis
VEGF
biologics
cancer
age-related macular degeneration
diabetic retinopathy

Current anti-VEGF biologics, such as bevacizumab and VEGF trap, have been successfully used as therapeutic agents for cancer and age-related macular degeneration (AMD). Since these strategies target VEGF systemically, their toxicity profile, including proteinuria and thromboembolic events, and need for frequent eye injections in AMD treatment, prevail. Therefore, the aim of this PhD thesis was to generate novel anti-VEGF biologics that inhibit VEGF activity specifically at the desired target site. Two classes of biologics were engineered that simultaneously bind VEGF and either: 1) the extracellular matrix (ECM) or 2) target-site specific antigens. The first subgroup, “sticky-traps”, is composed of VEGF trap linked to a sequence of hydrophobic amino acids, with affinity for heparin sulfate proteoglycans of the ECM. The second subgroup, “lassos”, is composed of a C-terminus positioned form of VEGF trap linked to single-chain variable domain antibodies specific for either HER2 (HER2/V lasso) or fibronectin extra domain B (EDB; EDB/V lasso), expressed on breast cancer cell surfaces or in the vascular bed of solid tumours, respectively. ii Using a novel transgenic method, piggyBac transposons, biologics were expressed in transgenic cancer cell lines in a doxycycline inducible manner. They were shown to inhibit VEGF activity and also retain the native function of their constituent domains. Specifically, the sticky-traps adhered to the ECM and the HER2/V lasso inhibited the proliferation of HER2 positive cancer cell lines. Sticky-traps as well as lassos were able to inhibit or delay tumour growth of A-673, Pc-3, SKOV-3 and HT-29 xenografts. In contrast to soluble VEGF trap, sticky-traps were retained at the tumour site and were undetectable in the circulation. Moreover, sticky-traps, in contrast to VEGF trap, did not delay wound healing and regression of trachea blood vessels. Furthermore, transgenic studies indicated that HER2/V lasso is more effective compared to anti-HER2 Ab and VEGF trap used alone or in combination. These novel classes of antiangiogenic molecules could be advantageous in a clinical setting. Using the principles established in my PhD thesis work, similar dual function biologics can be designed for inhibition of other molecules with disease relevance.
Design and Practical Implementation of Advanced Reconfigurable Digital Controllers for Low-power Multi-phase DC-DC Converters
Keywords: digital controller
high-frequency dc-dc converters
switch-mode power supply
digital pulse-width modulator
efficiency optimization
phase shedding
current estimation
thermal management
identification
sensorless average current-mode controller
current sensing
overload protection
fault protection
temperature protection
fast transient response
current-mode control
fault detection
power management
integrated circuit
low-power consumption
low-power applications
dynamic current sharing

The main goal of this thesis is to develop practical digital controller architectures for multi-phase dc-dc converters utilized in low power (up to few hundred watts) and cost-sensitive applications. The proposed controllers are suitable for on-chip integration while being capable of providing advanced features, such as dynamic efficiency optimization, inductor current estimation, converter component identification, as well as combined dynamic current sharing and fast transient response. The first part of this thesis addresses challenges related to the practical implementation of digital controllers for low-power multi-phase dc-dc converters. As a possible solution, a multi-use high-frequency digital PWM controller IC that can regulate up to four switching converters (either interleaved or standalone) is presented. Due to its configurability, low current consumption (90.25 μA/MHz per phase), fault-tolerant work, and ability to operate at high switching frequencies (programmable, up to 10 MHz), the IC is suitable to control various dc-dc converters. The applications range from dc-dc converters used in miniature battery-powered electronic devices consuming a fraction of watt to multi-phase dedicated supplies for communication systems, consuming hundreds of watts. A controller for multi-phase converters with unequal current sharing is introduced and an efficiency optimization method based on logarithmic current sharing is proposed in the second part. By forcing converters to operate at their peak efficiencies and dynamically adjusting the number of active converter phases based on the output load current, a significant improvement in efficiency over the full range of operation is obtained (up to 25%). The stability and inductor current transition problems related to this mode of operation are also resolved. At last, two reconfigurable digital controller architectures with multi-parameter estimation are introduced. Both controllers eliminate the need for external analog current/temperature sensing circuits by accurately estimating phase inductor currents and identifying critical phase parameters such as equivalent resistances, inductances and output capacitance. A sensorless non-linear, average current-mode controller is introduced to provide fast transient response (under 5 μs), small voltage deviation and dynamic current sharing with multi-phase converters. To equalize the thermal stress of phase components, a conduction loss-based current sharing scheme is proposed and implemented.
Growth and Characterization of ZnSe and ZnTe Alloy Nanowires
Keywords: Nanowires
II-VI semiconductors
Synthesis
Characterization

The objective of this thesis is to explore the synthesis and characterization of high quality binary ZnTe nanowires with great potential for development of optoelectronic devices including high efficiency photovoltaic cells for energy conversion and high sensitivity photodetectors for green fluorescent protein bioimaging at single molecule level. To systematically explore the fabrication process for high quality nanowires, a chemical vapour deposition system was built for nanowire growth. Computational fluid dynamics simulations were used to optimize the reactor and growth parameters. The simulations were validated by experimental measurements. Room temperature photoluminescence measurements showed that high crystal quality with very low defects by single step growth was achieved. This single step growth technique makes a great improvement compared to the reported growth followed by annealing, which achieved equivalent crystal quality. This simplification could be of use in large scale synthesis of nanowires. The simulation results also showed that reactant species concentration is a key factor influencing the growth. A metal-organic chemical vapour deposition system was thus built to independently control reactant concentrations for ZnTe nanowire growth. Temperature-dependent photoluminescence measurements of as-grown ZnTe nanowires showed a strong near band-edge emission. In addition, a deep level oxygen-related band was observed for the first time. From the detailed analysis of thermal quenching of the photoluminescence, it was shown that the deep level emission was partially from the intermediate band of the material. This is of great importance due to the theoretical absorption efficiency that is as high as 63% for intermediate band materials, which is more than two times of that of current single junction concentrators, and few materials possessing this property. Individual ZnTe nanowires, grown after optimization, were patterned and contacted, and their conductivity and photoconductivity were measured at room temperature. A single ZnTe nanowire serving as a photodetector was shown to have the highest reported visible responsivity of 360 A/W (at 530 nm), and a gain of 8,640 (at 3 V bias). The responsivity is roughly 18 times higher than that of silicon avalanche photodiodes. This demonstrates that ZnTe nanowires are strong candidates for single photon detection.
“Desire” Viewed through Ethical Optics: A Comparative Study of Dai Zhen and Levinas
Keywords: Philosophy of religion
Religious thought
Ethics
Comparative religious ethics
Chinese philosophy
Jewish philosophy
Jewish thought
Confucianism
Confucian thought
Confucian ethics
Neo-Confucianism
Dai Zhen
Emmanuel Levinas
the Other
Desire
Emotion
Human relationship

This research project investigates Confucian thinker Dai Zhen (1724-1777) and Jewish thinker Emmanuel Levinas’s (1906-1995) philosophical discourses on desire from a comparative perspective. First, I look at Dai Zhen and Levinas individually each in their own philosophical contexts, while framing my readings with parallel structure that pivots on a hermeneutic strategy to examine their ideas of desire within the larger prospect of the human relation with transcendence. Then, my inquiry leads to a critical analysis of several interesting issues yielded in my interpretive readings of the two thinkers as regards transcendence and immanence and the self-other relationship. Methodologically, my study combines careful textual analysis, philosophical reflection, and historical sensitivity. We might want to say that there is in fact no correlative of the Levinasian desire in Dai Zhen’s philosophy. Dai Zhen’s notion of desire perhaps comes closer to Levinas’s concept of need. However, the disparity of their conceptual formulations does not keep us from discerning their shared ethical concern for the other, the weak, marginalized, and underprivileged group of society, which provides me the very ground for a dialogical comparison between the two thinkers. Henceforth, my writing is hinged on a comprehension of their conception of desire as an articulation of human striving for what is lying beyond themselves, as a redefinition of the being or essence of humankind in relation to the transcendent which in both philosophers’ ethical thinking is translated into a sympathetic understanding of and care for the other, particularly the stranger, the widow, the orphan, the young, the weak and the like. Through the comparative study of the two thinkers’ ideas of desire, I want to argue that “desire,” which is most readily directed to human egoism and instinctive propensity in both Confucian and Western philosophical traditions, can be at once the very driving force to open us to the other beyond ourselves and an actual moral creativity to produce ethical being out of material existence.
The Role Of Homeodomain Transcription Factor Irx5 In Cardiac Contractility and Hypertrophic Response
Keywords: Transcription factor
Irx5
Contractility
Hypertrophy
Heart

Irx5 is a homeodomain transcription factor that negatively regulates cardiac fast transient outward K+ currents (Ito,f) via the KV4.2 gene and is thereby a major determinant of the transmural repolarization gradient. While Ito,f is invariably reduced in heart disease and changes in Ito,f can modulate both cardiac contractility and hypertrophy, less is known about a functional role of Irx5, and its relationship with Ito,f, in the normal and diseased heart. Here I show that Irx5 plays crucial roles in the regulation of cardiac contractility and proper adaptive hypertrophy. Specifically, Irx5-deficient (Irx5-/-) hearts had reduced cardiac contractility and lacked the normal regional difference in excitation-contraction with decreased action potential duration, Ca2+ transients and myocyte shortening in sub-endocardial, but not sub-epicardial, myocytes. In addition, Irx5-/- mice showed less cardiac hypertrophy, but increased interstitial fibrosis and greater contractility impairment following pressure overload. A defect in hypertrophic responses in Irx5-/- myocardium was confirmed in cultured neonatal mouse ventricular myocytes, exposed to norepinephrine while being restored with Irx5 replacement. Interestingly, studies using mice virtually lacking Ito,f (i.e. KV4.2-deficient) showed that reduced contractility in Irx5-/- mice was completely restored by loss of KV4.2, whereas hypertrophic responses to pressure-overload in hearts remained impaired when both Irx5 and Ito,f were absent. These findings suggest that Irx5 regulates cardiac contractility in an Ito,f-dependent manner while affecting hypertrophy independent of Ito,f. On the other hand, Irx5-ablation attenuated calcineurin (Cn)-induced hypertrophy in hearts and cultured cardiomyocytes, suggesting that the effect of Irx5 on hypertrophy involves the Cn-NFAT signalling cascade. Biochemical assessments further revealed that Irx5 can positively mediate Cn-NFAT activities as well as Nfatc3 and Gata4 expression, and interacts with Nfatc3 and Gata4, suggesting the formation of a transcription complex for hypertrophic gene regulation. Taken together, these studies have identified Irx5 as a vital cardiac transcription factor, important for contractile function of the heart by regulating Ito,f, and compensatory hypertrophic response to biomechanical stress in the heart by affecting the Cn-NFAT (and Gata4) signaling pathway.
Critical Investigation of the Sierra Leone Conlfict: A Moral Practical Reconstruction of Crisis and Colonization in the Evolution of Society
Keywords: critical social theory
contemporary social theory
critical pedagogy
discourse theory of law and democracy
procedural paradigm of law
political philosophy of justice
postmetaphysical thought
reconstruction of historical materialism
rational reconstruction
theory of social evolution
African crisis and conflict
critical African studies
politics of decolonization
The Sierra Leone conflict

This Sierra Leone Conflict arose from the society’s failure to institutionalize the requisite post-conventional organizing principle for collective will formation and for conflict resolution. In this post-traditional society - one artificially constructed from diverse political and cultural groups, without a shared ethos – only mutual (communicative) understanding can resolve differences and ensure solidarity. A lack of mutual understanding overburdens the adaptive capacity of the society, creating crises tendencies. Repression only intensified these tendencies, ensuring their eventual catastrophic explosion, 11 years civil conflict. State hindrances to social (communicative) interaction rendered the society incapable of realizing the requisite post conventional moral learning i.e. the social intelligence or problem-solving equipment required to resolve conflict, decolonize itself, neutralize normative power, shed dogmatic consciousness, change oppressive conventions, and influential customs. Thus, the study promotes civic virtues of post conventional morality (justice, truthfulness, moral rightness) as the key for liberating the society from its crisis-inducing colonial organizing principle. As the basis of sociology, the discipline the remains focused on society-wide problems, the theory of social evolution is adopted here to reconstruct the crisis in Sierra Leone’s constitutional democratic development. The study uses the rational reconstructive method to explicate problematic validity claims of norms, policy decisions, or the social order. The social order was rendered crisis-ridden because the reasons - the axis around which mutual understanding revolve - adduced for it cannot admit of consensus. The emerging social disintegration exemplifies use of deficient logic in social interaction, one below the requisite categorical moral cognitive consciousness. For this research, colonization is not necessarily externally induced, but forms of understanding in the political, legal, social, and educational interactions. The key point of the study is this: today Sierra Leone achieves solidarity, and decolonize from its conventional organizing principle, only if the state, economy, and civil society can find their limit in the socio-cultural domain.
Competition in Visual Working Memory
Keywords: Visual Working Memory
Biased Competition
Cognitive Neuroscience

The processing of information within the visual system is limited by several cognitive and neural bottlenecks. One critical bottleneck occurs in visual working memory (VWM), as the amount of information that can be maintained on-line is limited to three to four items. While numerous theories have addressed this limited capacity of VWM, it is unclear how processing bottlenecks in the initial selection and perception of visual information affect the number or precision of representations that can be maintained in VWM. The purpose of this dissertation was to examine whether early competition for resources within the visual system limits the number or precision of representation that can be maintained in VWM. To establish whether competitive interactions affect VWM, Chapters 1 – 4 tested whether performance on VWM tasks was related to the distance between memory items. The results of these experiments reveal that when objects are presented close together in space, VWM performance is impaired relative to when those same objects are presented further apart. Using a three-component model of continuous responses in a recall task, Chapters 3 – 4 demonstrated that the distance between objects primarily affects the precision of responses, and increases the number of non-target errors. Chapter 5 extended these findings to distractors, demonstrating that multiple distractors affect the precision and accuracy of VWM responses. Chapters 6 – 7 tested how attentional selection can bias memory representations, revealing that objects that are given high attentional priority were reported with greater precision. Finally, Chapters 8 and 9 examined bias-signals as a potential source of individual differences in VWM performance, revealing that high-performers have more precise representations of sub-capacity representations than low-performers. Together, these results reveal that VWM performance is limited by competition for representation within the visual system, and that attention plays a critical role in resolving competition and consequently, determining the contents of VWM.