VictorJuiz/thesis huggingface dataset:
Functional Magnetic Resonance - and Diffusion Tensor Imaging Investigations of Pure Adult Gilles de la Tourette Syndrome
Keywords: Neuroimaging, fMRI, DTI, Tourette Syndrome, Movement Disorders, Multivariate Statistics

Gilles de la Tourette syndrome (GTS) is a chronic neuropsychiatric disorder characterized by multiple motor and vocal tics, affecting approximately 1% of the population. The precise neuropathology of GTS has not yet been delineated, but current models implicate subcortical and cortical areas - the cortico-striato-thalamo-cortical (CSTC) circuit. The majority of studies in the literature have either dealt with GTS with comorbid conditions and/or children with GTS. As these factors are known to affect brain structure and function, it unknown what the neurobiological underpinnings of pure adult GTS are. The objective of this body of work was to use functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize differences in brain function and structure in pure adult GTS patients versus age- and sex-matched controls. I employed a series of three distinct analyses for this purpose, based upon current models of CSTC circuit-related dysfunction in GTS. In the first, GTS patients and control participants executed three finger-tapping paradigms that varied in both complexity and memory requirements. These finger-tapping tasks were modeled after previous studies that showed CSTC circuit-related activity in healthy individuals. Using a multivariate statistical technique to assess task-related patterns of activation across the whole brain, I found that, while there was much overlap in brain activation patterns between groups, sensorimotor cortical regions were differentially recruited by GTS patients compared to controls. In the second fMRI analysis, I measured low-frequency spontaneous fluctuations of the blood oxygen level dependent signal during rest, and found that GTS patients exhibited greater resting state functional connectivity with the left putamen compared to controls. In the final analysis, DTI was used to provide a whole-brain assessment of regional diffusion anisotropy in GTS patients and healthy volunteers and to investigate the fractional anisotropy in predetermined ROIs. This analysis found no differences between GTS patients and controls. Overall, my findings indicated that several CSTC-related regions shown to be atypical in GTS patients previously, are also atypical in pure adult GTS, and that sensorimotor cortical regions and the putamen may be regions of functional disturbance in pure adult GTS.
Cdc42 and Par Proteins Regulate the Trafficking of Apical Membrane Proteins to Stabilize Dynamic Adherens Junctions in the Drosophila Neuroectoderm
Keywords: Epithelial polarity
Cdc42

Epithelial sheets line the surfaces of the body, forming a barrier between the external environment and internal tissues. During development, regulation of epithelial architechture can drive morphogenesis and build the three-dimensional structures of the body. Epithelial form and function derive from the polarized morphology of epithelial cells, which have apical surfaces that face the external environment, lateral surfaces containing cell-cell junctions and basal surfaces that connect to the underlying tissue. A network of polarity proteins establishes the apico-basolateral axis, while a system of polarized membrane traffic ensures delivery of specialized cargo to distinct membrane surfaces. How these systems of polarity and trafficking are integrated is still poorly understood. The focus of my study was to investigate how the apical polarity proteins Cdc42, Par6, Bazooka and aPKC (the “Par complex”) regulate polarity and adherens junction (AJ) integrity during Drosophila development. Upon perturbation of Cdc42/Par activity during embryogenesis, apical membrane proteins accumulate in sorting endosomes. This trafficking defect occurs throughout the ectoderm, but in the ventral neuroectoderm (VNE) is accompanied by a concomitant depletion of the apical proteins from the plasma membrane (PM) and a loss of AJ integrity. I have demonstrated that the VNE phenotype is a consequence of the relatively high morphogenetic activity of this tissue. Furthermore, I have shown that the AJ defects are likely a downstream consequence of the depletion of important apical polarity factors, such as Crumbs, from the PM. To further characterize the mechanism of apical trafficking, I searched for interactors of Cdc42/Par in the membrane trafficking machinery. I describe interactions between several trafficking genes and Cdc42/Par and provide evidence that Vps26, a component of the retromer complex that retrieves proteins from endosomal membrane and delivers them to the Golgi for re-secretion, is phosphorylated by aPKC and acts as an aPKC effector in the recycling of apical membrane proteins. I propose that Cdc42/Par regulate the retromer to promote the PM localization of apical proteins, which is important to maintain AJ integrity in morphogenetically active tissues.
Sulphur Chemistry in KOH-SO2 Activation of Fluid Coke and Mercury Adsorption from Aqueous Solutions
Keywords: Sulphur chemistry
Chemical activation
Sulphur-impregnated activated carbon
mercury adsorption

The technical feasibility of producing sulphur-impregnated activated carbons (SIACs) from high-sulphur fluid coke by chemical activation was investigated. Using KOH and SO2, the activation process was able to produce SIACs with controllable specific surface area (SBET), pore size distribution and sulphur content. The highest SBET was over 2500 m2/g and the highest sulphur content was 8.1 wt%. K-edge X-ray Absorption Near Edge Structure (XANES) spectroscopy was employed to characterize the sulphur in fluid cokes and SIACs. The results revealed that the sulphur on fluid coke surface was mainly in the form of organic sulphide and thiophene (total 91-95 %), in addition to some sulphate (5 - 9%). The study of KOH-treated fluid coke suggested that KOH was effective in converting organic sulphide and thiophene to water soluble inorganic species which were readily removed by acid and water washing. SO2 treatment of fluid coke added sulphur to fluid coke through SO2-carbon reaction. Elemental sulphur was the main product, while part of the thiophene, sulphide and sulphate in the raw coke remained in the product. In KOH-SO2 activation, disulphide, sulphide, sulphonate and sulphate were identified on SIAC surface; no thiophene was found, suggesting a complete removal of thiophene. Sulphur content in specific forms in SIACs was therefore controllable by varying the ratio of KOH, SO2 and fluid coke. SIACs produced from KOH-SO2 activation showed a comparable Hg2+ adsorption capacity (43 – 72 mg/g) with those reported in the literature (35-100 mg/g) and that of a commercial SIAC (41 mg/g). Although a larger SBET often resulted in a greater Hg2+ adsorption capacity, the benefit started to diminish when SBET was greater than about 1000 m2/g. A statistically significant and positive correlation was found between Hg2+ adsorption capacity and total sulphur content. Elemental sulphur and reduced sulphur were largely responsible for the enhanced Hg2+ adsorption.
Rewriting the Social Contract: The Social Fund and Egypt's Politics of Retrenchment
Keywords: Egypt
social policy
micro-finance
small business

The politics surrounding retrenchment and social protection in the Middle East have been obscured by a broad ideological consensus that civil society has replaced the state as the site of social provisioning since the nineties. Contrary to the dominant “state retreat” narrative, the adoption of neo-liberalism in the region was not in fact uniformly accompanied by convergence around a minimal welfare regime. Why have processes of welfare retrenchment unfolded along contrasting patterns across the Middle East with some states explicitly redefining social policy frameworks, and others undermining access and effects of prevailing programs without dismantling them? The dissertation aims to contribute to our understanding of state-society relations in the region by closely examining recent welfare regime changes in Egypt. Why has Egypt pursued “hidden retrenchment” entailing dilution of universal benefits, conversion of social programs to new beneficiaries and institutional layering, without the explicit overhaul of welfare policy frameworks? What are the micro-level political influences shaping the retrenchment process on the ground? Using the Social Fund for Development as a window for understanding hidden retrenchment in Egypt, the dissertation demonstrates that external dynamics of globalization, and donor assistance do not mainly account for welfare regime restructuring. Similarly, the state’s fiscal status, and the underlying switch in development strategies cannot explain retrenchment patterns. Rather, I argue that the internationally dominant neoliberal development discourse has influenced some aspects of retrenchment reforms, and domestic political dynamics have molded hidden retrenchment in Egypt. The regime’s power maintenance logic and a prevailing moral economy of social entitlements explain the process. Micro-level qualitative and statistical analyses of retrenchment politics also reveal that intra-state agencies struggles, regime security concerns, the state’s tendency to fiscally penalize areas with a history of Muslim Brotherhood support, as well as the National Democratic Party’s patronage networks influence outcomes on the ground. My findings suggest that variations in retrenchment patterns across the region reflect important differences in states’ social bases of power, rather than external pressures or domestic economic dynamics.
Art and Politics of Appropriation
Keywords: appropriation
sampling
collage
found footage

This thesis works towards a theory of creative appropriation as critical praxis. Defining ‘appropriation’ as the re-use of already-authored cultural matter, I investigate how the ubiquity of aesthetically and commercially motivated appropriative practices has impacted concepts of creativity, originality, authorship and ownership. Throughout this thesis, appropriation is understood as bridging the artistic, political, economic, and scientific realms. As such, it strongly affects cultural and socio-political landscapes, and has become an ideal vehicle for effectively criticizing and, perhaps, radically changing dominant aesthetic, legal and ethical discourses regarding the (re)production, ownership and circulation of knowledge, artifacts, skills, resources, and cultural matter in general. Critical appropriation is thus posited as a political strategy that can draw together the different causes motivating appropriative processes across the globe, and organize them for the benefit of a multitude which values concepts of reusing, sharing and collectivity over concepts of the individually authored and the privately owned. My arguments regarding this critical potentiality are based on concrete practices emanating from several media (textual – visual – sonic – digital). The corpus includes Berlin Dadaist collage, ‘found footage’ filmmaking, audio sampling, and digital media art. It is critically contextualized in the fields of philosophy, law, and aesthetics, and paired with relevant examples from extra-aesthetic arenas (economics, industrial production and science). Following a trajectory from the analog to the digital, my thesis traces the emergence and tactical employment of critical appropriative practices in the context of different historical, philosophical, technological and economic circumstances. Focussing on conceptual and practical shifts from the analog to the digital furthermore enables me to draw connections between analytic perspectives founded in dialectic materialism and contemporary theories foregrounding issues of immaterial labor. The important qualitative changes that practices and perceptions of appropriation have undergone are argue to significantly amplify the critical potential of all appropriative practices. Ultimately, my comparative analyses thus establish appropriation as an ideal site for effectively challenging – both in terms of form and content – the ingrained, restrictive notions of original genius and naturalized authorship-qua-ownership on which present cultures and technologies of global capitalism are so heavily based.
Anticonvulsant Effects of Omega-3 Polyunsaturated Fatty Acids in Rodents
Keywords: Omega-3 polyunsaturated fatty acids
seizures
epilepsy

The present research examined the hypothesis that omega-3 polyunsaturated fatty acids would increase seizure threshold in rats in vivo, and reduce neuronal excitability in mouse hippocampal slices. Seizure thresholds were measured in rats using the maximal pentylenetetrazol and electrical stimulation seizure tests following α-linolenic acid (ALA) or docosahexaenoic acid administration. ALA raised seizure threshold in the maximal PTZ seizure test, but this effect probably occurred because ALA displaced DHA from liver to the brain. DHA itself was therefore tested in the PTZ and electrical stimulation seizure tests. Direct administration of DHA by subcutaneous injection raised seizure thresholds in the PTZ seizure test, which models tonic-clonic attacks in humans. Dietary enrichment with DHA raised afterdischarge seizure thresholds in the cortex and amygdala, which model simplex and complex partial seizures in humans, although this effect took some time to occur. In vitro, the application of DHA also reduced the incidence of excitatory sharp waves in mouse hippocampal slices. This effect did not appear to be due to either an increase in GABAergic inhibitory tone, nor to a decrease in glutamatergic drive. The fatty acid composition of phospholipids and unesterified fatty acids were measured in the brain following microwave fixation in order to determine whether the effects of DHA on seizure thresholds were due to its de-esterification from the phospholipid membrane. The assay surprisingly revealed that subcutaneous administration of DHA at a dose that raised seizure threshold, increased unesterified arachidonic acid, but not unesterified DHA concentrations during seizures. The results of these studies support the hypothesis that DHA raises seizure threshold in rats, and reduces neuronal excitability in vitro. The effects of DHA on seizure threshold are possibly mediated by the de-esterification of arachidonic acid, which is known to have effects on the voltage-dependent sodium channel.
Role of VEGF and VEGF Receptors in the Glomerulus
Keywords: VEGF
VEGF Receptors
Glomerulus
Podocyte

VEGF is a potent angiogenic and endothelial cell growth factor that is key for the development of the glomerulus, the main filtration unit of the kidney. It is continued to be expressed in the mature glomerulus, with podocytes being the major site of production. VEGF binds to two receptors, VEGFR-1 and VEGFR-2, which are expressed by the adjacent endothelial cells (ECs). VEGFR-2 is the primary mediator of VEGF signaling while VEGFR-1is thought to function as a ‘decoy’ receptor, sequestering VEGF away from VEGFR-2. Gene targeting studies in mice show that VEGF loss from the podocyte results in profound defects of the ECs, consistent with a paracrine signaling loop. However, the identification of VEGF receptors on podocytes in vitro suggests an additional autocrine signaling pathway for VEGF may exist. To further study the role of VEGF in the glomerulus and to address whether a VEGF autocrine loop is functional in vivo, we generated a transgenic mouse model with inducible VEGF upregulation in the podocyte and genetically deleted VEGFR-2 and VEGFR-1 from the podocyte using the Cre-loxP system. Increased VEGF production from the podocyte leads to increased glomerular permeability and ultrastructural changes in the glomerular filtration barrier depending on the time and length of induction. Podocyte-selective deletion of VEGFR-2 did not cause glomerular disease. In contrast, VEGFR-1 loss from the podocyte led to proteinuria and glomerular defects at 6 weeks of age with extensive podocyte foot process effacement. In keeping with the model that VEGFR-1 functions as a VEGF trap, similarities were observed between the glomerular lesions of VEGFR-1 mutant mice and transgenic mice that overexpress VEGF within podocytes. Strikingly, in vitro studies also revealed an increase in podocyte cell adhesion to sVEGFR-1, suggesting additional roles for sVEGFR-1. Together, these data suggest that a tight regulation of VEGF must be maintained in the adult glomerulus. Furthermore, these findings provide the first genetic evidence that VEGF autocrine signaling loop through VEGFR-2 is dispensable in normal glomeruli. In addition, podocytes express sVEGFR-1 and is required in podocytes in vivo to maintain glomerular integrity by regulating VEGF availability and podocyte cell adhesive properties.
The Establishment and Stabilization of Anterior-posterior Identity In the Hindbrain: On the Regulation of the Segmentation Gene MafB
Keywords: Hindbrain patterning
MafB regulation
Chromatin Remodeling
Polycomb Response Elements

In vertebrates, the embryonic hindbrain is transiently subdivided along its anterior-posterior (A-P) axis into 8 well defined segments termed rhombomeres (r1-8). Each rhombomere represents a true cellular compartment in transcriptional profile, lineage restriction and neuronal organization. Thus, the vertebrate hindbrain provides a beautiful model for studying mechanisms of anterior-posterior patterning, signal transduction and interpretation, initiation and maintenance of transcriptional profiles, cell sorting and border formation. The Kreisler/MafB gene, which encodes a basic leucine zipper (bZIP) transcription factor that regulates some Hox genes, is one of the first genes to be expressed segmentally in the hindbrain, and is subject to a dynamic and complex regulatory process. However, unlike the Hox genes, Kreisler/MafB is not located within a large cluster of genes and therefore provides a simple system for dissecting the molecular mechanisms involved in hindbrain compartmentalization. In dissecting the mechanisms that govern Kreisler/MafB regulation, we have identified the S5 regulatory element that directs early MafB expression in the future r5-r6 domain. We have found a binding site within S5 that is specific for the Variant Hepatocyte Nuclear Factor 1 (vHNF1) to be essential, but not sufficient for early induction of r5-r6-specific expression. Thus, early inductive events that initiate MafB expression are clearly distinct from later acting ones that modulate its expression levels. Using mouse mutants, we have shown that MafB is dependent on the M33 polycomb protein and other mechanisms of chromatin remodeling. We then utilized transgenic flies and mice as well as binding assays to identify and validate a PcG/trxG response element (PRE), PRE1 which acts to reorganize the surrounding chromatin, regulating S5-dependent expression. To our knowledge, PRE1 is the first validated vertebrate PcG/trxG response element. Thus, PRE1 provides a springboard for further exploration of the mechanisms governing chromatin remodeling.
Qur'anic Exegesis in Later Islamic Philosophy: Mulla Sadra's Tafsir Surat al-Fatiha
Keywords: Islamic Philosophy
Qur'anic Exegesis

The work of one of Islam’s most celebrated philosophers, Mulla Sadra Shirazi(d. 1045/1635 or 1050/1640), is characterized by a unique synthesis of the main strands of Islamic thought. Yet Sadra’s role as a philosopher was not simply to synthesize. His penetrating intellect and ability to cast new light on some of the fundamental problems of Islamic thought ensured that all of his books would be landmarks of intellectual achievement in their own right. Amongst his most significant but seriously neglected writings are his compositions on the Qur’an and its sciences. Broadly speaking, the present study investigates the manner in which scriptural exegesis, philosophy, and mysticism came together in Sadra’s writings on the Qur’an. More specifically, this study aims to examine the sophistication of the discussions to be found in Sadra’s Qur’anic works by focusing on his last complete and most mature tafsir, the Tafsir Surat al-fatiha. After surveying the history, reception, and content of Sadra’s writings on the Qur’an and presenting a coherent picture of the theoretical dimensions of his scriptural hermeneutics, we will go on to examine the Tafsir Surat al-fatiha’s structure and sources. This will set the stage for a careful analysis of the problems in cosmology, metaphysics, anthropology, theology, and soteriology addressed by Sadra in the work. Not only will our study demonstrate the manner in which Sadra reads scripture, but it will also afford us a window into the development of his religious thought, since the Fatiha provides him with the opportunity to recast many of his philosophical concerns within the Qur’an’s universe of discourse.
Molecular Characterization of the von Hippel-Lindau Tumour Suppressor Protein
Keywords: VHL
Hypoxia

Inheritance of one mutant von Hippel-Lindau (VHL) allele gives rise to the development of the autosomal dominant VHL disease, which affects approximately 1 in 36 000 individuals. The VHL tumour suppressor protein plays a critical role in the E3 ubiquitin ligase-mediated destruction of hypoxia-inducible factor (HIF) and the promotion of fibronectin extracellular matrix assembly. A failure in either process is associated with oncogenic progression. Work included in this thesis provides evidence that these tumour suppressor functions are mutually exclusive. Additionally, post-translational modification of VHL by NEDD8 is shown to act as a ‘molecular switch’, altering VHL protein associations and providing a mechanism of pathway segregation. As a result of HIF stabilization, the expression of a homophilic adhesion molecule E-cadherin is significantly down-regulated in primary renal clear-cell carcinoma (RCC) upon VHL loss. E-cadherin down-regulation is shown to increase the invasive potential and is of prognostic value in RCC. Finally, VHL and SOCS1 are shown to dimerize and negatively regulate the JAK2-STAT5 signalling cascade. Defects in this dimerization are shown to underlie Chuvash polycythemia and provide a molecular understanding of the phenotypic observations associated with VHL-related polycythemias.