VictorJuiz/thesis huggingface dataset:
The role of local structure propensity and nonnative interactions in protein folding

Despite many years of research, the roles of local as well as nonnative interactions in protein folding remain poorly understood. To bridge this gap in knowledge, this thesis is an investigation of the contributions of local structure propensity as well as nonnative interactions to the energetics of protein folding. To address the energetic principles of local structure propensity, a multiple substitution strategy was employed where the effect on protein folding kinetics of a large subset of mutants at a single surface-exposed position is examined. By taking advantage of the characteristic feature of folding transition states in being less tightly packed than the folded state, I demonstrated that folding kinetics may generally provide the best means to characterize the energetics of local structure propensities with less influence of packing, as opposed to equilibrium stability studies. Application of this principle to two surface exposed β strand positions in the Fyn SH3 domain suggested that it is possible to obtain a context-independent assessment of local structure propensities through transition state analysis. Once applied to a 310 helix position in the domain, an experimental propensity scale for 310 helices was established for the first time. Therefore, with the rapid growth in structural databases, the multiple substitution approach provides a means to characterize informational propensity values of a larger number of motifs, besides helices and sheets. My findings suggest that, during folding, normative interactions may mask the energetic contributions of local structure propensities. Moreover, quite contrary to the common perception, I observed that normative interactions can speed up folding and that the propensity to form normative contacts is not uniform along protein sequence. Thus, extra caution needs to be exercised in interpreting the results of Φ value analysis and those of pure native centric models, which assume that nonnative interactions are either nonexistent or do not positively influence folding.

Keywords: Molecular biology
Biochemistry
Biophysics
The evolution, population genetics, and conservation of lampsiline freshwater mussels (Bivalvia: Unionoida: Lampsilini)

The biodiversity of freshwater mussels is diminishing at a nearly unprecedented pace, with many species being added to legally protected lists. In response to this imperilment, this dissertation investigates the evolution and population genetics of mussels from the tribe Lampsilini of freshwater mussels. Species in the Order Unionoida require a host, usually a fish, to complete their life cycle. Females of most species show adaptations that increase the chances of glochidia larvae contacting a host. Using a suite of mitochondrial DNA sequences, a phylogenetic hypothesis for the evolution of the lampsiline species was created to test the evolution of host attracting structures and behaviours. It is necessary to investigate alternative ways to conserve the biological and genetic diversity of imperiled unionoids within the framework of conservation law. In order to clarify definitions and concepts for conservation units for unionoids, studies of unionoid evolution, population genetic structure, cryptic species, and taxonomic conflict are discussed. From this synthesis of studies, recommendations are made for the appropriate usage of these units under endangered species legislation. To assist in managing lampsiline species, population-level studies of the imperiled Northern Riffleshell (Epioblasma torulosa rangiana), Snuffbox (E. triquetra) and Wavy-rayed Lampmussel (Lampsilis fasciola) were conducted to test possible routes of post-glacial redistribution and for the existence of conservation units, population structure and genetic diversity. Analyses were made using mitochondrial DNA sequences and microsatellite loci, including six that were newly developed. For E. t. rangiana, mtDNA sequence data did not indicate significant geographic structure among populations. However, allelic data from the microsatellite loci revealed highly significant population structuring. For E. triquetra, the results indicated the occurrence of three glacial refugia: the Tennessee River, rivers south of the Ozark Crest, and the lower Ohio River drainage near the confluence with the Mississippi. The four sympatrically-occurring mantle display-types could not be distinguished genetically via an assessment of microsatellite DNA loci. Within-drainage gene flow was high and sampling localities within drainages displayed panmixia. For all species, efforts in artificial propagation and possible translocations programs to reintroduce or augment populations should be made to maintain significant levels of genetic variation while maintaining distinctiveness.
High-speed optical wireless communications using reduced-state sequence detection

Driven by the need for high-speed connectivity in short distances and the costs and difficulties of deploying cables, this thesis discusses the design of short-distance optical wireless data communications with the target speed of 1Gb/s. In addition to exploring the effect of individual components in this link, two blocks at the receiver side, the front-end transimpedance amplifier and the back-end detector, were designed and implemented and their performance summary are given below. A transimpedance amplifier with differential dc-coupled photocurrent sensing was integrated in a standard 0.35 μm CMOS. It achieves 33kΩ transimpedance gain and a bandwidth of 255 MHz with a 2pF photodiode capacitance. This design exhibits 40dB power supply rejection ratio and an average input noise of 6.8pA/[special characters omitted]. Power dissipation is 30mW from a 3V supply. Also, an active dc photocurrent rejection circuit was included in this circuit to prevent the circuit output from saturation under intense background light. A 1Gb/s analog Viterbi detector based on a 4-PAM duobinary scheme was designed in a 0.25μm CMOS process. This chip is the first integrated implementation of an analog reduced state sequence detector. Pipelining structure and parallel processing have been incorporated in this design for high-speed operation. Due to test equipment limitations, experimental results are given for 200 Mb/s operation while simulation results indicate a speed of 1Gb/s. Power dissipation is 55mW from a 2.5V supply while occupying 0.78mm 2 of area. Although a duobinary scheme has been the focus of this work for its application in optical links, this design can be readily modified or extended to other PRS schemes such as dicode and PR4.
Relationship between non-auto travel and characteristics of the built environment and trip makers: Empirical analysis and case study

The main objective of this study is to show descriptively how the built environment and socio economic factors might relate to selecting the mode of travel, with special emphasis on transit and subway mode shares, in order to better understand how these factors might encourage residents to walk, bike, or take transit as substitutes for automobile travel. In order to achieve this, two different approaches are presented. First, the relationship between the variations of those factors and mode shares is examined for several areas within close proximity to the subway line network using the 2001 TTS database. In the second approach, the same relationship over the period of 1986 to 2001 is studied for one specific neighbourhood. Eventually, to better understand this relationship, visits to three of the chosen neighbourhoods were conducted to better identify some related built environment characteristics that are not readily available in the databases.
The impact of global and local factors on drug accessibility in Egypt

Many studies have focused on the negative impact of globalization on the conditions of people in third world countries by highlighting labor cost-reduction mechanisms. This dissertation looks at the role of revenue-increasing market mechanisms which are aimed at increasing profit through monopoly behavior in directly affecting people's accessibility to essential medicines. More specifically, since the 1970s, the availability and affordability of essential drugs in Egypt has been reduced as a result of the increasing interaction between the pharmaceutical transnational corporations (TNCs) on the one hand and local producers on the other. Rather than increasing accessibility to drugs, the fierce unfair competition between the TNCs and national producers over the market share actually results in the market being filled with large amounts of non-essential drugs. Furthermore, the production of essential drugs suffers. For one thing, the prices of essential medicines become higher than the international levels, and private spending on drugs exceeds most other countries' averages. In addition, the conditions of the national industry have deteriorated, as indicated by the decreasing control of the means of production, such as raw materials, R D activities, and market outlets. The dissertation explores these developments and provides some recommendations for increasing the availability and affordability of essential drugs.
Rukh: the social construction of protest 1988-1992

This dissertation is a study of Rukh, the main national movement in Ukraine between 1988 and 1992. The time frame under study embraces the inception of Rukh, the period of Rukh's greatest influence on Ukrainian politics (including Ukraine's eventual declaration of independence from the USSR), and finally, the decline and splintering of the movement in the aftermath of independence. Using Ukraine as a case study, we see the rapid transition of ethnopolitics in the Soviet Union from ethnic federalism to ethnonationalism. There have been a variety of studies of nationalism and national movements in the Ukrainian (and former Soviet) social science literature. These works tended to focus largely on nationalism. But to round out our understanding of the complex changes going on in Ukraine between 1988 and 1992, it is necessary to study the movement as well. This dissertation utilizes the social construction approach (taken from the social movement literature developed in the West), and in particular, concepts of collective identity, frame alignment, and multiorganizational fields, which, taken together with traditional approaches to nationalism, allow us to understand more fully the rise and forms of ethnonationalism that occurred in Ukraine. First, the social construction approach lets us view the ways in which Rukh framed and guided the nationalist debate in Ukraine. Next, by examining how Rukh's opponents and allies changed their strategies for mobilizing support (due to factors within and outside Ukraine), the multiorganizational field helps us analyze how and why Rukh's support grew and-then faltered during the time frame studied. For example, in 1989, Rukh was the focal point of opposition to the Ukrainian Communist Party (CPU). But by the end of 1990, Rukh found itself competing not only with the hardline faction of the CPU, but with an increasing number of political parties (many of which were allies of Rukh), along with an increasingly pragmatic faction within the CPU led by Leonid Kravchuk. It is also argued here that it is important to examine the evolution of historical memories and myths of different regions of Ukraine to understand how and why Rukh leaders used varying strategies in Eastern and Western Ukraine to mobilize support. Overall, the social construction approach not only shows a great deal of potential for analyzing the evolution of Rukh, but also for examining the processes of nation and state building that are taking place in Ukraine today.
Writing from exile: Petrarch's humanism and the ethics of care of the self

The question of the nature and scope of Italian humanism, and particularly of humanist philosophy, has been an ongoing source of debate among historians. In this dissertation I explore the nature of humanist philosophy by complementing the traditional study of the "history of ideas" with that of the "history of practices." Concentrating on Petrarch's voluminous corpus of writing, I argue that Petrarch develops in his works a new ethical program, a new philosophy of self, at the centre of which is the assertion that "self" is above all a state of mind from which we are exiled and which we need to cultivate through constant practice, and particularly through the literary practice of writing (which is always intertwined with that of reading). In order to examine Petrarch's philosophy, therefore, this thesis focuses especially on his uses of writing as a spiritual exercise in his works, and the ways in which these uses both absorb and transform ancient and medieval traditions of writing. In Petrarch's vernacular poetry, I argue, writing serves mainly as a personal ritual and a meditative exercise that allows the poet to overcome his experience of fragmentation and exile by reviving and intensifying his desire. In the Latin works, in contrast, writing mostly serves as a vehicle for the cultivation of virtue and the eradication of desire, which is presented as the very source of the experience of exile. Nonetheless, the uses of writing in the Latin works, modeled mostly upon the example of Seneca, are in themselves persistently undermined by the "Ovidian" realization that writing is always tainted by desire, and is hence in itself part of the problem no less than the solution. This realization, in turn, also leads to the "Augustinian" backlash in Petrarch's works against secular writing in general. As a result, while this thesis argues that Petrarch's humanism is defined above all by his emphasis on care, his attempt to establish humanism as a form of secular spirituality, it also inevitably brings to the fore the tensions and contradictions that plagued his project from its onset.
Prediction of ischemic pain following uterine artery embolization for fibroids

Objective. To identify predictive factors for ischemic pain following uterine artery embolization (UAE) for treatment of uterine fibroids. Study design. A retrospective analysis of patients undergoing UAE in a prospective single arm trial, the Ontario Uterine Fibroid Embolization Study. Patients were classified into low and high pain groups. Multivariate logistic regression (LR), using a forward stepwise approach, was used to identify predictors of high pain (HP) after UAE. Results. The variables found to be related to HP in univarite LR were age <40 years, patients without children, currently employed, uterine size ≥1001 cm3 and dominant fibroid size ≥500 cm3. The final model predicts that patients <40 years (OR = 1.95, p < 0.01), with a dominant fibroid size ≥500 cm3 (OR = 1.63, p = 0.06), and/or who currently are employed (OR = 1.79, p = 0.04) have higher odds of experiencing HP after UAE. Conclusion. Patients who are younger than 40 years, have fibroids size larger than 500 cm3, and/or are currently employed have a higher likelihood of experiencing HP after the UAE procedure. The model needs to be validated in future studies.
Fatigue resistance of all-ceramic molar crowns manufactured with CAD/CAM technology

Purpose. To compare fracture strength and mechanical fatigue resistance of CAD/CAM-manufactured new zirconium-oxide (In-Ceram YZ, Vita)(YZ) and feldspathic all-ceramic crowns (Vita Mark II, Vita)(VMII). Methods. Forty replication dies of a prepared ivorine molar were made using an epoxy resin (Viade). Twenty VMII crowns and 20 YZ crowns were cemented to their respective dies using resin cement. Half of the crowns in each group were subjected to fatigue test in a universal testing machine. All crowns, except those that fractured during fatiguing, were then loaded to fracture. Statistical tests were ANOVA, Chi-Square and Fisher's Exact ( p < 0.05). Results. All VMII crowns exhibited no visible crack formation; 40% of YZ crowns fractured and the remainder developed cracks during the fatigue test. All the YZ crown fractures were located within the veneering layer. Mechanical fatiguing significantly decreased the fracture strength. Conclusions. VMII crowns showed more fatigue resistance than YZ crowns in-vitro and might better resist cracking when used clinically.
Generation of a mouse model for colorectal cancer

Colorectal cancer is one of the most common forms of cancer in the western world. In Canada, an estimated 17,000 new cases were reported and an estimated 6,500 colorectal cancer patients died from the disease in 2000. c-Src is a proto-oncogene product often found activated or overexpressed in colorectal cancer, but an activating mutation in the c-src gene has only been found in a small subset of colorectal cancer patients tested. While it is generally believed that c-Src contributes to the development of colorectal cancer, where along the multistep pathway of colorectal carcinogenesis it has an effect is still unclear. To address this issue, several transgenic mice with intestine-specific expression of an activated form of c-Src were generated and characterized.
Candidate genes on chromosome 6p in obsessive-compulsive disorder and schizophrenia

Obsessive-compulsive disorder (OCD) and schizophrenia (SCZ) are serious neuropsychiatric disorders that might involve autoimmune processes. Two genes, mapping to a risk region for OCD/SCZ, the myelin oligodendrocyte glycoprotein (MOG), which mediates the complement cascade, and the gamma-aminobutyric acid type B receptor 1 (GABBR1), which functions in the major inhibitory neurotransmitter system, represent candidates for OCD/SCZ. We investigated the transmission of alleles/haplotypes of four MOG and five GABBR1 polymorphisms for possible association with 191 SCZ case-control pairs, 160 OCD and 111 SCZ families using the transmission disequilibrium test, family-based association test or Kruskal-Wallis Test. Significant associations were observed for MOG-(TAAA)n (P = 0.022) with OCD and with OCD severity level (P = 0.020). The MOG haplotype-1.2.2.13 (P = 0.011) was associated with OCD. Trends of overtransmission of GABBR1-7265A variant (P = 0.071) and haplotype-2.1.1.2.1 (P = 0.065) were observed in OCD. Although our results suggest that MOG/GABBR1 were not associated with SCZ, both genes might play a role in OCD.
Modeling and design of next-generation heterogeneous wireless networks

The service integration of different wireless access technologies is envisioned as a viable approach to accommodate the expected increase in the demand on wireless resources. This vision originates a new networking paradigm that introduces a new vertical mobility dimension, which significantly magnifies the mobility impact on the system performance and creates new challenging design issues that necessitate adopting novel innovative approaches to handle the inherent system heterogeneity. Clearly, vertical mobility is completely dismissed in the current mobility models that are primarily developed for homogeneous cellular systems. Hence, the development of new mobility models that consider vertical mobility in heterogeneous systems evolves as a crucial requirement for proper system design and performance evaluation. These models should satisfy general mobility modeling requirements such as flexibility and analytical tractability. More importantly, they should accommodate the correlation between the mobile terminal (MT) cell residence time (CRT) and the durations spent by the MT under the umbrellas of different technological coverage cocktails. In this dissertation, we developed a novel CRT mobility modeling framework that realizes the aforementioned modeling requirements. This framework is used to develop mobility models for two-tier and n-tier heterogeneous systems. Based on these models, we developed generic performance evaluation frameworks to estimate several salient performance metrics. Additionally, we employed the developed mobility modeling and performance evaluation frameworks to study several interesting network planning and dimensioning problems. In a complementary research direction, we studied vertical mobility management in heterogeneous systems. The asymmetric nature of vertical mobility is a novel design challenge that invalidates the traditional handoff decision mechanisms, which are based on comparing the signal strength from different base Stations of the same network. Hence, the vertical handoff decision should adopt novel mechanisms that consider a predetermined set of user preferences and network design goals. Consequently, we developed a novel flexible vertical handoff approach that, can adapt to different operating parameters such as, user mobility, required handoff delay, and different application requirements.
Development and physicochemical characterization of solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl methacrylate) hydrogels

The purpose of this study was to characterize physicochemical parameters affecting the physical state of solid molecular dispersions of poorly water-soluble drugs in PHEMA hydrogels. Samples were prepared by an equilibrium solvent loading process and characterized by XRD, DSC and FTIR. The results confirm the existence of a threshold drug loading level above which a transition from amorphous to crystalline state may occur in the solid molecular dispersion. The onset of such change is accelerated at higher relative humidity levels during storage. The presence of hydrogen bonding between the polymer and the drug, as confirmed by FTIR, together with the glassiness of the polymer helps to retard crystallization below the loading threshold. An enhancement in dissolution rate is observed from such solid molecular dispersions. This study suggests that solid molecular dispersions based on PHEMA hydrogels can effectively enhance the apparent solubility and dissolution rate of poorly-water soluble drugs.
Role of angiopoietins and Tie2/TEK in astrocytoma angiogenesis

Diffuse astrocytomas are the most common primary malignant brain tumor. Despite advances in surgical resection, radiation therapy and understanding of their molecular pathogenesis, their prognosis remains very poor. One of the most characteristic and distinguishing features of malignant progression in astrocytomas is proliferative vascularity and robust angiogenesis. This had led to much research being focused on identifying the molecular regulators of tumor angiogenesis in astrocytomas in hopes of identifying novel and effective therapeutic strategies to restrict growth of these highly aggressive tumors. Since the early 1970s when Judah Folkman, began the research campaign for tumor angiogenesis research there has been a tremendous increase in our understanding of the tumor angiogenic process, and astrocytoma angiogenesis has benefited from these advances. However, despite identifying key regulatory angiogenic factors that are critical in the vascular growth of astrocytomas, an effective therapeutic target has not yet been designed. This in part is due to the complexity of the cascade that regulates tumor angiogenesis. In order to improve our understanding of the orchestration involved between various angiogenic pathways, we have chosen to investigate the contribution of an endothelial cell specific pathway, Angiopoietins and their cognate receptor tyrosine kinase Tie2/TEK to the vascular growth of astrocytomas.