VictorJuiz/thesis huggingface dataset:
P-glycoprotein in a lipid bilayer support, 3D reconstruction from electron micrographs

The experimental approaches available to study the structure of most membrane proteins are limited. X-ray crystallography or electron crystallography rely on the availability or creation of 3D or 2D crystals to obtain high resolution structural information of membrane proteins. Single particle imaging of detergent solubilized protein is also possible, but removes the protein from its native environment. To recreate such an environment, we have developed a method which permits membrane proteins to be visualized in a lipid bilayer support. A 3D reconstruction of P-glycoprotein, a protein implicated in multidrug resistance, is presented here. This refined reconstruction is helpful when compared to preexisting models of the structure of P-gp. This new technique has the potential to be of great value in obtaining structural information on many membrane proteins in a lipid bilayer environment, whether they are attached, anchored in the membrane or are truly transmembrane molecules.
The electrical properties of electrochemically fabricated nickel nanowires

Metallic Ni nanowires were deposited electrochemically into porous anodic alumina template. The technique produces arrays of parallel wires embedded in alumina, with a narrow distribution of pore diameters and lengths. Recently developed methods greatly improve the periodicity of the porous alumina arrays and truly make the templated fabrication of various nanostructures in AAO a viable alternative to the expensive lithographic techniques. The ordered arrangement of nanowires has been utilized to measure the resistance of single wires with the Scanning Tunneling Microscope (STM). Measurements reveal high nanowire resistivity compared to the bulk Ni. It is thought to be due to the disorder of the material and possibly due to the quasi-1D effects. The electrodeposited nanowires have been characterized with Scanning and Transmission Electron Microscopy (SEM and TEM) electron and X-ray diffraction and density measurements.
Targeted disruption of the Grb4 and Nck loci and generation of homozygous null nck mice

Adaptor proteins are a subset of signaling proteins that lack catalytic function. Adaptor proteins of the Grb2 family have been shown to be critical signaling components downstream of receptor tyrosine kinases (RTKs) that mediate interactions with other signaling molecules through their protein binding domains. Nck and Grb4, the only known mammalian members of the Nck family, are composed of three amino-terminal SH3 domains followed by a carboxy-terminal SH2 domain. Recent biochemical studies and work undertaken in invertebrates have suggested that this family of adaptors may mediate signaling which regulates the actin cytoskeleton and axon guidance in response to RTK stimulation. To better assess the function of these adaptor proteins in mammalian development, a strategy was undertaken to target a mutation into the genomic loci of both Nck and Grb4. Targeting of embryonic stem cells and the generation of chimeric animals was successful for both genes. Furthermore, the targeted Nck locus was transmitted into the murine germline allowing the generation of homozygous null nck mice. This targeting strategy also introduced the $\beta$-galactosidase reporter gene into the Nck locus. Analysis of the embryonic expression pattern of $\beta$-galactosidase indicates that there are restricted regions of the fetal mouse that highly express nck during embryogenesis. The generation of these mice, antibodies that can discern between Nck and Grb4, and fibroblast cell lines lacking Nck resulting from this work will aid in elucidating the in vivo function of Nck and Grb4 in mammalian development.
The legal and political evolution of federal tobacco control legislation

This thesis analyzes the legal and political factors influencing the evolution of federal tobacco control legislation throughout the last century. This thesis takes a case study approach in order to demonstrate the inherent difficulties in enacting national tobacco control legislation to regulate tobacco products in two areas: (1) advertising and sponsorship; and (2) packaging and labelling. This thesis argues that the 'Charter' poses the greatest legal barrier to positive legislative outcomes from the perspective of antismoking advocates. It is argued that notwithstanding the 'Charter ' constraints, the greatest barriers to enacting tobacco control legislation are political. For most of this century, public policy in this area has been shaped and controlled by pro-tobacco interest groups, resulting in too few tobacco control laws which enhance the greater public good. This thesis demonstrates that the evolution of federal tobacco control from symbolic legislation (early 1900s) to industry-self regulation (1960s to the 1980s) to government regulation (late 1980s to the present) has been the predictable outcome under a public choice analysis of the political process.
Structural analysis of oncogenic H-Ras mutants G12A and G13A

About 30% of human cancers are due to point mutations in one of the H-, K-, and N-Ras genes. These small GTPases act as early switch molecules turning on and off cell proliferation processes in response to exocellular stimuli. Common mutations at Gly12, Gly13 and Gln61 prevent Ras from hydrolyzing GTP into GDP in the presence of a GAP (GTPase activating protein), prolonging the lifetime of the active state, therefore rendering the protein oncogenic. From previous mutational and crystallographic studies, we know that too big a side chain at position 12 would sterically hinder the correct positioning of the Gln61 side chain for catalysis. To answer the questions why G12A is oncogenic while G12P is not and why a small change from a hydrogen to a methyl group at Gly13 also makes the protein transforming, we studied crystal structures of G12A and G13A H-Ras. Free G12A/GDP was crystallized and subsequent modeling of its structure into the complex of H-Ras and p120GAPGRD showed that C ß of Ala12 occupied the same position as that of Pro12. The G13A/GDP structure revealed no sign of involvement of the 13th residue with any other part of the molecule or with GAP. Therefore, it appears that a full understanding of the influences of amino acid changes at these positions will require complex structures of H-Ras mutants and the catalytic domain of GAP.
Human factors of personal Web information spaces

How do people use World Wide Web bookmarks? This in-depth empirical study of WWW human factors describes a user's personal Web information space. It is based on interviews of 12 users, a survey of 322 people, a mental maps survey of 27 users, and an analysis of the bookmark files of 56 users and the usage data of 23 users over 6 weeks. The WWW is a complex information space with five defining properties: (1) users are overload with information, (2) the Web is polluted with redundant, erroneous and low quality information, (3) it progresses toward disorder according to the principle of entropy, (4) it has no aggregate structure which organizes distinct Web localities, and (5) users have no global view of the entire WWW from which to forage for relevant Web pages. In dealing with this complex information space, users find localities of interest, create bookmarks to return to them, conceptualize WWW access through metaphors, and create a personal information space with the bookmarks they collect. Users employ this personal information space to counteract five problems of a complex information space in the following ways. (1) They prevent information overload by incrementally building a small archive. (2) They avoid pollution by selecting only useful items and creating a known source of high value. (3) They reduce entropy through maintenance, although they organize only when necessary. (4) They add structure by cost-tuning their information environment. (5) They compensate for the lack of a global view by creating their own personal view. As a user's bookmark archive grows, it can begin to exhibit the properties of a complex information space. Thus, users are continually challenged with maintaining an effective personal Web information space.
The multiple dimensions of punishment, intermediate sanctions and interchangeability with imprisonment

Reform strategies, and sentencing legislation for both adults and youth in Canada and elsewhere have attempted to create 'intermediate' sanctions that can be made equivalent and interchangeable with sentences of imprisonment. These sanctions may have the potential to reduce the use of imprisonment through interchangeability, so long as sanctions can be equivalent to imprisonment in severity. Implicit in these theories of punishment, however, is the assumption of the acceptability of interchangeable, 'intermediate' sanctions. It is assumed that the most critical dimension to punishment is severity. This thesis challenges these simplistic conceptualizations of punishment, and presents an analysis of the perceived appropriateness of punishment. I argue it is critical to examine the functions that punishments are seen (by judges and the public) as serving. Authors writing about interchangeability, and sentencing legislation for adults and youth, however, have given insufficient attention to the offence being punished and the offender who is the recipient of the punishment. It is suggested that these approaches to sentencing and punishment will be inadequate until a combination of factors are addressed that are part of the sentencing process. The findings demonstrate that fines, community service orders, and conditional sentences cannot be assumed to be generally accepted as equally interchangeable with imprisonment across all purposes, offences, or offenders--adults and youth. Different punishments were seen as appropriate in different contexts. The four studies presented in Chapters two through five demonstrate that denunciation is viewed as an important purpose by members of the public and judges for offences involving violence. In these cases, 'intermediate' sanctions were seen as lacking the denunciatory power that the prison achieves, and were less likely to be viewed as appropriate than imprisonment for violent and sexual offences. It may be possible to create punishments that are seen as equivalent to imprisonment in severity. This thesis reveals, however, that there are multiple dimensions to punishment--beyond severity--that are considered by the public and judges when assessing the appropriateness of punishment. Punishments must be understood as being complex and varying along qualitative as well as quantitative dimensions.
On-line measurement of the PVT properties of polymer/CO¦2 solutions using a gear pump

This study presents an innovative dilatometer that can accurately measure the pressure-volume-temperature (PVT) properties of polymer/CO2 solutions. The density (or equivalently, the specific volume) of a polymer/CO 2 solution is determined by measuring the mass and volume flow rates of the solution. A positive-displacement gear pump mounted on an extruder is used to measure the volume flow rate of the solution. The positive-displacement volume of the gear pump was determined in calibration experiments with water and oil with the aid of a syringe pump. The gear pump was mounted on a tandem extrusion line. The temperature of melt was precisely controlled and homogenized by using the second extruder and a heat exchanger, which included a static mixer. The pressure was controlled by the rotational speed of the screw in the second extruder. In order to reduce leakage across the gear pump, the difference between the upstream and downstream pressures was minimized using a variable resistance die attached to the downstream outlet of the gear pump. A critical set of experiments was carried out to measure the specific volumes of various pure polymers. (Abstract shortened by UMI.)
The effects of aging and time-distorted speech material on short-term memory performance

Many age-related changes in perception and cognition have been reported. Well documented is a decrease in several aspects of perceptual as well as cognitive processes. In fact, perceptual and cognitive processes are largely correlated in older adults. This led to the suggestion that changes in perception may cause changes in cognition. Studies testing this hypothesis demonstrated that when younger and older adults were equated for the degree of perceptual stress age differences disappeared on several cognitive tasks. Indeed, when listening situations have been equated it appears that the ability to use linguistic knowledge and context improve with age (Pichora-Fuller, Schneider, & Daneman, 1995; Speranza, Daneman, & Schneider, 2000). In order to compensate for age-related losses older adults are believed to develop certain skills and to reallocate available processing resources. In the present study younger and older adults were equally perceptually stressed by manipulating the temporal aspects of speech in a paired-associate recall paradigm of unrelated words. Twenty-five younger and 25 older participants were tested in two experiments. Adjusting for perceptual stress along a temporal dimension did not eliminate age-differences in cued-recall such that a decline of memory performance with age was observed. Indeed, temporal distortion did not contribute to the age differences in performance. The results are compared to similar studies in which babble and white noise were presented to equate perceptual stress. Differences in performance across studies are interpreted in terms of perceptual learning and the reallocation of processing resources.
Hydraulic linkage between the cerebrospinal fluid compartment and cervical lymphatics

Previous reports have demonstrated that about one-half of the total volume of cerebrospinal fluid (CSF) removed from the cranial vault in sheep is transported into extracranial lymphatics, especially cervical lymphatic vessels in the neck. It has also been noted that increasing intracranial pressure results in elevated recovery of a CSF protein tracer in cervical lymph. In this study we tested the hypotheses that an elevation of intracranial pressure (ICP) would increase cervical lymphatic pressure and lymph flow rates in anesthetized sheep, and that blockage of CSF access to cervical lymphatics would increase resistance to CSF outflow (Rout). To test the relationship between ICP and cervical lymphatic pressure and flow, catheters were inserted into both lateral ventricles, the cisterna magna, cervical lymphatics and jugular vein. To test the effect of blocking access of CSF to the cervical lymphatics, a catheter was inserted into one lateral ventricle and the cisterna magna. A constant-flow syringe pump was used to administer bolus injections of artificial CSF, and the extracranial aspect of the cribriform plate was exposed and sealed. (Abstract shortened by UMI.)
Linearizable shared objects for asynchronous message passing systems

We consider linearizable implementations of shared objects in asynchronous message passing systems using failure detectors. Objects are replicated for reasons of fault-tolerance, and Atomic Multicast is used to ensure that the same sequence of operations is performed on each replica. However, for an object implementation to be linearizable, the ordering of this sequence must be consistent with the real-time ordering of operations. We identify a property called Linear Order that allows this constraint to be met, and show that this property is satisfied by every Atomic Multicast algorithm. Operations that do not modify an object's state do not require the ordering semantics of Atomic Multicast. We therefore define a new multicast primitive, called Linear Multicast, that satisfies Linear Order without totally ordering messages, and allows these operations to be implemented efficiently. We also show that Chandra and Toueg's Atomic Multicast algorithm can be enhanced to also implement Linear Multicast.
The Triangle Program, experiences of lesbian, bisexual and gay students in the classroom

Toronto has an alternative high school program, the Triangle Program, for students who leave school because of homophobia. Eleven Triangle Program students were asked about the following: why they came to the program; their experiences at other schools; the advantages and disadvantages of the program; and how had it developed their social, emotional and intellectual skills. Four of the Triangle Program staff were asked about the following: the strengths and weaknesses of the program; the needs that it meet; the barriers that it had to overcome; and the ways in which issues of race, gender and bisexuality were integrated into the lesbigay curriculum. The data obtained showed that these lesbigay students, had little support from educators, family and peers and had endured severe homophobic harassment in their former schools. The Triangle team provided the safety and the social, psychological, academic and economic support lesbigay youth needed to continue with their education. However, issues surrounding race, gender, bisexuality and the transition into other schools needed to be addressed.
Maternal attributions and attachment

This research investigated the relationship between a mother's attributional style and representations of attachment, measured by the AAI. It is hypothesized that the cognitive schema's defined by each of the theories may be describing a similar cognitive appraisal process. Attributional style was measured in two ways. One method involved the completion of inventories that assessed dimensions of attributional style. To supplement the inventories a qualitative assessment of global and specific attributional styles was performed. The results revealed a significant relationship between the qualitative assessment of the global/specific attribution dimensions and attachment. The specific dimension was evenly distributed between attachment categories. However, the global dimension significantly differentiated secure mothers from those classified as insecure. Insecure mothers did not make responses that reflected the global dimension. None of the attributional dimensions assessed through the questionnaires were significantly related to representations of attachment. The results provide preliminary evidence suggesting that attributional processes may be related to attachment security.
Structural studies of two macromolecular complexes, the synaptic complex of Cre recombinase and the decameric structure of rattlesnake venom lectin

Recent advances in synchrotron sources, detector technology, software and computing capabilities have made the determination of large macromolecular complexes easier today than ever before. In this thesis, I describe the work done towards the determination of the three dimensional structures of two macromolecular complexes, the Cre synaptic complex and the decameric structure of Rattlesnake Venom Lectin. Cre recombinase is a member of the integrase family of conservative, site-specific recombinases that share a common catalytic mechanism involving a 3'-phosphotyrosine linkage between the protein and the DNA target. With the aid of half-site oligonucleotides that trap an intermediate of the recombination reaction, I purified a stable complex called the synaptic complex. Steps leading to the purification and crystallization of the Cre synaptic complex, including preliminary experiments conducted with a related protein, Flp recombinase, are described. Preliminary results from X-ray data collection experiments indicate that the Cre synaptic complex, as prepared by the methods described in this thesis, diffract to at least 2 Å. Rattlesnake Venom Lectin, a member of the C-type lectin family, contributes to the aggregation of platelets in a calcium and galactose dependent manner, although its physiological role has yet to be determined. Using a combination of multiple isomorphous replacement techniques and molecular replacement, I solved the 2.2 Å structure of this lectin. The structure forms a decamer composed of two disk-like pentamers, each 104 Å by 32 Å, joined together by disulphide bonds. A large internal cavity, of unknown function, is found in the structure between the two pentameric disks. The arrangement of the monomers in the pentamer involves a novel interface for C-type lectins, and illustrates the versatility of the modular carbohydrate recognition domain. The ten carbohydrate binding sites, each occupied by lactose in the RSL-lactose co-crystal complex, are positioned along the rim of the structure and suggest a role for multivalent interactions.
Formalizing requirements in a commercial setting, a case study

Formal description techniques (FDTs) have long been advocated as a solution to problems posed by requirements specified in natural language; however, successful applications of FDTs have been confined mostly to safety-critical projects. This thesis describes a research project conducted in collaboration with Nortel to investigate the technical and the economic feasibility of applying FDTs in a commercial setting. By first interviewing the Nortel engineers, we identified problems with their development process and proposed criteria for our quantitative formal description method evaluation. We selected a method that was suitable to our project and usable in the Nortel environment and applied it to a multimedia-messaging subsystem; the resulting model was used to identify requirements errors and to derive test suites, shadowing the existing development process and keeping track of a variety of productivity data. By amortizing the cost of formalization to the testing phase, we showed that the use of FDTs could increase the quality of the software without lengthening the development cycle.
Distribution and the circadian regulation of Gq/11[alpha] porteins in the vertebrate retina

Recent studies have demonstrated that the retina of mammals contain an intrinsic circadian clock. The molecular components of this machinery have not been entirely identified. The expression of some signal transduction proteins have been shown to oscillate over a 24 hour light-dark cycle and as such they may play an important role in circadian regulatory processes. I have used this system to explore the cellular distribution and circadian regulation of Gq/11$\alpha$ in rat retina. Gq/11$\alpha$ was found to be expressed in the inner and outer plexiform layers of the retina. Quantitation of Gq/11$\alpha$ and Gt$\alpha$ concentrations during light-dark cycles indicate that their concentrations change in a cyclic manner. The regulation of Gq/11$\alpha$ and Gt$\alpha$ were determined to be circadian in nature by quantitating G protein concentrations under constant dark and light conditions. My results also suggest that Gt$\alpha$ and Gq/11$\alpha$ concentrations may be regulated through different mechanisms. These findings may help us understand circadian regulatory mechanisms within the retina and their role in maintaining the health of the retina.
Stress response syndrome in first-episode schizophrenia

The primary purpose of this secondary analysis was to understand whether the psychological experience of the individual in response to an initial episode of schizophrenia encompasses attributes of stress response syndrome. An additional purpose of the study was to assess the construct validity of the Impact of Event Scale (ILES) designed to measure the stress response symptoms of intrusion and avoidance in the first episode schizophrenia population. Data from thirty eight participants who completed the study instruments that measure stress response syndrome, engulfment, hopelessness, symptomatology, and coping were used to answer the research questions and address the study hypotheses. The study results provide evidence for the presence of stress response syndrome in individuals recovering from a first episode of schizophrenia. Although the results did not provide support for the construct validity of the IES with the first episode schizophrenia population, emotion oriented coping was found to be a moderating variable between stress response syndrome and engulfment.