VictorJuiz/thesis huggingface dataset:
Understanding RAR[alpha] chimeric proteins associated with acute promyelocytic leukemia: evidence supporting the deregulation of NPM in APL

Nearly all cases of acute promyelocytic leukemia (APL) are associated with the expression of the PML-RARα chimeric protein that has been strongly implicated in APL pathogenesis because of its interactions with growth suppressors and retinoid signalling molecules. Rare variant APL translocations result in fusion genes that also encode RARα chimeric proteins, which in addition to altering retinoid signalling, may contribute to APL by disrupting RARα partner protein function. We describe the molecular characterization of a variant t(5;17)(q35;q21) APL translocation. Nucleophosmin (NPM) was identified as the RARα partner gene on chromosome 5. The effects of the NPM-RARα chimeric protein on the intracellular localization of PML, RXRα, NPM and PLZF were examined, in situ . In patient t(5;17) APL cells, PML localization was normal whereas NPM and PLZF localization was disrupted. NPM, RXRα and NPM-RARα co-localized in the nuclei of these cells. Full-length NPM-RARα cDNA molecules were generated by a modified overlap extension PCR. To target RARα chimeric proteins, we engineered epitope-tagged versions of PML-RARα, PLZF-RARα, NPM-RARα and NuMA-RARα (X-RARαV5) and generated stable COS cell lines expressing X-RARαV5. Strikingly, X-RARα proteins displayed distinct intracellular localization patterns, in situ. NPM and NuMA co-localized and interacted with NPM-RARα and NuMA-RARα, respectively. In patient APL cells expressing PML-RARα, we observed that NPM was delocalized in a manner similar to that observed in t(5;17) patient cells. This unexpected result prompted us to examine whether NPM played a more universal role in APL. In COS X-RARαV5 cells, NPM localization and expression appeared deregulated. A novel interaction between NPM and RXRα was observed in preliminary experiments, which led to the hypothesis that NPM may play a role in retinoid signalling. Our data support the hypothesis that X-RARα proteins play a major role in APL pathogenesis by sequestering retinoid signalling factors and RARα partner proteins. The distinct intracellular localization patterns, combined with the shared ability of X-RARα to interact with X, further implicate disrupted X function in the development of APL. To our knowledge, our studies are the first to show evidence that NPM deregulation may be a common molecular consequence in APL, and that NPM may play a role in retinoid signalling.
Objectified knowledge and abstracted discourse: Excluding abused women's lived realities from Canadian child custody law

Research into abused women's experiences of the family law system reports that they experience a profound sense of betrayal, as they disclose intimate violence to various professionals. Consistently, these studies show that women's revelations are distorted and minimized in custody negotiation processes and then ignored as women are pressured to accept difficult and, at times, dangerous custody arrangements. These experiences occur fundamentally because the system is permeated with objectified knowledge and particularized discursive meanings and images about high conflict violence, abused women, children's best interests, and the 'proper' family. This dissertation presents the findings of an institutional ethnography of abused women's experiences of custody negotiation. Data were collected through 32 in-depth interviews with abused women of differing social locations, women's advocates, family law lawyers, and child custody mediators and assessors. The analyses document how women's experiences of intimate relationship violence---fear, isolation, pain, and anger---become inserted into, altered, and silenced by disciplinary knowledge---the standardized, official accounts produced by policy, institutional, and professional discourses and practices. Interviews with professionals revealed how their routine and mandated practices altered women's stories, so that these are hearable within the system. The thesis concludes by discussing the implications of the findings for professional practice, policy, and research.
Idiom comprehension: typical development, and atypical function and relations with corpus callosum dysmorphology in children with spina bifida and hydrocephalus

Idioms are phrases with a figurative meaning that is not evident from the literal meaning of the phrase. Comprehension of idioms in adults varies with compositionality (the extent to which the idiom parts contribute to figurative meaning), literality (the extent to which a literal interpretation is plausible), and the presence of a supportive linguistic context. It is not known how these features affect the development of idiom comprehension. While nondecomposable and decomposable idioms may differ with respect to both acquisition and mature function (e.g., Gibbs et al., 1989a; Gibbs, 1991), the details of acquisition over the school years has not been studied. Literality influences on idiom processing have been described in adults (e.g., Popiel & McRae; Cronk & Schweigert, 1992), but not children. Finally, the underlying neural bases of idiom processing are largely unknown. This thesis reports three studies designed to investigate the normal development, aberrant development, and neural bases of idiom comprehension: a normal developmental study of acquisition of idiom comprehension in typically developing children, a study of aberrant development in children with spina bifida, and a study of developmental brain dysmorphology in the corpus callosum, which is considered important for figurative language. The results of this series of studies provide converging evidence that the two forms of idiom, decomposable and nondecomposable, are developmentally, functionally, and neuroanatomically distinct. Study 1 showed that the two forms of idiom have different acquisition courses. Study 2 showed that the two forms are differently affected by a neurodevelopmental disorder. Study 3 showed that idiom comprehension varied with dysmorphology of the corpus callosum. Further, all three studies suggest that both the literal and figurative meanings of idioms are accessed and must be suppressed during idiom processing in childhood, at least in children with poor comprehension. The results also suggest that the corpus callosum is important for interhemispheric transfer during idiomatic language processing. Moreover, they suggest that both cerebral hemispheres may be important for processing of nondecomposable idioms and more literally plausible idioms, while decomposable idioms and less literally plausible idioms may be processed with less integration of information between the two hemispheres.
The experience of growing up in tandem with another and its implications for parenting and educating: an inquiry into the stories of twins and other multiples

Within this paradigm, alternate texts---story, poetry, drawing, photograph, and interview transcript---are used to communicate knowledge when traditional prose cannot. Accordingly, my co-twin and I, along with 24 multiple-birth participants, share our experiences of growing up in tandem with another in a variety of these forms. The result is a blend of descriptive and interpretative prose. A descriptive writing style is used in the literature review and methodology chapters. The remaining chapters blend descriptive and interpretative prose to introduce, support, and reflect on participant interviews. Meaning is generated by placing my multipleship, the interpersonal relationship between my co-twin and me, beside my participants' experiences. In this dissertation, I engage hermeneutic phenomenological inquiry as articulated by Max Van Manen (1990) to explore the question, " What is the experience of growing up in tandem with another and its implications for parenting and educating?" In this text, the phrase, "growing up in tandem with another", refers to individuals born in twos (twins) and threes (triplets). While other approaches to hermeneutic phenomenological inquiry exist within the area of curriculum inquiry (Short, 1991), I chose this method for its strong pedagogical orientation. I discover that the multiple-birth experience is a complex construct. It is composed of numerous inter-connected and multi-dimensional (Bartel and Radocy, 2002) themes that organize into four analytical categories: complex, challenging, dynamic, and emotional. The core of this document consists of explicating each category, their connected themes, the stories, interview transcripts, and/or drawings that support them, and the pedagogical practices that link to them. The practices form the "so what" (Wolcott, 1990) of this research, its practical value to parents and teachers of multiples and to multiples themselves. Personal reflections and resonations (Conle, 1996) along with salient comments from multiple-birth educators, psychologists, and researchers, parallel each stage.

Keywords: Twins, Psychology
Twins, Education
Multiple birth, Psychological aspects
Parenting
Long-distance quantum key distribution over telecom fiber

We present two long-distance quantum key distribution (QKD) systems over telecom fiber. The first one is the Sagnac QKD system implementing standard BB84 protocol. Novel polarization-insensitive phase modulators are used to simplify the conventional architecture. We are able to achieve a stable quantum bit error rate of 4-6.5% over 40km fiber loop over one hour without recalibration. The second one is the fiber-based QKD system using Gaussian-modulated coherent states. We have overcome the challenges imposed by the requirements for high detector sensitivity, long-term stability, and low signal crosstalk. Our GMCS QKD system is the first practical fiber-based one-way demonstration and is able to achieve a sifted secret key rate of 15.5 kbits/s over a transmission distance of 5km fiber. Experimental QKD is still in its infancy. The results presented in this thesis represent a significant step forward towards the practical QKD over conventional fiber networks.
Decentralized diagnosers in a state-based framework

2007 Fault diagnosis in the state-based discrete-event system framework is studied. First, the resonating-cycle test for diagnosability of centralized diagnosers is derived, leading to an efficient algorithm which significantly reduces computational complexity. Second, design parameters of agents and communication protocols of decentralized state-based diagnosers are examined. Third, basic principles for state estimation are derived, and a simple condition to test consistency of state estimators is determined. Finally, three decentralized state-based diagonsers (DSBDs) are studied in detail. DSBD A involves communication of observations. It can be decoupled into subsystems which can be analyzed using earlier methods. Algorithms to optimize DSBD A networks are examined. DSBD B involves communication of observations and confirmed faults. DSBD C involves communication of observations and fault estimates. For both DSBD B and DSBD C, a consistent state estimator is specified, and diagnosability conditions stated. A structure-based diagnosability test is also derived for DSBD B.
Studies of stimuli-responsive hydrogel nanoparticle containing membranes and the development of a closed-loop glucose-responsive insulin delivery device

The purpose of this Ph. D project was to study the mechanism of pH- and glucose-responsiveness and properties of polymeric composite membranes containing pH-sensitive poly(N-Isopropylacrylamide-co-metharcylic acid) hydrogel nanoparticles for controlled drug delivery, and to develop a closed-loop glucose-responsive insulin delivery device using these pH-sensitive hydrogel nanoparticles. The internal pH kinetics and spatial distribution of the membranes were studied using a ratiometric fluorescence dye pH mapping methodology. Approaches to improving the physicochemical and mechanical properties of the stimuli-responsive membranes were explored. Finally, a closed-loop glucose-responsive insulin delivery device regulating insulin delivery in response to changes in glucose concentration was developed and tested under in vitro conditions in this thesis.

Keywords: Pharmacy
Reconciling conflicts between trademark and geographical indications: how to protect geographical indications in China

Now, old mode (certification mark mode) and new mode (registration of geographical indication mode) to protect geographical indication (“GI”) co-exist in China. However, many challenging legal concerns under this dual protection model have arisen as a result. This thesis aims to analyze the relationship between GI and trademarks and examine the issues under the dual modes of protection in China. The central argument I advance is: Since there are differences between trademarks and GIs in right holder and right execution, conflicts thus arise under the co-existing protection modes. I choose four typical cases to highlight the various conflicts. After studying the rules and proposals in TRIPS Agreement and international organizations, I tentatively propose some suggestions to resolve the issues resulting from the dual protection. I conclude that “first in time, first in right” priority may be as a basic principle to resolve such issues in the future.

Keywords: Trademarks, China
Patent laws and legislation, China
Copper-catalyzed cross-coupling reactions of organotrifluoroborate salts and organoboronic acids: Formation of enol esters and sulfones

This thesis includes two chapters. Chapter one describes enol ester formations from carboxylate salts and alkenyl potassium trifluoroborate salts. The optimized conditions utilize a catalytic amount of copper (I) salts with DMAP as ligand/base in MeCN at 60°C over 24h under an atmosphere of oxygen in the presence of 4Å molecular sieves. This protocol was extended to carboxylic acids as coupling partners without adding extra base. Chapter two describes a mild protocol for preparation of aryl and alkenyl sulfones from organoboronic acids and sulfinic acid salts. The method tolerates a wide variety of substituents on the boronic acid, including amide, aldehyde, halide and nitro functionalities, as well as ortho-substituents. In general, the reaction is found to be influenced by electronic factors on the boronic acids, with neutral and electron-rich organoboronic acids giving good to excellent yields of the sulfones.
Proteomic investigation of biosynthesis exopolysaccharide by Ophiostoma ulmi

The dutch elm tree disease casual agent, Ophiostoma ulmi, was investigated for its ability to produce exopolyssacharides (EPS), which have great industrial potential. This is the first proteomic work based on O. ulmi. EPS biosynthesis was studied using proteomics tools with the purpose of identifying the proteins/enzymes that were responsible for EPS biosynthesis. The extracellular O. ulmi protein profile under various culture conditions was obtained with SDS PAGE and then compared. The gel bands were then excised and treated with trypsin, followed by protein identification by a matrix assisted laser desorption/ionization time of flight (MALDI-TOF) instrument. It was found that sucrose synthase, acyl carriers proteins and various transferases were induced by substrate (sucrose), or nitrogen source (asparagine), which indicated an intracellular biosynthesis pathway. However, glucoamylase, another protein that could be involved in the extracelluar synthesis also appeared. A future study of intracellular proteins is suggested.
A 1.8 V 2.5 GHz PLL with on-chip charge pump-based supply regulation

This thesis presents a fully integrated PLL with an on-chip low-dropout supply regulation using a capacitive DC-DC converter. The design is implemented in TSMC CMOS 6M/1P 0.18 mum technology with a nominal supply voltage of 1.8 V.A charge pump boosts up the reference voltage to 2.5 V, which is then regulated to provide a 1.5 V supply to the PLL. The regulator has achieved a PSR of>-28 dB in simulation, but the measured result is only -18 dB at best. The 1.5V PLL is designed with a fully differential control path and operates at frequencies ranging from 1.5 GHz to 3 GHz with a currentsteering amplifier based ring oscillator. The PLL achieves a cycle-to-cycle jitter level of 11.1 ps RMS with a quiet supply. After the regulator, a jitter level of 46 ps RMS is achieved with +/-5% 2 MHz square wave on the supply. The total power dissipation is 22 mW for the PLL with the regulator.
Radioimmunoimaging of p21(WAF-1/CIP-1) intracellular epitopes in breast cancer

Radioimmunoimaging of intracellular epitopes in tumours is restricted by the inability of most immunoglobuline (IgG) to traverse the cell membrane. It was hypothesized that 13-mer peptides [GRKKRRQRRRPPQ] harboring the membrane translocation and nuclear import sequences of HIV-1 tat protein (underlined) site-specifically linked to the Fc-domain of monoclonal antibodies would be able to image intracellular epitopes such as the cyclindependent kinase inhibitor, p21WAF-1/CIP-1, in breast cancer xenografts in athymic mice. The response of the p21WAF-1/CIP-1 gene in MDA-MB-468 and MCF-7 breast cancer cells to selected treatments [gamma-radiation, campotothecin, or human epidermal growth factor (hEGF)J was studied. Moderate (up to 2-5-fold) increase in p21WAF-1/CIP-1 was detected by Western blot. Prototypic immunoconjugates were constructed by conjugating the tat peptides to periodate-oxidized mouse IgG (mIgG) through a Shiff base linkage. Tat-mIgG was labeled with 123I. Tat-mIgG showed a 15-fold decrease in binding affinity for anti-mouse IgG (Fab specific) antibodies (alpha-mFab) compared to mIgG. The binding of 123I-alpha-mFab to lysate from MDA-MB-468 cells importing tat-mIgG was 17-fold higher than to lysate from unexposed cells. Imported tat-mlgG competed with tat-mIgG for displacement of binding of 123I-mIgG to alpha-mFab. Nuclear localization was observed in vitro for 123I-tat-mIgG, which was significantly higher than 123I-mlgG in three phenotypically different human breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB468). Nuclear localization was also found in vivo in MDA-MB-468 tumour xenografts and in cells of the liver, spleen, and kidneys of athymic mice following intravenous injection of 123I-tatmIgG. Conjugation of mIgG to tat peptides had no effect on its biodistribution. Specific tat-antip21 WAF-1/CIP-1 monoclonal antibodies (tat-alpha-p21WAF-1/CIP-1) immunoconjugates were then constructed. Nuclear localization of 123I-tat-alpha-p21WAF-1/CIP-1 in MDA-MB-468 cells was significantly higher than for 123I-alpha-p21WAF-I/CIP-1 . Imported tat-alpha-p21WAF-1/CIP-1 blocked G 1 arrest in MDA-MB-468 cells caused by hEGF-induced p21WAF-1/CIP-1 Tumour uptake of 123I-tat-alphap21WAF-1/CIP-1 24 hours after intravenous injection in athymic mice was significantly higher following intratumoural injections of hEGF to induce p21WAF-1/CIP-1 than in mice not receiving hEGF or mice injected with 123 I-alpha-p21WAF-l/C1P-1 and receiving hEGF. 123I-tat-alpha-p21WAF-1/CIP-1 showed increased tumour uptake on images of hEGF-injected mice compared to control mice. Further optimization of the tumour signal is required. I conclude that tat-immunoconjugates are promising vehicles for radioimmunoimaging of p21WAF-l/CIP-1 intracellular epitopes in breast cancer.
A new cross-linked dendrido hemoglobin

A hexa-functional acyl methyl phosphate monoester N, N', N"--Tris[bis(sodium methyl phosphate) isophthalyl)-1,3,5-Benzenetricarboxylate was synthesized with commercially available reagents. This multifunctional acylating reagent selectively cross-linked hemoglobin tetramers through beta domains. The highest molecular weight product appears to be a cross-linked dendrido hemoglobin containing a total of the equivalent of five alphabeta dimers and a molecular weight of 160 kDa. Reaction with a three-fold excess of linker reagent and deoxyhemoglobin in sodium borate buffer (0.05 M, pH 8.5) at 37°C gave the best yield ( sim;46%) of this cross-linked dendrido hemoglobin. The products were isolated by gel filtration chromatography. The high efficiency and specificity of this hexa-functional site-directed acylating reagent to cross-link hemoglobin make it a potential candidate to produce cross-linked hemoglobin dendrimers as a possible red cell substitute. The properties of this reagent also verified that multifunctional site-directed acylating reagents might specifically modify proteins with better efficiency.
Acutely increasing alpha calcium/calmodulin-dependent protein kinase II in lateral amygdala enhances auditory fear conditioning memory

Alpha calcium/calmodulin-dependent protein kinase II (alphaCaMKII) is a calcium-activated enzyme that is highly expressed in the brain. Previous studies show that disrupting alphaCaMKII function impairs several forms of memory. In the present study we assessed the effects of locally increasing alphaCaMKII levels on memory. To this end, we used a replication-defective herpes simplex viral (HSV) vector to express alphaCaMKII or control vectors into the lateral amygdala (LA), a region known to be critical for auditory fear memory. Mice received bilateral microinfusion of HSV vectors aimed at the LA 2 days before fear conditioning training. During fear conditioning a tone was paired with a shock. Memory was assessed 24 hours following training as the percentage of time spent freezing during subsequent tone presentation. We found that acutely increasing aCaMKII levels in LA neurons enhanced auditory fear memory. Importantly, locomotor activity and anxiety behaviour were not altered by overexpression of alphaCaMKII, suggesting that the observed increase in fear memory cannot be attributed to a non-specific increase in anxiety. These findings indicate that local and acute overexpression of alphaCaMKII enhances fear memory.
The river of radical imagination: community arts and the promise of integrative feminist values

This thesis explores the often-unacknowledged promise of radical feminist values at the heart of progressive community arts practice. It makes visible feminist values that are central to community arts while proposing new levels of commitment to these values, informed by integrative feminist theory, lived community arts practice and scholarly reflection on that practice. As a contribution to an ongoing conversation between community-based artists and practitioners, this thesis offers a vision for community arts practices that aim to reinstate to the centre the multiple meanings and desires of our human lives: our beliefs; our ideas, inventions and artistry; our hopes and dreams, our loves; our ability to celebrate and mourn; our viable future on this planet.

Keywords: Community arts projects, Ontario
Feminism and art, Ontario
Feminist theory
Feminist ethics
Women's shelters, Ontario
Aesthetics
Investigating the role of VSX1 in corneal dystrophies

Posterior polymorphous corneal dystrophy (PPCD) is an endothelial dystrophy mapped to 20p 12-q 12 (PPCD1). Mutations in VSX1, a transcription factor of the disease interval, were found in PPCD and keratoconus patients. However, no change was identified in the family used for mapping the locus. This thesis explores the possible additional mutation mechanisms to clarify the pathogenicity of VSX1 in corneal dystrophies. Six (4 novel) transcript variants of VSX1 were characterized by a 3'RACE assay but did not show any mutations in PPCD1 families. Six cis- regulatory modules were predicted in the vicinity of VSX1 (100 kb) but did not reveal any disease-associated mutations. Semiquantitative real-time RT-PCR detected expression of VSX1 in neonatal human cornea. Recombination events refine the disease interval in the original PPCD1 family from 20 to 16.44 cM. The refined interval contains CHED1 and a recently described PPCD locus for Czech families. Mutation analysis of PPCD1 families did not reveal any mutations in two candidate genes of the new interval.