VictorJuiz/thesis huggingface dataset:
Investigation of Accelerometry, Mechanomyography, and Nasal Airflow Signals for Abnormal Swallow Detection
Keywords: biomedical signal processing
deglutition
dysphagia

Dysphagia (swallowing disorder) is a common health problem that degrades the quality of life of many people. The videofluoroscopic swallowing study (VFSS) is the current gold standard in dysphagia assessment but is associated with high cost, long wait times, and a lack of portability. As a result, there is a pining need for an alternative technique that can serve day-to-day monitoring of dysphagia as well as screening for VFSS referral. The primary objective of this thesis was to investigate three non-invasive signal modalities, namely dual-axis accelerometry, submental mechanomyography (MMG), and nasal airflow, for their potential as alternatives to VFSS. To this end, signals were acquired from 17 healthy individuals and 24 patients with dysphagia, with various stimuli. In a characterization study, the anterior-posterior (A-P) and superior-inferior (S-I) axes in dual-axis accelerometry were found to contain non-overlapping information about swallowing, justifying the extension of single-axis (A-P only) to dual-axis (A-P and S-I) accelerometry. Also, several dual-axis accelerometry signal features were found to be stimulus dependent, and the observed stimulus effects were linked to slower swallowing function with increasing bolus viscosity. Age and stimulus effects on submental MMG were scrutinized, as an analogy to previous electromyography (EMG) studies of similar design. Similarities to EMG confirmed the validity of MMG as a muscle activity measurement tool in swallowing research. Automatic swallow segmentation, which is a crucial precursory step to swallow diagnosis, was investigated with artificial neural networks. Segmentation performance was shown to improve as more signal modalities were included, verifying the value of multi-sensor fusion. When all signal modalities were utilized, an adjusted accuracy of 89.6% was achieved. Automatic discrimination between healthy and abnormal swallows was investigated in two studies. Using previously collected pediatric data, a radial basis classifier based only on A-P accelerometry resulted in an adjusted accuracy of 81.3% in aspiration detection. In an adult study, linear discriminant classifiers resulted in adjusted accuracies of 74.7%, 83.7%, and 84.2% for aspiration, valleculae residue, and pyriform sinus residue detection, respectively. It was concluded that the three signal modalities analyzed in this thesis possess promising potential for abnormal swallow detection.
The Biological Basis of Joint Ankylosis: Studies in the ank/ank Mouse
Keywords: Chondrocyte Hypertrophy
ank mouse
Osteoarthritis
Ankylosing Spondilitis

The first objective of my work was to use the ank/ank (progressive ankylosis) mutant mice, which have a deficiency in inorganic pyrophosphate transport, to address the role of Ank in joint ankylosis. I observed the presence of hypertrophic chondrocytes in the uncalcified ank/ank mice articular cartilage. This novel phenotype is likely due to a dysregulation of chondrocyte maturation as these chondrocytes expressed hypertrophic chondrocyte markers (collagen type X and tissue non-specific alkaline phosphatase). I also showed by immunohistochemical staining that beta-catenin expression was upregulated and localized in the nuclei of articular ank/ank chondrocytes, suggesting activation of Wnt/beta-catenin signaling in these chondrocytes. The second objective was to use ank/ank mice as an informative model for understanding ankylosis mechanisms in human ankylosing spondylitis (AS) patients, as WNT/beta-catenin signaling plays an important role in ankylosis in AS patients. We attempted rescue of joint ankylosis in ank/ank mice by gene transfer of noggin, an antagonist of BMP signaling. Paradoxically, noggin-treated ank/ank mice had accelerated ankylosis, as evidenced by joint pathology and IHC staining of beta-catenin showed more intense signals in the spinal chondrocytes of the treated mice. As noggin and sclerostin (an antagonist of beta-catenin signaling) form a mutually inhibitory complex, we hypothesize that the formation of this complex results in relieving suppression of both beta-catenin and BMP signaling, leading to more severe ankylosis in ank/ank mice. By quantitative molecular imaging, I have demonstrated that ankylosis in these mutant mice developed simultaneously in distal and axial joint, instead of being a centripetal process. In summary, I have made three original observations in the ank/ank mice: the hypertrophic chondrocyte phenotype; activation of beta-catenin signaling and the simultaneous development of ankylosis in distal and axial joints. These mutant mice serve as valuable model for pre-clinical studies which enable modeling and testing of novel anti-ankylosis treatments.
Measuring and Navigating the Gap Between FPGAs and ASICs
Keywords: FPGAs
FPGA to ASIC gap
Transistor Sizing
Area Delay Trade-offs

Field-programmable gate arrays (FPGAs) have enjoyed increasing use due to their low non-recurring engineering (NRE) costs and their straightforward implementation process. However, it is recognized that they have higher per unit costs, poorer performance and increased power consumption compared to custom alternatives, such as application specific integrated circuits (ASICs). This thesis investigates the extent of this gap and it examines the trade-offs that can be made to narrow it. The gap between 90 nm FPGAs and ASICs was measured for many benchmark circuits. For circuits that only make use of general-purpose combinational logic and flipflops, the FPGA-based implementation requires 35 times more area on average than an equivalent ASIC. Modern FPGAs also contain "hard" specific-purpose circuits such as multipliers and memories and these blocks are found to narrow the average gap to 18 for our benchmarks or, potentially, as low as 4.7 when the hard blocks are heavily used. The FPGA was found to be on average between 3.4 and 4.6 times slower than an ASIC and this gap was not influenced significantly by hard memories and multipliers. The dynamic power consumption is approximately 14 times greater on average on the FPGA than on the ASIC but hard blocks showed promise for reducing this gap. This is one of the most comprehensive analyses of the gap performed to date. The thesis then focuses on exploring the area and delay trade-offs possible through architecture, circuit structure and transistor sizing. These trade-offs can be used to selectively narrow the FPGA to ASIC gap but past explorations have been limited in their scope as transistor sizing was typically performed manually. To address this issue, an automated transistor sizing tool for FPGAs was developed. For a range of FPGA architectures, this tool can produce designs optimized for various design objectives and the quality of these designs is comparable to past manual designs. With this tool, the trade-off possibilities of varying both architecture and transistor-sizing were explored and it was found that there is a wide range of useful trade-offs between area and delay. This range of 2.1 X in delay and 2.0 X in area is larger than was observed in past pure architecture studies. It was found that lookup table (LUT) size was the most useful architectural parameter for enabling these trade-offs.
Sadomasochism Once Removed: S/m in the Socio-legal Imaginary
Keywords: Law
Sexuality
Psychiatry
Film
Gender

This dissertation considers sadomasochism (s/m) as an object of knowledge that incites multiple and interpenetrative discourses. I deconstruct psychiatric, feminist, and cinematic articulations of s/m, and consider the ways in which these narratives interact with each other and influence the legal regulation of s/m. My analysis is framed by Foucault’s account in the History of Sexuality, which helps to bring s/m into focus as a discursive product that emerges out of a “knowledge-power-pleasure” regime. Viewed in this light, I argue that when the scientific, feminist, cinematic and legal actors flex their power in producing truth-claims about s/m, this does not shut down pleasure, but proliferates it. To further interrogate the discursive underpinnings that uphold these truth-claims, I draw upon theories of abjection, disgust and expulsion. Part I traces the construction of s/m within the scientific realm, from the early pioneers in sexology, to the recent academic literature that challenges the pathologization of s/m in the Diagnostic and Statistical Manual of Mental Disorders. Part II surveys the “sex wars” in the eighties and nineties, where the issue of s/m (along with other sex-related issues) violently ruptured feminist communities. In Part III, I analyze the cinematic representation of s/m in popular culture, arguing that while the prevailing tone is pejorative, the narratives nonetheless betray a desire for s/m sexuality and its imagined forbidden pleasures. Part IV reviews the legal treatment of s/m pornography in Canada, which until recently has invariably found s/m imagery to be violent, degrading and/or dehumanizing, conspicuously reflecting the anti-s/m feminist perspective. Part V examines the legal treatment of s/m practice in Canada, in which the pathologizing gaze of psychiatry gets replicated. I argue that the law, rather than being a haven of rationality and coherence in its consideration of s/m, has reflected certain essentialist notions of sexuality produced in the non-legal cultural arena. In conclusion, I posit that the reification of s/m in the socio-legal imaginary allows for multiple entries of epistemic resistance. Attempts to foreclose s/m from the realm of acceptable sexuality have ironically offered sadomasochists frameworks for asserting their own subjectivity and membership in the community.
Periconceptional Iron Supplementation and Iron and Folate Status among Pregnant and Non-pregnant Women in Rural Bangladesh
Keywords: periconceptional, iron, folate, international nutrition

In 2007, Bangladesh’s national strategy to reduce anemia included adolescents and newly married women as target groups for iron and folic acid (IFA) supplementation. This thesis is comprised of a pilot study and a double-blinded randomized controlled trial (RCT) aimed at providing evidence-based research to inform decision-making on periconceptional IFA programs in rural Bangladesh. Results from the pilot study indicate that women who marry during adolescence had significantly longer intervals to first pregnancy compared to adult brides; however, the time interval was not long enough to delay family formation beyond adolescence. Education, age at marriage and contraceptive use were significant factors for delaying time to first pregnancy. The RCT examined the effect of daily periconceptional iron (60 mg) and folic acid (400 μg) vs. folic acid (FA) on iron and folate indictors. Of 272 women, 37% were anemic (Hb <120 g/L), 13% had low plasma folate levels (≤10 nmol), 15% were iron deficient (plasma ferritin <12 μg/L or TfR>4.4 mg/L), 11% were iron deficient and anemic and 81% were estimated to have <500 mg of iron stores. Adolescents had significantly lower plasma ferritin and body iron stores vs. adults. Among 88 pregnant women (PW), an interaction between treatment and adherence was significantly associated with change in Hb (p=0.04) and anemia (p=0.05). During pregnancy, group differences for iron status were not significant. Among NPW (n=146), IFA reduced anemia by 80.0% (95% CI: 0.04, 1.00, p=0.05) and significantly improved change in plasma ferritin concentrations by level of adherence in a dose-response relationship (p=0.01). In both groups, mean plasma folate concentrations increased from 16.9 to31.8 nmol/L and the prevalence of low plasma folate concentrations (<10 nmol/L) was reduced from 14% to 8%. Results suggest that periconceptional iron supplementation along with adequate folic acid intake is efficacious in reducing the prevalence of anemia during pregnancy and improving body iron stores before pregnancy when adherence is high. The effectiveness of periconceptional IFA supplementation remains unclear. Further research needs to examine maternal and infant functional and health outcomes, ways to increase adherence and cost-effectiveness.
Structural and Functional Studies of AlgK: A Protein Required for the Secretion of High-molecular Weight Alginate in Pseudomonas aeruginosa
Keywords: AlgK
x-ray crystallography
alginate
Pseudomonas aeruginosa

Alginate is an exopolysaccharide secreted by Pseudomonas aeruginosa and is a major component of biofilms that infect the lungs of cystic fibrosis patients. Ten proteins have been implicated in alginate polymerization, modification and export, and are believed to assemble into a multi-protein complex that spans the cell envelope and coordinates the synthesis and secretion of alginate. AlgK is a protein encoded in the alginate biosynthetic operon, which is required for the secretion of high-molecular weight alginate. This study describes structural and functional studies of AlgK to improve our understanding of AlgK’s role in alginate biosynthesis. To shed light on the function of AlgK, C14-palmitic acid labeling and sucrose gradient fractionation studies confirmed that AlgK is an outer membrane lipoprotein. Cellular fractionation experiments also found that AlgK is involved in the proper localization of AlgE, the alginate secretion pore in the outer membrane. The structure of AlgK was determined to 2.5 Å resolution by X-ray crystallography and revealed that the protein folds into 22 alpha-helices that pack into a flexible right-handed solenoid. Closer examination of the amino acid sequence revealed that AlgK carries 9.5 tetratricopeptide repeat (TPR)-like elements. Given the role that TPR motifs generally play in protein-protein interaction and the assembly of multi-protein complexes, the presence of these motifs in AlgK suggests that it can bind to one or more proteins. Based on the results presented in this study, we propose that AlgK acts as a scaffold for the assembly of the alginate secretion complex. By mapping highly conserved residues onto the surface of our model, three putative sites of protein-protein interaction were identified. We hypothesize that the N-terminus of AlgK binds to AlgE in the outer membrane, and the C-terminus of AlgK binds to periplasmic and/or inner membrane Alg proteins, thereby acting as a linker between the inner and outer membrane components of the alginate biosynthetic complex. We further hypothesize that together AlgE and AlgK constitute a novel exopolysaccharide secretin. The alginate biosynthetic complex appears to be distinct from the canonical capsular polysaccharide systems currently described.
Aspects of Composite Likelihood Inference
Keywords: Composite likelihood inference
Pairwise likelihood
Asymptotic relative efficiency
Higher-order asymptotics

A composite likelihood consists of a combination of valid likelihood objects, and in particular it is of typical interest to adopt lower dimensional marginal likelihoods. Composite marginal likelihood appears to be an attractive alternative for modeling complex data, and has received increasing attention in handling high dimensional data sets when the joint distribution is computationally difficult to evaluate, or intractable due to complex structure of dependence. We present some aspects of methodological development in composite likelihood inference. The resulting estimator enjoys desirable asymptotic properties such as consistency and asymptotic normality. Composite likelihood based test statistics and their asymptotic distributions are summarized. Higher order asymptotic properties of the signed composite likelihood root statistic are explored. Moreover, we aim to compare accuracy and efficiency of composite likelihood estimation relative to estimation based on ordinary likelihood. Analytical and simulation results are presented for different models, which include multivariate normal distributions, times series model, and correlated binary data.
Gene Expression Changes in Immune Cells During Human Immunodeficiency Virus 1 (HIV-1) Infection
Keywords: HIV
interferon response
gene expression
immune cells

Human immunodeficiency virus infection is a chronic condition causing significant changes in the immune system, which are reflected in the altered gene expression patterns of the immune cells. By studying these patterns through gene expression profiling it is possible to describe not only the current states the cells are in, but also to extrapolate the proximal signals that resulted in the observed patterns. In the studies described herein, we have applied this approach to better understand the alterations in the immune function that occur in HIV infection. First, we have obtained transcriptional profiles of CD4+ and CD8+ T cells from patients in early infection, in chronic infection, and in non-progressive infection, and we compared these profiles to each other and to the profiles from uninfected donors. The analyses of the profiles revealed no discernable changes in the T cells of the non-progressive patients when compared to the uninfected individuals. On the other hand, T cells from patients with progressive infection, both early and late, showed patterns characteristic of type I interferon (IFN) exposure. We next examined experimentally the possible proximal causes of the observed transcriptional profiles. We analyzed the gene expression patterns induced by TGFβ, 13 type I interferons, as well as recombinant HIV Tat protein, in T cells and peripheral blood mononuclear cells. The TGFβ responses were inconsistent with the transcriptional profiles seen in HIV-infected patients, whereas both type I IFNs and HIV Tat induced genes in patterns consistent with those seen in patients. In fact, the thirteen IFN-induced patterns were indistinguishable from each other. Tat treatments induced interferon-stimulated genes (ISGs) as well as other genes and the response was not dependent on the presence of plasmacytoid dendritic cells (pDCs), suggesting monocytes as the possible source of the interferon response. In the last study, we examined the responses of plasmacytoid dendritic cells (pDCs) to HIV and other stimuli in healthy and HIV-infected subjects. We observed induction of IFN genes in pDCs of all subjects in response to influenza virus and TLR7 agonist imiquimod, but not to HIV virus. In summary, HIV infection results in chronic induction of type I IFN response in cells of the immune system. The source of this response is likely to be type I IFNs produced by monocytes/macrophages rather than plasmacytoid cells. The monocytic production of type I IFN may be a Tat-dependent response.
Unprotected Amino Aldehydes in Organic Synthesis
Keywords: Amino aldehyde
aziridine
multicomponent
domino reaction
cyclic peptide
macrocyclization
amphoteric
protecting group free

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.
Protecting Group-free Chemical Modifications on Carbohydrates
Keywords: Carbohydrates
Glycosidation

The synthesis of glycoconjugates has facilitated a wide variety of techniques for the detailed study of carbohydrates and their interactions in biological systems. However, when only small amounts of the isolated oligosaccharide are available, multistep synthetic approaches are not possible. This thesis explores new synthetic methods for the preparation of glycoconjugates without protecting group manipulations. A new glycosidation method was developed which introduces N-glycopyranosylsulfonohydrazides as glycosyl donors for the protecting group-free synthesis of O-glycosides, glycosyl azides and oxazolines. The glycosyl donors were synthesized in a single chemical step by condensing p-toluenesulfonylhydrazide with the corresponding mono- and disaccharides. The N-glycopyranosylsulfonohydrazides were activated with NBS and subsequently glycosylated with the desired alcohol or transformed to the oxazoline or glycosyl azide. Recent advances in chemoselective ligation methods for the functionalization of unprotected carbohydrates have provided new routes towards complex glycoconjugates. Despite the wide use of those chemoselective methods, the properties of these linkages have not been thoroughly investigated. Characterization of a series of glycoconjugates formed by chemoselective ligation of xylose, glucose and N-acetylglucosamine with either an acyl hydrazide, a p-toluenesulfonylhydrazide or an N-methylhydroxylamine were carried out to gain further insight into the optimal conditions for the formation and the stability of these useful conjugates. Their apparent association constants (9-74 M-1) at pD 4.5, as well as rate constants for hydrolysis were determined at pH 4.0, 5.0 and 6.0. The half-lives of the conjugates varied between 1 h and 300 days. All the compounds were increasingly stable as the pH approached neutrality. Finally, selective chemical modification of a glycosaminoglycan chondroitin sulfate was attempted at the non-reducing end by utilizing the Δ4-uronic acid functional group formed upon cleavage of the glycosaminoglycan with a bacterial lyase enzyme. The captodative double bond of the unique Δ4-uronic acid functionality was unreactive towards Michael addition, even if the carboxylate was methylated. Trials towards radical addition using thiyl radicals were unsuccessful, although a synthesized model phenyl Δ4-uronic acid monosaccharide was successfully functionalized under the same conditions.