Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Watson and Crick’s double-helical model of DNA is considered to be one of the great discoveries in biology. However, in 1976, two groups of scientists, one in New Zealand, the other in India, independently published essentially the same radical alternative to the double helix. The alternative, Side-By-Side (SBS) or ‘warped zipper’ conformation for DNA is not helical. Rather than intertwine, as do Watson and Crick’s helices, its two exoskeletal strands are topologically independent. Thus, unlike the double helix, they may separated during replication without unwinding. This dissertation presents, but does not arbitrate among scientific arguments. Its concerns are meta-scientific; in particular, why and how the individuals who invented the & ‘warped zipper’ came to do so. Against Popper and most recent philosophers of science, it is taken to be “the business of epistemology to produce what has been called a ‘rational reconstruction’ of the steps that have led the scientist to a discovery [Popper (1972), p.31, emphasis in the original].” On the received view, the invention of the ‘warped zipper’ must be irrational or, at best, non-rational thereby excluding from philosophical investigation. I establish that this philosophical dogma is not true a priori, as is usually supposed, and, in the case of the SBS structure of DNA, false a posteriori. The motivation for, and development of the SBS structure for DNA reveals a process best characterized as significantly, though not entirely, rational.

Watson and Crick’s double-helical model of DNA is considered to be one of the great discoveries in biology. However, in 1976, two groups of scientists, one in New Zealand, the other in India, independently published essentially the same radical alternative to the double helix. The alternative, Side-By-Side (SBS) or ‘warped zipper’ conformation for DNA is not helical. Rather than intertwine, as do Watson and Crick’s helices, its two exoskeletal strands are topologically independent. Thus, unlike the double helix, they may separated during replication without unwinding. This dissertation presents, but does not arbitrate among scientific arguments. Its concerns are meta-scientific; in particular, why and how the individuals who invented the & ‘warped zipper’ came to do so. Against Popper and most recent philosophers of science, it is taken to be “the business of epistemology to produce what has been called a ‘rational reconstruction’ of the steps that have led the scientist to a discovery [Popper (1972), p.31, emphasis in the original].” On the received view, the invention of the ‘warped zipper’ must be irrational or, at best, non-rational thereby excluding from philosophical investigation. I establish that this philosophical dogma is not true a priori, as is usually supposed, and, in the case of the SBS structure of DNA, false a posteriori. The motivation for, and development of the SBS structure for DNA reveals a process best characterized as significantly, though not entirely, rational.

The homeodomain leucine zipper (HDZip) proteins constitute a plant-specific family of transcription factors, that based on sequence criteria have been grouped into four classes, HDZip I-IV. This thesis describes the phylogeny, function, expression patterns and regulation of the HDZip class I genes in the model species Arabidopsis thaliana. The phylogenetic analyses, traced duplication history and exon/intron organisation of the 17 class I genes in Arabidopsis show that the genes form six monophyletic groups, clades, with an origin in early plant evolution. All genes are expressed in broad tissue distribution patterns and the majority are responsive to water availability and/or light conditions. The expression of the genes show different patterns and dependence on environmental stress conditions, indicating evolutionary changes within and between clades. Ectopic expression of the genes suggest that they regulate genes in part by conserved mechanisms. Therefore, different functional roles seem to have evolved by a divergence mainly in the regulatory properties of the genes. Detailed expression analyses of the paralogous HDZip I genes ATHB7 and ATHB12 show that they have essentially overlapping patterns of activity in response to abscisic acid, ABA, or water deficit in leaves, stems and roots. The water deficit response of ATHB7 and -12 is mediated by ABA and depends on the protein phosphateses ABI1 and ABI2. Transgenic plants with ectopic expression of ATHB7 and/or -12, and athb7 and athb12 mutants, reveal that the genes in roots mediate the growth inhibitory effects of ABA. In this aspect of their function they do not overlap. In leaves and stems, the genes might act as growth regulators redundantly with other factors. Taken together these data suggest that ATHB7 and -12 regulate growth in response water deficit and that other HDZip I genes have related functions in response to environmental stress conditions.

Chevron braced steel frames require large beams to redistribute the unbalanced vertical forces exerted on the beams after brace buckling. A new frame configuration similar to chevron brace was proposed in literature, where zipper columns were attached between mid-spans of the beams from second to top story. During severe ground motion, the unbalanced vertical forces caused by buckling of lower story braces are in this case redistributed to the upper story braces by these zipper columns. Consequently, all story braces buckle successively from first to top story brace instead of concentration of inelastic action in one story. This system has been improved recently by adding an elastic hat truss between the top two stories to prevent formation of a full zipper mechanism and to prevent collapse. Two-phase numerical study is undertaken in this study to evaluate the response of chevron and suspended zipper braced frames, where the objective of the first phase is to observe the change in the performance of the configurations for different sets of initial imperfection and rotational spring stiffness values. Rotational springs are added at the end nodes of the braces to represent the effects of gusset plates and initial imperfection is assigned to the mid-length of the braces to achieve proper buckling behavior. The objective of the second phase is to compare the response of chevron and suspended zipper brace frames. For this purpose, three, nine and twenty-story buildings are designed for both brace configurations. The designed buildings are analyzed under static and dynamic loadings.

This thesis explores how basic region/leucine zipper (bZIP) transcription factors target gene regulatory sequences. The GCN4 bZIP binds to more than one target site [CRE (TGACGTCA) and cognate AP-1 (TGACTCA)] and exhibits flexibility in -helical structure. These observations suggest that the GCN4 bZIP can establish sequence-selective DNA binding at noncognate target sites. Studies on such noncognate but sequence-selective binding can provide insights into how bZIP proteins search for and localize to their cognate target sites. This thesis investigates DNA binding by the GCN4 bZIP and its structural and functional mimic, the wild-type (wt) bZIP, at noncognate gene regulatory sequences C/EBP (TTGCGCAA), E-box (CACGTG), HRE (GCACGTAG), XRE1 (TTGCGTGA), and related DNA sequences. These DNA-binding activities are sequence-selective, as confirmed by DNase I footprinting and electrophoretic mobility shift assay (EMSA). Full- and half-site DNA-binding affinities, determined by EMSA titrations, decrease from cognate to noncognate binding. At noncognate target sites, the bZIP proteins form a dimer of -helices, as indicated by circular dichroism (CD) spectroscopy and EMSA. These results demonstrate that the bZIP proteins can establish noncognate but sequence-selective DNA binding, and suggest such DNA binding potentially contributes to structure preorganization and rapid translocation of the bZIP proteins when they search for their cognate target sites, to which they then bind with high affinity. This thesis also indicates a highly dynamic DNA-binding model for the bZIP proteins to establish strong and sequence-selective DNA binding. The C/EBP site includes two 5H-LR (TTGCG) half-sites, each of which comprises two 4-bp subsites. The in vitro and in silico results together demonstrate that the basic region at 5H-LR recognizes the 4-bp subsites alternately as distinct units, which requires it to translocate between the subsites, potentially by sliding or hopping. Taken as a whole, this thesis provides further insights into how bZIP transcription factors accomplish sequence-selective DNA binding.

This thesis explores how basic region/leucine zipper (bZIP) transcription factors target gene regulatory sequences. The GCN4 bZIP binds to more than one target site [CRE (TGACGTCA) and cognate AP-1 (TGACTCA)] and exhibits flexibility in -helical structure. These observations suggest that the GCN4 bZIP can establish sequence-selective DNA binding at noncognate target sites. Studies on such noncognate but sequence-selective binding can provide insights into how bZIP proteins search for and localize to their cognate target sites. This thesis investigates DNA binding by the GCN4 bZIP and its structural and functional mimic, the wild-type (wt) bZIP, at noncognate gene regulatory sequences C/EBP (TTGCGCAA), E-box (CACGTG), HRE (GCACGTAG), XRE1 (TTGCGTGA), and related DNA sequences. These DNA-binding activities are sequence-selective, as confirmed by DNase I footprinting and electrophoretic mobility shift assay (EMSA). Full- and half-site DNA-binding affinities, determined by EMSA titrations, decrease from cognate to noncognate binding. At noncognate target sites, the bZIP proteins form a dimer of -helices, as indicated by circular dichroism (CD) spectroscopy and EMSA. These results demonstrate that the bZIP proteins can establish noncognate but sequence-selective DNA binding, and suggest such DNA binding potentially contributes to structure preorganization and rapid translocation of the bZIP proteins when they search for their cognate target sites, to which they then bind with high affinity. This thesis also indicates a highly dynamic DNA-binding model for the bZIP proteins to establish strong and sequence-selective DNA binding. The C/EBP site includes two 5H-LR (TTGCG) half-sites, each of which comprises two 4-bp subsites. The in vitro and in silico results together demonstrate that the basic region at 5H-LR recognizes the 4-bp subsites alternately as distinct units, which requires it to translocate between the subsites, potentially by sliding or hopping. Taken as a whole, this thesis provides further insights into how bZIP transcription factors accomplish sequence-selective DNA binding.

Fish and fish waste can be used to produce various value added by products such as proteins, oil, omega-3 fatty acids, biodiesel, amino acids, peptides, collagen, gelatin and silage, each of which has various applications in the food industry, renewable energy and medicinal purposes. Fish protein contains amino acids and many bioactive peptides . Fish proteins are found in the flesh, head, frames, fin, tail, skin and guts in varying quantities. After removing the flesh, all other parts are considered waste which is not properly utilized. The aim of this study was to evaluate the enzymatic extraction of amino acids from fish protein for use as substrates in the microbial production of jadomycin, an antimicrobial agent and potential anti-cancer drug. In this study, enzymatic extraction of proteins was carried out using Alcalase enzyme at three enzyme concentrations (0.5, 1 or 2%) and four time intervals (1, 2, 3 and 4 h). The fish protein hydrolysate was dried using spray dryer to obtain protein powder. The highest protein yield (76.30% from whole fish and 74.53% from the frame) was obtained using 2.0% enzyme concentration after 4 h of hydrolysis. The enzymatic extraction of amino acids were carried out using the enzymes Alcalase and Neutrase (individually and in combination) and the effect of reaction time (24 and 48 h) on the hydrolysis of proteins was studied. The profiling of amino acids was carried out using gas chromatography. Fourteen amino acids were extracted from fish proteins of which twelve amino acids have been used by researchers for the production of jadomycins. These are: alanine (7.59%), glycine (5.82%), histidine (3.59%), isoleucine (5.30%), leucine (9%), lysine (7.34%) methionine (2.2%), phenylalanine (4.2%), serine (4.3%), threonine (5.40%), tyrosine (3.17%) and valine (7.2%). Tryptophan which is suitable of producing jadomycin was not present in the fish protein. No reports were found in the literature for jadomycin production from glutamic acid. Therefore, glutamic acid (9.85%), and proline (0.98%) which are present in the fish protein should be investigated for possible production of jadomycins.

Användargränssnitt är en viktig del av kommunikationen mellan människor och maskin. Tidigare så kallat människa-datorinteraktion var baserad på användning av hålkort vid kommunikation med datorer, detta ändrades under andra halvan av 1900-talet. Där användningen av det grafiska användargränssnittet och kommandoradsgränssnitt började ta över. I dag finns det flera olika sorters användargränssnitt till flera olika maskiner och enheter, bland annat touch-gränssnittet som används till alla våra smarttelefon. Touch-gränssnittet ansågs som något lättanvänt och gav möjligheter till andra gränssnitt i detta fält. Ett av dem är det haptiska gränssnittet som ger användaren möjligheten att ändra data direkt i verkligheten, inte digitalt.I denna studie presenterar vi ett påtagligt gränssnitt (tangible interface) i form av ett interaktivt blixtlås. Syftet med denna studie är att använda en teknisk uppfinning med ett så kallat Tangible interface för att samla in data i form av en skala och sedan jämföra den med en numerisk skala representerad på papper. Ett experiment användes vid insamlingen av data, den var baserad på två sorters enkäter, det ena var pappersbaserad, medan den andra var baserad på det interaktiva blixtlåset. Hela experimentet avslutades med en utvärdering. Resultatet från experimentet visade att skillnaderna mellan en numerisk skala i form av papper inte skilde sig åt så mycket från det interaktiva blixtlåset. / User Interfaces are necessary for us when communicating with the machines. Early human-computer interactions were based upon the usage of puncture card to communicate with the computer, that later transformed into Graphical User Interfaces and Command Line Interfaces during the latter half of the 20th century. Today there are a lot of different kinds of interfaces for various types of devices, such as the touch interface for our smartphones. Due to the ease and possibilities of using the touch, further development in this area has been desired. An interface that gives the user the possibility to manipulate data in real life, is called a haptic interface. In this paper an interactive zipper is presented as a tangible interface that is part of the haptic interface. The study focuses on how a technological invention with a tangible interface can be used to gather feedbacks in the form of a numeric scale and how it compares to a numeric scale presented on paper. An experiment based on two questionnaires was used to gather the feedbacks, one was paper-based and the other based upon the interactive zipper, and it ended with an evaluation of the interactive zipper. The results showed that there are not any big differences between the numeric scale presented on paper compared to the interactive zipper.

Les lésions hépatiques observées au cours de l'obésité (NAFLD, stéatopathie non alcoolique) s'étendent de la stéatose isolée à la stéatohépatite (NASH, stéatohépatitie non alcoolique), la fibrose, la cirrhose et au carcinome hépatocellulaire. L'identification des mécanismes de recrutement des cellules immunitaires par le foie stéatosique est une étape clé dans la compréhension du déclenchement de l'inflammation hépatique et la recherche de nouvelles cibles thérapeutiques. Au cours de l’obésité, la stéatose sensibilise le foie au lipopolysaccharide (LPS), qui active la voie pro-inflammatoire NFκB. Nous avons récemment montré que: 1) la stéatose induisait une augmentation du recrutement lymphocytaire (TCD4+, TCD8+ et B) vers le foie mais également une augmentation de la réponse des lymphocytes TCD4+ à la chimiokine CXCL12 (SDF-1α), dont le récepteur est CXCR4 ; 2) GILZ (Glucocorticoid-Induced Leucine Zipper), une protéine induite par les glucocorticoïdes (GCs), inhibait la voie NFkB et jouait un rôle clé dans l’inflammation hépatique au cours de la consommation excessive d’alcool.Le but de ce travail était d’étudier les mécanismes de l’inflammation hépatique liée à l’obésité. Au cours de mon travail, nous avons montré que le chimiotactisme des lymphocytes TCD4+ à la chimiokine CXCL12 était augmenté non seulement chez les souris obèses mais également chez des patients ayant une NASH. L’augmentation de l’effet chimiotactique de CXCL12 était due à une augmentation de l’affinité de CXCL12 à son récepteur CXCR4. La migration anormale des lymphocytes T CD4+ vers le foie stéatosique était réversible pharmacologiquement en inhibant la liaison de CXCL12 à CXCR4 par AMD3100 (antagoniste deCXCR4). Le déficit d’expression et l’altération de l’induction du facteur anti-inflammatoire GILZ dans les cellules des Kupffer des souris obèses étaient responsables de la sensibilisation de ces cellules au LPS. Cette altération était liée à la diminution de l’expression du récepteur aux glucocorticoïdes (GR) dans les cellules de Kupffer des souris obèses. La surexpression de GILZ dans l’obésité en utilisant des souris trangéniques restaurait la tolérance hépatique au LPS. Ces anomalies des lymphocytes TCD4+ et de l’expression de GILZ dans les cellules de Kupffer participent au déclenchement d’une inflammation hépatique sur un foie stéatosique et pourraient représenter de nouvelles cibles thérapeutiques / Non alcoholic fatty liver disease (NAFLD) includes a spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The identification of the mechanisms involved in the recruitment of immunity cells by the fatty liver is a key in the comprehension of the onset of liver and the finding of new therapeutic targets. In obesity, steatosis sensitizes the liver to the lipopolysaccharide (LPS) from the gastrointestinal tract and the NFkB pro-inflammatory pathway is activated. We recently showed that: 1) the steatosis led to an increase recruitment of lymphocytes (TCD4+, TCD8+ and B) by the liver but also an hyperresponsive of CD4+T cells to CXCL12 (SDF-1"), the ligand of CXCR4; 2) GILZ(Glucocorticoid-Induced Leucine Zipper), a protein induced by glucocorticoids (GCs), inhibits the nuclear factor kB pathway and plays a key role in alcoholic hepatitis.This aim of my work was to study the mechanisms involved in obesity-related liver inflammation.I demonstrated that the chemotaxis of CD4+T cells to CXCL12 was increased not only in obese mice but also in patients with NASH. This increased chemotactisme of CXCL12 was due to an increase of the affinity ofCXCL12 to its receptor. The abnormal migration of CD4+T lymphocytes to the fatty liver was reversible by pharmacologically inhibiting the binding of CXCL12 to CXCR4 using AMD3100.The decreased expression and the impairment of the induction of the anti-inflammatory factor GILZ in Kupffer cells from obese mice was responsible for a sensitization of these cells to LPS. This impairment was due to a decrease of the glucocorticoid receptor (GR) expression in Kupffer cells from obese mice. The overexpression of GILZ level in obese transgenic mice restored the liver tolerance to LPS. These abnormalities of CD4+T lymphocytes and the GILZ expression in Kupffer cells contribute to the onset of liver inflammation in obesity and may represent new therapeutic targets.