Motivation: The quality of progressive sequence alignments strongly depends on the accuracy of the individual pairwise alignment steps since gaps that are introduced at one step cannot be removed at later aggregation steps. Adjacent insertions and deletions necessarily appear in arbitrary order in pairwise alignments and hence form an unavoidable source of errors. Idea: Here we present a modified variant of progressive sequence alignments that addresses both issues. Instead of pairwise alignments we use exact dynamic programming to align sequence or profile triples. This avoids a large fractions of the ambiguities arising in pairwise alignments. In the subsequent aggregation steps we follow the logic of the Neighbor-Net algorithm, which constructs a phylogenetic network by step-wisely replacing triples by pairs instead of combining pairs to singletons. To this end the three-way alignments are subdivided into two partial alignments, at which stage all-gap columns are naturally removed. This alleviates the “once a gap, always a gap” problem of progressive alignment procedures. Results: The three-way Neighbor-Net based alignment program aln3nn is shown to compare favorably on both protein sequences and nucleic acids sequences to other progressive alignment tools. In the latter case one easily can include scoring terms that consider secondary structure features. Overall, the quality of resulting alignments in general exceeds that of clustalw or other multiple alignments tools even though our software does not included heuristics for context dependent (mis)match scores.

Les metal·lotioneïnes (MTs), pèptids amb una excepcional capacitat coordinant, constitueixen una gran família de metal·loproteïnes presents en gairebé tots els éssers vius. L'estudi de les propietats coordinants i estructurals de les diverses isoformes de MT és important per a aportar noves dades a la resolució de les funcions que duen a terme, fins ara relacionades amb la destoxicació de metalls pesants i l'homeòstasi de zinc i coure. En aquesta tesi doctoral s'ha estudiat la metal·lotioneïna del cranc Callinectes sapidus CuMT-II (MTC en aquest treball), per la seva atípica estructura primària dins les MTs de crustaci i per contenir triplets de cisteïna, motiu molt poc habitual en aquestes proteïnes. Aquesta MT s'ha obtingut per enginyeria genètica en medis suplementats amb zinc, amb coure i amb ambdós metalls. Els complexos metàl·lics formats en aquestes síntesis s'han caracteritzat mitjançant ESI-MS, CD, UV i ICP-AES. Així mateix, fent ús d'aquestes tècniques, s'ha aprofundit en les propietats coordinants de MTC mitjançant la reconstitució de la forma demetal·lada apoMTC i la valoració de ZnMTC i apoMTC amb diversos ions metàl·lics. Finalment, s'ha estudiat per RMN la proteïna reconstituïda amb 113Cd.Amb aquests estudis s'ha establert que per a una millor estructuració amb coure, aquesta proteïna també ha de contenir ions zinc i que, a diferència del que estava àmpliament acceptat per a altres metal·lotioneïnes, l'estequiometria dels complexos que estableix MTC amb Cd(II) no s'ajusta exactament amb la que estableix amb Zn(II). Els treballs de RMN han permès establir que l'estructuració de MTC amb ions cadmi té lloc en dos dominis, cadascun dels quals coordina 3 - 4 ions Cd(II).Addicionalment, s'ha aportat noves dades sobre el mecanisme de funcionament de les MTs en el seu paper antiinflamatori en lesions cerebrals, mitjançant l'estudi funcional dels dominis de MT-1 de mamífer en ratolins criolesionats, knockout per MT-1/-2 (amb els gens de MT-1 i MT-2 inactivats), concloent que el domini β presenta unes millors condicions antiinflamatòries. / Metallothioneins (MTs), peptides with an exceptional heavy metal coordination capacity, constitute a superfamily of ubiquitous metalloproteins. Study of MTs metal coordinating properties and their structure is necessary to contribute to the determination of their physiological functions. Nowadays, detoxification of heavy metals and homeostasis of zinc and copper are some of the principal functions proposed for MTs.The principal aim of our work is to study the binding properties of isoform CuMT-II form the crab Callinectes sapidus (MTC), a crustacean MT with an atypical peptide sequence containing two cysteine triplets, which is a very unusual motif in MTs. MTC was obtained by genetic engineering protocols in zinc, copper and zinc plus copper supplemented media. The metal complexes recovered were analyzed by ESI-MS, CD, UV and ICP-AES spectroscopies. Metal coordination properties of MTC were deeper studied by means of metal reconstitution from apoMTC and by titration of ZnMTC and apoMTC with Cd(II) and Cu(I). Structural NMR studies of MTC reconstituted with 113Cd have also been carried out.MTC requires the binding of some Zn(II) ion to acquire the most chiral structure in the presence of Cu(I). Interestingly, cadmium total metallated protein shows slightly higher metal to MT stoichiometries than in the case of zinc in contrast with the equal Zn and Cd stoichiometries shown for most MTs. Moreover, NMR studies have shown that CdMTC is structured in two domains, with 3 - 4 Cd(II) ions in each of them.Additionally, we have contribute to determine the mechanism of MTs anti-inflammatory activity in brain, by studying the rule of the α and β domains of mammalian MT-1 in cryolesioned MTKO mice, which indicate that the β domain shows better anti-inflammatory properties than the α domain.

Infant mortality is viewed as an important indicator of the health and social conditions of a population. However, the infant mortality rate in the United States is estimated to be much lower than those of other developed nations. This dissertation analyzes the hazard of fetal and infant death for twins and triplets in the United States between the years of 1995 and 2000. This dissertation had two main objectives: first, to examine the effects of the birthweight and gestational age on the hazards of fetal, neonatal, postneonatal, and infant death; and second, to better understand the timing of mortality among multiples during their early life. I show that after controlling for relevant characteristics of the mother and child, gestational age and birthweight significantly influence the hazard of mortality for twins and triplets. The major finding in this dissertation shows that there is a higher hazard for twins than triplets. The unexpected higher hazard of mortality for twins compared to triplets may well be due to the social and demographic characteristics of parents of twins and triplets, particularly the possible use of Assisted Reproductive Technologies.

This thesis concerns the study of extended Higgs sectors at future colliders. Such studies are well motivated since enlarged Higgs models are a necessity in many extensions of the Standard Model (SM), although these structures may be considered purely in the context of the SM, to be called the 'non-minimal SM'. The continuous theme of the thesis is the task of distinguishing between the (many) theoretically sound non-minimal Higgs sectors at forthcoming colliders. If a Higgs boson is found it is imperative to know from which model it originates. In particular, the possible differences between the Higgs sectors of the Minimal Supersymmetric Standard Model (MSSM) and the non-minimal SM are highlighted. Considered first are the detection prospects of light charged Higgs scalars (H(^±)) at e(^+)e(^-) colliders. The discovery of a H(^±) would provide unambiguous evidence for a non- minimal Higgs sector. We show that in certain (but not all)non-minimal models a light H(^±) may exist i.e. be within the mass range accessible at LEP2 (M(_H)(_ ±) ≤ Mw). In particular the MSSM requires M(_H±) ≥ Mw, and thus detection of a at LEP2 is strong evidence against the MSSM. We discuss ways of distinguishing between the models which may contain a light H(^±) by exploiting differences in the decay channels. Attention is then given to the neutral Higgs bosons of the non-minimal SM. It is possible that these particles may possess a greatly different phenomenology to that of the mammal SM and MSSM, and we explore the feasibility of observing these differences at LEP2 and the LHC It is found that distinct, sometimes spectacular signatures are possible. The thesis next considers a more exotic Higgs representation, namely that of Higgs triplets, and compares its phenomenology at LEP2 with that of the non-minimal models covered thus far The phenomenon of Higgs bosons decoupling from the fermions(fermiophobia) arises naturally in the above triplet model, and this concept is studied in more depth in the final chapter. It is emphasized that such particles are not possible in the MSSM.

Les amplifications de répétitions de triplets CTG dans le gène DMPK humain sont à l'origine de la dystrophie myotonique de type 1 ou DM1. Les répétitions CUG présentes dans les ARNm DMPK séquestrent le facteur d'épissage MBNL1 au sein de foci nucléaires et dérégulent l'épissage des pré-ARNm cibles de MBNL1. Par ailleurs, 9 isoformes de MBNL1, produites par épissage alternative, coexistent dans les cellules. Dans un premier temps nous avons recherché quels exons constitutifs ou alternatifs étaient requis pour la reconnaissance des ARN, la régulation de l'épissage et la localisation cellulaire de MBNL1. Nous avons ensuite entrepris de rechercher par l'approche SELEX les séquences de haute affinité pour MBNL1. Nous avons ainsi identifié une séquence conservée de 12 nucléotides de long, contenant un seul motif de fixation pour MBNL1 et adoptant une structuration tige-boucle particulière. L'importance de cette structuration a été confirmée par l'existence de mutants compensatoires au sein des ARN sélectionnés. Finalement nous avons étudié les mécanismes de régulation de l'inclusion de l'exon 5 du pré-ARNm de la troponine T cardiaque humaine (hcTNT). Une approche in cellulo nous a permis d'identifier les séquences minimales requises pour la régulation de l'épissage en conditions normales et en présence des répétitions CUG. Au sein de ces séquences nous avons identifié 6 nouveaux sites MBNL1 dont nous avons montré l'importance fonctionnelle in cellulo et in vitro. Nous avons également mis en évidence l'implication d'autres séquences régulatrices dans la régulation de l'inclusion de l'exon 5 du pré-ARNm hcTNT et un rôle de la protéine hnRNP H dans ces régulations. L'ensemble de ces données apportent de nouveaux éléments d'information importants pour la compréhension de la DM1 / Amplifications of CTG motifs in the human DMPK gene are responsible for Myotonic Dystrophy of type 1. The resulting CUG repeats in pre-mRNAs capture the MBNL1 splicing factor, leading to mis-regulation of MBNL1 pre-mRNA targets. Due to the recent discovery of MBNL1 and its numerous isoforms (9) resulting from alternative splicing, little is known on how MBNL1 regulates splicing and how a decreased level of available MBNL1 generates splicing miss-regulations. First, we defined which of the MBNL1 alternative and constitutive exons are required for: i) RNA binding, ii) splicing activity and, iii) MBNL1 sub-cellular localization. Second, for a more precise definition of the MBNL1 RNA binding properties, we performed SELEX experiments using a library of RNA stem-loop structures containing a 18-nt long randomized sequence. Its leads to the identification of 12-nt long sequence adopting a peculiar stem-loop structure, whose importance for MBNL1 binding was revealed by its preservation by compensatory base-pair mutations. Finally, based on the above data, we studied the mechanisms involved in regulation of hcTNT exon 5 splicing. By in cellulo assays, we defined the hcTNT pre-mRNA region required for both normal inclusion and for the trans-dominant effect of CUG repeats. Within this region, we identified six new potential MBNL1 sites and demonstrated their functional role by in vitro and in cellulo assays. We also identified several additional splicing regulatory elements involved in normal and CUG-deregulated exon 5 inclusion and already showed a role of hnRNP H in splicing regulation. Altogether, our data bring new information important for understanding the pathology

Mothers' and fathers' perceptions of the quality of coparenting – the way in which they work together in their role as parents – forms the focus of three papers that comprise this thesis. Using a novel sample of ‘intact' families with young twins, this research extends the existing coparenting literature beyond its typical focus on first-born children, to include more complex families. Participants were families who were part of the Twins, Family and Behaviour (TFaB) Study, a longitudinal, multimethod study of UK families with twins born in 2009/10 conducted by myself and my colleague over a two-year period. Paper 1 examines bidirectional associations between coparenting and the marital relationship during the transition-to-school period. Controlling for cross-sectional associations and temporal stability, parents' perceptions of higher quality coparenting were associated with their subsequent report of a higher quality marital relationship. Reciprocal associations between the marital relationship and subsequent coparenting, however, were not evidenced. These findings highlight the salience of coparenting for the marital relationship, and suggest that interventions seeking to improve the couples' marital relationship should pay close attention to their coparenting. Paper 2 focuses on parenting sense of competence (PSOC), examining the role of children's disruptive behaviour, coparenting, and their interaction. For both mothers and fathers there was a significant interaction between their perceptions of coparenting and children's disruptive behaviour such that high quality coparenting may protect the PSOC of parents dealing with high levels of children's disruptive behaviour. These findings imply that practitioners and interventions concerned with promoting PSOC should pay due attention to the quality of coparenting as an important family context. Paper 3 examines family-wide and child-specific effects of coparenting and coercive parenting on the development of children's disruptive behaviour. Mothers' perceptions of coparenting interacted with maternal overall coercive parenting such that high quality coparenting intensified the toxicity of maternal coercive parenting for children's disruptive behaviour. This novel – and unexpected – finding indicates that the influence of high quality coparenting is not necessarily always positive. Coparenting interventions aiming to improve child outcomes would therefore be well-advised to also consider parenting strategies. Further research is encouraged to explore these research questions within samples of socioeconomic diversity and across family types, as well as studies designed to examine twin and non-twin family differences.

No description available.

A fingerprint matching algorithm with a novel set of matching parameters based on core points and triangular descriptors is proposed to discover rarity in fingerprints. The algorithm uses a mathematical and statistical approach to discover rare features in fingerprints which provides scientific validation for both ten-print and latent fingerprint evidence. A feature is considered rare if it is statistically uncommon; that is, the rare feature should be unique among N (N>100) randomly sampled prints. A rare feature in a fingerprint has higher discriminatory power when it is identified in a print (latent or otherwise). In the case of latent fingerprint matching, the enhanced discriminatory power from the rare features can help in delivering a confident court judgment. In addition to mining the rare features, a parallel algorithm for fingerprint matching on GPUs is also proposed to reduce the run-time of fingerprint matching on larger databases. Results show that 1) matching algorithm is useful in eliminating false matches. 2) each of the 30 fingerprints randomly selected to mine rare features have a small set of highly distinctive statistically rare features some of whose occurrence is one in 1000 fingerprints. 3) the parallel algorithm implemented on GPUs for larger databases is around 40 times faster than the sequential algorithm. / Master of Science

In order to deliver statistical and qualitative backing to latent fingerprint evidence, algorithms are proposed (1) to perform fingerprint matching to aid in quality assessment, and (2) to discover statistically rare features or patterns in fingerprints. These features would help establish an objective minimum-quality baseline for latent prints as well as aid in the latent examination process in making a matching comparison. The proposed methodologies use minutiae triplet-based features in a hierarchical fashion, where not only minutia points are used, but ridge information is used to help establish relations between minutiae. Results show (1) that our triplet-based descriptor is useful in eliminating false matches in the matching algorithm, and (2) that a set of distinctive features can be found that have sufficient discriminatory power to aid in quality assessment. / Master of Science

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