Low-linewidth and tunable single frequency 1x2 multimode-interferometer-Fabry-Perot laser diode

In this paper, we present a novel 1x2 multi-mode-interferometer-Fabry-Perot (MMI-FP) laser diode, which demonstrated tunable single frequency operation with more than 30dB side mode suppression ratio (SMSR) and a tuning range of 25nm in the C and L bands, as well as a 750 kHz linewidth. These lasers do not require material regrowth and high resolution gratings; resulting in a simpler process that can significantly increase the yield and reduce the cost.

Molecular protein function prediction using sequence similarity-based and similarity-free approaches

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

The white gene and locomotor recovery from anoxia in Drosophila melanogaster

Locomotor recovery from anoxia is complicated and little is known about the molecular and cellular mechanisms regulating anoxic recovery in Drosophila. For this thesis I established a protocol for large-scale analysis of locomotor activity in adult flies with exposure to a transient anoxia. Using this protocol I observed that wild-type Canton-S flies recovered faster and more consistently from anoxia than the white-eyed mutant w1118, which carries a null allele of w1118 in an isogenic genetic background. Both Canton-S and w1118 are commonly used controls in the Drosophila community. Genetic analysis including serial backcrossing, RNAi knockdown, w+ duplication to Y chromosome as well as gene mutation revealed a strong association between the white gene and the timing of locomotor recovery. I also found that the locomotor recovery phenotype is independent of white-associated eye pigmentation, that heterozygous w+ allele was haplo-insufficient to induce fast and consistent locomotor recovery from anoxia in female flies, and that mini-white is insufficient to promote fast and consistent locomotor recovery. Moreover, locomotor recovery was delayed in flies with RNAi knockdown of white in subsets of serotonin neurons in the central nervous system. I further demonstrated that mutations of phosphodiesterase genes (PDE) displayed wild-type-like fast and consistent locomotor recovery, and that locomotor recovery was light-sensitive in the night in w1118. The delayed locomotor recovery and the light sensitivity were eliminated in PDE mutants that were dual-specific or cyclic guanosine monophosphate (cGMP)-specific. Up-regulation of cGMP using multiple approaches including PDE mutation, sildenafil feeding or specific expression of an atypical soluble guanylyl cyclase (Gyc88E) was sufficient to suppress w-RNAi induced delay of locomotor recovery. Taken together, these data strongly support the hypothesis that White transports cGMP and promotes fast and consistent locomotor recovery from anoxia.

Unraveling flp-11/flp-32 dichotomy in nematodes

FMRFamide-like peptide (FLP) signalling systems are core to nematode neuromuscular function. Novel drug discovery efforts associated with nematode FLP/FLP receptor biology are advanced through the accumulation of basic biological data that can reveal subtle complexities within the neuropeptidergic system. This study reports the characterisation of FMRFamide-like peptide encoding gene-11 (flp-11) and FMRFamide-like peptide encoding gene-32 (flp-32), two distinct flp genes which encode the analogous peptide, AMRN(A/S)LVRFamide, in multiple nematode species - the only known example of this phenomenon within the FLPergic system of nematodes. Using bioinformatics, in situ hybridisation, immunocytochemistry and behavioural assays we show that: (i) flp-11 and -32 are distinct flp genes expressed individually or in tandem across multiple nematode species, where they encode a highly similar peptide; (ii) flp-11 does not appear to be the most widely expressed flp in Caenorhabditis elegans; (iii) in species expressing both flp-11 and flp-32, flp-11 displays a conserved, restricted expression pattern across nematode clades and lifestyles; (iv) in species expressing both flp-11 and flp-32, flp-32 expression is more widespread and less conserved than flp-11; (v) in species expressing only flp-11, the flp-11 expression profile is more similar to the flp-32 profile observed in species expressing both; and (vi) FLP-11 peptides inhibit motor function in multiple nematode species. The biological significance and evolutionary origin of flp-11 and -32 peptide duplication remains unclear despite attempts to identify a common ancestor; this may become clearer as the availability of genomic data improves. This work provides insight into the complexity of the neuropeptidergic system in nematodes, and begins to examine how nematodes may compensate for structural neuronal simplicity. From a parasite control standpoint this work underscores the importance of basic biological data, and has wider implications for the utility of C. elegans as a model for parasite neurobiology.

Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns.

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD(+) acute myeloid leukaemia (AML). The paucity of valid pre-clinical models has restricted investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. We generated selective FLT3 inhibitor-resistant cells by treating the FLT3-ITD(+) human AML cell line MOLM-13 in vitro with the FLT3-selective inhibitor MLN518, and validated the resistant phenotype in vivo and in vitro. The resistant cells, MOLM-13-RES, harboured a new D835Y tyrosine kinase domain (TKD) mutation on the FLT3-ITD(+) allele. Acquired TKD mutations, including D835Y, have recently been identified in FLT3-ITD(+) patients relapsing after treatment with the novel FLT3 inhibitor, AC220. Consistent with this clinical pattern of resistance, MOLM-13-RES cells displayed high relative resistance to AC220 and Sorafenib. Furthermore, treatment of MOLM-13-RES cells with AC220 lead to loss of the FLT3 wild-type allele and the duplication of the FLT3-ITD-D835Y allele. Our FLT3-Aurora kinase inhibitor, CCT137690, successfully inhibited growth of FLT3-ITD-D835Y cells in vitro and in vivo, suggesting that dual FLT3-Aurora inhibition may overcome selective FLT3 inhibitor resistance, in part due to inhibition of Aurora kinase, and may benefit patients with FLT3-mutated AML.

Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutations.

The efficacy of tyrosine kinase (TK) inhibitors on non-cycling acute myeloid leukaemia (AML) cells, previously shown to have potent tumourigenic potential, is unknown. This pilot study describes the first attempt to characterize non-cycling cells from a small series of human FMS-like tyrosine kinase 3 (FLT3) mutation positive samples. CD34+ AML cells from patients with FLT3 mutation positive AML were cultured on murine stroma. In expansion cultures, non-cycling cells were found to retain CD34+ expression in contrast to dividing cells. Leukaemic gene rearrangements could be detected in non-cycling cells, indicating their leukaemic origin. Significantly, the FLT3-internal tandem duplication (ITD) mutation was found in the non-cycling fraction of four out of five cases. Exposure to the FLT3-directed inhibitor TKI258 clearly inhibited the growth of AML CD34+ cells in short-term cultures and colony-forming unit assays. Crucially, non-cycling cells were not eradicated, with the exception of one case, which exhibited exquisite sensitivity to the compound. Moreover, in longer-term cultures, TKI258-treated non-cycling cells showed no growth impairment compared to treatment-naive non-cycling cells. These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted.

Repeated evolution of heat responsiveness among Brassicaceae COPIA transposable elements

Eukaryotic genomes contain repetitive DNA sequences. This includes simple repeats and more complex transposable elements (TEs). Many TEs reach high copy numbers in the host genome, owing to their amplification abilities by specific mechanisms. There is growing evidence that TEs contribute to gene transcriptional regulation. However, excess of TE activity may lead to reduced genome stability. Therefore, TEs are suppressed by the transcriptional gene silencing machinery via specific chromatin modifications. In contrary, effectiveness of the epigenetic silencing mechanisms imposes risk for TE survival in the host genome. Therefore, TEs may have evolved specific strategies for bypassing epigenetic control and allowing the emergence of new TE copies. Recent studies suggested that the epigenetic silencing can be, at least transiently, attenuated by heat stress in A. thaliana. Heat stress induced strong transcriptional activation of COPIA78 family LTR-retrotransposons named ONSEN, and even their transposition in mutants deficient in siRNA-biogenesis. ONSEN transcriptional activation was facilitated by the presence of heat responsive elements (HREs) within the long terminal repeats, which serve as a binding platform for the HEAT SHOCK FACTORs (HSFs). This thesis focused on the evolution of ONSEN heat responsiveness in Brassicaceae. By using whole-transcriptome sequencing approach, multiple Arabidopsis lyrata ONSENs with conserved heat response were found and together with ONSENs from other Brassicaceae were used to reconstruct the evolution of ONSEN HREs. This indicated ancestral situation with two, in palindrome organized, HSF binding motifs. In the genera Arabidopsis and Ballantinia, a local duplication of this locus increased number of HSF binding motifs to four, forming a high-efficiency HRE. In addition, whole transcriptome analysis revealed novel heat-responsive TE families COPIA20, COPIA37 and HATE. Notably, HATE represents so far unknown COPIA family which occurs in several Brassicaceae species but is absent in A. thaliana. Putative HREs were identified within the LTRs of COPIA20, COPIA37 and HATE of A. lyrata, and could be preliminarily validated by transcriptional analysis upon heat induction in subsequent survey of Brassicaeae species. Subsequent phylogenetic analysis indicated a repeated evolution of heat responsiveness within Brassicaceae COPIA LTR-retrotransposons. This indicates that acquisition of heat responsiveness may represent a successful strategy for survival of TEs within the host genome.

Bento Box Discovery

Poster presentation at the University of Maryland Libraries Research & Innovative Practice Forum on June 8, 2016. The poster proposes that the UMD Libraries should evaluate adoption of Bento Box Discovery for improved user search experience.

The clinical significance of 15q11.2 BP1-BP2 duplications: - Where do we stand?

The 15q11.2-q13 region has been well characterized, being associated with a range of syndromatic copy number variants (CNVs), and comprises five established break points sites (BP1 to BP5). While the clinical effect for BP1-BP3, BP2-BP3 and BP4-BP5 CNVs is well established, the same cannot be said for BP1-BP2 CNVs. Recently the 15q11.2 BP1-BP2 deletion has been reviewed, emerging as a microdeletion syndrome with low penetrance and variable expressivity being the CNV frequently inherited from a healthy parent. This microdeletion is considered to be a risk factor for several neurodevelopment disorders. For the reciprocal duplication the picture has been less conclusive. Aiming for a better understanding of the clinical significance of this CNV, we collected patients with intellectual disability and/or other clinical features, referred for microarray testing, gathering clinical details for the ones with the duplication. Data was collected from two genetic laboratories. With a total of 1545 patients, we identified eleven carrying the duplication at 15q11.2 BP1-BP2. It was possible to assess inheritance in only four cases, all inherited from a healthy parent. All patients presented intellectual disability,and facial dysmorphism was the second most common feature observed. Microcephaly, autism, congenital abnormalities, dystonia and cataplexy where reported individually. The magnitude of the effect of 15q11.2 duplication remains elusive, and the outcome unclear, posing a major challenge to genetic counseling. Nevertheless, we expect the collection of more of these cases will establish this gain, as it happened with the reciprocal deletion, as a microduplication syndrome with low penetrance and variable expressivity.

Planifier un développement adapté aux caractéristiques hydrographiques et biophysiques du milieu pour l’aménagement d’un quartier durable à Weedon, Québec

La municipalité de Weedon, en Estrie, a récemment acquis un terrain vacant à proximité du village. La municipalité désire un développement intégrant le concept de développement durable dans le plan d’aménagement du terrain et dans la construction des infrastructures. L’objectif général de ce travail est de recommander à la municipalité de Weedon des moyens pour adapter l’écoquartier aux caractéristiques hydrographiques et biophysiques du milieu. Premièrement, le milieu biophysique et hydrographique est caractérisé grâce à l’analyse de données géospatiales et par photointerprétation de photographies aériennes. Le potentiel de développement est analysé grâce à l’outil ArcGIS afin de déterminer les zones propices à l’urbanisation ainsi que les zones à exclure. Il est recommandé de concentrer le développement du site dans la zone n’ayant aucune contrainte et de limiter la densité des habitations dans les espaces présentant des contraintes. Selon ces suggestions, il sera possible de développer environ 40 bâtiments sur le site. Deuxièmement, les systèmes de gestion des eaux usées (le système septique individuel, le système décentralisé et le système centralisé) sont décrits en fonction de leurs avantages, de leurs inconvénients et de leurs limites. Ces points sont ensuite comparés et la création d’un arbre de décision permet de recommander le système le mieux adapté au milieu. Les zones avec contraintes de développement devraient utiliser des systèmes de traitement septiques. Pour ce qui est de la zone sans contraintes, le système de traitement septique est recommandé uniquement si la densité est égale ou inférieure à 5 unités d’habitations par hectare. Si la densité désirée par la municipalité est plus élevée pour cette zone, le raccordement au système de traitement centralisé est recommandé. Troisièmement, les mesures de gestion des eaux pluviales sont présentées selon différentes caractéristiques adaptées au site. Leur recommandation est basée sur une analyse multicritère pondérée. Les pratiques de gestion optimales qui devraient être utilisées conjointement sur le site sont la collecte et la réutilisation de l’eau de pluie pour la gestion sur le site, la noue engazonnée avec drain pour la gestion en réseau et le marais artificiel pour la gestion en fin de réseau. Les recommandations présentées dans ce travail visent à privilégier des modes de développement alternatifs à l’urbanisation classique afin d’établir les bases pour le développement d’un quartier durable à Weedon.

La séquestration naturelle de carbone en milieu urbain : un outil de lutte contre les changements climatiques à promouvoir!

La lutte contre les changements climatiques représente un enjeu majeur en ce XXIe siècle. L'objectif principal de cet essai est d'évaluer le rôle que peut jouer la séquestration naturelle de carbone en milieu urbain dans ce combat au Québec. L’absorption du CO2, principal gaz à effet de serre, par la photosynthèse s'avère être une alternative permettant de compenser en partie les émissions carboniques en milieu urbain — un milieu propice pour effectuer divers types d'aménagement de verdissement urbain, comme aménager des toits verts, des murs végétaux ainsi que planter des arbres. À ces égards, les principales conditions favorisant la séquestration de carbone en milieu urbain ont été étudiées. Aussi, une analyse économique a permis d’évaluer la faisabilité de l'implantation de ces techniques de verdissement dans un contexte urbain québécois. En fait, il s'avère économiquement intéressant de procéder aux verdissements des villes puisque les avantages financiers, sociaux et environnementaux qui en découlent justifient l’investissement. À titre d'exemple, soulignons qu'un arbre moyen représente des bénéfices socio-environnementaux de 100 $ annuellement globalement pour la collectivité et l’individu. L’essor du verdissement urbain est favorisé par ailleurs par des mesures incitatives à ce sujet. Quelques pays et villes ont également été cités pour mettre en perspective les incitatives financières et réglementaires qu’ils utilisent. Qui plus est, il a été calculé, de façon sommaire, que le potentiel combiné de séquestration de CO2 par ces principales techniques de verdissement urbain est considérable. À titre de référence, si 50 % des toits et des murs étaient végétalisés et que le couvert arboré au Québec atteignait également 50 %, alors c’est plus de 3 M t CO2 / an qui pourraient être séquestré en milieu urbain, soit une quantité représentant près de 5 % des émissions annuelles de CO2 québécois. En outre, la séquestration naturelle de carbone en milieu urbain pourrait jouer un double rôle dans la lutte contre les changements climatiques; celui de la séquestration de carbone, certes, mais également en matière de la conscientisation environnementale — élément pouvant favoriser un mouvement de masse pour mieux lutter contre les changements climatiques.

Efficient split eld FDTD analysis of third-order nonlinear materials in two-dimensionally periodic media

In this work the split-field finite-difference time-domain method (SF-FDTD) has been extended for the analysis of two-dimensionally periodic structures with third-order nonlinear media. The accuracy of the method is verified by comparisons with the nonlinear Fourier Modal Method (FMM). Once the formalism has been validated, examples of one- and two-dimensional nonlinear gratings are analysed. Regarding the 2D case, the shifting in resonant waveguides is corroborated. Here, not only the scalar Kerr effect is considered, the tensorial nature of the third-order nonlinear susceptibility is also included. The consideration of nonlinear materials in this kind of devices permits to design tunable devices such as variable band filters. However, the third-order nonlinear susceptibility is usually small and high intensities are needed in order to trigger the nonlinear effect. Here, a one-dimensional CBG is analysed in both linear and nonlinear regime and the shifting of the resonance peaks in both TE and TM are achieved numerically. The application of a numerical method based on the finite- difference time-domain method permits to analyse this issue from the time domain, thus bistability curves are also computed by means of the numerical method. These curves show how the nonlinear effect modifies the properties of the structure as a function of variable input pump field. When taking the nonlinear behaviour into account, the estimation of the electric field components becomes more challenging. In this paper, we present a set of acceleration strategies based on parallel software and hardware solutions.

A inquietante estranheza no transexualismo

Dissertação de Mestrado apresentada no Instituto Superior de Psicologia Aplicada para obtenção do grau de Mestre na especialidade de Clínica

ALIANZAS ESTRATÉGICAS ENTRE LA BIBLIOTECA PÚBLICA DE PURISCAL Y LA BIBLIOTECA DARÍO FLORES HERNÁNDEZ

Con la premisa de que las bibliotecas públicas y escolares son pilares fundamentales en la sociedad costarricense, que cumplen una función primordial, especialmente en las últimas décadas y considerando que su importancia se ha enfatizado, en el desarrollo del campo educativo, formal e informal, social y cultural; esta práctica pretende identificar procesos, recursos y servicios que pueden compartir las bibliotecas de la Escuela Darío Flores y la Biblioteca Pública de Puriscal, y utilizar esta información como un caso de estudio.La práctica consistirá proponer y ejecutar actividades claves por medio de una alianza estratégica entre ambas instituciones, para facilitar la coordinación de actividades conjuntas, evitar la duplicidad de esfuerzos y mejorar la calidad en los servicios de información que se ofrecen a la comunidad de Puriscal.

Functional XPB/RAD25 redundancy in Arabidopsis genome: characterization of AtXPB2 and expression analysis

The xeroderma pigmentosum complementation group B (XPB) protein is involved in both DNA repair and transcription in human cells. It is a component of the transcription factor IIH (TFIIH) and is responsible for DNA helicase activity during nucleotide (nt) excision repair (NER). Its high evolutionary conservation has allowed identification of homologous proteins in different organisms, including plants. In contrast to other organisms, Arabidopsis thaliana harbors a duplication of the XPB orthologue (AtXPB1 and AtXPB2), and the proteins encoded by the duplicated genes are very similar (95% amino acid identity). Complementation assays in yeast rad25 mutant strains suggest the involvement of AtXPB2 in DNA repair, as already shown for AtXPB1, indicating that these proteins may be functionally redundant in the removal of DNA lesions in A. thaliana. Although both genes are expressed in a constitutive manner during the plant life cycle, Northern blot analyses suggest that light modulates the expression level of both XPB copies, and transcript levels increase during early stages of development. Considering the high similarity between AtXPB1 and AtXPB2 and that both of predicted proteins may act in DNA repair, it is possible that this duplication may confer more flexibility and resistance to DNA damaging agents in thale cress. (C) 2004 Elsevier B.V. All rights reserved.