Functionalized polyhydroquinolines from amino acids using a key one-pot cyclization cascade and application to the synthesis of (±)-Δ7-mesembrenone

Substituted polyhydroquinolines are ubiquitous skeletal cores found in drugs and bioactive natural products. As a new route to access this motif, we successfully developed a one-pot cyclization cascade with high chemocontrol and diastereoselectivi-ty. The sequence generates two cycles, three carbon-carbon bonds, and an all-carbon quaternary center in a highly conver-gent process. Functionalized polyhydroquinolines and congeners are accessible from commercially available amino acids. This versatile and robust strategy was applied to the synthesis of (±)-D7-mesembrenon

Développement d’une cascade réactionnelle convergente comme outil pour la mise sur pied d'une librairie de polyhydroquinoléines polysubstituées

Cette thèse porte sur le développement d’une nouvelle cascade réactionnelle pour accéder à des polyhydroquinoléines substituées à partir de substrats simples. Le premier chapitre fait état d’une preuve de concept pour démontrer l’utilisation de l’éther d’énol méthylé comme relais dans une cascade réactionnelle avec un nucléophile interne. En deuxième lieu, l’étude de l’addition de différents nucléophiles sur l’ion oxocarbénium intermédiaire en fonction de différents paramètres est présentée. Enfin, une troisième étude est présentée sur les types de dinucléophiles utilisés pour la mise au point de la deuxième cyclisation qui génèrerait le squelette polyhydroquinoléine. Le deuxième chapitre présente les ajustements faits au niveau du formamide pour favoriser la formation du squelette de polyhydroquinoléine. Il s’en suit une optimisation des conditions pour obtenir un composé neutre et isolable. L’étendue de la méthodologie développée est présentée au chapitre trois et appliquée à divers substrats. La substitution au centre quaternaire, la taille de cycle formé, la substitution sur le cycle carboné de la polyhydroquinoléine ainsi que la diastéréosélectivité ont été évaluées. Au quatrième chapitre, la tolérance des groupements fonctionnels impliqués dans la cascade réactionnelle a été mise à l’épreuve. À la lumière des résultats présentés aout au long de ce document, des clarifications mécanistiques sont apportées

Prédiction de la distribution des diamètres des arbres à l’aide de métriques tirées de la donnée lidar aéroporté pour les forêts boréales du Québec et de l’ouest de Terre-Neuve

La forêt occupe une proportion importante du territoire Canadien et son exploitation nécessite une connaissance approfondie de la structure des peuplements forestiers. La distribution des diamètres des arbres (DDA) permet d’estimer plusieurs attributs forestiers, notamment le volume de bois ou le taux de croissance. Cette étude vise à prédire la DDA à une résolution fine (20 m²) à partir de données de LiDAR aéroporté pour les forêts boréales de conifères au Québec et à l’ouest de Terre Neuve. La donnée LiDAR aéroportée permet de produire un modèle de hauteur de canopée. Conséquemment, le premier objectif vise à améliorer les estimés de DDA avec la contribution de métriques texturales dérivées du modèle de hauteur de canopée combinées aux métriques LiDAR standards. Le deuxième objectif consiste à déterminer la meilleure approche pour modéliser les DDA : soit en différentiant a priori la modalité des DDA selon leur modalité (uni/bimodales) ou non. La modélisation de la DDA passe par la prédiction des paramètres de la fonction Weibull ajustée aux DDA unimodales et non-différentiées. Pour les DDA bimodales, un finite mixture model, composé de deux fonctions Weibull, permet d’extraire les paramètres des deux composantes Weibull ajustées à la DDA. Les paramètres, échelle et forme, des fonctions Weibull décrivant les DDA unimodales et non différenciées ont été prédits avec des R² acceptables (0.40-0.55) comparativement aux paramètres moyenne, proportion et écart type des DDA bimodales (R² moyen<0.30). L’utilisation de métriques de texture a permis d’améliorer la précision globale de la différentiation des modalités de 4%, ce qui a fait augmenter en moyenne de 0.10 le R² pour les paramètres des DDA unimodales et non-différentiées, et 0.17 pour les DDA différentiés bimodales. De plus, les DDA unimodales ont prédit en moyenne 79% des diamètres mesurés et 75% pour les bimodales. Les DDA non-différentiées ont prédit 76% des diamètres mesurés. Cependant, les DDA bimodales présentaient des R² faibles, causé par l’absence de deux modes clairement distincts ainsi eu par la difficulté de prédire les faibles diamètres

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

The Dust Properties of Hot R Coronae Borealis Stars and a Wolf-Rayet Central Star of a Planetary Nebula: In Search of the Missing Link

We present new Spitzer IIRS spectra of two hot R Coronae Borealis (RCB) stars, one in the Galaxy,V348 Sgr, and one lying in the Large Magellanic Cloud, HV 2671. These two objects constitute a link between the RCB stars and the [WCL] class of central stars of planetary nebula (CSPNe) that has little or no hydrogen in their atmospheres such as CPD -560 8032. HV 2671 and V348 Sgr are members of a rare subclass that has significantly higher effective temperatures than most RCB stars, but sharing the traits of hydrogen deficiency and dust formation that define the cooler RCB stars. The [WC] CSPNe star, CPD -560 8032, displays evidence for dual-dust chemistry showing both PAHs and crystalline silicates in its mid-IR spectrum. HV 2671 shows strong PAH emission but shows no sign of having crystalline silicates. The spectrum of V348 Sgr is very different from those of CPD -56deg 8032 and HV 2671. The PAH emission seen strongly in the other two stars is only weakly present. Instead, the spectrum is dominated by a broad emission centered at about 8.5 microns. This feature is not identified with either PAHs or silicates. Several other novae and post-asymptotic giant branch stars show similar features in their IR spectra. The mid-IR spectrum of CPD -56deg 8032 shows emission features associated with C60 . The other two stars do not show evidence for C60. The nature of the dust around these stars does not help us in establishing further links that may indicate a common origin

Nursing interventions designed to improve healthcare in general healthcare settings for adults living with mental illness: a scoping review

Abstract: People living with mental illness have difficulty obtaining quality physical care services. Nurses find it hard to fully assume their role and adopt a person-centered approach when they care for people with both physical and mental health problems. A scoping review was carried out to document the breadth and depth of literature on nurse interventions designed to improve nursing care in general healthcare settings for adults living with mental illness. Two researchers independently screened titles, abstracts and full documents to obtain publications, and the relevant data was extracted from individual studies. Of the 384 studies identified, 16 documents were included in the study. Few interventions have been the subject of scientific publications and they are scattered in their objectives and very heterogeneous in their content. Interventions are often included in a large program that may be difficult to apply in various care settings. There are many different nursing roles and activities in care-management and in support of behavioral changes although their main measured outcomes differ. This study highlights a tendency for interventions to relegate people with mental health problems to specialized services, which reinforces the dichotomization of services and does not favor a holistic and person-centered approach. There is an urgent need to develop and evaluate nursing interventions in general healthcare settings for adults living with mental illness. The development of relevant continuing education and training must take into account both the point of view of the people living with mental illness and that of nurses

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis

Vlado Perkovic and colleagues show, through a systematic review and meta-analysis of cohort studies, that there is a strong and continuous association between proteinuria and subsequent risk of coronary heart disease