Progrès vers la synthèse totale de la calyciphylline B

Les alcaloïdes Daphniphyllum constituent une vaste famille de produits naturels isolés à partir de plantes à feuillage persistant couramment utilisés dans la médecine chinoise traditionnelle. Ils affichent une gamme impressionnante d'activités biologiques; antipyrétique, anti-inflammatoire, antioxydant et même anticancéreux. La calyciphylline B appartient à cette famille et possède un motif original comprenant sept stéréocentres adjacents, dont un stéréocentre quaternaire tout carbone, avec un échafaudage hexacyclique. Sa structure a été déterminée par données spectroscopiques, plus précisément par des techniques de RMN 2D. Malgré le peu d'information sur son activité biologique, sa synthèse représente sans le moindre doute un grand défi pour les chimistes organiciens. Le groupe de recherche du Prof. Hanessian a entrepris la synthèse totale de la calyciphylline B en 2010, laquelle est toujours en cours. Une nouvelle approche a été développée pour la préparation d'un intermédiaire azabicyclo[3.3.0]octane avancé. Ce mémoire résume les travaux de recherche de l'auteur sur les progrès réalisés pour la voie alternative élaborée par le groupe du prof. Hanessian. Le travail effectué comprend la formation d'un stéréocentre quaternaire, l'alkylation d'un énolate sur un triflate d'alkyle secondaire, une réduction diastéréosélective, une cyclisation réductrice ainsi qu'une oxydation de Wacker régiosélective.The Daphniphyllum alkaloids constitute a broad class of natural products isolated from a genus of evergreen plants extensively used in traditional Chinese medicine. These alkaloids display an impressive range of biological activities, including antipyretic, anti-inflammatory, antioxidant, and even anticancer properties. Calyciphylline B is a structurally unique member of this family containing seven contiguous stereocenters including an all-carbon quaternary stereocenter with a fused-hexacyclic ring scaffold. Its structure was determined by spectroscopic methods, especially 2D NMR techniques. Despite the sparse availability of information on its biological activity, its synthesis is undoubtedly a great challenge for synthetic chemists. The research group of Prof. Hanessian embarked on the total synthesis of calyciphylline B in 2010 and the project is still ongoing. A new route was developed for the preparation of an advanced azabicyclo[3.3.0]octane intermediate. This thesis summarizes the research work of the author on the progress made for the synthetic route developed by the Hanessian group. The work done includes the formation of a quaternary stereocenter, alkylation of an enolate using a secondary alkyl triflate, diastereoselective reduction, reductive cyclization, and a regioselective Wacker oxidation

A Benchmark Comparison of Python Malware Detection Approaches

While attackers often distribute malware to victims via open-source, community-driven package repositories, these repositories do not currently run automated malware detection systems. In this work, we explore the security goals of the repository administrators and the requirements for deployments of such malware scanners via a case study of the Python ecosystem and PyPI repository, which includes interviews with administrators and maintainers. Further, we evaluate existing malware detection techniques for deployment in this setting by creating a benchmark dataset and comparing several existing tools, including the malware checks implemented in PyPI, Bandit4Mal, and OSSGadget's OSS Detect Backdoor. We find that repository administrators have exacting technical demands for such malware detection tools. Specifically, they consider a false positive rate of even 0.01% to be unacceptably high, given the large number of package releases that might trigger false alerts. Measured tools have false positive rates between 15% and 97%; increasing thresholds for detection rules to reduce this rate renders the true positive rate useless. In some cases, these checks emitted alerts more often for benign packages than malicious ones. However, we also find a successful socio-technical malware detection system: external security researchers also perform repository malware scans and report the results to repository administrators. These parties face different incentives and constraints on their time and tooling. We conclude with recommendations for improving detection capabilities and strengthening the collaboration between security researchers and software repository administrators.Comment: 12 pages, 3 figures, 3 table

Effects of different feeds and stocking densities on growth and survival rates of mud crab (<em>Scylla paramamosain</em>) at the stage from megalopa to crablet-1

Mud crabs (Scylla genus) are luxury foods in high demand internationally. The efficient techniques for mud crab hatcheries are vital for providing breeds for their aquaculture, which is rapidly growing in many countries. This study aims to investigate the effects of different feeds and stocking densities on mud crabs' growth and survival rates (Scylla paramamosain) in the stage from megalopa to crablet-1 stage. Two separate experiments were conducted indoors in the 60-liter round plastic tanks (containing 50 liters of water at a 28‰ salinity). Experiment 1 investigated four feeds: frozen Artemia biomass, pureed shrimp meat, Lansy pellet feed (48% protein), and NRD pellet feed (55% protein). Megalopae (mean weight of 5.8 mg) were stocked at a density of 10/L. In experiment 2, the megalopae (mean weight of 5.4 mg) were stocked at densities of 20, 30, and 40/L and were fed the Lansy pellet feed, which was the best one selected from experiment 1. High survival rates were obtained at all four feeds (82.2–87.5%) and three stocking densities (88.4–90.1%). The growth performances in Lansy feed and frozen Artemia biomass were better than those in pureed shrimp meat and NRD pellet feed, which was seen through higher indicators of daily weight gain (DWG) and specific growth rate in weight (SGRw) (p p > 0.05). The investigated feeds and stocking densities suit the nursing mud crab (S. paramamosain) megalopa. In contrast, the Lansy pellet feeds had a stocking density of 20/L, resulting in the highest nursing efficiency

The MtSNF4b subunit of the sucrose non-fermenting-related kinase complex connects after-ripening and constitutive defense responses in seeds of Medicago truncatula

Dormant seeds are capable of remaining alive in the hydrated state for extended periods of time without losing vigor, until environmental cues or after-ripening result in the release of dormancy. Here, we investigated the possible role of the regulatory subunit of the sucrose non-fermenting-related kinase complex, MtSNF4b, in dormancy of Medicago truncatula seeds. Expression of MtSNF4b and its involvement in a high-molecular-weight complex are found in dormant seeds, whereas imbibition of fully after-ripened, non-dormant seeds leads to dissociation of the complex. MtSNF4b is capable of complementing the yeast Δsnf4 mutant and of interacting with the MtSnRK1 α-subunit in a double hybrid system. Transcriptome analyses on freshly harvested and after-ripened RNAi Mtsnf4b and wild-type embryos implicate MtSNF4b in the defense response in hydrated dormant embryonic tissues, affecting the expression of genes encoding enzymes of flavonoid and phenylpropanoid metabolism, WRKY transcription factors and pathogenesis-related proteins. Silencing MtSNF4b also increased the speed of after-ripening during dry storage, an effect that appears to be related to a change in base water potential. No significant difference in ABA content or sensitivity was detected between mutant and wild-type seeds. Pharmacological studies using hexoses and sugar analogs revealed that mannose restored germination behavior and expression of the genes PAL, CHR and IFR in RNAi Mtsnf4b seeds towards that of the wild-type, suggesting that MtSNF4b might act upstream of sugar-sensing pathways. Overall, the results suggest that MtSNF4b participates in regulation of a constitutively activated defense response in hydrated, dormant seeds

Genetic landscape of autism spectrum disorder in Vietnamese children

Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children

‘I’m not like that, why treat me the same way?’ The impact of stereotyping international students on their learning, employability and connectedness with the workplace

A significant body of literature on international education examines the experiences of international students in the host country. There is however a critical lack of empirical work that investigates the dynamic and complex positioning of international students within the current education-migration nexus that prevails international education in countries such as Australia, Canada and the UK. This paper addresses an important but under-researched area of the education-migration landscape by examining how the stereotyping of students as mere &lsquo;migration hunters&rsquo; may impact their study and work experiences. It draws on a four-year research project funded by the Australian Research Council that includes more than 150 interviews and fieldwork in the Australian vocational education context. Positioning theory is used as a conceptual framework to analyse how generalising international students as &lsquo;mere migration hunters&rsquo; has led to the disconnectedness, vulnerability and marginalization of the group of international students participating in this research

COPPER-MODIFIED MCM-22 AS CATALYSTS FOR HYDROCARBON SELECTIVE CATALYTIC REDUCTION OF NOX

Joint Research on Environmental Science and Technology for the Eart