178 research outputs found

    Stereospecific Allylic Functionalization:The Reactions of Allylboronate Complexes with Electrophiles

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    Allylboronic esters react readily with carbonyls and imines (π-electrophiles), but are unreactive toward a range of other electrophiles. By addition of an aryllithium, the corresponding allylboronate complexes display enhanced nucleophilicity, enabling addition to a range of electrophiles (tropylium, benzodithiolylium, activated pyridines, Eschenmoser's salt, Togni's reagent, Selectfluor, diisopropyl azodicarboxylate (DIAD), MeSX) in high regio- and stereocontrol. This protocol provides access to key new functionalities, including quaternary stereogenic centers bearing moieties such as fluorine and the trifluoromethyl group. The allylboronate complexes were determined to be 7 to 10 orders of magnitude more reactive than the parent boronic ester.</p

    Development of HTS Current Leads for the ITER Project

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    The HTS current leads for the ITER project will be the largest ever operated, with unprecedented currents, up to 68 kA and voltages, up to 14 kV. According to the ITER agreement they will be provided in-kind by China. After an extensive development program at the Hefei Institute of Plasma Physics (ASIPP), the ITER current leads were designed and qualified. The following discusses the main highlights of this development, with particular emphasis on the description of the design of the different types of ITER current leads and their final qualification in dedicated cold tests in nominal conditions

    Uncovering mechanisms of transcriptional regulations by systematic mining of cis regulatory elements with gene expression profiles

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    <p>Abstract</p> <p>Background</p> <p>Contrary to the traditional biology approach, where the expression patterns of a handful of genes are studied at a time, microarray experiments enable biologists to study the expression patterns of many genes simultaneously from gene expression profile data and decipher the underlying hidden biological mechanism from the observed gene expression changes. While the statistical significance of the gene expression data can be deduced by various methods, the biological interpretation of the data presents a challenge.</p> <p>Results</p> <p>A method, called CisTransMine, is proposed to help infer the underlying biological mechanisms for the observed gene expression changes in microarray experiments. Specifically, this method will predict potential cis-regulatory elements in promoter regions which could regulate gene expression changes. This approach builds on the MotifADE method published in 2004 and extends it with two modifications: up-regulated genes and down-regulated genes are tested separately and in addition, tests have been implemented to identify combinations of transcription factors that work synergistically. The method has been applied to a genome wide expression dataset intended to study myogenesis in a mouse C2C12 cell differentiation model. The results shown here both confirm the prior biological knowledge and facilitate the discovery of new biological insights.</p> <p>Conclusion</p> <p>The results validate that the CisTransMine approach is a robust method to uncover the hidden transcriptional regulatory mechanisms that can facilitate the discovery of mechanisms of transcriptional regulation.</p

    Development of HTS Current Leads for the ITER Project

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    The HTS current leads for the ITER project will be the largest ever operated, with unprecedented currents, up to 68 kA and voltages, up to 14 kV. According to the ITER agreement they will be provided in-kind by China. After an extensive development program at the Hefei Institute of Plasma Physics (ASIPP), the ITER current leads were designed and qualified. The following discusses the main highlights of this development, with particular emphasis on the description of the design of the different types of ITER current leads and their final qualification in dedicated cold tests in nominal conditions

    Novel Quinazolinone MJ-29 Triggers Endoplasmic Reticulum Stress and Intrinsic Apoptosis in Murine Leukemia WEHI-3 Cells and Inhibits Leukemic Mice

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    The present study was to explore the biological responses of the newly compound, MJ-29 in murine myelomonocytic leukemia WEHI-3 cells in vitro and in vivo fates. We focused on the in vitro effects of MJ-29 on ER stress and mitochondria-dependent apoptotic death in WEHI-3 cells, and to hypothesize that MJ-29 might fully impair the orthotopic leukemic mice. Our results indicated that a concentration-dependent decrease of cell viability was shown in MJ-29-treated cells. DNA content was examined utilizing flow cytometry, whereas apoptotic populations were determined using annexin V/PI, DAPI staining and TUNEL assay. Increasing vital factors of mitochondrial dysfunction by MJ-29 were further investigated. Thus, MJ-29-provaked apoptosis of WEHI-3 cells is mediated through the intrinsic pathway. Importantly, intracellular Ca2+ release and ER stress-associated signaling also contributed to MJ-29-triggered cell apoptosis. We found that MJ-29 stimulated the protein levels of calpain 1, CHOP and p-eIF2α pathways in WEHI-3 cells. In in vivo experiments, intraperitoneal administration of MJ-29 significantly improved the total survival rate, enhanced body weight and attenuated enlarged spleen and liver tissues in leukemic mice. The infiltration of immature myeloblastic cells into splenic red pulp was reduced in MJ-29-treated leukemic mice. Moreover, MJ-29 increased the differentiations of T and B cells but decreased that of macrophages and monocytes. Additionally, MJ-29-stimulated immune responses might be involved in anti-leukemic activity in vivo. Based on these observations, MJ-29 suppresses WEHI-3 cells in vitro and in vivo, and it is proposed that this potent and selective agent could be a new chemotherapeutic candidate for anti-leukemia in the future

    Extensive Characterisation of Copper-clad Plates, Bonded by the Explosive Technique, for ITER Electrical Joints

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    Cable-in-conduit conductors will be extensively implemented in the large superconducting magnet coils foreseen to confine the plasma in the ITER experiment. The design of the various magnet systems imposes the use of electrical joints to connect unit lengths of superconducting coils by inter-pancake coupling. These twin-box lap type joints, produced by compacting each cable end in into a copper - stainless steel bimetallic box, are required to be highly performing in terms of electrical and mechanical prop- erties. To ascertain the suitability of the first copper-clad plates, recently produced, the performance of several plates is studied. Validation of the bonded interface is carried out by determining microstructural, tensile and shear characteristics. These measure- ments confirm the suitability of explosion bonded copper-clad plates for an overall joint application. Additionally, an extensive study is conducted on the suitability of certain copper purity grades for the various joint types
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