42 resultados para 312.432


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Thursday, October 27 · 7:00pm - 8:00pm
Location
Brooklyn College
Studio 312 in Roosevelt Hall, Bedford Ave.
Brooklyn, NY
Created By
Cory Bracken

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Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected β-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead β-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and β-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.

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This latest edition of J. S. Bach’s B-minor Mass, by Ulrich Leisinger, described by the publisher as a ‘hybrid edition’, aptly addresses the needs of present-day performers and at the same time fulfils the scholarly expectations of new critical editions to conform to the current study environment

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This article analyses the use of equality as a concept central to the implementation of the 1998 Good Friday Agreement in Northern Ireland. The authors argue that, although equality legislation is succeeding in redressing previous discrimination in society, the discourses that have emerged around it have exacerbated competition and polarization between communities for two main reasons. Firstly, in " selling' the Agreement to their supporters, political elites have appropriated community-specific definitions of the concept, thus reinforcing rather than weakening group differences. Secondly, the practice of equality legislation involves the definitive categorization of individuals as members of particular groups. This article examines these processes and their effects through the analysis of the discourse of nationalist and Unionist Party elites and of individual Catholics and Protestants. This is done in order to capture the dynamics of change in political communication and identification rather than simply describing institutional alterations.

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