1,771,347 research outputs found
Enabling, Decagram-Scale Synthesis of Macrocyclic MCL‑1 Inhibitor ABBV-467
No full textABBV-467 is a highly potent and selective MCL-1 inhibitor
that
was advanced to a phase I clinical trial for the treatment of multiple
myeloma. Due to its large size and structural complexity, ABBV-467
is a challenging synthetic target. Herein, we describe the synthesis
of ABBV-467 on a decagram scale, which enabled preclinical characterization.
The strategy is convergent and stereoselective, featuring a hindered
biaryl cross coupling, enantioselective hydrogenation, and conformationally
preorganized macrocyclization by C–O bond formation as key
steps
CSM-467: Quotient Geometric Crossovers
Full text linkGeometric crossover is a representation-independent definition of crossover based on the distance of the search space interpreted as a metric space. It generalizes the traditional crossover for binary strings and other important recombination operators for the most frequently used representations. Using a distance tailored to the problem at hand, the abstract definition of crossover can be used to design new problem specific crossovers that embed problem knowledge in the search. In previous work we have started studying how metric transformations of the distance associated with geometric crossover affect the original geometric crossover. In particular, we focused on the product of metric spaces. This metric transformation gives rise to the notion of product geometric crossover that allows to build new geometric crossovers combining pre-existing geometric crossovers in a simple way. In this paper, we study another metric transformation, the quotient metric space, that gives rise to the notion of quotient geometric crossover. This turns out to be a very versatile notion. We give many examples of application of the quotient geometric crossover
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Band 6, 467 (Sammlung Friedlaender)
No full textBAND 6, 467 (SAMMLUNG FRIEDLAENDER)
Band 6, 467 (Sammlung Friedlaender) (Public Domain) (1
Band 2, 467 (Sammlung Friedlaender)
No full textBAND 2, 467 (SAMMLUNG FRIEDLAENDER)
Band 2, 467 (Sammlung Friedlaender) (Public Domain) (1
El Tlacuache Núm. 467 (2011). 467 Año 11 (2011) mayo. El Tlacuache
No full textDe la “Dissimulación” en una pintura por Mónica Bolton Graff. -Mónica Bolton Graff por Luz Elelena Ramírerez Gochicoa. -Copalquáhuitl, “Arbol de copal” Bursera cuneata por Alma Graciela de la Cruz
Band 3, 467 (Sammlung Friedlaender)
No full textBAND 3, 467 (SAMMLUNG FRIEDLAENDER)
Band 3, 467 (Sammlung Friedlaender) (Public Domain) (1
- …
