1,720,985 research outputs found
Antibiotic Drug Discovery: New Targets and Molecular Entities.
No full textComprising a total of eight chapters and almost 300 pages, this book is the 58th volume of the appreciated Drug Discovery Series of the Royal Society of Chemistry.
The book deals with one the most compelling problems medicinal chemistry is facing right now: bacterial resistance. The spread of bacteria resistant to the available antibiotic armamentarium is a serious threat to human health. The World Health Organization (WHO) predicts that by 2050, bacterial resistance will cause 50 million deaths, thus becoming the leading cause of death worldwide. The scientific community is on alert, and solutions must be found rapidly; at present, even under the resurgence of antibiotic drug discovery, the pipeline of new antibiotics under development is slim, thus not encouraging that solutions are at hand. To fight resistant bacteria, the discovery and validation of new targets is crucial, and only innovative drugs with new modes of action can be a viable solution to curb the continued emergence and spread of antibiotic‐resistant bacteria. Internationally coordinated actions as well as consistent and continuous investments to support research in antibiotic drug discovery are necessary to increase the chances of success.
In this perspective, the book discusses recent results on antibacterial drug discovery with particular attention to new targets and innovative strategies implemented to combat bacterial resistance. The book will be of interest to a large audience, not only to medicinal chemists in the field, to whom it can serve as a valuable point of reference, but to anyone wishing to follow the latest approaches in antibiotic drug design. The book is also valuable as a textbook for postgraduate students in medicinal chemistry: concepts are explained clearly and concisely throughout all chapters; sections are well organized and nicely illustrated; the quality of the diagrams and schemes, especially with regard to chemical structures, is uniform throughout the book. Most chapters have a reasonable length of around 20 to 40 pages with sufficient key references and one or more color figures, comprehensive tables, and detailed lists of discussed chemical analogues. Contents are easily accessible through the table of contents, while a subject index helps the reader to navigate the volume
Novel targets and mechanisms in antimicrobial drug discovery
Full text linkThe spread of infections resistant to available anti-infective drugs is a serious menace to human health [...]
Stepped boat-tails: a proposal for the control of the aerodynamic loads on bluff bodies
No full textNew geometrical configurations of the afterbodies of both axisymmetric and cylindrical bluff bodies that are elongated in the free-stream direction are proposed for the control of the aerodynamic loads. Special attention is dedi-cated to the mean aerodynamic drag, considering its importance for the reduction of the fuel consumption of terrestrial vehicles; however, the varia-tions of the cross-flow forces on the lateral surfaces, which may be of interest in different applications, are also considered. Steady-flow numerical simula-tions, carried out by means of a RANS code, seem to suggest that the new geometries have the potential of delaying the global separation of the bound-ary layer, and thus of reducing the afterbody drag and changing the value and position of the resultant cross-flow force. A research program to study in greater detail the potential advantages and the limits of the new configura-tions for different practical applications is also delineated
Ten Years with New Delhi Metallo-β-lactamase-1 (NDM-1): From Structural Insights to Inhibitor Design
No full textThe worldwide emergence of New Delhi metallo-β-lactamase-1 (NDM-1) as a carbapenemase able to hydrolyze nearly all available β-lactam antibiotics has characterized the past decade, endangering efficacious antibacterial treatments. No inhibitors for NDM-1 are available in therapy, nor are promising compounds in the pipeline for future NDM-1 inhibitors. We report the studies dedicated to the design and development of effective NDM-1 inhibitors. The discussion for each agent moves from the employed design strategy to the ability of the identified inhibitor to synergize β-lactam antibiotics. A structural analysis of NDM-1 mechanism of action based on selected X-ray complexes is also reported: the intrinsic flexibility of the binding site and the comparison between penicillin/cephalosporin and carbapenem mechanisms of hydrolysis are evaluated. Despite the valuable progress in terms of structural and mechanistic information, the design of a potent NDM-1 inhibitor to be introduced in therapy remains challenging. Certainly, only the deep knowledge of NDM-1 architecture and of the variable mechanism of action that NDM-1 employs against different classes of substrates could orient a successful drug discovery campaign
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
