1,720,953 research outputs found
The influence of positively charged nitrogen species on compound accumulation and activity in gram-negative bacteria
Get PDFMultidrug resistant Gram-negative bacterial infections are on the rise, and with no FDA approvals for new classes of broad-spectrum antibiotics in over 50 years, these infections constitute a major threat to human health. A significant challenge is the inability of most compounds to accumulate in Gram-negative bacteria. Recently developed predictive guidelines called the eNTRy rules show that appending a primary amine to an appropriately shaped compound can enhance Gram-negative accumulation and antibacterial activity. However, in certain cases addition of a primary amine resulted in the disruption of target engagement. Therefore, it would be advantageous to have alternate functional groups that facilitate accumulation in Gram-negative bacteria but offer different interactions with a given target protein.
Here we report that other positively charged nitrogen functional groups, namely N-alkyl guanidiniums and pyridiniums, can also facilitate compound uptake into Gram-negative bacteria. Accumulation of a set of 60 non-antibiotic compounds, consisting of 20 primary amines derived from the Complexity-to-Diversity strategy and their corresponding guanidiniums and pyridiniums, was assessed in Escherichia coli. We also installed these alternate functional groups onto six antibiotic scaffolds and assessed their accumulation and antibacterial activity in Gram-negative bacteria. In addition, computational studies were performed to predict whether additional charged functional groups will be able to facilitate Gram-negative uptake. The results suggest that other positively charged, nitrogen-containing functional groups should be considered when designing antibiotics with Gram-negative activity.
Finally, retrospective analysis of commercial screening libraries showed a lack of compounds containing primary amines. This is likely a major reason for the failures within the pharmaceutical industry to find lead compounds with whole cell activity from high throughput screening campaigns. Here strategies for addressing this problem through efficient amine installation strategies are discussed and applied to compounds from the CtD collection and their antimicrobial activity assessed.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2022-12-01The student, Sarah Perlmutter, accepted the attached license on 2020-11-23 at 12:13.The student, Sarah Perlmutter, submitted this Dissertation for approval on 2020-11-23 at 13:00.This Dissertation was approved for publication on 2020-11-25 at 11:56.DSpace SAF Submission Ingestion Package generated from Vireo submission #15939 on 2021-03-04 at 16:19:47Made available in DSpace on 2021-03-05T21:42:39Z (GMT). No. of bitstreams: 7
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Previous issue date: 2020-11-25Embargo set by: Seth Robbins for item 117210
Lift date: 2023-03-05T21:43:00Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Onl
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Development of a tandem Diels-Alder/Pauson-Khand strategy for the synthesis of tetracycles
No full textVariations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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