1,720,964 research outputs found
Isolation and Characterization of New Antibacterial Active Secondary Metabolites from Microorganisms as Potential Starting Points for Drug Discovery
Full text linkOnce considered the ‘magic bullet’, antibiotics no longer satisfy the wonder drug label as antimicrobial resistance (AMR) has largely eradicated the advantages given when first discovered more than 100 years ago. Stopped research efforts after ‘The Golden Age’ of antibiotics and the major challenges of antibacterial drug development (e.g., discovery of new compounds, performing clinical trials, economic value) resulted in the existing therapeutic gap contributing to the resistance crisis mankind is currently facing. As most large pharmaceutical companies dropped out of antibiotic research, small firms and research groups are left in the frontline. In order to prevent the 21st century from turning into the ‘post antibiotic era’, innovative partnerships between academia and industry combining innovative research with expertise represent one promising strategy.[ ] For this purpose, the Public Private Partnership between Fraunhofer IME and Sanofi (later Evotec) was established in 2014. The defined Target Product Profile (TPP) towards discovery of novel antibacterial compounds dictated a main focus on Gram negative (GN) ESKAPE pathogens and M. tuberculosis (Mtb). Rising to the tremendous challenge based on natural product (NP) research, a discovery platform was built on the Sanofi Fraunhofer strain collection harboring more than 120,000 different organisms further incorporating innovative screening approaches and focusing on underexplored phyla. Within this pipeline, isolation and structure elucidation of active metabolites focusing especially on novel chemistry remains a crucial part as it allows the identification of potential hit compounds for further hit expansion and lead generation.
In the present PhD thesis, four ‘active extract-to-hit’ (AE2H) projects covering both GN and Mtb active secondary metabolites from fungal and bacterial producers including the phylum Bacteroidetes were successfully accomplished. In total, the structures of all eight compounds identified by dereplication to cause the initial activity were elucidated comprising four so far unknown NPs. Additionally, 24 analogs were isolated including 14 new metabolites. Overall, the 32 compounds belong to four different NP classes: polyoxygenated and N heterocyclic arenes, linear peptides as well as amino- and phospholipids. Diverse isolation protocols were developed utilizing various techniques to obtain compounds of interest in sufficient quantity and of adequate purity. Therefore, optimization of fermentation conditions was beneficial. Structure elucidation was achieved by conclusive NMR spectroscopy and strongly supported by ESI QTOF MS/MS analysis. Assignment of relative and absolute configuration employed analytical methods (e.g., 2D ROESY NMR analysis) as well as chemical derivatization (e.g., Marfey’s Analysis) and stereoselective total synthesis. Moreover, synthetic chemistry was used to perform first SAR studies. For hit confirmation, bioactivity properties of all isolated and synthesized compounds was extensively investigated (MIC determination, in vitro TLR2/TLR4 and cytotoxicity assays). Overall, generated data finally encourage further efforts as promising starting points for future projects were presented.Bundeslände
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
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
Svetamycins A-G, Unusual Piperazic Acid-Containing Peptides from Streptomyces sp
No full textSeven new halogenated peptides termed svetamycins A-G (1-7) have been isolated from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are cyclic depsipeptides whereas svetamycin E is a linear analogue of svetamycin C. Their structures were determined using extensive spectroscopic analysis, and their stereochemical configuration was established by a combination of NMR data, quantum mechanical calculations, and chemical derivatizations. Svetamycins are characterized by the presence of a hydroxyl acetic acid and five amino acids including a rare 4,5-dihydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, a γ-halogenated piperazic acid, and a novel δ-methylated piperazic acid in svetamycins B-C, E, and G. Moreover, isotope-labeled substrate feeding experiments demonstrated ornithine as the precursor of piperazic acid and that methylation at the δ position of the piperazyl scaffold is S-adenosyl-L-methionine (SAM)-dependent. Svetamycin G, the most potent antimicrobial of this suite of compounds, inhibited the growth of Mycobacterium smegmatis with an MIC80 value of 2 μg/mL
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