1,721,076 research outputs found
Investigation of the Mode of Action of the Protein VapA of Rhodococcus Equi on Phagosome Membranes
No full textThe intracellular pathogen R. equi manages to survive the phagosome maturation by arresting phagosomes in a prephagolysosomal state. The rhodococcal virulence-associated protein A (VapA) contributes to this process [1]. We propose a pore forming activity for VapA.Based on experiments with model membranes mimicking the phagosome membrane we suggest a five-step mode of action for VapA. Biosensor experiments indicated a binding of VapA to the bilayers (1) being accompanied by an increase of membrane rigidity. In contrast to common pore-forming molecules only a weak intercalation dependent on the lateral membrane pressure occured (2). AFM analysis revealed a strong aggregation of VapA on cholesterol-poor lipid domains (3). This induced a reorganization of the domain structure of the bilayer. Defined and undefined lesions increasing the permeability of the reconstituted membranes (4) and finally the induction of membrane disintegration by VapA (5) were observed using electrophysiological measurements on freestanding membranes and a fluorescence based nanopore dye release assay.We assume two different interaction states for VapA defined by different protein orientation which depend on lipid package, lipid composition and pH value. The potential relevance of these observations for understanding of R. equi virulence will be discussed.References[1] von Bargen, C. and Haas, A., 2009, FEMS Microbiol Rev 33: 870-891
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
Variations 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
Entwicklung einer Softpellet Formulierung für die inhalative Hoch-Dosis Therapie
No full textTuberculosis is a difficult-to-treat disease caused by mycobacterium tuberculosis, which is one of the top 10 causes of death and the deadliest infectious disease worldwide. In 80 % of the patients, the primary infection occurs in the lungs. The standard treatment for the disease is systemic administration of a combination of different antibiotics in high doses over a period of at least 6 months. In tuberculosis, however, the pathogen may be encapsulated in granulomas which are difficult to access for systemically administered drugs. At the same time, patient compliance is reduced due to the long duration of therapy and frequent side effects. In addition to other factors, these complications can lead to subtherapeutic concentrations in the target tissue, which favors the development of multidrug-resistant pathogens and thus compromises the success of the therapy. One approach to solve this problem is the administration of high-dose antibiotics via the inhalation route. This procedure allows high drug concentrations to be achieved in the target tissue while keeping systemic exposure low, thus minimising the incidence of side effects.
To implement this new treatment method, a dry powder formulation for inhalation was developed in this thesis. Powders intended for inhalation must have aerodynamic particle diameters in the micronised range (1 - 5 μm), which makes them exhibit strong cohesive forces and difficult to handle. For this reason, controlled agglomerates, so-called softpellets, were produced from the raw materials by using a continuous process based on vibration. Due to the reduced surface area, softpellets show simplified handling, while the interparticle forces are low enough to allow deagglomeration during inhalation. Since softpellets can be produced from pure active ingredient and thus the amount of powder to be inhaled can be kept to a minimum for the patient, they are ideally suited for high-dose inhalation.
By further developing the production device, the yield obtained in this work could be increased from 27 % to 80 %, which corresponds to an increase of almost threefold. The size of the softpellets could be controlled by using sieves with different mesh sizes for pre-agglomeration.
The antibiotics used for tuberculosis treatment, rifampicin and isoniazid, were used as starting material. In the Twister, a FPF of 54 % and a FPD of 20 mg could be achieved with rifampicin softpellets, and a FPF of 11 % and a FPD of 4 mg with isoniazid
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softpellets. For all experiments, a positive effect on FPF was observed when the dose was divided into several single inhalations. By using coarse lactose particles, the ED in the Twister of rifampicin softpellets could be increased from 65 % to 74 %, resulting in an increase in FPD to 24 mg.
In addition, the development of the Micro-Force apparatus made it possible for the first time to determine the energy required to compress a softpellet.
Overall, this work has shown that the production method on a vibrating chute represents a continuous process with which softpellets with spherical morphology and high yields can be obtained. The softpellets showed the potential to transport large amounts of active substances in the mg range into the lungs and, therefore, to be suitable for inhaled high-dose therapy
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