1,721,044 research outputs found

    Diels–Alder hydrogels for controlled antibody release: Correlation between mesh size and release rate

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    Eight-armed PEG, molecular mass 10 kDa, was functionalized with furyl and maleimide groups, respectively; the obtained macromonomers were cross-linked via Diels-Alder chemistry. The mesh size (xi) of the prepared hydrogels was determined by swelling studies, rheology, and low field NMR spectroscopy. The in vitro release of fluorescein isothiocyanate labeled dextrans (FDs) and bevacizumab was investigated. The average mesh size (xi(avg)) increased from 5.8 +/- 0.1 nm to 56 +/- 13 nm during degradation, as determined by swelling studies. The result of the rheological measurements (8.0 nm) matched the initial value of xi(avg). Low field NMR spectroscopy enabled the determination of the mesh size distribution; the most abundant mesh size was found to be 9.2 nm. In combination with the hydrodynamic radius of the molecule (R-h), the time-dependent increase of xi(avg) was used to predict the release profiles of incorporated FDs applying an obstruction-scaling model. The predicted release profiles matched the experimentally determined release profiles when R-h = xi(avg), most likely due to the statistical distribution of xi in real polymer networks. The release profile of bevacizumab differed from those of equivalently sized FDs. The delayed release of bevacizumab was most likely a result of the globular structure and rigidity of the protein. The observed correlation between xi and the release rate could facilitate the design of controlled release systems for antibodies

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Nanoparticles for the treatment of ocular neovascularizations

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    Neovascular diseases of the posterior eye like age-related macular degeneration, proliferative diabetic retinopathy or retinopathy of prematurity carry a tremendous burden for patient and health care system alike. Although intravitreal injections of anti-VEGF based therapeutics have significantly improved the visual outcome for many patients, current therapeutic options still show significant drawbacks such as the injection-related risk of contracting an infection. Due to their ability to encapsulate drugs with otherwise poor bioavailability, accumulate in areas of increased vascular permeability and control the release of active ingredients over time, nanoparticle systems have been widely researched to enhance current therapeutic strategies and expand the therapeutic arsenal. In this review, emphasis is placed both on the possibilities and drawbacks that a systemic nanoparticle-based therapy could have in the context of neovascular posterior eye diseases. Recent investigations into intravenous and intravitreal administration of nanomaterials and their potential to deliver potent drugs and genes to pathologic lesions will also be presented. Furthermore, we will focus on the exceptional anti-oxidative and anti-angiogenic properties of selected nanoscale systems that carve out new paths for the treatment of these severe posterior eye diseases. (C) 2015 Elsevier B.V. All rights reserved

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    On the uncertainty of the correlation between nanoparticle avidity and biodistribution

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    The specific delivery of a drug to its site of action also known as targeted drug delivery is a topic in the field of pharmaceutics studied for decades. One approach extensively investigated in this context is the use ligand functionalized nanoparticles. These particles are modified to carry receptor specific ligands, enabling them to accumulate at a desired target site. However, while this concept initially appears straightforward to implement, in-depth research has revealed several challenges hindering target site specific particle accumulation - some of which remain unresolved to this day. One of these challenges consists in the still incomplete understanding of how nanoparticles interact with biological systems. This knowledge gap significantly compromises the predictability of particle distribution in biological systems, which is critical for therapeutic efficacy. One of the most crucial steps in delivery is the attachment of nanoparticles to cells at the target site. This attachment occurs via the formation of multiple ligand receptor bonds. A process also referred to as multivalent interaction. While multivalency has been described extensively for individual molecules and macromolecules respectively, little is known on the multivalent binding of nanoparticles to cells. Here, we will specifically introduce the concept of avidity as a measure for favorable particle membrane interactions. Also, an overview about nanoparticle and membrane properties affecting avidity will be given. Thereafter, we provide a thorough review on literature investigating the correlation between nanoparticle avidity and success in targeted particle delivery. In particular, we want to analyze the currently uncertain data on the existence and nature of the correlation between particle avidity and biodistribution

    General sites of nanoparticle biodistribution as a novel opportunity for nanomedicine

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    The development of nanomedical devices has led to a considerable number of clinically applied nanotherapeutics. Yet, the overall poor translation of nanoparticular concepts into marketable systems has not met the initial expectations and led to increasing criticism in recent years. Most novel nano approaches thereby use highly refined formulations including a plethora of active targeting sequences, but ultimately fail to reach their target due to a generally high off-target deposition in organs such as the liver or kidney. In this context, we argue that initial nanoparticle (NP) development should not entirely become set on conventional formulation aspects. In contrast, we propose a change of focus towards a prior analysis of general sites of NP in vivo deposition and an assessment of how accumulation in these organs or tissues can be harnessed to develop therapies for site-related pathologies. We therefore give a comprehensive overview of existing nanotherapeutic targeting strategies for specific cell types within three of the usual suspects, i.e. the liver, kidney and the vascular system. We discuss the physiological surroundings and relevant pathologies of described tissues as well as the implications for NPmediated drug delivery. Additionally, successful cell-selective NP concepts using active targeting strategies are assessed. By bringing together both (patho)physiological aspects and concepts for cell-selective NP formulations, we hope to show a novel opportunity for the development of more promising nanotherapeutic devices
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