1,721,063 research outputs found
Evaluating the Compatibility of Three Aluminum Salt-Adjuvanted Recombinant Protein Antigens (Trivalent NRRV) Combined with a Mock Trivalent Sabin-IPV Vaccine: Analytical and Formulation Challenges (Dataset)
No full textComparisons of Two Different Analytical Methodologies for the Characterization of Sub-Visible Particles in Therapeutic Protein Formulations
Full text linkThe US and EU pharmacopeias require sub-visible particle (SbVP) testing of parenteral drug products by either light obscuration (LO) or light microscopy. According to the USP/EP, the LO method requires the use of four measurements consuming a total volume of 25 ml per sample. This large sample volume makes the compendia test not only cost-intensive for biopharmaceutics, but in certain cases impractical, especially in early stage development when clinical supplies are often limited. The first part of this work therefore presents a set of experimental data for evaluation of a small scale, lower volume LO method (1.2 ml per sample). Limitations for detecting various translucent particles such as glass splinters, silicone oil droplets and non-soluble protein aggregates have been considered for both of these LO methods. In addition, a relatively new technology - Micro Flow Digital Imaging (MDI) - has been introduced, which may be a viable add-on to measure SbVP. The purpose of the second phase of this research was to evaluate the advantages and limitations of MDI by directly comparing LO and MDI, and also by comparing two different MDI instruments (i.e., Micro Flow Imaging (MFI) and FlowCam), with regards to subvisible particle counts, size distribution and morphology parameter analysis. As protein subvisible particles vary widely in shape and size, it is difficult to quantitatively describe the limitations of MDI and LO for actual samples of a protein therapeutic drug. Moreover, real-life protein formulations can differ in optical properties such as turbidity, color, refractive index which may potentially influence SbVP detection. During this work, MDI technologies have been improved for the use on a routine basis with protein samples (e.g., FlowCam counting ability was improved by adding a syringe pump for controlled flow, and MFI optical system was enhanced with the so called set-point 3). The effect of solution optical properties on SbVP particle sizing and counting was addressed subsequently using the latest MDI instrument and three different LO instruments. In addition, translucent particles such as glass and irregular shaped particles in development as "false protein standard" (to mimic properties of real life proteinaceous particles) were evaluated in this work
Effect of pH and light on aggregation and conformation of an IgG1 mAb
Full text linkDuring the purification process, monoclonal antibodies may be exposed to parts of UV-C (200 to 290 nm), UV-B (290 to 320 nm) and visible light (400 to 760 nm) under a variety of buffer and pH conditions. Together, these conditions can promote both chemical and physical degradation which may result in conformational changes. To examine this possibility, the impact of UV light on an IgG1 mAb at pH 3.5, 5 and 8 was studied at multiple protein concentrations. Exposure to 302 nm light resulted in a pH-dependent formation of high molecular weight species where the degree of oligomerization increased with increasing pH. Characterization by SDS-PAGE under reducing and non-reducing conditions, and SEC-MALS, revealed that the predominant species were non-reducible dimeric, trimeric and higher order oligomeric species which occurred through processes other than intermolecular disulfide bond formation. Biophysical characterization by differential scanning calorimetry demonstrated an overall loss of heat capacity suggesting a loss of conformational integrity with light exposure. A decrease in tryptophan fluorescence was paralleled by a significant decrease in the transition temperature measured during heat-induced unfolding following light exposure also suggesting a significant change in conformational integrity. The observations by fluorescence spectroscopy coincided with pH dependent changes in the alterations of secondary structure characterized by Fourier transform infrared spectroscopy and far UV circular dichroism with the most acidic pH showing the greatest degree of change in the beta-sheet structure. Exposure to UV light resulted in aggregation with pH-dependent yields decreasing in the following order, 8.05.03.5, while the opposite trend was observed for conformational changes, with pH-dependent extents decreasing in the following order:3.55.08.0. These pH-dependent trends suggest that different strategies will be required to stabilize the protein against these modifications during processing
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
Techniques to Improve the Characterization of Protein Particles in Biologic Drug Products
Full text linkThe characterization of particulate matter, especially protein aggregates, in the sub-visible and visible size range has become an area of focus in the biopharmaceutical industry. This heightened focus is due, in part, to increasing concern around particles causing immunogenicity, and increased queries from regulatory bodies. There has been extensive research in this area, with many recent publications on related methodologies, mechanisms and influencing factors. Two areas of interest are the characterization of these particles using material sparing approaches and the effect of the presence of silicone oil particles on protein solutions. With the focus on high concentration drug products (¡Ý50 mg/mL), and the drive toward conserving drug product by producing fewer batches, there is a real need for characterization techniques that require less sample. In addition, there is significant interest by the regulatory agencies in obtaining information on particulate matter in biologic drug products over a broad range of sizes. Queries are being generated by the FDA and other regulatory bodies, asking for particle count and any additional compositional information. They are requiring the pharmaceutical industry to have a deeper understanding of the formation of protein particles as well as methods for monitoring a broad range of sizes, over the shelf life of the product. The propensity exists for increased protein aggregation at higher concentrations, yet companies are generating less sample material for testing during development. The focus of this dissertation was to develop approaches for characterizing protein aggregation (particulates) using minimal sample amounts. To develop validatable methods for ongoing drug product monitoring as well as more novel approaches to better understand the nature of particulate matter present in biologic drug products. Silicone oil is present in many drug product contact surfaces and was chosen for further study on the effect of protein aggregation. The methods developed during this research were utilized to characterize protein and/or silicone oil particles, and to provide differentiation between protein and non-protein particles
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
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