1,720,956 research outputs found
Resolution limit of image analysis algorithms
Get PDFThe resolution of an imaging system is a key property that, despite many advances in optical imaging methods, remains difficult to define and apply. Rayleigh’s and Abbe’s resolution criteria were developed for observations with the human eye. However, modern imaging data is typically acquired on highly sensitive cameras and often requires complex image processing algorithms to analyze. Currently, no approaches are available for evaluating the resolving capability of such image processing algorithms that are now central to the analysis of imaging data, particularly location-based imaging data. Using methods of spatial statistics, we develop a novel algorithmic resolution limit to evaluate the resolving capabilities of location-based image processing algorithms. We show how insufficient algorithmic resolution can impact the outcome of location-based image analysis and present an approach to account for algorithmic resolution in the analysis of spatial location patterns
Phagocytosis of antibody-opsonized tumor cells leads to the formation of a discrete vacuolar compartment in macrophages
No full textDespite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome. Furthermore, the size of the phagosome-associated vacuole is increased by inhibition of the mTOR pathway. Collectively, the identification of this vacuolar compartment has implications for understanding the subcellular trafficking processes leading to the destruction of phagocytosed, antibody-opsonized cancer cells by macrophages.</p
Studying the Dynamics of Fc-Engineered Antibodies Using Advanced Imaging Methods
Get PDFThe past decade has seen an enormous increase in FcRn-targeted engineering strategies to generate antibodies with therapeutic and diagnostic implications. The neonatal Fc receptor, FcRn, is a multifunctional receptor expressed abundantly throughout the body. The trafficking of engineered antibodies in the body is a multiscale process, taking place at subcellular, intracellular, and organ/tissue levels. In this study, various advanced imaging modalities are employed to capitulate the dynamics of Fc-engineered antibodies at different scales. The study investigates the fate of antibody-opsonized tumor cells after phagocytosis in macrophages, an intracellular/micrometer-scale process, using microscopy techniques. Results show a vacuole-like structure associated with the phagosomes exhibiting distinct characteristics. They are lysosomal in nature and impermeable to certain solutes, as seen using fluorescence microscopy analyses. The identification of this vacuole-like compartment has implications for understanding the subsequent processes involved in the degradation of antibody-opsonized tumor cells.
The use of advanced imaging approaches to study subcellular dynamics provides mechanistic insight with excellent spatiotemporal resolution. We imaged the 3D dynamics of two engineered FcRn-inhibitors at the subcellular/nanometer level, using an advanced imaging platform- rMUM. rMUM is capable of imaging the dynamics of the single molecule and the cellular organelles they interact with, in 3D. This enables compensation of the motion of a single molecule with the organelle's movement, thus giving a real snapshot of the dynamics. To that end, we utilized this multi-dimensional, nanometer resolution microscopy technique to image two engineered FcRn-inhibitors in endosomes in cells.
At the macro level, we investigate the effective clearance of antigens by an engineered Fc-antigen fusion protein (HER2-Seldeg), consequently improving contrast during whole-body imaging in mice. HER2-Seldeg is designed to selectively capture anti HER2 antibodies, bind to FcRn with enhanced affinity, and direct them to degradative lysosomes in FcRn-expressing cells. Positron emission tomography (PET) imaging of HER2-Seldeg revealed rapid clearance of radiolabeled antibodies from the systemic circulation following tumor localization and consequently improved contrast
Selective depletion of radiolabeled HER2-specific antibody for contrast improvement during PET
No full textThe prolonged in vivo persistence of antibodies results in high background and poor contrast during their use as molecular imaging agents for positron emission tomography (PET). We have recently described a class of engineered Fc fusion proteins that selectively deplete antigen-specific antibodies without affecting the levels of antibodies of other specificities. Here, we demonstrate that these Fc fusions (called Seldegs, for selective degradation) can be used to clear circulating, radiolabeled HER2-specific antibody during diagnostic imaging of HER2-positive tumors in mice. The analyses show that Seldegs have considerable promise for the reduction of whole-body exposure to radiolabel and improvement of contrast during PET.</p
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
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