1,721,067 research outputs found

    MODELING AND MEASUREMENTS OF NETWORK FORMATION AND VISCOELASTIC BEHAVIOR OF FOLDED PROTEIN-BASED HYDROGELS

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    Proteins play a fundamental role in virtually every aspect of our daily lives, from essential bodily functions such as oxygen transport and muscle movement to our sensory perceptions. Beyond their biological functions, proteins are also integral to the development of biocompatible materials. These materials are crafted by leveraging chemical reactions to link specific amino acids, forming intricate protein lattice networks. Despite advancements in understanding the strength of individual protein building blocks through single molecule measurements, predicting the mechanical properties of these biomaterials remains challenging due to the inherent randomness in molecular orientation within the network. To address this complexity, it is crucial to grasp how nanoscale mechanics influence macroscopic characteristics, enabling the design of predictable and adjustable biomaterials. My research endeavors to bridge the vast scale disparity of six orders of magnitude, employing a diverse array of experimental and computational methods. Specifically, I utilized Single Molecule Magnetic Tweezers to gauge the mechanical properties of protein L along the N-C pulling trajectory. Complementing this approach, Steered Molecular Dynamics Simulations (SMDS) were employed to simulate off-axis pulling geometries inaccessible experimentally. The SMDS outcomes provided insights into the relative stability of different pulling geometries and facilitated the creation of free energy landscapes, modeling protein unfolding via coarse-grained Brownian dynamics simulations. Furthermore, I developed a network formation model to simulate biomaterials composed of folded protein domains using Brownian dynamics simulations. By analyzing these simulated networks, I calculated the average force experienced by each domain when subjected to external stress, simulating real-world scenarios. These simulated networks were then subjected to applied stress using a global force vector, allowing the network to adapt and protein domains to unfold. After a simulated duration, the resulting extensions of the biomaterials were compared to experimental data, confirming the model's ability to predict realistic behavior. This multidisciplinary approach offers valuable insights into the mechanics of biomaterials, facilitating the design of more effective and predictable materials for various applications.2026-05-2

    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

    An Assessment of BSA Protein Hydrogel Biocompatibility in the Vertebrate Intestinal Tract

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    The fields of biomedicine and pharmacology have a mission to design methods to treat disease while minimizing adverse side effects using novel drug delivery systems. In developing new therapeutic systems, it is crucial to test that drug delivery systems target pathological cells and tissue and is non-toxic in healthy tissue. One promising method for targeted drug delivery is the use of hydrogels as carriers. Here, we studied the effects of bovine serum albumin (BSA) hydrogel consumption to assess the potential for hydrogel use in treating intestinal disease via oral administration. We investigated intestinal architecture and cell populations following hydrogel treatments in adult zebrafish. Our studies revealed that consumption of BSA hydrogels results in normal intestinal villi architecture and bowel wall integrity. Furthermore, we demonstrated that intestinal goblet cell appearance and abundance did not change, and eosinophil populations remain constant over the course of treatment compared to control tissue. We confirmed this by comparing control- and hydrogel-fed tissue to tissue with chemically-induced inflammation. This study is important for the future development of biocompatible drug delivery systems using hydrogels.2021-08-3

    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

    IMPLEMENTING FRET SPECTROMETRY USING TIME RESOLVED FLUORESCENCE MICROSCOPY FOR DETERMINATION OF PROTEIN OLIGOMER SIZE AND GEOMETRY IN LIVE CELLS

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    Fӧrster or Fluorescence Resonance Energy Transfer (FRET) is a biological phenomenon that occurs when energy is transferred non-radiatively from an excited donor molecule to an unexcited acceptor molecule when they are a certain distance from each other. One method of conducting FRET experiments is using FRET spectrometry which was previously introduced by the Raicu Lab. This method generates histograms of FRET efficiencies at pixel level called FRET spectrograms, that are fitted with models to determine the quaternary structure of protein oligomers as opposed to traditional FRET experiments which average over all FRET efficiencies. Currently, FRET spectrometry is implemented with spectrally resolved fluorescence microscopy to allow the computation of FRET efficiencies where the size of the oligomer is unknown.Another technique, Fluorescence Lifetime Imaging Microscopy (FLIM) has been successfully used to compute FRET efficiencies by fitting fluorescence decay curves with one or two exponential fits in order to determine the fluorescence lifetimes in the presence and absence of the donors and acceptors. However, using FLIM to study oligomers of arbitrary size is limited by the prerequisite knowledge of the distinct oligomeric configurations, as well as the mathematical limitation of extracting more than two lifetimes from a single decay. The tiFRET method was developed to address these limitations by numerically integrating the fluorescence decay curves at each pixel in order to determine the pixel level FRET efficiencies and generate FRET spectrograms. The tiFRET method was initially tested on cytoplasmic constructs of Cerulean, Venus, and Amber and compared to the traditional FLIM measurements using one and two lifetime fits. This method was then applied to a biological system that was known to oligomerize and compared to traditional FRET spectrometry experiments. G protein coupled receptors (GPCRs) are the largest family of membrane proteins. These receptors mediate most cellular responses to external stimuli, making them ideal candidates for drug research and development. In this study, the human muscarinic acetylcholine receptor M2 (M2R), one of five human muscarinic acetylcholine receptors, a class A- rhodopsin like GPCR was used. M2R is primarily responsible for slowing down the heart rate by controlling the rate of depolarization of the cell membrane by causing an outward flow of potassium ions. There are various studies that show the tendency of the muscarinic receptors to oligomerize, which was ideal for this study. Using two variants of the green fluorescent protein (GFP2, green fluorescent protein and YFP, yellow fluorescent protein) as fluorescent markers, two-photon fluorescence microscopy was used to collect temporally resolved fluorescence images and spectrally resolved fluorescence images of live cells. The tiFRET method was applied to the temporally resolved fluorescence images to calculate the pixel level distributions of apparent FRET efficiencies and obtain FRET spectrograms. The spectrally resolved fluorescence images were analyzed using the currently established method of performing FRET spectrometry to obtain FRET spectrograms. FRET metahistograms were generated and fit with a theoretical model in order to determine the oligomeric configuration of M2R. Both metahistograms were compared to determine the viability of the novel tiFRET method. In this study, the results of this comparison and future research are presented

    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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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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