1,720,963 research outputs found
Stability and potential degradation of the α′,β′-epoxyketone pharmacophore on ZnO nanocarriers: insights from reactive molecular dynamics and density functional theory calculations
No full textWe investigate the structure and dynamics of a zinc oxide nanocarrier loaded with Carfilzomib, an epoxyketone proteasome inhibitor developed for treating multiple myeloma. We demonstrate that, even though both bare and functionalized zinc oxide supports have been used for drug delivery, their interactions with the reactive functional groups of the ligands could be detrimental. This is because pharmacophores like α′,β′-epoxyketones should preserve the groups required for the drug activity and be capable of leaving the vehicle at the target site. Earlier studies showed that even when ZnO is functionalized with oleic acid surfactants, the drug could reach parts of the surface and remain stably adsorbed. Herein, we have used reactive molecular dynamics simulations and quantum chemistry calculations to explore the potential interactions of the Carfilzomib functional groups with the typical surfaces of ZnO supports. We have found that Carfilzomib can adsorb on the (0001)Zn-terminated polar surface through the carbonyl oxygens and the epoxyketone moiety. These strong connections could prevent the drug release and induce the epoxy ring opening with its consequential inactivation. Therefore, regulating the dosage to maintain the desired level of drug bioavailability is paramount. These findings emphasize the need for appropriate carrier functionalizations to efficiently entrap, transport, and release the cargo at the target sites and the crucial role played by predictive/descriptive computational techniques to complement and drive experiments to the most appropriate selections of the materials to optimize drug delivery
Disclosing gate-opening/closing events inside a flexible metal-organic framework loaded with CO2 by reactive and essential dynamics
No full textWe have combined reactive molecular dynamics simulations with principal component analysis to provide a clearer view of the interactions and motion of the CO2 molecules inside a metal-organic framework and the movements of the MOF components that regulate storage, adsorption, and diffusion of the guest species. The tens-of-nanometer size of the simulated model, the capability of the reactive force field tuned to reproduce the inorganic-organic material confidently, and the unconventional use of essential dynamics have effectively disclosed the gate-opening/closing phenomenon, possible coordinations of CO2 at the metal centers, all the diffusion steps inside the MOF channels, the primary motions of the linkers, and the effects of their concerted rearrangements on local CO2 relocations
Exploring the Interaction of Water with Open Metal Sites in MIL-101(Cr) by 1H NMR Relaxometry and ReaxFF Molecular Dynamics Simulations
No full textIn this work, we investigated the state of water in the metal-organic framework MIL-101(Cr) by combining 1H magic angle spinning (MAS) NMR, NMR relaxometry, and molecular dynamics (MD) simulations based on a reactive force field. The MD simulations indicated that water molecules are coordinated to the open metal sites and are organized in shells. Through 1H T2 and T1 relaxation measurements at the fixed Larmor frequency of 21 MHz, water in the intergrain spaces was distinguished from that in the intragrain mesopores of MIL-101(Cr). 1H MAS NMR measurements showed that water in the mesopores is structurally ordered, as revealed by the presence of 1H-1H residual dipolar interaction. The 1H NMR relaxometric behavior of water located in the intergrain spaces of MIL-101(Cr) as a function of the magnetic field strength, determined by fast field cycling NMR relaxometry, was interpreted extending an existing model, generally applied to paramagnetic aqua ions in solution, to the case of Cr3+ ions fixed on the surface of the metal-organic framework. The model predicts the exchange of water between the first and second shell of a Cr3+ ion, giving access to the water residence time in the first shell that would be difficult to determine using other techniques. In the temperature interval of 25-70 °C, water residence times in the range of tens of nanoseconds were found and a limited accessibility of water to the open metal sites located on the external grain surface was observed
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
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
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
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