1,720,996 research outputs found
Cavitation-enhanced permeability in a vessel on a chip
Full text linkMethods combining ultrasound and microbubbles (USMB) offer the unique capability of non-invasively, locally and transiently increase endothelial permeability [1]. This is crucial for the delivery of pharmaceutical agents, injected into the blood circulation, since the real efficiency of a therapy depends on the rate and ability of a macromolecules to cross the endothelial barrier and reach the intended target. Molecule passage through this biological barrier is hampered by the endothelium, lining the innermost surface of blood vessels, consisting of a continuum layer of specialized cells close together to form a size-selective membrane. In this contest, cavitation-assisted permeation shows promise for reversibly altering the barrier integrity, opening gaps between endothelial cells and doing so facilitating the diffusion of pharmaceutical agents out of vessel.
Although acoustic cavitation is already exploited in in vivo animal models for drug delivery testing, the in vitro approach offers the possibility to obtain well-controlled procedures, saving in cost and time [2]. Here, a platform integrating in vitro blood vessels and acoustic cavitation is used to test the feasibility of micro bubbles (MBs) cavitation-enhanced endothelial permeability.
We induce MBs (Sonovue® contrast agent) stable cavitation, evoked by low-intensity ultrasound exposure (Mechanical Index (MI) = 0.4, 0.72), in a microfluidic device purposely designed [3] to mimic micro-blood vessel. The bio-inspired device consists in a PDMS microfluidic network with a central circular tissue compartment enclosed by two independent vascular channels mimicking the three-dimensional morphology, size and flow characteristics of a micro vessel in vivo. The device is previously cultured with Human Umbilical Vein Endothelial Cells (HUVECs) with a reliable and reproducible protocol [4] that allows endothelial cells to form a complete lumen under physiological shear stresses. Immunofluorescence microscopy is then exploited in order to monitor vascular integrity following vascular endothelial cadherin (VE-Cadherin), the most determinant protein for vascular permeability.
The endothelial membrane permeability is evaluated through a dedicated optical/acoustic set-up in presence of ultrasound-activated MBs driven by 1 MHz-unfocused transducer. The basic set up is designed and adapted to host the bio-inspired device, the piezoelectric transducers within a water-filled and temperature-controlled costume chamber located on the microscope stage.
Measurements of fluorescent dye diffusion towards the biological membrane has been carried out with a time lapse acquisition under a confocal microscope operated in epifluorescence mode. An
image analysis on the intensity change due to fluorescence accumulation in the tissue compartment is performed to obtain quantification of permeability.
Intercellular gaps were firstly identified by inspection using ImageJ software and then post-processed in order to increase the contrast and binarize the image using a threshold method with the same cut-off value for all Regions of Interest. The gap area was then quantified counting the black pixels of the central connected blob in each binarized image. The results show that MBs amplify the ultrasound effect, leading to the formation of inter-endothelial gaps, proportionally to the applied acoustic pressure, and causing barrier permeabilization. Moreover, endothelium recovery was completely achieved after 45 minutes from the USMB exposure with gap area distribution returning to the control levels.
To conclude, the proposed integrated platform allows for precise and repeatable in vitro measurements of cavitation-enhanced endothelium permeability providing a novel methodology for the quantitative understanding of cavitation assisted drug delivery.
[1] K. Kooiman, H. J. Vos, M. Versluis, and N. de Jong, “Acoustic behaviour of microbubbles and implications for drug delivery,” Advanced drug delivery reviews, vol. 72, pp. 28–48, 2014.
[2] Peruzzi, G. Perspective on cavitation enhanced endothelial layer permeabiliry, Colloids and surface B: biointerfaces 168 (2018), 3-93
[3] S.P.Deosarkar, et al. A novel dynamic neonatal blood-brain barrier on a chip, Plos One, 10(11) (2015), p. e014272
Wall pressure coherence in supersonic turbulent boundary layers
No full textA numerical database (Bernardini & Pirozzoli, Phys. Fluids, vol. 23, 2011, 085102) is analysed to investigate cross-statistics of wall-pressure fluctuations induced by supersonic turbulent boundary layers developing over a rigid smooth wall without a pressure gradient. The Mach number spans from 2 to 4 and a relatively large range of Reynolds numbers is considered. It is shown, for the first time, that the cross-statistics of wall-pressure fluctuations at such high Mach numbers is very similar to that usually observed in incompressible flow conditions. Furthermore, it is demonstrated that theoretical predictions provided by the well-known Corcos and Efimtsov models continue to apply
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
- …
