1,721,029 research outputs found

    Investigation of the nanomechanical properties of soft biomaterials using atomic force microscopy (AFM)

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    This study presents a systematic investigation of two types of soft biomaterials: phospholipid-based microbubbles (MBs) and agarose hydrogels, using atomic force microscopy (AFM) force-distance curves. Microbubbles are used widely in several applications, especially in medical applications, where they are used as ultrasound contrast agents (UCAs) and as vehicles for transporting the drugs and genes to their targets, which is commonly known as drug/gene delivery. Although plenty of attention has been paid to these materials by medical researchers there is a shortage of engineering research on the properties of these materials. The present study tries to address this gap by studying these materials from the engineering perspective; therefore, the aim of this study is to investigate the mechanical properties of MBs and hydrogels. In this research, phospholipid-based microbubbles (MBs), commercially called SonoVue® microbubbles and used as UCAs, were investigated to measure their mechanical properties using an AFM mode of operation called force-distance curves (or force spectroscopy mode); this mode allows for direct mechanical tests to acquire the force-deformation (F-Δ) behaviour of the MBs. The compression tool was a flat (tipless) cantilever moved at constant speed, whereas the variable was MB size. The MBs behaviour was assessed by calculating several mechanical properties, which were the stiffness, Young’s modulus (three different models were applied), hysteresis, plasticity, adhesion forces, nonlinearity and instability. The stiffness and the Young’s modulus values were measured to be in the same range as found in similar studies. A phenomenon was observed that the local stiffness of the MB increases after each unstable step provided that the MB stays within the linear elastic region. The Young’s modulus was calculated applying three models, two for estimating the elastic modulus of the shell and the third for modulus of elasticity of the whole MB. The stretching component of the membrane theory was found to provide the best prediction of the Young’s modulus value. To investigate the effect of the tip geometry on the mechanical properties of the MBs, the MBs were studied with different cantilever/tips, including a conical-tipped cantilever. The study concluded that there is no impact of the contact geometry on the mechanical properties of the MBs if the applied forces and the spring constant of the cantilever are the same. The same phenomenon, increasing the local stiffness of the MB after each unstable step, was found however with a higher rate. Hydrogels were also studied in this research using AFM and adopting a nanoindentation technique. The indenter was a conical tip moving toward the sample surface with constant speed and applying similar forces on all samples, where the variable was the gel concentration. In addition to the previous mechanical properties, other properties were investigated, such as hardness, universal hardness and pressure. An effect of the gel concentration on the mechanical properties of the gels was observed. There is a difference in the results compared to those reported in the literature review, where some of the results are in the same range as those found here, while others were either higher or lower, due to the influence of factors such as the indenter geometry, the applied force and the load rate; moreover, it was found that the viscoelastic behaviour of the gels played a significant role

    Acoustic characterisation of ultrasound contrast agents at high frequency

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    This thesis aims to investigate the acoustic properties of ultrasound contrast agents (UCAs) at high ultrasound frequencies. In recent years, there has been increasing development in the use of high frequency ultrasound in the fields of preclinical, intravascular, ophthalmology and superficial tissue imaging. Although research studying the acoustic response of UCAs at low diagnostic ultrasonic frequencies has been well documented, quantitative information on the acoustical properties of UCAs at high ultrasonic frequencies is limited. In this thesis, acoustical characterisation of three UCAs was performed using a preclinical ultrasound scanner (Vevo 770, VisualSonics Inc., Canada). Initially the acoustical characterisation of five high frequency transducers was measured using a membrane hydrophone with an active element of 0.2 mm in diameter to quantify the transmitting frequencies, pressures and spatial beam profiles of each of the transducers. Using these transducers and development of appropriate software, high frequency acoustical characterisation (speed and attenuation) of an agar-based tissue mimicking material (TMM) was performed using a broadband substitution technique. The results from this study showed that the acoustical attenuation of TMM varied nonlinearly with frequency and the speed of sound was approximately constant 1548m·s-1 in the frequency range 12-47MHz. The acoustical properties of three commercially available lipid encapsulated UCAs including two clinical UCAs Definity (Lantheus Medical Imaging, USA) and SonoVue (Bracco, Italy) and one preclinical UCAs MicroMarker (untargeted) (VisualSonics, Canada) were studied using the software and techniques developed for TMM characterisation. Attenuation, contrast-to-tissue ratio (CTR) and subharmonic to fundamental ratio were measured at low acoustic pressures. The results showed that large off-resonance and resonant MBs predominantly contributed to the fundamental response and MBs which resonated at half of the driven frequency predominantly contributed to subharmonic response. The effect of needle gauge, temperature and injection rate on the size distribution and acoustic properties of Definity and SonoVue was measured and was found to have significant impacts. Acoustic characterisations of both TMM and UCAs in this thesis extend our understanding from low frequency to high frequency ultrasound and will enable the further development of ultrasound imaging techniques and UCAs design specifically for high frequency ultrasound applications

    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

    Response of contrast agents to ultrasound

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    Microbubbles are used as ultrasonic contrast agents that enhance the ultrasound signals of the vascular bed. The recent development of site-targeted microbubbles opened up the possibility for molecular imaging as well as localised drug and gene delivery. Initially the microbubbles' physical properties and their response to the ultrasound beam were not fully understood. However, the introduction of fast acquisition microscopy has allowed the observation of the microbubble behaviour in the presence of ultrasound. In addition, acoustical techniques can determine the scatter of single microbubbles. Sonoporation experiments promise high-specificity drug and gene delivery, but the responsible physical mechanisms, particularly for in vivo applications, are not fully understood.. An improvement of microbubble technology may address variability related problems in both imaging and drug/gene delivery. (C) 2008 Elsevier B.V. All rights reserved.</p

    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

    Theoretical modelling of ultrasound contrast agents

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    This thesis compares theoretical models of ultrasound contrast agents to the acoustic response from single Microbubbles(MBs). The acoustic response was compared using a range of driving parameters. A rigid shelled contrast agent and a lipid shelled contrast agent were used in the comparison. While attempts to model the behaviour of some contrast agents at low mechanical index (MI) have been successful at higher MI the behaviour of MBs is still not well understood. Understanding and predicting the response ofMBs to medical ultrasound can lead to improvements in the clinical use of MBs through improved contrast agent design or improved signal processing. Numerical models were developed to compare to three specific cases; 1) Rigid shelled contrast agents 2) Lipid shelled contrast agents 3) Responses from lipid shelled contrast agents that are hit by subsequent driving pulses. Three models were used to compare to the responses from single rigid shelled contrast agents. Two of these models have been used before and the third was developed based on the optical observations of the responses of these rigid shelled agents at these MI. Two shelled models were used to compare to the response of single lipid shelled MBs. Using statistical methods the parameters defining the shell properties were found. The parameters that gave best agreement with the lipid shelled data was then used with a model to account for the molecular diffusion of gas from a MB and a new model to account for the optically observed shedding of the shell from a MB to compare to the multiple response from single MBs. While the theoretical prediction of an acoustic response of a suspension of MBs or the radial oscillation of single MBs has been compared before to experimental data, the successful comparison of the acoustic response of single MBs to the theoretical prediction is the first of it’s kind known to the author. The new theoretical model of the rigid shelled MB that was developed in this thesis gave better agreement with the experimental data than the other previously used models. The shell parameters of the lipid shelled MB were determined for the lowest driving amplitude and were in agreement with those measured previously from optical observations. Finally, the model for the shedding of the shell was shown to give quantitative agreement with the multiple acoustic responses from single MBs. When shedding of the shell was included the choice of constitutive equation for the shell was shown to strongly affect subsequent responses from the MB

    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

    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
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