1,720,966 research outputs found
Development of engineered human-derived brain-on-a-chip models for electrophysiological recording
No full textThe study of the central nervous system represents a great challenge in the field of neuroscience. For years, various techniques have been developed to study neuronal cells in-vitro as it is difficult to conduct in-vivo experiments due to ethical problems deriving from its anatomical location. Consequently, both in-vivo and in-vitro animal models have been used extensively to gain new insights into basic functioning principles of neuronal tissue and therapeutic approaches for brain diseases. Over time, we have seen that there is a poor correlation between the clinical diagnosis and the underlying pathological mechanisms. In fact, some symptoms that may occur in the patient are not replicated in the animal, making many promising approaches in animal studies not translatable in the clinic. With the advent of human-induced pluripotent stem cells (h-iPSC) several protocols for the generation of human-neuronal cells are becoming available for all laboratories. The importance of this technique lies in the opportunity to develop a human model derived directly from the patient: the patient's in-vitro cells will exhibit the same genetic and epigenetic modifications as the in-vivo cells. This has raised hopes for the generation of engineered brain models that can be coupled to sensors / actuators in order to better investigate their functional properties in-vitro (i.e. brain-on-a-chip). A reliable method for evaluating the functionality of neuronal cultures is the study of the spontaneous electrophysiological activity using microelectrode arrays (MEA). There are numerous studies in the literature that used h-iPSC on MEAs, showing the characterization of neuronal patterns of patient-derived cultures, demonstrating how this platform is valid for disease phenotyping, drug discovery and translational medicine. Although these models helped to shed light on fundamental biological mechanisms, the majority is based on two-dimensional neuronal cultures, which lack some key features to mimic in-vivo behavior. Three-dimensional h-iPSC-derived models possess a microenvironment, tissue architecture and potential to model network activity with greater complexity than two-dimensional models. Depending on the purpose of the study, we can choose different approaches to recreate 3D in-vitro brain, from those that aim to reproduce the trajectories of neurodevelopment (i.e. brain-organoids) to the use of synthetic materials that reproduce the functionalities of the extracellular matrix (ECM) (i.e. scaffold-based) (Chiaradia and Lancaster, 2020, Tang et al., 2006). Although h-iPSC-derived brain models summarize many aspects of network function in the human brain, they are subject to variability and still do not perfectly mimic behavior in-vivo. Therefore, to reach the full potential of this model we need improvements in differentiation methods and bioengineering, making these models engineered and reproducible. The aim of this PhD thesis was to implement different 3D neuronal culture generation methodologies that can be integrated on MEA devices to offer robust engineered platforms for functional studies
PRELIMINAR ANALYSIS OF ENGINEERED FUNCTIONALLY ACTIVE HUMAN DERIVED CORTICAL NEUROSPHEROIDS FOR DRUG SCREENING AND PRECISION MEDICINE
No full textThe continue development of differentiation protocols to generate human neural cells in vitro, allows more accurate investigations of the functional mechanisms arising in such complex networks, and generates great expectations for new treatments in neurodegenerative diseases for which effective therapies are not yet available. The use of 3D aggregates for neuropharmacological in vitro studies has shown great potentials and the advent of human patient specific in vitro models opens new avenues in the field of drug screening and precision medicine. Moreover, Neuronal Stem Cell (NSC) transplantation has the potential to revolutionize brain disease research, but still presents limitations that hamper the use in therapeutics. It has been shown how the injection of NSCs directly into the host, leads to a random integration into the tissue, while a targeted transplant is needed in the specific area affected by degeneration. An alternative approach would be to produce an already differentiated healthy 3D tissue, that shows all the functional and morphological features suitable for transplant into the degenerated area. To this end, we optimized a fast differentiation protocol to engineer excitatory cortical neurospheres with 1:1 ratio between neurons and astrocytes. We first evaluated its morphology by imaging and then we evaluated its functionality (i.e. electrophysiological activity) with glassbased 60 and CMOS-based 4096 micro-electrode arrays (MEAs). Our preliminary results show how the generated structures are viable and functionally active throughout their development. Furthermore, CMOS-MEAs revealed network properties that did not emerge from standard MEAs. Although the obtained results are preliminary, all neurospheroids adhered to substrates and developed functionally active neuritic arborizations, suggesting their efficient use for functional drugs screening applications and for future in vivo transplantation
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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