1,720,961 research outputs found
Modern approaches for ensuring patient access to gene therapies in public health care systems
No full textOptimization of properties for the biological drug ipilimumab using molecular modelling techniques
Full text linkMelanom je zaradi imunogene narave pogosto obdan z regulatornimi T celicami (Treg), ki na svoji površini izražajo s citotoksičnimi limfoctiti T povezani protein 4 (CTLA-4). Na ta način melanom utiša imunski odziv v svojem mikrookolju. Novejše raziskave, ki obravnavajo mehanizem delovanja imunoterapevtskega protitelesa za melanom ipilimumab, izpostavljajo Treg celice in njihovo smrt kot glavni mehanizem protirakavega delovanja. Pomembno vlogo pri tem ima konstantna (Fc) regija ipilimumaba, ki posreduje citotoksični učinek na celice Treg z vezavo na gama receptorje konstantne regije (FcγR), ki se nahajajo na površini efektorskih celic imunskega sistema. Za doseganje terapevtske učinkovitosti je ključna vezava podtipov FcγRIIa in FcγRIIIa na regijo Fc ipilimumaba. Namen naloge je bil z uporabo molekularnega modeliranja preveriti vpliv mutacije, ki dokazano povzroča boljšo vezavo tega protitelesa na FcγRIIa in FcγRIIIa, kar bi lahko pripomoglo k večji učinkovitosti terapije. Z uporabo homolognega modeliranja smo pridobili model celotnega protitelesa ipilimumab. Afiniteta vezave izbranih FcγR na Fc regijo ipilimumaba je bila ocenjena z uporabo molekularne dinamike s programom CHARMM. Genetsko variabilnost posameznika pri terapiji opisuje farmakogenomika in je pomemben faktor učinkovitosti terapije. Farmakogenomski pogled terapije z zdravilom ipilimumab smo ovrednotili z uporabo strežnika GenProBiS, ki omogoča napoved vezavnih mest in izpis dokumentiranih variacij v vezavnih mestih. Z rezultati nismo potrdili hipoteze večje afinitete vezave FcγRIIIa in FcγRIIa na mutirano Fc regijo ipilimumaba. Opravljeno delo pa prispeva k razumevanju simulacij molekularne dinamike za potencialno izboljšanje farmakoloških lastnosti bioloških zdravil.Melanoma is often surrounded with regulatory T cells (Treg) due to its immunogenic nature, which express on their surface the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This way the melanoma dampens the immune response in its microenviroment. Recent studies regarding the mode of action for the immunotherapeutic antibody ipilimumab, emphasize that the cellular death of Treg cells is the main mechanism behind the anticancerous effect. The constant (Fc) region of ipilimumab plays a crucial role in this strategy as it mediates the cytotoxic effect on Treg cells via binding to the fragment crystallizable gamma receptor (FcγR) found on immune effector cells. To achieve the best therapeutic efficacy subtypes of FcγRIIa and FcγRIIIa need to bind to the Fc region. The purpose of this work was to use molecular modeling techniqes to asses an antibody mutation, which was shown to increase binding affinity of FcγRIIa and FcγRIIIa and in turn could lead to greater efficacy of therapy. Using homology modeling we modeled the entire structure of ipilimumab. The binding affinity was assessed after molecular dynamics simulation using the program CHARMM. An important aspect to consider in the efficacy of such therapies is the genetic variability of the individual which is described by pharmacogenomics. This aspect of ipilimumab therapy was assessed using the web server GenProBiS, which predicts binding sites of proteins and outputs the corresponding documented variations. Our current results do not confirm our hypothesis of greater binding affinity of the mutated Fc region to FcγRIIa and FcγRIIIa. The work done contributes to understanding the importance of molecular dynamics simulations in potential improvments to pharmacological properties of biological drugs
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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