1,720,970 research outputs found
Combination of hyaluronic acid conjugates with immunogenic cell death inducer and CpG for glioblastoma local chemo-immunotherapy elicits an immune response and induces long-term survival
No full textThe efficacy of standard glioblastoma (GBM) treatments has been limited due to the highly immunosuppressive tumor immune microenvironment, interpatient tumor heterogenicity and anatomical barriers, such as the blood brain barrier. In the present work, we hypothesized that a new local therapy based on the combination of doxorubicin (DOX) as an immunogenic cell death (ICD) inducer and CpG, a Toll-like receptor (TLR)-9 agonist, would act synergistically to eradicate GBM. DOX and CpG were first tested in an orthotopic GL261 GBM model showing enhanced survival. To improve the outcome with a reduced dose, we designed bioresponsive hyaluronic acid (HA)-drug conjugates for effective in situ chemoimmunotherapy. HA was derivatized with CpG. The new HA-CpG conjugate showed high efficacy in re-educating protumoral M2-like microglia into an antitumoral M1-like phenotype, inducing the expression of immune-stimulatory cytokines. DOX was also conjugated to HA. DOX conjugation increased ICD induction in GL261 cells. Finally, a combination of the conjugates was explored in an orthotopic GL261 GBM model. The local delivery of combined HA-DOX + HA-CpG into the tumor mass elicited antitumor CD8+ T cell responses in the brain tumor microenvironment and reduced the infiltration of M2-like tumor-associated macrophages and myeloid-derived suppressor cells. Importantly, the combination of HA-DOX and HA-CpG induced long-term survival in >66% of GBM-bearing animals than other treatments (no long-term survivor observed), demonstrating the benefits of conjugating synergistic drugs to HA nanocarrier. These results emphasize that HA-drug conjugates constitute an effective drug delivery platform for local che-moimmunotherapy against GBM and open new perspectives for the treatment of other brain cancers and brain metastasis
Otkrytoe slovo di Lidija Čukovskaja. Una proposta di traduzione
No full textL'elaborato ha come oggetto principale una proposta di traduzione in lingua italiana della raccolta "Otkrytoe slovo" della scrittrice sovietica Lidija Čukovskaja, pubblicata dalla casa editrice Chronika a New York nel 1976. Sono inclusi nella tesi anche altri due capitoli, dedicati rispettivamente al commento della traduzione e all'analisi dell'opera in questione, corredata di informazioni biografiche sull'autrice e sul contesto storico e sociale in cui i tesi furono scritti.
The main purpose of this dissertation is to propose a translation from Russian into Italian of the collection of texts "Otkrytoe slovo", written by Soviet author Lidiya Chukovskaya and published by Chronika Press in New York (1976). Included in the dissertation are also two more chapters, respectively dedicated to a translation commentary and to an analysis of the collection at issue, accompanied by some information about the author and the historical and social context in which the texts were written
A strange picture of karyotype and good response to higher dosage of GH
No full textIntroduction: Genes on Xp chromosome are central for stature. In Turner Syndrome and SHOX mutation GH therapy should generally begin as soon as growth failure occurs and for a good reaction higher doses are required. Monosomy X is found in about 45% of patient with Turner syndrome; in the remaining patients is found structural chromosome abnormality or mosaicism. The phenotype of TS is extraordinarily broad. Individuals with a 45,X tend to have a more severe phenotype than those who are mosaic with a normal cell line (45,X/46,XX or 45,X/46,XY). However, there is no predictable phenotype-genotype correlation.
Case report: We report a 4 years old girl with growth failure: she was small for gestational age (SGA) : BW -2SDS, height -2/-3SDS with a Mid Parent Height +1/+2SDS; she has been treated with GH therapy (0.2 mg/kg/week). As we noted no growth improvement, we performed a chromosome analysis, discovering a picture of Turner-like Syndrome:46 X,Xqter ->Xp22.3->Xq13->Xqter karyotype. So we increased GH therapy(0.3 mg/kg/week) and statural growth passed from -2,5 to M SDS (+ 2,5 Delta SDS). To explain the surprising growth enhancement we performed FISH analysis with specific probe for centromere and subtelomeric regions of X chromosome long arm (Xq) and short arm (Xp) and MLPA analysis for subtelomeric region in particular SHOX gene. We found two centromeres and a partial duplication of Xq and there was no SHOX gene deficit.
Conclusion: We are going to perform other genetic analyses (such as array-CGH) for the understanding of the low stature and of the very good answer to GH therapy and besides we must remember that sometimes phenotype of duplication syndromes is similar to the deletion ones
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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