1,720,965 research outputs found
TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, t cell fitness, and sensitization of tumor milieu
No full textAdoptive transfer of T cells gene-engineered with antigen-specific T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to target immunogenic epitopes that are related to oncogenesis and selectively expressed by tumor tissue, and implement strategies that result in optimal T cell fitness. In addition, in particular for the treatment of solid tumors, it is equally necessary to include strategies that counteract the immune-suppressive nature of the tumor micro-environment. Here, we will provide an overview of the current status of TCR gene therapy, and redefine the following three challenges of improvement: "choice of target antigen"; "fitness of T cells"; and "sensitization of tumor milieu." We will categorize and discuss potential strategies to address each of these challenges, and argue that advancement of clinical TCR gene therapy critically depends on developments toward each of the three challenges
Engineering of T cell receptor genes to advance T cell therapy: studies into TCR pairing, signaling and binding strength
Get PDFThe incidence of cutaneous melanoma has increased dramatically over the past 40
years. The yearly increase in incidence rates in the Netherlands is on average 4.1%.
Although the 10-year survival rates improved over the last fifteen years, the yearly
mortality rates are further increasing with 2.3%, mainly in elderly patients. In case
cutaneous melanoma metastasizes, the 10-year survival rate drops dramatically to less
than 10%. Table 1.1 lists the U.S. Food and Drug Administration (FDA)-approved treatments
for melanoma. The current standard cares of treatment for melanoma are either
administration of the alkylating agent Dacarbazine, which induces DNA damage, or
administration of high-dose IL-2, which serves as a T cell growth factor. However, both
treatments demonstrate fairly low response rates and significant adverse effects. More
recent FDA-approved treatments for melanoma include: Ipilimumab, an antibody that
blocks the T cell inhibitory molecule CTLA-4 to lower the threshold of T cell activation; Vemurafenib, a drug that inhibits the serine-threonine protein kinase B-RAF (BRAF),
a kinase that is constitutively active in 36 to 54% of melanoma patients due to a V600E
mutation; and pegylated interferon α2b, used as an adjuvant that demonstrates
anti-proliferative effects on melanoma cells and modulates immune responses
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Beneficial health effects of chitin and chitosan
No full textChitin and chitosan have been recognised for their beneficial health effects since the 1980s. Over the past few decades, numerous studies and several clinical trials have been performed which demonstrated that these compounds can reduce body weight and cardiovascular disease (CVD), improve wound healing, but can also modulate the immune system and demonstrate antifungal and antibacterial activity. In particular, weight reduction and improvement of cardiovascular status are interesting targets as the prevalence of obesity and CVD are increasing. Both diseases are associated with various pathological disorders, including diabetes and hypertension and put a strain on healthcare costs and capacity. In general, lifestyle‐based interventions such as the oral intake of chitin and/or chitosan are becoming increasingly popular as these are easily integrated into current treatments and improve the self‐assertiveness of patients. Of interest, but beyond the scope of this chapter, is the use of chitin‐glucans as supplements in cosmetics. Several studies have demonstrated that chitin‐glucan reduced wrinkling and skin‐ageing, suggesting an interaction between the chitin‐glucan and cells of the epidermis. Although these effects may not be attributed to chitin alone, this does demonstrate the strong biological potential of chitin on cells of the human body. In this chapter, scientific literature has been reviewed that demonstrated the beneficial health effects of chitin and chitosan from an immunomodulatory point‐of‐view. First, we provide an overview of in vitro studies that offer in‐depth mechanistic insights, followed by describing preclinical animal studies. Finally, we list various human intervention trials that most clearly demonstrate the beneficial health effects of chitin and chitosan. Furthermore, we purposely discriminate between data on chitin and chitosan as they are chemically distinct and therefore possibly demonstrate unique effects on healt
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