1,721,070 research outputs found
Can Systems Biology Advance Clinical Precision Oncology?
Full text linkPrecision oncology is perceived as a way forward to treat individual cancer patients. However, knowing particular cancer mutations is not enough for optimal therapeutic treatment, because cancer genotype-phenotype relationships are nonlinear and dynamic. Systems biology studies the biological processes at the systems’ level, using an array of techniques, ranging from statistical methods to network reconstruction and analysis, to mathematical modeling. Its goal is to reconstruct the complex and often counterintuitive dynamic behavior of biological systems and quantitatively predict their responses to environmental perturbations. In this paper, we review the impact of systems biology on precision oncology. We show examples of how the analysis of signal transduction networks allows to dissect resistance to targeted therapies and inform the choice of combinations of targeted drugs based on tumor molecular alterations. Patient-specific biomarkers based on dynamical models of signaling networks can have a greater prognostic value than conventional biomarkers. These examples support systems biology models as valuable tools to advance clinical and translational oncological research
MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance
Full text linkThe RAS/RAF/MEK/MAPK kinase pathway has been extensively studied for more than 25 years, yet we continue to be puzzled by its intricate dynamic control and plasticity. Different spatiotemporal MAPK dynamics bring about distinct cell fate decisions in normal vs cancer cells and developing organisms. Recent modelling and experimental studies provided novel insights in the versatile MAPK dynamics concerted by a plethora of feedforward/feedback regulations and crosstalk on multiple timescales. Multiple cancer types and various developmental disorders arise from persistent alterations of the MAPK dynamics caused by RAS/RAF/MEK mutations. While a key role of the MAPK pathway in multiple diseases made the development of novel RAF/MEK inhibitors a hot topic of drug development, these drugs have unexpected side-effects and resistance inevitably occurs. We review how RAF dimerization conveys drug resistance and recent breakthroughs to overcome this resistance
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
Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects
No full textTreatment of cancer patients with ATP-competitive inhibitors of BRAF/CRAF kinases surprisingly increases total kinase activity, especially in wild-type BRAF cells, subverting the desired clinical outcome. Similar inhibition resistance is observed for numerous kinases involving homo/ heterodimerization in their activation cycles. Here, I demonstrate that drug resistance resulting from kinase dimerization can be explained using thermodynamic principles. I show that allosteric regulation by inhibitors is described by thermodynamic factors that quantify inhibitor-induced changes in kinase dimerization and the difference in the drug affinity for a free monomer versus a dimer harboring one drug molecule. The analysis extends to kinase homo- and heterodimers, allows for their symmetric and asymmetric conformations, and predicts how thermodynamic factors influence dose-response dependencies. I show how two inhibitors, ineffective on their own, when combined can abolish drug resistance at lower doses than either inhibitor applied alone. Thus, the mechanistic models suggest ways to overcome resistance to kinase inhibitors.European Commission - Seventh Framework Programme (FP7
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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