1,721,005 research outputs found
Nicotinic acid-free diet and NAPRT inhibitors as a means to sensitize cancer cells to NAMPT inhibitors
No full textDepleting NAD levels in tumors by interrupting their NAD-biosynthetic routes is an attractive anti-cancer strategy. Yet, suppressing the predominant NAD-producing salvage pathway by nicotinamide phosphoribosyltransferase (NAMPT) inhibitors failed in clinical trials, indicating that tumors can exploit alternative NAD-biosynthetic routes to escape NAMPT blockade. In this regard, the contribution of the Preiss-Handler (PH) pathway to NAD production in tumors is gaining great momentum. This pathway utilizes nicotinic acid (NA) as a substrate, which can be obtained from the diet or the gut microbiome. Herein, we demonstrate that blocking the PH pathway with an NA-free diet restored the activity of the NAMPT inhibitor FK866 in an ovarian cancer xenograft model. This combined intervention significantly reduced tumor volumes, blunted NAD levels, and impaired the energy status and metabolic activity of the tumors, while showing no systemic toxicity. In addition, combining an NA-free diet with antibiotics (to eliminate microbiota-derived NA) delayed tumor progression in the absence of NAMPT inhibitors. Furthermore, we also aimed at identifying new inhibitors to the rate-limiting enzyme of the PH pathway nicotinic acid phosphoribosyltransferase (NAPRT). We took advantage of in silico screening techniques and were able to annotate and characterize two NAPRT inhibitors that showed anti-cancer efficacy at micromolar concentrations while possessing favorable drug-like profiles. Since some NAMPT inhibitors are being currently evaluated in clinical trials, this work provides a rationale to couple NA-free diets or NAPRT inhibitors with NAMPT inhibitors in cancer patients
Sparse nonlinear methods for predicting structured data
Get PDFGaussian processes are now widely used to perform key machine learning tasks such as nonlinear
regression and classification. An attractive feature of Gaussian process models is the behaviour
of the error bars, which grow in regions away from observations where there is high uncertainty
about the interpolating function. The complexity of these models scales as O(N3) with sample
size, which causes difficulties with large data sets. The goals of this work are to develop
nonlinear, nonparametric modelling techniques for structure learning and prediction problems
in which there are structured dependencies among the observed data, and to equip our models
with sparse representations which serve both to handle prior sparse connectivity assumptions
and to reduce computational complexity.
We present Kernel Dynamical Structure Learning, a Bayesian method for learning the structure
of interactions between variables in multivariate time-series. We design a mutual information
kernel to handle time-series trajectories, and show that prior knowledge about network sparsity
can be incorporated using heavy-tailed priors over parameters. We evaluate the feasibility of our
method on synthetic data, and extend the inference methodology to the handling of uncertain
input data.
Next, we tackle the problem of belief propagation in Bayesian networks with nonlinear node
relations. We propose an exact moment-matching approach for nonlinear belief propagation in
any tree-structured graph. We call this Gaussian Process Belief Propagation. We extend this
approach by the addition of hidden variables which allow nodes sharing common influences to
be conditionally independent. This constitutes a novel approach to multi-output regression on
bivariate graph structures, and we call this Dependent Gaussian Process Belief Propagation.
We describe sparse inference methods for both models, which reduce computational by learning
compact parameterisations of the available training data. We then apply our method to the
real-world systems biology problem of protein inference in transcriptional networks
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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