Search results for "FDA"
showing 10 items of 24 documents
Tetrabromobisphenol A (TBBPA)-stimulated reactive oxygen species (ROS) production in cell-free model using the 2′,7′-dichlorodihydrofluorescein diace…
2016
t Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant, applied in a variety of commercial and household products, mainly electronic ones. Since the production of reactive oxygen species (ROS) is considered one of the principal cytotoxicity mechanisms, numerous studies undertake that aspect of TBBPA’s mechanism of action. The present study verifies if the fluorogenic substrate 2′,7′- dichlorodihydrofluorescein diacetate (H2DCFDA) should be used to detect ROS production induced by TBBPA. To determine the ability of TBBPA alone to stimulate the conversion of H2DCFDA to its fluorescent product 2’, 7’- dichlorofluorescein (DCF), we used a cell-free model. In the experiments…
Kinase Inhibitors in Multitargeted Cancer Therapy
2017
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…
Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning.
2021
Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2′-o-ribose methyltransferase). Supported by…
Iron-loaded transferrin (Tf) is detrimental whereas iron-free Tf confers protection against brain ischemia by modifying blood Tf saturation and subse…
2018
Despite transferrin being the main circulating carrier of iron in body fluids, and iron overload conditions being known to worsen stroke outcome through reactive oxygen species (ROS)-induced damage, the contribution of blood transferrin saturation (TSAT) to stroke brain damage is unknown. The objective of this study was to obtain evidence on whether TSAT determines the impact of experimental ischemic stroke on brain damage and whether iron-free transferrin (apotransferrin, ATf)-induced reduction of TSAT is neuroprotective. We found that experimental ischemic stroke promoted an early extravasation of circulating iron-loaded transferrin (holotransferrin, HTf) to the ischemic brain parenchyma.…
Evaluation of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer: Data from phase 1 and phase 2 studies.
2021
5509 Background: The accelerated FDA approval of pembrolizumab validated the efficacy of anti–PD-(L)1 therapy for pts with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in pts with PD-L1 expressing tumors. HPV infection is implicated in > 95% of cervical cancers and is linked to upregulation of TGF-β signaling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. We report pooled safety and efficacy in pts with immune checkpoint inhibitor–naive, recurrent/metastatic cervical cancer treated with…
Depth-based methods for clustering of functional data.
2017
The problem of detecting clusters is a common issue in the analysis of functional data and some interesting intuitions from approaches relied on depth measures can be considered for construction of basic tools for clustering of curves. Motivated by recent contributions on the problem clustering and alignment of functional data, we also consider the problem of aligning a set of curves when classification procedures are implemented. The variability among curves can be interpreted in terms of two components, phase and amplitude; phase variability, or misalignment, can be eliminated by aligning the curves, according to a similarity index and a warping function. Some approaches address the misal…
La aceptación tecnológica de las Apps y su influencia en la co-creación, el engagement y la calidad de la relación: crear valor para el cliente en el…
2022
Impulsada por la acelerada proliferación de las tecnologías de la información y la comunicación, la economía colaborativa ha surgido como una tendencia emergente en el comportamiento del consumidor que cambia la forma en que se proporcionan y consumen los productos y servicios. El propósito de este estudio fue crear y probar un modelo holístico que explique las intención de uso y de co-creación de los usuarios de aplicaciones de entrega de comida a domicilio – FDA en Colombia a partir del contexto de la economía colaborativa. Sobre la base de varios enfoques académicos, este estudio se propuso a partir del Modelo de Aceptación Tecnológica – TAM, la lógica dominante del servicio, la teoría d…
Filling in long gap sequences by performing jointly EOF and FDA
2012
In this paper the EOF methodology is performed jointly with the FDA approach on a spatiotemporal multivariate data set with the aim to fill in missing values as accurately as possible when long gap sequences occur. Simulated data sets, containing ”artificial” gaps, are considered in order to test the performance of two proposed procedures; in the first one, observed data are reconstructed by EOF and then converted into functional ones; in the second one, observed data are transformed into functional ones and then EOF reconstruction is applied. By comparing some performance indicators computed for the two procedures, it is shown that a pre-processing of data by FDA, followed by the EOF, may …
Long gaps in multivariate spatio-temporal data: an approach based on functional data analysis
2015
The main aim of this paper is to perform Functional Principal Component Analysis (FPCA) taking into account spatio-temporal correlation structures, in order to fill in missing values in spatio-temporal multivariate data set. A spatial and a spatio-temporal variant of the classical temporal FPCA is considered; in other words, FPCA is carried out after modeling data with respect to more than one dimension: space (long, lat) or space+time. Moreover, multidimensional FPCA is extended to multivariate context (more than one variable). Information on spatial or spatiotemporal structures are efficiently extracted by applying Generalized Additive Models (GAMs). Both simulation studies and some perfo…
Extending Functional kriging to a multivariate context
2020
Environmental data usually have a spatio-temporal structure; pollutant concentrations, for example, are recorded along time and space. Generalized Additive Models (GAMs) represent a suitable tool to model spatial and/or temporal trends of this kind of data, that can be treated as functional, although they are collected as discrete observations. Frequently, the attention is focused on the prediction of a single pollutant at an unmonitored site and, at this aim, we extend kriging for functional data to a multivariate context by exploiting the correlation with the other pollutants. In particular, we propose two procedures: the first one (FKED) combines the regression of a variable (pollutant),…