Search results for "SCAD"
showing 10 items of 348 documents
Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy.
2010
Drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. It is a goal of drug development programs to design selective ligands that act on single disease targets to obtain highly effective and safe drugs with low side effects. Although this strategy was successful for many new therapies, there is a marked decline in the number of new drugs introduced into clinical practice over the past decades. One reason for this failure may be due to the fact that the pathogenesis of many diseases is rather multi-factorial in nature and not due to a single cause. Phytotherapy, whose therapeutic efficacy is based on th…
A Regulatory Mechanism Involving TBP-1/Tat-Binding Protein 1 and Akt/PKB in the Control of Cell Proliferation
2011
Abstract TBP-1 /Tat-Binding Protein 1 (also named Rpt-5, S6a or PSMC3) is a multifunctional protein, originally identified as a regulator of HIV-1-Tat mediated transcription. It is an AAA-ATPase component of the 19S regulative subunit of the proteasome and, as other members of this protein family, fulfils different cellular functions including proteolysis and transcriptional regulation. We and others reported that over expression of TBP-1 diminishes cell proliferation in different cellular contexts with mechanisms yet to be defined. Accordingly, we demonstrated that TBP-1 binds to and stabilizes the p14ARF oncosuppressor increasing its anti-oncogenic functions. However, TBP-1 restrains cell…
2-Hydroxyoleic Acid Induces ER Stress and Autophagy in Various Human Glioma Cell Lines
2012
Background: 2-Hydroxyoleic acid is a synthetic fatty acid with potent anti-cancer activity which does not induce undesired side effects. However, the molecular and cellular mechanisms by which this compound selectively kills human glioma cancer cells without killing normal cells is not fully understood. The present study was designed to determine the molecular bases underlying the potency against 1321N1, SF-767 and U118 human glioma cell lines growth without affecting non cancer MRC-5 cells. Methodology/Principal Findings: The cellular levels of endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and autophagy markers were determined by quantitative RT-PCR and immunoblotting …
JNK phosphorylation relieves HDAC3-dependent suppression of the transcriptional activity of c-Jun
2003
The AP-1 transcription factor c-Jun is a prototypical nuclear effector of the JNK signal transduction pathway. The integrity of JNK phosphorylation sites at serines 63/73 and at threonines 91/93 in c-Jun is essential for signal-dependent target gene activation. We show that c-Jun phosphorylation mediates dissociation of an inhibitory complex, which is associated with histone deacetylase 3 (HDAC3). The subsequent events that ultimately cause increased mRNA synthesis are independent of c-Jun phosphorylation and its interaction with JNK. These findings provide an 'activation by de-repression' model as an explanation for the stimulatory function of JNK on c-Jun.
Protein dynamics observed by tunable mid-IR quantum cascade lasers across the time range from 10 ns to 1 s
2017
We have developed a spectrometer based on tunable quantum cascade lasers (QCLs) for recording time-resolved absorption spectra of proteins in the mid-infrared range. We illustrate its performance by recording time-resolved difference spectra of bacteriorhodopsin in the carboxylic range (1800–1700 cm− 1) and on the CO rebinding reaction of myoglobin (1960–1840 cm− 1), at a spectral resolution of 1 cm− 1. The spectrometric setup covers the time range from 4 ns to nearly a second with a response time of 10–15 ns. Absorption changes as low as 1 × 10− 4 are detected in single-shot experiments at t > 1 μs, and of 5 × 10− 6 in kinetics obtained after averaging 100 shots. While previous time-res…
Mathematical formulation of pulse amplitude modulation selective harmonic elimination in multilevel three phase inverters
2022
In this paper multilevel cascaded H-bridges (CHB) three phase inverters with 2n dc sources, n=1,2,3,... are considered and a mathematical formulation providing both 2n switching angles and dc voltage source to eliminate n+1 harmonics and their respective multiple from their output voltage waveform, is proposed. The computed angles don't depend on modulation index and the source voltages linearly vary with it. The proposed procedure finds the solution through an analytical formula that avoids to solve transcendental systems and presents very low computational cost. A lot of low order harmonics are eliminated, returning a very low total harmonic distortion (THD). Particularly for 9-level conf…
Feature Selection for Ensembles of Simple Bayesian Classifiers
2002
A popular method for creating an accurate classifier from a set of training data is to train several classifiers, and then to combine their predictions. The ensembles of simple Bayesian classifiers have traditionally not been a focus of research. However, the simple Bayesian classifier has much broader applicability than previously thought. Besides its high classification accuracy, it also has advantages in terms of simplicity, learning speed, classification speed, storage space, and incrementality. One way to generate an ensemble of simple Bayesian classifiers is to use different feature subsets as in the random subspace method. In this paper we present a technique for building ensembles o…
Ensemble Feature Selection Based on Contextual Merit and Correlation Heuristics
2001
Recent research has proven the benefits of using ensembles of classifiers for classification problems. Ensembles of diverse and accurate base classifiers are constructed by machine learning methods manipulating the training sets. One way to manipulate the training set is to use feature selection heuristics generating the base classifiers. In this paper we examine two of them: correlation-based and contextual merit -based heuristics. Both rely on quite similar assumptions concerning heterogeneous classification problems. Experiments are considered on several data sets from UCI Repository. We construct fixed number of base classifiers over selected feature subsets and refine the ensemble iter…
Regulation ofMUC1Expression in Human Mammary Cell Lines by the c-ErbB2 and Ras Signaling Pathways
2001
The MUC1 protein is a highly O-glycosylated transmembrane molecule that is expressed at the luminal surface of most glandular epithelial cells and is upregulated in carcinomas. Here, we report the effect of the activation of the c-ErbB2 --Ras pathway on the expression of the MUC1 gene in the nontumorigenic mammary cell lines MTSV1-7 and HB2 and in the malignant cell lines T47D and ZR75. Endogenous levels of MUC1 mRNA and protein in HB2 clones permanently overexpressing c-ErbB2 or V12-H-Ras were markedly reduced compared with levels in the parental cell lines. Furthermore, in transient transfection assays, the transcription of a CAT reporter construct driven by the MUC1 promoter was inhibite…
Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells
2011
Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…