In: Revista latinoamericana de estudios del discurso: revista latinoamericana de estudos do discurso = latin american journal of discourse studies, Band 6, Heft 1, S. 120
<p>The objective of this paper is to propose the application of the SARX model to arrive at industrial power consumption forecasts in Brazil, which are critical to support decisionmaking in the energy sector, based on technical, economic and environmentally sustainable grounds. The proposed model has a seasonal component and considers the influence of exogenous variables on the projection of the dependent variable and utilizes an autoregressive process for residual modeling so as to improve its explanatory power. Five exogenous variables were included: industrial capacity utilization, industrial electricity tariff, industrial real revenues, exchange rate, and machinery and equipment inflation. In addition, the model assumed that power forecast was dependent on its own time lags and also on a dummy variable to reflect 2009 economic crisis. The study used 84 monthly observations, from January 2003 to December 2009. The backward method was used to select exogenous variables, assuming a 0.10 descriptive value. The results showed an adjusted coefficient of determination of 93.9% and all the estimated coefficients were statistically significant at a 0.10 descriptive level. Forecasts were also made from January to May 2010 at a 95% confidence interval, which included actual consumption values for this period. The SARX model has demonstrated an excellent performance for industrial power consumption forecasting in Brazil.</p>
Half of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mutp53 reactivators and anticancer agents was investigated in human tumor cells and xenograft mouse models. By analysis of their anti-proliferative effect on a panel of p53-null NCI-H1299 tumor cells ectopically expressing highly prevalent mutp53, the compound SLMP53-2 was selected based on its potential reactivation of multiple structuralmutp53. In mutp53-Y220C-expressing hepatocellular carcinoma (HCC) cells, SLMP53-2-induced growth inhibition was mediated by cell cycle arrest, apoptosis, and endoplasmic reticulum stress response. In these cells, SLMP53-2 restored wild-type-like conformation and DNA-binding ability of mutp53-Y220C by enhancing its interaction with the heat shock protein 70 (Hsp70), leading to the reestablishment of p53 transcriptional activity. Additionally, SLMP53-2 displayed synergistic effect with sorafenib, the only approved therapy for advanced HCC. Notably, it exhibited potent antitumor activity in human HCC xenograft mouse models with a favorable toxicological profile. Collectively, SLMP53-2 is a new mutp53-targeting agent with promising antitumor activity, particularly against HCC. ; Funding: This work was supported by National Funds through Fundação para a Ciência e Tecnologia, I.P. via the projects UID/QUI/50006/2019 and PTDC/QUI-QOR/29664/2017. Acknowledgments: Authors acknowledge the financial support from European Union (FEDER funds POCI/01/0145/FEDER/007728 through Programa Operacional Factores de Competitividade—COMPETE) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement UID/DTP/04138/2019 (iMed.ULisboa), UID/NEU/04539/2013, UID/NEU/04539/2019. CENTRO-01-0145-FEDER-000012-HealthyAging2020, UID/BIO/04469/2019, BioTecNorte operation (NORTE-01-0145-FEDER-000004), and the projects (3599-PPCDT) PTDC/DTP-FTO/1981/2014—POCI-01-0145-FEDER-016581, and POCI-01-0145-FEDER-028736. We also thank FCT for the financial support through the grant CEECIND/01772/2017 (M. M. M. Santos), and fellowships SFRH/BD/96189/2013 (S. Gomes), PD/BD/143126/2019 (V. Barcherini), SFRH/BD/117949/2016 (L. Raimundo), SFRH/BD/119144/2016 (H. Ramos), SFRH/BD/128673/2017 (J. B. Loureiro), and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences; PD/00016/2012). We also acknowledge the support from the Italian Association for Cancer Research, AIRC (IG#18985 to AI).