Fault activity studies in the Lower Tagus valley and Lisbon region using geophysical data

he Metropolitan Area of Lisbon and the Lower Tagus Valley (LTV) region are located in central Portugal and inhabited by nearly 4 million people. The region has suffered throughout its history the effect of destructive earthquakes caused by hidden faults, possibly related to the plate boundary, which is sited approximately 400 km south of the region (Figure 1). In spite of low slip-rates and big recurrence times that have been estimated for these local, regional faults, they can produce moderate-to-large earthquakes that cause large damage and loss of life, as in 1344, 1531, or 1909 (e.g. Justo and Salwa, 1998; Cabral et al., 2003; 2013). The shorter occurrence time of the earthquakes might be owing to the existence of multiple active faults and/or time clustering owing to stress drop caused by proximal faults (e.g. Carvalho et al., 2006). Therefore, the seismic hazard and risk evaluation of the region has long been a reason of concern. Geological outcrop and geomorphologic mapping identified several regional faults in the LTV region that could be the source the historical earthquakes, but some of them do not affect. Quaternary sediments and lacked the proofs that they were active faults. On the other side, in the vast quaternary alluvial plains that cover the region, it was difficult to identify active faults, as the sedimentation/erosion rates erase any possible surface rupture caused by the low slip-rate faults (<0,35 mm/y). By the late-20th century, seismic reflection data that had been acquired for the oil-industry till the beginning of the 1980s began to be used to identify the major hidden fault zones (e.g. Cabral et al., 2003; Vilanova and Fonseca, 2004; Carvalho et al., 2006). Potential field data was also used to locate active faults in the areas where no seismic data is available (Carvalho et al., 2008; 2011). Though a few more active faults have been proposed, the vast majority of authors agree that the following active faults threaten the region: Nazaré-Caldas da Rainha, Lower Tagus Valley, Ota, Azambuja, Vila Franca de Xira (VFX), Pinhal Novo and Porto Alto faults (Garcia-Mayordomo et al., 2012; Vilanova et al., 2014). In this work, we discuss the acquisition, processing and interpretation of near surface geophysical works carried out over three of these faults — the VFX, Porto Alto and Azambuja faults — in order to confirm they have had activity during the Holoceneera. Their location is shown in Figure 2. We further estimate some of its fault parameters (vertical displacement, slip-rate, length, etc.) and respective implications in terms of seismic hazard

Abstract 4444: Targeted delivery of siRNAs to tumor cells and the tumor microenvironment

Abstract The limited effectiveness of conventional treatment strategies has generated considerable interest on the development of new types of anticancer agents, with improved molecular target specificity. In this context, gene silencing technology constitutes such new class of anticancer agents. The identification of activated oncogenes, as fundamental genetic differences relative to normal cells has made it possible to consider such genes as targets for antitumor therapy. A tumor is an organ, not a single cell type, which encompasses multiple cell types, each one contributing to the overall tumor aggressiveness. It is now recognized that novel therapeutic strategies should envisage the simultaneous inhibition of multiple targets or pathways, at different cell levels within a tumor, that regulate processes promoting tumor development. The main goal of this work was to design a novel ligand-mediated targeted lipid-based nanocarrier, containing a nucleic acid (siRNA), aiming at targeting, simultaneously, human breast cancer and endothelial cells from angiogenic vessels. We have been able to develop a novel ligand-targeted sterically stabilized lipid-based nanoparticle with adequate features for systemic administration: it is characterized by high siRNA encapsulation efficiency, efficient protection of siRNA, average size around 200 nm, and charge close to neutrality. Our results have shown that the covalent attachment of a specific ligand at the extremity of poly(ethylene glycol) chains, brings a major advantage as it significantly improves the internalization of the lipid-based nanoparticle by both human cancer cells (MDA-MB-435 and MDA-MB-231) and endothelial cells from angiogenic blood vessels (HMEC-1). Moreover, it was not observed a significant internalization by the non-transformed cell line, BJ fibroblasts, indicating the cellular specificity of the developed targeted nanoparticle. In order to evaluate the potential of the developed targeted nanoparticle to silence a target gene, the green fluorescent protein (GFP)-overexpressing MDA-MB-435 cells were used. A specific downregulation of GFP, both at the protein and mRNA levels, was further observed with the targeted nanoparticle when compared with the non-targeted counterpart. As the developed nanoparticle is adequate for the encapsulation and delivery of any siRNA sequence, studies with a siRNA targeting a validated molecular target are now ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4444. doi:10.1158/1538-7445.AM2011-4444</jats:p

Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling in the ES-2 Ovarian Carcinoma Cell Line, Influencing Cell Proliferation, Quiescence, and Chemoresistance in a Cell-of-Origin-Specific Manner

Background: The cell-free DNA (cfDNA) is an extracellular fragmented DNA found in body fluids in physiological and pathophysiological contexts. In cancer, cfDNA has been pointed out as a marker for disease diagnosis, staging, and prognosis; however, little is known about its biological role. Methods: The role of cfDNA released by ES-2 ovarian cancer cells was investigated, along with the impact of glucose bioavailability and culture duration in the cfDNA-induced phenotype. The effect of cfDNA on ES-2 cell proliferation was evaluated by proliferation curves, and cell migration was assessed through wound healing. We explored the impact of different cfDNA variants on ES-2 cells’ metabolic profile using nuclear magnetic resonance (NMR) spectroscopy and cisplatin resistance through flow cytometry. Moreover, we assessed the protein levels of DNA-sensitive Toll-like receptor 9 (TLR9) by immunofluorescence and its colocalization with lysosome-associated membrane protein 1 (LAMP1). Results: This study demonstrated that despite inducing similar effects, different variants of cfDNA promote different effects on cells derived from the ES-2 cell line. We observed instant reactions of adopting the metabolic profile that brings back the cell functioning of more favorable culture conditions supporting proliferation and resembling the cell of origin of the cfDNA variant, as observed in unselected ES-2 cells. However, as a long-term selective factor, certain cfDNA variants induced quiescence that favors the chemoresistance of a subset of cancer cells. Conclusions: Therefore, different tumoral microenvironments may generate cfDNA variants that will impact cancer cells differently, orchestrating the disease fate

Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling, Sustaining Proliferation, Quiescence, and Migration in MDA-MB-231, a Triple-Negative Breast Carcinoma (TNBC) Cell Line

Background: The clinical relevance of circulating cell-free DNA (cfDNA) in oncology has gained significant attention, with its potential as a biomarker for cancer diagnosis and monitoring. However, its precise role in cancer biology and progression remains unclear. cfDNA in cancer patients’ blood has been shown to activate signaling pathways, such as those mediated by toll-like receptors (TLRs), suggesting its involvement in cancer cell adaptation to the tumor microenvironment. Methods: This impact of cfDNA released from MDA-MB-231, a triple-negative breast cancer (TNBC) cell line was assessed, focusing on glucose availability and culture duration. The impact of cfDNA on the proliferation of MDA-MB-231 cells was investigated using proliferation curves, while cellular migration was evaluated through wound healing assays. The metabolic alterations induced by distinct cfDNA variants in MDA-MB-231 cells were investigated through nuclear magnetic resonance (NMR) spectroscopy, and their effect on cisplatin resistance was evaluated using flow cytometry. Furthermore, the expression levels of DNA-sensitive Toll-like receptor 9 (TLR9) were quantified via immunofluorescence, alongside its colocalization with lysosome-associated membrane protein 1 (LAMP1). Results: This study indicates that cfDNA facilitates metabolic adaptation, particularly under metabolic stress, by modulating glucose and glutamine consumption, key pathways in tumor cell metabolism. Exposure to cfDNA induced distinct metabolic shifts, favoring energy production through oxidative phosphorylation. The anti-cancer activity of cfDNA isolated from conditioned media of cells cultured under stressful conditions is influenced by the culture duration, emphasizing the importance of adaptation and se-lection in releasing cfDNA that can drive pro-tumoral processes. Additionally, cfDNA exposure influenced cell proliferation, quiescence, and migration, processes linked to metastasis and treatment resistance. These findings underscore cfDNA as a key mediator of metabolic reprogramming and adaptive responses in cancer cells, contributing to tumor progression and therapy resistance. Furthermore, the activation of TLR9 signaling suggests a mechanistic basis for cfDNA-induced phenotypic changes. Conclusions: Overall, cfDNA serves as a crucial signaling molecule in the tumor microenvironment, orchestrating adaptive processes that enhance cancer cell survival and progressio

Abstract 2603: Cancer stem cells and dedifferentiation: the stromal match-point.

Abstract Bypassing all the research advances in the last decades, cancer remains as a major public health problem affecting more than 1.5 million (M) new individuals each year just in the USA, and killing more than 0.5 M. Recent research emphasized the major role of cancer stem cells (CSCs) in the metastatic disease, the main cause of cancer patients mortality. CSCs drive tumorigenesis and differentiation, contributing to tumors’ heterogeneity and to their relative chemo- and radiotherapy resistance and eventually relapse. Following CSCs identification, targeted therapeutic approaches have been developed to abolish them. However, CSCs can reemerge through dedifferentiation of tumor-committed stromal cells condemning this therapeutics. The mechanisms behind dedifferentiation are still unclear and are the main focus of our investigation. Lung cancer is one of the main causes of cancer-related deaths worldwide. Its prevalence is increasing due to the widespread smoking habits and increasing accumulation of atmosphere pollutants. In this work hexavalent chromium [Cr(VI)] was selected as a model of cancer carcinogenesis mainly due to is increasing occupational relevance. The non-malignant human bronchial epithelial cell line BEAS-2B was malignantly transformed into the RenG2 system using low density culture in the presence of Cr(VI). A parallel control cell line (Cont1) was produced under the same conditions, though, in the absence of Cr(VI). Two additional cell lines (DRenG2 and DDRenG2) were attained following serial rounds of injection in nude mice. Metabolic studies using [18F]fluoro-2-deoxyglucose) and nuclear magnetic resonance spectroscopy performed in all the cell lines revealed a more glycolytic phenotype for the derivatives (DRenG2 and DDRenG2), compatible with a quiescent phenotype. Subsequent karyotype and real time PCR-based cellular characterization identified different cellular sub-populations within each cell line, strengthening the hypothesis on the CSCs presence. The sphere-formation assay, used to search for CSCs presence, revealed the presence of CSCs only DRenG2 and in DDRenG2 cell lines. This suggested that a dedifferentiation process featured the formation of CSCs during RenG2 derivation in nude mice. The involvement of mice stroma in this process was uncovered by surgical isolation of mouse stromal cells of the subcutaneous compartment and subsequent co-culture with RenG2 cells for 30-60 days (time needed to induce tumors in mice with RenG2), which resulted in the emergence of a CSCs sub-population. A cytokine multiplex array analysis performed in the conditioned medium of the co-cultured cells in parallel with comparative genome hybridization array (aCGH) analysis performed in all the cell lines under study revealed a panel of potential paracrine orchestrators of this stromal-induced dedifferentiation process. Citation Format: Carlos F. Rodrigues, Mariana Val, Inês P. Rodrigues, Susana Ferreira, Filomena Botelho, José Ramalho, Anatoly Zhitkovich, Isabel M. Carreira, Carmen Alpoim. Cancer stem cells and dedifferentiation: the stromal match-point. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2603. doi:10.1158/1538-7445.AM2013-2603</jats:p

Conformational Analysis of 1‑Chloro- and 1‑Bromo-2-propanol

The conformational isomerism of 1-chloro- (<b>1</b>) and 1-bromo-2-propanol (<b>2</b>) was theoretically and spectroscopically (NMR) analyzed. Conformers with the X–C–C–O (<i>X</i> = Cl and Br) fragment in the gauche orientation were found to be strongly prevalent both in the gas phase and solution, as analyzed by means of coupling constants in the diastereotopic methylene hydrogens. The gauche effect was calculated to be due to hyperconjugation rather than intramolecular X···HO hydrogen bond, indicating the rule of the stereochemical control in compounds with motifs (halohydrins) widely found in pharmaceutical and agrochemical products and intermediates

Diffusion Coefficients of Fluorinated Surfactants in Water: Experimental Results and Prediction by Computer Simulation

Intradiffusion coefficients of 2,2,2-trifluoroethanol in water have been measured by the pulsed field gradient (PFG)-NMR spin–echo technique as a function of temperature and composition on the dilute alcohol region. The measurements extend the range of compositions already studied in the literature and, for the first time, include the study of the temperature dependence. At the same time, intradiffusion coefficients of 2,2,2-trifluoroethanol, 2,2,3,3,3-pentafluoropropan-1-ol, and 2,2,3,3,4,4,4-heptafluorobutan-1-ol in water were obtained by computer simulation (molecular dynamics) as a function of composition and temperature. The intradiffusion coefficients of 2,2,2-trifluoroethanol in water obtained by simulation agree with the experimental results, while those of 2,2,3,3,3-pentafluoropropan-1-ol and 2,2,3,3,4,4,4-heptafluorobutan-1-ol are the first estimation of this property for those systems. The molecular dynamics simulations were also used to calculate the intradiffusion coefficients of perfluoro­octanesulfonic acid and perfluoro­octanoic acid in water at infinite dilution as a function of temperature, which are very difficult to obtain experimentally because of the very low solubility of these substances. From the dependence of the intradiffusion coefficients on temperature, diffusion activation energies were estimated for all the solutes in water

Noites jozephinas de Mirtilo : sobre a infausta morte do Serenissimo Senhor D. Joze Principe do Brazil, dedicadas ao consterna do povo luzitano /

Engravings by Ventura da Silva Neves, Gaspar Fróis Machado, Jerónimo de Barros Ferreira, J.L. da Costa, Fróis Machado, Manuel da Silva Godinho and J.J. Ramalho, after J.T. da Fonseca and Barros Ferreira.Error in paging: p. [248] wrongly numbered 148.An elegy in 12 cantos.Soares, E. Hist. da gravura artística em Portugal,Silva, I.F. da. Diccionário bib. portuguez,SabinPalau y DulcetGrässe,Mode of access: Internet