Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infection

Double-edged lipid nanoparticles combining liposome-bound TRAIL and encapsulated doxorubicin showing an extraordinary synergistic pro-apoptotic potential

Although TRAIL (TNF-related apoptosis-inducing ligand, also known as Apo2L) was described as capable of inducing apoptosis in transformed cells while sparing normal cells, limited results obtained in clinical trials has limited its use as an anti-tumor agent. Consequently, novel TRAIL formulations with enhanced bioactivity are necessary for overcoming resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumors. Our group has generated artificial liposomes with sTRAIL anchored on their surface (large unilamellar vesicle (LUV)-TRAIL), which have shown a greater cytotoxic activity both in vitro and in vivo when compared to sTRAIL against distinct hematologic and epithelial carcinoma cells. In this study, we have improved LUV-TRAIL by loading doxorubicin (DOX) in its liposomal lumen (LUVDOX-TRAIL) in order to improve their cytotoxic potential. LUVDOX-TRAIL killed not only to a higher extent, but also with a much faster kinetic than LUV-TRAIL. In addition, the concerted action of the liposomal DOX and TRAIL was specific of the liposomal DOX and was not observed when with soluble DOX. The cytotoxicity induced by LUVDOX-TRAIL was proven to rely on two processes due to different molecular mechanisms: a dynamin-mediated internalization of the doxorubicin-loaded particle, and the strong activation of caspase-8 exerted by the liposomal TRAIL. Finally, greater cytotoxic activity of LUVDOX-TRAIL was also observed in vivo in a tumor xenograft model. Therefore, we developed a novel double-edged nanoparticle combining the cytotoxic potential of DOX and TRAIL, showing an exceptional and remarkable synergistic effect between both agents

Laser remote sensing applications (LiDAR) in forest hydrology and the management of river ecosystems.

La utilización de sensores láser desde plataformas aéreas (LiDAR) ofrece nuevas posibilidades en el cartografiado de sistemas fluviales, tanto en áreas densamente cubiertas por vegetación, como en aquellas que presentan una escasa cubierta. La información topográfica de alta resolución que se obtiene a partir de las medidas láser puede ser utilizada en el análisis y estimación de diversas variables hidrológicas, y en el estudio de diferentes componentes del medio fluvial. Entre éstas, cabe citar la vegetación riparia, la morfología fluvial, el régimen hidrológico o el grado de alteración de los ecosistemas debido a las presiones de origen antrópico. La gestión del medio fluvial puede ser mejorada en gran medida gracias a la precisión y fiabilidad de esta información. En muchas ocasiones, el escaso relieve de los valles fluviales y la densa cubierta vegetal que existe en ellos han dificultado la aplicación de otras técnicas de teledetección. Sin embargo, los datos obtenidos mediante altimetría láser son especialmente aconsejables para estos trabajos, mediante análisis numéricos o a través de la simple interpretación de las imágenes obtenidas. Este artículo muestra las posibilidades de uso de los datos LiDAR en hidrología forestal y en la gestión de zonas húmedas, a lo largo de tramos con condiciones climáticas bien diferenciadas. En todas ellas, se comparan los resultados obtenidos mediante la aplicación de distinto software, con el fin de mostrar la mejor metodología de tratamiento de la información láser. Asimismo, se muestra la diferencia con otras técnicas de teledetección, y se muestra la fácil integración de los datos LiDAR con otras herramientas y metodologías de estudio de las variables citadas

Satellite Constellation Launch, Deployment, Replacement and End-of -Life Strategies

The considerable surge in satellite constellations has brought to the fore the imperative need for an efficient satellite constellation management plan. To address this emerging need, GMV has analyzed the possible strategies for constellation launch, set-up, replacement of failed satellites and end-of-life policy. The constellation launch and deployment has been divided into the launch site and launcher selection, the evaluation of the injection and the transfer strategies, and the set-up phase. The main replacement strategies investigated are based on in-orbit spares, spare satellites in parking orbits and spare satellites on the ground. Finally, end-of-life policies for LEO, MEO and GEO satellites are presented. As such, the analysis accomplished encompasses most of the fundamental phases of constellation life cycle. A representative constellation of small satellites has been taken into account to assess the effectiveness and the commercial viability of the strategies outlined. This study case has been handled using in-house software tools and algorithms

Determinants of the adherence to an "a priori" defined Mediterranean dietary pattern

Background: A prospective cohort study with university level participants was initiated to study the effect of Mediterranean diet on health. Aims: The objective of this study was to identify possible lifestyle and socioeconomic variables associated with the consumption of a Mediterranean dietary pattern (MDP). Method: This analysis includes 1587 males and 2260 females. MDP was defined “a priori” by summing the standardized residuals of nutrients and foods after adjusting a regression model using total energy intake as the independent variable. Multiple regression and non-parametric locally weighted regression models were adjusted with the relative adherence to the MDP as the dependent variable in males and females. Results: Women were more compliant than men with the MDP (Coefficient regression (b) = 4.1; Confidence Interval (CI) 95 % = 3.2 to 4.9). The compliance with the MDP was significantly poorer among younger participants both in men and women (p < 0.001 in men and in women). Participants who were more physically active were more likely to fulfill the traditional MDP (p = 0.01 in men and p < 0.001 in women). Conclusions: Our findings provide evidence supporting the progressive departure from the traditional MDP in younger and highly educated subjects of the Mediterranean area. A more active life-style is associated with a better compliance with the MDP

Lipid nanoparticles decorated with TNF-related aptosis-inducing ligand (TRAIL) are more cytotoxic than soluble recombinant TRAIL in sarcoma

Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells. Only few clinical trials have used TRAIL-based treatments in sarcoma, but they show only low or moderate efficacy of TRAIL. Consequently, novel TRAIL formulations with an improved TRAIL bioactivity are necessary. Our group has developed a novel TRAIL formulation based on tethering this death ligand on a lipid nanoparticle surface (LUV-TRAIL) resembling the physiological secretion of TRAIL as a trasmembrane protein inserted into the membrane of exosomes. We have already demonstrated that LUV-TRAIL shows an improved cytotoxic activity when compared to soluble recombinant TRAIL both in hematological malignancies and epithelial-derived cancers. In the present study, we have tested LUV-TRAIL in several human sarcoma tumor cell lines with different sensitivity to soluble recombinant TRAIL, finding that LUV-TRAIL was more efficient than soluble recombinant TRAIL. Moreover, combined treatment of LUV-TRAIL with distinct drugs proved to be especially effective, sensitizing even more resistant cell lines to TRAIL

Interpretable global-local dynamics for the prediction of eye fixations in autonomous driving scenarios

Human eye movements while driving reveal that visual attention largely depends on the context in which it occurs. Furthermore, an autonomous vehicle which performs this function would be more reliable if its outputs were understandable. Capsule Networks have been presented as a great opportunity to explore new horizons in the Computer Vision field, due to their capability to structure and relate latent information. In this article, we present a hierarchical approach for the prediction of eye fixations in autonomous driving scenarios. Context-driven visual attention can be modeled by considering different conditions which, in turn, are represented as combinations of several spatio-temporal features. With the aim of learning these conditions, we have built an encoder-decoder network which merges visual features' information using a global-local definition of capsules. Two types of capsules are distinguished: representational capsules for features and discriminative capsules for conditions. The latter and the use of eye fixations recorded with wearable eye tracking glasses allow the model to learn both to predict contextual conditions and to estimate visual attention, by means of a multi-task loss function. Experiments show how our approach is able to express either frame-level (global) or pixel-wise (local) relationships between features and contextual conditions, allowing for interpretability while maintaining or improving the performance of black-box related systems in the literature. Indeed, our proposal offers an improvement of 29% in terms of information gain with respect to the best performance reported in the literature.The authors would like to thank the authors from DR(eye)VE Project [49] for the support provided during this work, as well as the Multimedia Processing Group from the Universidad Carlos III de Madrid for their entire personal and academic implication

Avaliação de metodos de contribuição de grupos para uso em calculos de equilibrio liquido-vapor

Orientador: Saul Gonçalves D'AvilaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuimicaResumo: Uma metodologia para a predição de curvas de equilíbrio líquido-vapor (ELV) utilizando métodos de contribuição de grupos é proposta. A partir da fórmula estrutural do composto, são preditos valores de temperatura normal de ebulição, propriedades críticas, fator acêntrico, segundo coeficiente virial, pressão de vapor, coeficiente de atividade e volume molar de líquido que são as propriedades demandadas em cálculos de ponto de bolha e de orvalho, isotérmicos e isobárico. A utilização dos programas de computador de cálculo de ELV escritos em linguagem C é comandada pelo programa GERENTE.C, desenvolvido de modo a interagir diretamente com o usuário, que fornece apenas as estruturas de grupos do composto no cálculo de cada propriedade. Foram realizados 988 cálculos de equilíbrio líquido-vapor para 25 compostos diferentes, totalizando 30 sistemas binários extraídos do ¿VLE Standard Date Base¿ de Danner e Gess (1990). Foram ainda realizados 12 cálculos envolvendo sistemas binários e quaternários. A predição dos dados de equilíbrio líquido-vapor usando métodos de contribuição de grupos de um modo geral pode ser considerada boa e adequada para uso em cálculos preliminares de processos de separação. No entanto, a qualidade da predição, expressa em termos de desvios de T, P e concentrações das fases calculadas em relação aos valores experimentais é função direta tanto dos valores preditos de pressão de saturação de componentes puros como dos valores dos coeficientes da atividade... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digitalAbstract: A methodology for predicting vapour-liquid equilibrium curves using group contribution methods is proposed. From the molecular structure of the compound, values of normal boiling temperature, critical properties, acentric factor, second virial coefficients, vapor pressure, activity coefficients and molar liquid volume are required since they are necessary in isothermic and isobaric bubble- and dew- points calculations. The utilization of the developed C language computer programs is directed by an interactive executive program GERENTE. C which requires only the group structures of the compounds for each property calculation. In this work, a number (988) of vapour-liquid equilibrium calculations has been obtained for 25 different compounds summing up 30 binary systems which were extracted from ¿VLE Standard Data Base¿ (Danner and Gess, 1990). Following the same procedure, 12 more calculations were made envolving ternary and quaternary systems. In general, the prediction of vapour-liquid equilibrium data using group contribution can be considered good and suitable to be used in preliminary separation process calculations. Nevertheless, the prediction quality, expressed in terms of pressure, temperature and phase concentration deviations calculated in relation to the experimental values is a function of both predicted pure component vapor pressure and activity coefficients values... Note: The complete abstract is available with the full electronic digital thesis or dissertationsMestradoDesenvolvimento de Processos QuímicosMestre em Engenharia Químic