Analyzing the Effect of Crowds on Passenger Behavior Inside Urban Trains through Laboratory Experiments—A Pilot Study

The objective is to study the distribution of passengers inside urban trains for different levels of crowding. The study is carried out through the observation of videos made by laboratory experiments in which a mock-up of a carriage represented the boarding and alighting process. The Fruin’s Level of Service (LOS) was adopted, but with a different approach, in which the train is divided into five zones (central hall, central aisle, side aisle, central seats and side seats). The experiments are based on the behavior of passengers in the London Underground; however, this study could be expanded to any conventional rail or LRT system. For the laboratory experiments, it is proposed to build a metro carriage and a corresponding platform section, and the scenarios will include different levels of crowding of passengers boarding and alighting to produce a variation in the density on the platform. According to the crowding level, the results allow obtaining the distribution and movements generated by passengers in the five zones for different instants of time during the process of boarding and alighting. It is observed that passengers are distributed according to safety and efficiency conditions. For example, passengers tried to avoid contact with each other unless it is inevitable. In relation to comfort, the seats of the carriage are always used even if there is a low level of crowding. If the crowding level increases, the boarding and alighting time go up. In addition, passengers will spend one or two seconds more if the “let’s get off before getting on the carriage” behavior is breached. This kind of experiment can be used in further research as a way to test “what-if” scenarios using this new method of discretization of the space inside the train, which cannot be tested in existing stations due to restrictions such as the weather, variability of the train frequency, current design of the trains, among others. New experiments are necessary for future research to include other types of passengers such as people with disabilities or reduced mobility

Zinc-phthalocyanine-loaded extracellular vesicles increase efficacy and selectivity of photodynamic therapy in co-culture and preclinical models of colon cancer

Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Ceramide and palmitic acid inhibit macrophage-mediated epithelial-mesenchymal transition in colorectal cancer (vol 468, pg 153, 2020)

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Ceramide and palmitic acid inhibit macrophage-mediated epithelial-mesenchymal transition in colorectal cancer

Accumulating evidence indicates that ceramide (Cer) and palmitic acid (PA) possess the ability to modulate switching of macrophage phenotypes and possess anti-tumorigenic effects; however, the underlying molecular mechanisms are largely unknown. The aim of the present study was to investigate whether Cer and PA could induce switching of macrophage polarization from the tumorigenic M2- towards the pro-inflammatory M1-phenotype, and whether this consequently altered the potential of colorectal cancer cells to undergo epithelial-mesenchymal transition (EMT), a hallmark of tumor progression. Our study showed that Cer- and PA-treated macrophages increased expression of the macrophage 1 (M1)-marker CD68 and secretion of IL-12 and attenuated expression of the macrophage 2 (M2)-marker CD163 and IL-10 secretion. Moreover, Cer and PA abolished M2 macrophage-induced EMT and migration of colorectal cancer cells. At the molecular level, this coincided with inhibition of SNAI1 and vimentin expression and upregulation of E-cadherin. Furthermore, Cer and PA attenuated expression levels of IL-10 in colorectal cancer cells co-cultured with M2 macrophages and downregulated STAT3 and NF-kappa B expression. For the first time, our findings suggest the presence of an IL-10-STAT3-NF-kappa B signaling axis in colorectal cancer cells co-cultured with M2 macrophages, mimicking the tumor microenvironment. Importantly, PA and Cer were powerful inhibitors of this signaling axis and, consequently, EMT of colorectal cancer cells. These results contribute to our understanding of the immunological mechanisms that underlie the anti-tumorigenic effects of lipids for future combination with drugs in the therapy of colorectal carcinoma.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Fast and reliable calibration of solid substrate fermentation kinetic models using advanced non-linear programming techniques

Calibration of mechanistic kinetic models describing microorganism growth and secondary metabolite production on solid substrates is difficult due to model complexity given the sheer number of parameters needing to be estimated and violation of standard conditions of numerical regularity. We show how advanced non-linear programming techniques can be applied to achieve fast and reliable calibration of a complex kinetic model describing growth of Gibberella fujikuroi and production of gibberellic acid on an inert solid support in glass columns. Experimental culture data was obtained under different temperature and water activity conditions. Model differential equations were discretized using orthogonal collocations on finite elements while model calibration was formulated as a simultaneous solution/optimization problem. A special purpose optimization code (IPOPT) was used to solve the resulting large-scale non-linear program. Convergence proved much faster and a better fitting model was achieved in comparison with the standard sequential solution/optimization approach. Furthermore, statistical analysis showed that most parameter estimates were reliable and accurate

Methodological Guidelines for Engineering Self-organization and Emergence

The ASCENS project deals with the design and development of complex self-adaptive systems, where self-organization is one of the possible means by which to achieve self-adaptation. However, to support the development of self-organising systems, one has to extensively re-situate their engineering from a software architectures and requirements point of view. In particular, in this chapter, we highlight the importance of the decomposition in components to go from the problem to the engineered solution. This leads us to explain and rationalise the following architectural strategy: designing by following the problem organisation. We discuss architectural advantages for development and documentation, and its coherence with existing methodological approaches to self-organisation, and we illustrate the approach with an example on the area of swarm robotics

Effect of a single nutritional intervention previous to a critical period of fat gain in university students with overweight and obesity: A randomized controlled trial

Indexación: ScopusBackground: the present study aimed to investigate the effects of a single nutritional preventive session previous to a critical period linked to fat gain in university students with overweightness and obesity, emulating a nutritional session of a public health system. Methods: In this single-blind randomized controlled trial, 23 students met all the criteria to be included (20.91 ± 2.52-year-old; 52.2% women) who were divided into two groups: intervention group (IG) and control group (CG). Fat mass (FM) by dual-energy X-ray absorptiometry (DXA), physical activity by accelerometry, feeding evaluation through three questionnaires, and a set of healthy lifestyle recommendations were evaluated before and after the national holidays (NH). Results: Our findings showed that FM increased significantly in the CG, but not in the IG (CG = 428.1g; IG = 321.9g; ∆ = 106.2g; p = 0.654 [95% CI = −379.57, 591.92]). However, no differences were found during the NH between them (Hedges’ g effect size = 0.19; p = 0.654). In addition, no statistical differences were observed between groups in feeding evaluations, the set of recommendations performed, and physical activity. Conclusion: a single preventive session before a critical period, using a similar counselling approach as used in the public health system, might not be enough to promote changes in eating and physical activity patterns and preventing fat gain in overweight/obese university students. Long-term interventions are a must. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.https://www.mdpi.com/1660-4601/17/14/514

Papel de la disbiosis intestinal en la patogénesis de la enfermedad de hígado graso no alcohólico (NAFLD) asociada a obesidad en pacientes

1 p.El objetivo del trabajo es Estudiar la composición y la diversidad de las comunidades. Resumen de un estudio resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16) de bacterias presentes en muestras fecales de 20 individuos sanos delgados, 36 pacientes obesos con NAFLD y 17 pacientes obesos sin NAFLD. Para ello, se amplificó la región V3-V4 del ARNr 16S, seguido de un análisis de pirosecuenciaciónS

Bile Acids Specifically Increase Hepatitis C Virus RNA-Replication

<div><h3>Background</h3><p>Hepatitis C virus (HCV) patients with high serum levels of bile acids (BAs) respond poorly to IFN therapy. BAs have been shown to increase RNA-replication of genotype 1 but not genotype 2a replicons. Since BAs modulate lipid metabolism including lipoprotein secretion and as HCV depends on lipids and lipoproteins during RNA-replication, virus production and cell entry, BAs may affect multiple steps of the HCV life cycle. Therefore, we analyzed the influence of BAs on individual steps of virus replication.</p> <h3>Methods</h3><p>We measured replication of subgenomic genotype (GT) 1b and 2a RNAs as well as full-length GT2a genomes in the presence of BAs using quantitative RT-PCR and luciferase assays. Cell entry was determined using HCV pseudoparticles (HCVpp). Virus assembly and release were quantified using a core-specific ELISA. Replicon chimeras were employed to characterize genotype-specific modulation of HCV by BAs. Lunet CD81/GFP-NLS-MAVS cells were used to determine infection of Con1 particles.</p> <h3>Results</h3><p>BAs increased RNA-replication of GT1b replicons up to 10-fold but had no effect on subgenomic GT2a replicons both in Huh-7 and HuH6 cells. They did not increase viral RNA translation, virus assembly and release or cell entry. Lowering replication efficiency of GT2a replicons rendered them susceptible to stimulation by BAs. Moreover, replication of full length GT1b with or without replication enhancing mutations and GT2a genomes were also stimulated by BAs.</p> <h3>Conclusions</h3><p>Bile acids specifically enhance RNA-replication. This is not limited to GT1, but also holds true for GT2a full length genomes and subgenomic replicons with low replication capacity. The increase of HCV replication by BAs may influence the efficacy of antiviral treatment in vivo and may improve replication of primary HCV genomes in cell culture.</p> </div

Nueve jueces entran en diálogo con nueve hipótesis acerca de la prueba de los hechos en el contexto penal

This article formulates nine hypotheses concerning the proof of facts in criminal proceedings, which are analysed by nine judges of Chilean criminal Courts (Tribunal de Juicio Oral y de Garantía). Seven hypotheses aimed at describing different practices that take place in the courts and two of them concern how judges should act in certain hard cases. The matters are grouped in the following categories: a) scopes of the compromise that judges should have in order to operate with true stories as support of their decisions; b) difficulties that arise as consequence of the epistemic weakness of the evidence available in trials and the possible slants in their interpretation; c) requirements of the evaluation of the proof according to the sana crítica; and d) meaning that should have the standard of proof beyond reasonable doubt. In this way, a dialogue between the system of beliefs of judges and of jurists takes place