Graph Element Networks: adaptive, structured computation and memory

We explore the use of graph neural networks (GNNs) to model spatial processes in which there is no a priori graphical structure. Similar to finite element analysis, we assign nodes of a GNN to spatial locations and use a computational process defined on the graph to model the relationship between an initial function defined over a space and a resulting function in the same space. We use GNNs as a computational substrate, and show that the locations of the nodes in space as well as their connectivity can be optimized to focus on the most complex parts of the space. Moreover, this representational strategy allows the learned input-output relationship to generalize over the size of the underlying space and run the same model at different levels of precision, trading computation for accuracy. We demonstrate this method on a traditional PDE problem, a physical prediction problem from robotics, and learning to predict scene images from novel viewpoints.Comment: Accepted to ICML 201

Wine routes in Spain: A case study

Spain is a country with an enormous wine-growing tradition and with a huge tourist industry, although it has not made the importance of wine tourism profitable. Thus, it was not until 2000 that different official wine routes seemed to appear, with the main objective, amongst others, being to help develop rural areas where wine production is of crucial importance and to offer alternatives to traditional sun and beach tourism. In this paper, we will present an analysis of wine tourism in Spain based on the premise that wine (and regional cuisine) may be, and very frequently is, the main reason for visiting a certain area. To investigate this, we will present the results of an empirical study carried out in one of the official wine routes of Andalusia, a Spanish region where sun and beach tourism and cultural tourism represent a highly significant part of tourist activity. We have analysed how this tourist route is bringing about significant socioeconomic changes to the geographical area. To achieve this aim, we have conducted a survey of the companies involved in the wine route in order to ascertain their opinions on the impact and influence of the route. The main results of the study demonstrate the need to consolidate the development of such routes through collaboration between public institutions, ensuring the participation of all the different social actors involved

On the nonlinear hunting stability of a high-speed train bogie

The hunting phenomenon is an intrinsic swaying motion appearing in railway vehicles due to the vehicle's forward speed and the wheel-rail contact forces. Hunting motion consists of wheelset and other vehicle's components oscillations that arise above a certain vehicle's speed known as critical or hunting speed. These oscillations are of unstable nature and represent a safety hazard as they could lead to the vehicle's derailment. This article analyses the stability of a bogie nonlinear model for a Spanish high-speed train when this is travelling at speeds near the hunting speed. The vehicle's stability is studied by means of root loci methods, and the value of the critical speed is found. In addition to this, the behaviour of the vehicle is studied in both stable and unstable regions and the existence of limit cycles is discussed in this work. Finally, a sensitivity analysis of the axle load and suspension parameters is performed. The results show that the axle load, the vertical stiffness of the primary suspension and the lateral damping of the secondary suspension have a significant influence on the value of the critical speed.The research work described in this paper is part of the R&D and Innovation projects MC4.0 PID2020-116984RB-C21 and MC4.0 PID2020-116984RB-C22 supported by the MCIN/AEI/10.13039/501100011033 and by the Universidad Carlos III de Madrid through the "Ayudas para la movilidad de investigadores de la UC3M en centros de investigación nacionales y extranjeros en sus dos modalidades 2019" project

Carbohydrate effect of novel arene Ru(II) phenanthroline-glycoconjugates on metastatic biological processes

Novel water-soluble half-sandwich ruthenium(II) polypyridyl-glycoconjugates [Ru(p-cymene)Cl{N-(1,10-phenanthroline-5-yl)-& beta;-glycopyranosylamine}][Cl] (glycopyranosyl = D-glucopyranosyl (1), D-mannopyranosyl (2), L-rhamnopyranosyl (3) and L-xylopyranosyl (4)) have been synthesized and fully characterized. Their behaviour in water under physiological conditions has been studied by nuclear magnetic resonance spectroscopy, revealing their hydrolytic stability. Interactions of the novel compounds with duplex-deoxiribonucleic acid (dsDNA) were investigated by different techniques and the results indicate that, under physiological pH and saline conditions, the metal glycoconjugates bind DNA in the minor groove and/or through external, electrostatic interactions, and by a non-classical, partial intercalation mechanism in non-saline phosphate buffered solution. Effects of compounds 1-4 on cell viability have been assessed in vitro against two human cell lines (androgen-independent prostate cancer PC-3 and non-tumorigenic prostate RWPE-1), showing moderate cytotoxicities, with IC50 values higher than those found for free ligands [N-(1,10-phenanthroline-5-yl)-& beta;-glycopyranosylamine] (glycopyranosyl = D-glucopyranosyl (a), D-mannopyranosyl (b), L-rhamnopyranosyl (c) and L-xylopyranosyl (d)) or corresponding metal-aglycone. Cell viability was assayed in the presence and absence of the glucose transporters (GLUTs) inhibitor [N4-{1-(4-cyanobenzyl)-5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl}-7-fluoroquinoline-2,4dicarboxamide] (BAY-876), and the results point to a negligible impact of the inhibition of GLUTs on the cytotoxicity caused by Ru(II) compounds 1-4. Remarkably, glycoconjugates 1-4 potently affect the migration pattern of PC-3 cells, and the wound healing assay evidence that the presence of the carbohydrate and the Ru(II) center is a requisite for the anti-migratory activity observed in these novel derivatives. In addition, derivatives 1-4 strongly affect the matrix metalloproteinase MMP-9 activities of PC-3 cells, while proMMP-2 and especially proMMP-9 were influenced to a much lesser extent

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: 0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.This work has been supported by grants given by Fondo de Investigación de Sanidad en España (FIS) [Spanish Health Founds for Research] [grant numbers PI14CIII/00011, PI15CIII/00024 and PT13/0001]. MAJS, LMM, and AFR are supported by “Instituto de Salud Carlos III” [grant numbers CD13/00013, CD14/00002 and CP14/0010].S

TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients

TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.This study is supported by grants from Instituto de Salud Carlos III (ISCIII) (grant # PI20CIII/00004 to S.R.). M.A.J.-S. and A.F.-R. are supported by “Instituto de Salud Carlos III” (grant # CP17CIII/00007 and CP14CIII/00010, respectively).S

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study

BACKGROUND: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. METHODS: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). RESULTS: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP's association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). CONCLUSIONS: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.This work has been supported by grants given by Instituto de Salud Carlos III (ISCIII) (grant numbers PI14CIII/00011 and PI17CIII/00003 to SR). AFR is also supported by ISCIII (grant numbers CP14CIII/00010).S

Temporal patterns in coral reef, seagrass and mangrove communities from Chengue bay CARICOMP site (Colombia): 1993-2008

Few monitoring programs have simultaneously assessed the dynamics of linked marine ecosystems (coral reefs, seagrass beds and mangroves) to document their temporal and spatial variability. Based on CARICOMP protocol we evaluated permanent stations in coral reefs, seagrass beds and mangroves from 1993 to 2008 in Chengue Bay at the Tayrona Natural Park, Colombian Caribbean. Overall, the studied ecosystems showed a remarkable stability pattern over the monitoring period. While there were annual variations in coral reefs (coral cover) and mangroves (litterfall) caused by hurricane Lenny in 1999, particular trends in seagrass (leaf area index and leaf productivity) appear to reflect the natural variability in this ecosystem. We suggest that monitoring sites at the three marine ecosystems had in general a healthy development in the last 16 years. Our results are critical to locally improve the management strategies (Tayrona Natural Park) and to understand the long-term dynamics of closely associated marine ecosystems in the Caribbean. Copyright © 2011 Elsevier B.V. All rights reserved