Optimal Time-dependent Sequenced Route Queries in Road Networks

In this paper we present an algorithm for optimal processing of time-dependent sequenced route queries in road networks, i.e., given a road network where the travel time over an edge is time-dependent and a given ordered list of categories of interest, we find the fastest route between an origin and destination that passes through a sequence of points of interest belonging to each of the specified categories of interest. For instance, considering a city road network at a given departure time, one can find the fastest route between one's work and his/her home, passing through a bank, a supermarket and a restaurant, in this order. The main contribution of our work is the consideration of the time dependency of the network, a realistic characteristic of urban road networks, which has not been considered previously when addressing the optimal sequenced route query. Our approach uses the A* search paradigm that is equipped with an admissible heuristic function, thus guaranteed to yield the optimal solution, along with a pruning scheme for further reducing the search space. In order to compare our proposal we extended a previously proposed solution aimed at non-time dependent sequenced route queries, enabling it to deal with the time-dependency. Our experiments using real and synthetic data sets have shown our proposed solution to be up to two orders of magnitude faster than the temporally extended previous solution.Comment: 10 pages, 12 figures To be published as a short paper in the 23rd ACM SIGSPATIA

The Use of Latent Semantic Indexing to Mitigate OCR Effects of Related Document Images

Due to both the widespread and multipurpose use of document images and the current availability of a high number of document images repositories, robust information retrieval mechanisms and systems have been increasingly demanded. This paper presents an approach to support the automatic generation of relationships among document images by exploiting Latent Semantic Indexing (LSI) and Optical Character Recognition (OCR). We developed the LinkDI (Linking of Document Images) service, which extracts and indexes document images content, computes its latent semantics, and defines relationships among images as hyperlinks. LinkDI was experimented with document images repositories, and its performance was evaluated by comparing the quality of the relationships created among textual documents as well as among their respective document images. Considering those same document images, we ran further experiments in order to compare the performance of LinkDI when it exploits or not the LSI technique. Experimental results showed that LSI can mitigate the effects of usual OCR misrecognition, which reinforces the feasibility of LinkDI relating OCR output with high degradation.CNPq[557976/2008-1]FAPESP[05/60038-5]FAPESP[05/60729-8]FAPESP[06/58984-2]FAPESP[09/14292-8]FAPESP[2009/05504-1]Spanish Ministerio de Ciencia e Innovacion[TIN2008-06566-C04-04]FEDERXunta de Galicia[07SIN005206PR]Innolution Sistemas de Informatic

(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis

We acknowledge Rita Ramos for support with qRT-PCR and Regina Menezes for the selection of primers; Antonio Temudo and Ana M. Nascimento for imaging support; The IMM-JLA Flow Cytometry Facility. We also thank Prof. Kuninori Suzuki (Tokyo Institute of Technology, Yokohama, Japan) for the 2xmCherry-ATG8 plasmid. TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. This work was supported by Fundacao para a Ciencia e Tecnologia [iNOVA4Health: UID/Multi/04462/2013, SFRH/BD/73429/2010 and IMM/BI/78-2017 to DM, SFRH/BD/86584/2012 to IF, IF/01097/2013 to CNS, SFRH/BPD/35767/2007 and SFRH/BPD/101646/2014 to ST]. BacHBerry FP7 KBBE-2013-7 613793 to CNS, DM and CJ, Marie Curie International Reintegration Grant and an EMBO Installation Grant to TFO. TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. The author(s) would like to acknowledge the STSM to AFA and networking support by the COST Action FA 1403 POSITIVe (Interindividual variation in responseto consumption of plant food bioactives and determinants involved), supported by COST (European Cooperation in Science and Technology).Parkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.publishersversionpublishe

Attenuation of motor deficits by hydroethanolic extract of Poincianella pyramidalis in a Parkinson's disease model

The present study aimed to evaluate the possible neuroprotective effect of the hydroethanolic extract of Poincianella pyramidalis (EFIPp) (Tul.) L. P. Queiroz (Fabaceae), an endemic plant found in Northeastern Brazil, commonly used in folk medicine, on the motor deficits induced by repeated treatment with reserpine (RES) in rats. Adult male Wistar rats received 10 s.c. injections of 0.1 mg/kg RES or vehicle (VR), every 48 h, and daily i.p. injections daily of HEPp (25 mg/kg) or vehicle (VE). Throughout treatment, catalepsy behavior and oral movements were scored. After behavioral tests, superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the prefrontal cortex, hippocampus and striatum. RES treatment induced a progressive increase of catalepsy time in the treated group compared to control groups starting at day 15. RES also increased the number of vacuous chewing movements, tongue protrusions and duration of facial twitching. Treatment with HEPp attenuated the motor deficit in the catalepsy test and delayed the onset of oral movements induced by RES. No significant changes were observed in the antioxidant assay. Taken together, these results show a beneficial effect of HEPp on motor deficits induced by reserpine, suggesting a neuroprotective effect in a rat model of PD.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundação de Apoio a Pesquisa e a Inovação Tecnologica do Estado de Sergipe (FAPITEC)Pro-reitoria de Pesquisa da Universidade Federal de Sergipe (POSGRAP/UFS)Univ Fed Sergipe, Dept Physiol, Sao Cristovao, SE, BrazilUniv Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USAMinist Educ, CAPES Fdn, BR-70040020 Brasilia, DF, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sergipe, Dept Biosci, Itabaiana, SE, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilWeb of Scienc

Extracellular vesicles from pancreatic cancer stem cells lead an intratumor communication network (EVNet) to fuel tumour progression

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.Objective: Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour. Design: We have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs). Results: We demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin+ EVs show a significant increased risk of disease progression. Conclusion: PDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.The work was supported by NORTE-01–0145-FEDER-000029, Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund and national funds through FCT—Foundation for Science and Technology POCI-01–0145-FEDER-32189. Programa Operacional Regional do Norte and co-financed by European Regional Development Fund under the project "The Porto Comprehensive Cancer Center" with the reference NORTE-01-0145-FEDER-072678 - Consórcio PORTO.CCC – Porto.Comprehensive Cancer Center. CFR is supported by FCT (SFRH/BD/131461/2017), NB by (SFRH/BD/130801/2017), IB by FCT (SFRH/BD/144854/2019), and BA by FCT (PD/BD/135546/2018). DG’s contribution was supported by the NCI (R21 CA179907). We acknowledge the support of the i3S Scientific Platforms: Translational Cytometry, Animal Facility, Bioimaging and Histology and Electron Microscopy are members of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01–0145-FEDER-022122). Proteomics was performed at the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC), ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.info:eu-repo/semantics/publishedVersio

Enhancing Network Slicing Architectures with Machine Learning, Security, Sustainability and Experimental Networks Integration

Network Slicing (NS) is an essential technique extensively used in 5G networks computing strategies, mobile edge computing, mobile cloud computing, and verticals like the Internet of Vehicles and industrial IoT, among others. NS is foreseen as one of the leading enablers for 6G futuristic and highly demanding applications since it allows the optimization and customization of scarce and disputed resources among dynamic, demanding clients with highly distinct application requirements. Various standardization organizations, like 3GPP's proposal for new generation networks and state-of-the-art 5G/6G research projects, are proposing new NS architectures. However, new NS architectures have to deal with an extensive range of requirements that inherently result in having NS architecture proposals typically fulfilling the needs of specific sets of domains with commonalities. The Slicing Future Internet Infrastructures (SFI2) architecture proposal explores the gap resulting from the diversity of NS architectures target domains by proposing a new NS reference architecture with a defined focus on integrating experimental networks and enhancing the NS architecture with Machine Learning (ML) native optimizations, energy-efficient slicing, and slicing-tailored security functionalities. The SFI2 architectural main contribution includes the utilization of the slice-as-a-service paradigm for end-to-end orchestration of resources across multi-domains and multi-technology experimental networks. In addition, the SFI2 reference architecture instantiations will enhance the multi-domain and multi-technology integrated experimental network deployment with native ML optimization, energy-efficient aware slicing, and slicing-tailored security functionalities for the practical domain.Comment: 10 pages, 11 figure

Chagas Cardiomyopathy Manifestations and Trypanosoma cruzi Genotypes Circulating in Chronic Chagasic Patients

Chagas disease caused by Trypanosoma cruzi is a complex disease that is endemic and an important problem in public health in Latin America. The T. cruzi parasite is classified into six discrete taxonomic units (DTUs) based on the recently proposed nomenclature (TcI, TcII, TcIII, TcIV, TcV and TcVI). The discovery of genetic variability within TcI showed the presence of five genotypes (Ia, Ib, Ic, Id and Ie) related to the transmission cycle of Chagas disease. In Colombia, TcI is more prevalent but TcII has also been reported, as has mixed infection by both TcI and TcII in the same Chagasic patient. The objectives of this study were to determine the T. cruzi DTUs that are circulating in Colombian chronic Chagasic patients and to obtain more information about the molecular epidemiology of Chagas disease in Colombia. We also assessed the presence of electrocardiographic, radiologic and echocardiographic abnormalities with the purpose of correlating T. cruzi genetic variability and cardiac disease. Molecular characterization was performed in Colombian adult chronic Chagasic patients based on the intergenic region of the mini-exon gene, the 24Sα and 18S regions of rDNA and the variable region of satellite DNA, whereby the presence of T.cruzi I, II, III and IV was detected. In our population, mixed infections also occurred, with TcI-TcII, TcI-TcIII and TcI-TcIV, as well as the existence of the TcI genotypes showing the presence of genotypes Ia and Id. Patients infected with TcI demonstrated a higher prevalence of cardiac alterations than those infected with TcII. These results corroborate the predominance of TcI in Colombia and show the first report of TcIII and TcIV in Colombian Chagasic patients. Findings also indicate that Chagas cardiomyopathy manifestations are more correlated with TcI than with TcII in Colombia

Prevalence and risk factors for Hepatitis C and HIV-1 infections among pregnant women in Central Brazil

<p>Abstract</p> <p>Background</p> <p>Hepatitis C (HCV) and human immunodeficiency virus (HIV) infections are a major burden to public health worldwide. Routine antenatal HIV-1 screening to prevent maternal-infant transmission is universally recommended. Our objectives were to evaluate the prevalence of and potential risk factors for HCV and HIV infection among pregnant women who attended prenatal care under the coverage of public health in Central Brazil.</p> <p>Methods</p> <p>Screening and counselling for HIV and HCV infections was offered free of charge to all pregnant women attending antenatal clinic (ANC) in the public health system, in Goiania city (~1.1 million inhabitants) during 2004–2005. Initial screening was performed on a dried blood spot collected onto standard filter paper; positive or indeterminate results were confirmed by a second blood sample. HCV infection was defined as a positive or indeterminate sample (EIA test) and confirmed HCV-RNA technique. HIV infection was defined according to standard criteria. Factors associated with HIV and HCV infections were identified with logistic regression. The number needed to screen (NNS) to prevent one case of infant HIV infection was calculated using the Monte Carlo simulation method.</p> <p>Results</p> <p>A total of 28,561 pregnant women were screened for HCV and HIV-1 in ANC. Mean maternal age was 23.9 years (SD = 5.6), with 45% of the women experiencing their first pregnancy. Prevalence of HCV infection was 0.15% (95% CI 0.11%–0.20%), and the risk increased with age (p < 0.01). The prevalence of anti-HIV infection was 0.09% (95% CI 0.06%–0.14%). Black women had a 4.9-fold (95% CI 1.42–16.95) greater risk of HIV-1 infection compared to non-black women. NNS to prevent one case of infant HIV infection ranged from 4,141 to 13,928.</p> <p>Conclusion</p> <p>The prevalence of HIV and HCV infections were low among pregnant women, with high acceptability rates in the opt-in strategy in primary care. Older maternal age was a risk factor for HCV and antenatal HCV testing does not fulfill the requirements for screening recommendation. The finding of higher risk of HIV-1 infection among black women despite being in consonance with the HIV-1 ethnic pattern in some American regions cannot be ruled out to be a surrogate marker of socio-economic condition.</p

INVENTÁRIO E DIAGNÓSTICO DA ARBORIZAÇÃO URBANA VIÁRIA DE RIO BRANCO, AC

O presente trabalho foi desenvolvido dentro do perímetro urbano da cidade de Rio BrancoAC, localizada entre as coordenadas geográficas de 9°58’29’’ de latitude sul e 67°48’36’’ de longitude oeste. Teve como objetivo geral o levantamento e diagnóstico da arborização viária. A metodologia estatística utilizada foi definida tomando-se como unidade amostral o quarteirão. Encontrou-se pouquíssimos espécimes nas calçadas dos quarteirões amostrados, totalizando 292 indivíduos distribuídos por 39 espécies, sendo 11 nativas e 28 exóticas. A média por quarteirão foi de 1,83 árvores, e por quilômetro de calçada foi de 4,57 árvores. Concluiu-se que o número de árvores existentes nas calçadas foi muito pequeno, tendo-se como referência 100 árvores por quilômetro de calçada como ideal. A maioria das espécies encontrada era exótica (78,57%), a despeito da cidade encontrar-se numa região com uma das maiores diversidades de espécies arbóreas do planeta. Quanto ao estado físico, a copa normal foi predominante, exceto na região central. As recomendações indicadas foram primeiramente de se elaborar um plano de arborização urbana para o município, contendo referências técnicas para escolha das espécies, técnicas de manejo e programa de educação ambiental