Periodic vehicle routing problem in a health unit

In logistics of home health care services in the Health Units, the managers and nurses need to carry out the schedule and the vehicles routes for the provision of care at the patients' homes. Currently, in Portugal, these services are increasingly used but the problem is still, usually, solved manually and without computational resources. The increased demand for home health care due to the boost of the elderly people number entails a high associated cost which, sometimes, does not guarantee the quality of the service. In this sense, the periodic vehicle routing problem is a generalization of the classical vehicle routing problem in which routes are determined for a time horizon of several days. In this work, it is provided a periodic vehicle routing problem applied in the Health Unit in Bragança. An integer linear programming formulation for the real database, allowed to solve the problem in an efficient and optimized way using the CPLEXR software.Programa Operacional Temático Factores de Competitividade(POCI-01-0145-FEDER-007043

A systematic review and bibliometric analysis of wildland fire behavior modeling

Wildland fires have become a major research subject among the national and international research community. Different simulation models have been developed to prevent this phenomenon. Nevertheless, fire propagation models are, until now, challenging due to the complexity of physics and chemistry, high computational requirements to solve physical models, and the difficulty defining the input parameters. Nevertheless, researchers have made immense progress in understanding wildland fire spread. This work reviews the state-of-the-art and lessons learned from the relevant literature to drive further advancement and provide the scientific community with a comprehensive summary of the main developments. The major findings or general research-based trends were related to the advancement of technology and computational resources, as well as advances in the physical interpretation of the acceleration of wildfires. Although wildfires result from the interaction between fundamental processes that govern the combustion at the solid- and gas-phase, the subsequent heat transfer and ignition of adjacent fuels are still not fully resolved at a large scale. However, there are some research gaps and emerging trends within this issue that should be given more attention in future investigations. Hence, in view of further improvements in wildfire modeling, increases in computational resources will allow upscaling of physical models, and technological advancements are being developed to provide near real-time predictive fire behavior modeling. Thus, the development of two-way coupled models with weather prediction and fire propagation models is the main direction of future work.This work was supported by the Portuguese Foundation for Science and Technology (FCT) within the R&D Units Project Scope UIDB/00319/2020 (ALGORITMI) and R&D Units Project Scope UIDP/04077/2020 (METRICS) and through project: PCIF/GRF/0141/2019: “O3F—An Optimization Framework to reduce Forest Fire

A functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis

Exposure of human pancreatic beta cells to pro-inflammatory cytokines or metabolic stressors is used to model events related to type 1 and type 2 diabetes, respectively. Quantitative real-time PCR is commonly used to quantify changes in gene expression. The selection of the most adequate reference gene(s) for gene expression normalization is an important pre-requisite to obtain accurate and reliable results. There are no universally applicable reference genes, and the human beta cell expression of commonly used reference genes can be altered by different stressors. Here we aimed to identify the most stably expressed genes in human beta cells to normalize quantitative real-time PCR gene expression. We used comprehensive RNA-sequencing data from the human pancreatic beta cell line EndoC-βH1, human islets exposed to cytokines or the free fatty acid palmitate in order to identify the most stably expressed genes. Genes were filtered based on their level of significance (adjusted P-value >0.05), fold-change (|fold-change| <1.5) and a coefficient of variation <10%. Candidate reference genes were validated by quantitative real-time PCR in independent samples. We identified a total of 264 genes stably expressed in EndoC-βH1 cells and human islets following cytokines–or palmitate-induced stress, displaying a low coefficient of variation. Validation by quantitative real-time PCR of the top five genes ARF1, CWC15, RAB7A, SIAH1 and VAPA corroborated their expression stability under most of the tested conditions. Further validation in independent samples indicated that the geometric mean of ACTB and VAPA expression can be used as a reliable normalizing factor in human beta cells

Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.Foundation for the Science and Technology (FCT–Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development) for financial support through the research centers PEst-C/QUI/UI686/2011and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoralgrants attributed to R.C.C. and R.T.L. (SFRH/BPD/68344/2010 and SFRH/BPD/68787/2010, respectively). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

'Is your city pretty anyway?' Perspectives on graffiti and the urban landscape

Drawing on survey and focus group research completed in New Zealand in 2009 this article examines young peoples’ perspectives on graffiti and tagging. The results further demonstrate that graffiti writing is an activity invested with considerable cultural meaning by many of those engaged in it and that their understanding of graffiti is considerably at odds with prevailing political, media and policy discourse that sees it purely in terms of criminal damage and antisocial behaviour. While graffiti can be conceptualised as an alternative way of ‘reading’ urban space, the results of this study show that writers recognised that graffiti had damaging consequences and was inappropriate in some contexts. Graffiti was not simply nihilistic destructive behaviour but one in which perceptions of criminality were leavened by aesthetic judgements and the allure and excitement of potential local celebrity

Indirect calibration between clinical observers - application to the New York Heart Association functional classification system

<p>Abstract</p> <p>Background</p> <p>Previous studies showed an inter-observer agreement for the NYHA classification of approximately 55%. The aim of this study was to calibrate the New York Heart Association (NYHA) classification system between observers, increasing its reliability.</p> <p>Results</p> <p>Among 1136 community-dwellers in Porto, Portugal, aged ≥ 45 years, 265 reporting breathlessness answered a 4-item questionnaire to characterize symptom severity. The questionnaire was administered by 7 physicians who also classified the subject's functional capacity according to NYHA. Each subject was assessed by one physician. We calibrated NYHA classifications by the concurrent method, using 1-parameter logistic graded response model. Discrepancies between observers were assessed by differences in ability thresholds between NYHA classes I-II and II-III. The ability estimated by the model was used to predict the NYHA classification for each observer.</p> <p>Estimates of the first and second thresholds for each observer ranged from -1.92 to 0.46 and from 1.42 to 2.30, respectively. The agreement between estimated ability and the observers' NYHA classification was 88% (kappa = 0.61).</p> <p>Conclusions</p> <p>The study objectively indicates the main reason why several studies have reported low inter-observer is the existence of discrepant thresholds between observers in the definition of NYHA classes. The concurrent method can be used to minimize the reliability problem of NYHA classification.</p

An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells

Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.P30 DK097512/DK/NIDDK NIH HHS/United States UC4 DK104166/DK/NIDDK NIH HHS/United States MR/P010695/1/MRC_/Medical Research Council/United Kingdompublished version, accepted version, submitted versio

Consequences Of On-Track Competition In Railways By Use Of Simulations

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Large-scale optimization with the primal-dual column generation method

The primal-dual column generation method (PDCGM) is a general-purpose column generation technique that relies on the primal-dual interior point method to solve the restricted master problems. The use of this interior point method variant allows to obtain suboptimal and well-centered dual solutions which naturally stabilizes the column generation. As recently presented in the literature, reductions in the number of calls to the oracle and in the CPU times are typically observed when compared to the standard column generation, which relies on extreme optimal dual solutions. However, these results are based on relatively small problems obtained from linear relaxations of combinatorial applications. In this paper, we investigate the behaviour of the PDCGM in a broader context, namely when solving large-scale convex optimization problems. We have selected applications that arise in important real-life contexts such as data analysis (multiple kernel learning problem), decision-making under uncertainty (two-stage stochastic programming problems) and telecommunication and transportation networks (multicommodity network flow problem). In the numerical experiments, we use publicly available benchmark instances to compare the performance of the PDCGM against recent results for different methods presented in the literature, which were the best available results to date. The analysis of these results suggests that the PDCGM offers an attractive alternative over specialized methods since it remains competitive in terms of number of iterations and CPU times even for large-scale optimization problems.Comment: 28 pages, 1 figure, minor revision, scaled CPU time

Maximizing the expected number of transplants in kidney exchange programs with branch-and-price

In this paper, we propose a branch-and-price approach for solving the problem of maximizing the expected number of transplants in Kidney Exchange Programs (KEPs). In these programs, the decision on which transplants will be conducted is usually made with the support of optimization models with the assumption that all operations will take place. However, after a plan of transplants is defined, a pair may leave the KEP or a more accurate compatibility evaluation exam may invalidate a transplant. To model these possible events we consider probabilities of failure of vertices and of arcs and the objective of maximizing the expected number of transplants. The proposed approach is based on the so-called cycle formulation, where decision variables are associated with cycles. Built on the concept of type of cycle a branch-and-price algorithm is conceived. One subproblem is defined for each type of cycle. We present computational results of the proposed branch-and-price algorithm and compare them with solving directly the cycle formulation (with a general purpose mixed integer programming solver—CPLEX) showing that the proposed approach is the only one suitable for larger instances.This work is financed by the ERDF—European Regional Development Fund through the Operational, Programme for Competitiveness and Internationalization—COMPETE 2020, Programme and by National Funds through the Portuguese funding agency, FCT—Fundação para a Ciência e a Tecnologia within project “mKEP—Models and optimization algorithms for multi-country kidney exchange programs” (POCI-01-0145-FEDER-016677), is also financed by COMPETE: POCI-01-0145-FEDER-007043 and FCT within the Project Scope: UID/CEC/00319/2013 and FCT Project SFRH/BPD/101134/2014.info:eu-repo/semantics/publishedVersio