Soluções aproximadas para o problema de Localização Simples : algorítmo Simulated Annealing

Mestrado em Métodos Matemáticos para Economia e Gestão de EmpresasO problema de Localização Simples (SPU) consiste na determinação da localização de equipamentos (fábricas, hospitais, bancos, armazéns, etc) de modo a minimizar os custos (maximizar os lucros) de satisfazer procuras previamente conhecidas. Em geral são considerados custos fixos de instalação e custos de transportes entre serviços e destinatários. O Problema de Localização Simples é um problema NP-difícil que embora tenha uma estrutura simples e bastante abrangente no sentido em que, com pequenas modificações, permlte obter a formulação de muitos outros problemas Neste trabalho, começaremos por apresentar alguns dos principais problemas de localização e sua formalização Serão apresentados alguns dos métodos de resolução do Problema de Localização Simples que têm sido propostos na literatura . Uma atenção especial será dedicada a um método exacto, proposto por Bilde - Krarup e Erlenkotter, que até hoje tem vindo a ser considerado o melhor método de resolução. Por fim será feita uma apresentação do método “Simulated Annealing" para a resolução de problemas de optimização combinatória e das implementações que dele realizámos para a resolução aproximada do SPL. Serão apresentados resultados computacionais comparativos, para um conjunto de problemas retirados da literatura, relativos a diversas alternativas quanto à escolha da solução inicial e dos valores a atribuir aos parâmetros do método.info:eu-repo/semantics/publishedVersio

Gemcitabine-Induced Bullous Acral Erythema

O eritema acral da quimioterapia é caracterizado por áreas eritematosas e dolorosas, envolvendo predominantemente as mãos e pés, com formação de bolhas em casos severos. A gemcitabina é responsável frequentemente por reacções adversas cutâneas, embora estas sejam habitualmente transitórias e ligeiras. Relatamos o caso de um doente sob quimioterapia paliativa com gemcitabina por adenocarcinoma ductal pancreático, que desenvolveu lesões bolhosas em ambos os pés, de maiores dimensões à esquerda. A histopatologia foi consistente com eritema acral. A variante bolhosa do eritema acral da quimioterapia é uma reacção rara e, embora descrita para agentes citotóxicos estruturalmente semelhantes, não tem sido associada à gemcitabina. No doente apresentado, os antecedentes pessoais de doença arterial periférica podem ter desempenhado um papel importante na apresentação clínica final.Chemotherapy-induced acral erythema is characterized by areas of painful erythema affecting predominantly hands and feet, and in severe cases bullous lesions may develop. Gemcitabine is frequently responsible for cutaneous side effects, but these are usually mild and transient. We report a patient under palliative chemotherapy for pancreatic ductal adenocarcinoma with gemcitabine, who presented large bullous lesions on both feet, but of larger size on the left. Histopathology was consistent with acral erythema. The bullous variant of chemotherapy-induced acral eythema is a rare reaction, and although described for structurally similar cytotoxic agents, it has not been reported in association with gemcitabine. In our case, the patient’s medical history of significant peripheral arterial disease may have also played an important role in the overall clinical presentation

Vacinação contra a COVID-19- A imagem que viajou pelo mundo:o poder das redes sociais

info:eu-repo/semantics/draf

Theoretical modelling of epigenetically modified DNA sequences

We report herein a set of calculations designed to examine the effects of epigenetic modifications on the structure of DNA. The incorporation of methyl, hydroxymethyl, formyl and carboxy substituents at the 5-position of cytosine is shown to hardly affect the geometry of CG base pairs, but to result in rather larger changes to hydrogen-bond and stacking binding energies, as predicted by dispersion-corrected density functional theory (DFT) methods. The same modifications within double-stranded GCG and ACA trimers exhibit rather larger structural effects, when including the sugar-phosphate backbone as well as sodium counterions and implicit aqueous solvation. In particular, changes are observed in the buckle and propeller angles within base pairs and the slide and roll values of base pair steps, but these leave the overall helical shape of DNA essentially intact. The structures so obtained are useful as a benchmark of faster methods, including molecular mechanics (MM) and hybrid quantum mechanics/molecular mechanics (QM/MM) methods. We show that previously developed MM parameters satisfactorily reproduce the trimer structures, as do QM/MM calculations which treat bases with dispersion-corrected DFT and the sugar-phosphate backbone with AMBER. The latter are improved by inclusion of all six bases in the QM region, since a truncated model including only the central CG base pair in the QM region is considerably further from the DFT structure. This QM/MM method is then applied to a set of double-stranded DNA heptamers derived from a recent X-ray crystallographic study, whose size puts a DFT study beyond our current computational resources. These data show that still larger structural changes are observed than in base pairs or trimers, leading us to conclude that it is important to model epigenetic modifications within realistic molecular contexts

NON-HERLITZ JUNCTIONAL EPIDERMOLYSIS BULLOSA - THE IMPORTANCE OF PRENATAL DIAGNOSIS

A epidermólise bolhosa juncional é uma genodermatose caracterizada por fragilidade cutânea e formação de erosões e bolhas a nível da junção dermo-epidérmica, após trauma minor. Reportamos o caso clínico de um recém-nascido, sexo masculino, caucasiano, com erupção cutânea caracterizada por bolhas tensas e erosões nas mãos, abdómen e couro cabeludo. Realizou-se uma biopsia cutânea para imunoflurescência directa com painel de anticorpos, que foi compatível com o diagnóstico de epidermólise bolhosa juncional não-Herlitz. No estudo genético identificou-se 2 mutações no gene COL17A1. Destaca-se nos antecedentes familiares, um irmão com dermatose bolhosa, falecido na terceira semana de vida por intercorrência infeciosa, sem ter sido possível efectuar o diagnóstico definitivo que possibilitasse o diagnóstico pré-natal. Salientamos a importância da referenciação rápida destes doentes a centros especializados, de forma a possibilitar o diagnóstico precoce desta patologia, uma orientação clínica adequada e um correto aconselhamento genético, incluindo o diagnóstico pré-natal em futuras gravidezes.Junctional epidermolysis bullosa is a group of inherited blistering diseases characterized by increased skin fragility, blisters and erosions after minor trauma, due to tissue cleavage at the dermal-epidermal junction. We report the case of a male Caucasian infant, born with erosions and tense blisters on the hands, abdomen and scalp. Immunoflurescence antigen mapping revealed paucity of collagen XVII immunolabelling, compatible with the diagnosis of non-Herlitz junctional epidermolysis bullosa. Molecular analysis of the COL17A1 gene revealed compound heterozygosity for two frameshift mutations. Family history was positive for a brother with a bullous dermatosis, who died from sepsis on the 3rd week of life without a definitive diagnosis that could enable precise risk estimation and prenatal diagnosis. We emphasize the importance of rapid referral to specialized centers, to provide early accurate diagnosis, adequate clinical management and prenatal diagnosis in subsequent pregnancies

Multiprofessional care of patients with diabetes mellitus at the endocrinology outpatient clinic of the university hospital of the Ribeirão Preto school of medicine (HCFMRP-USP)

The present study describes the flow of care delivery and activities with patients carriers of diabetes mellitus by a health multiprofessional team from the Endocrinology Outpatient Clinic of the University Hospital of the Ribeirão Preto School of Medicine. This program, according to the proposal of the America’s Declaration about Diabetes, aims at assuring to diabetes carriers conditions to acquire knowledge and skills regarding self-care.O presente estudo descreve o fluxo de atendimento e as atividades desenvolvidas pela equipe multiprofissional de saúde do Ambulatório de Endocrinologia e Metabologia do HCFMRPUSP, junto aos pacientes com diabetes mellitus. Este programa, em consonância aos propósitos da Declaração das Américas sobre Diabetes, visa assegurar que os pacientes com diabetes estejam em condições de adquirir conhecimentos e aptidões para o autocuidado

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Characterization of Platelet-Derived Growth Factor-A Expression in Mouse Tissues Using a lacZ Knock-In Approach

Expression of the platelet-derived growth factor A-chain gene (Pdgfa) occurs widely in the developing mouse, where it is mainly localized to various epithelial and neuronal structures. Until now, in situ mRNA hybridization (ISH) has been the only reliable method to identify Pdgfa expression in tissue sections or whole mount preparations. Validated protocols for in situ detection of PDGF-A protein by immunohistochemistry is lacking. In particular, this has hampered understanding of Pdgfa expression pattern in adult tissues, where ISH is technically challenging. Here, we report a gene targeted mouse Pdgfa allele, Pdgfa(ex4COIN), which is a combined conditional knockout and reporter allele. Cre-mediated inversion of the COIN cassette inactivates Pdgfa coding while simultaneously activating a beta-galactosidase (lacZ) reporter under endogenous Pdgfa transcription control. The generated Pdgfa(ex4COIN-INV-lacZ) allele can next be used to identify cells carrying a Pdgfa null allele, as well as to map endogenous Pdgfa expression. We evaluated the Pdgfa(ex4COIN-INV-lacZ) allele as a reporter for endogenous Pdgfa expression patterns in mouse embryos and adults. We conclude that the expression pattern of Pdgfa(ex4COIN-INV-lacZ) recapitulates known expression patterns of Pdgfa. We also report on novel embryonic and adult Pdgfa expression patterns in the mouse and discuss their implications for Pdgfa physiology