One-Pot Aqueous Synthesis of Fluorescent Ag-In-Zn-S Quantum Dot/Polymer Bioconjugates for Multiplex Optical Bioimaging of Glioblastoma Cells

Cancer research has experienced astonishing advances recently, but cancer remains a major threat because it is one of the leading causes of death worldwide. Glioblastoma (GBM) is the most malignant brain tumor, where the early diagnosis is vital for longer survival. Thus, this study reports the synthesis of novel water-dispersible ternary AgInS2 (AIS) and quaternary AgInS2-ZnS (ZAIS) fluorescent quantum dots using carboxymethylcellulose (CMC) as ligand for multiplexed bioimaging of malignant glioma cells (U-87 MG). Firstly, AgInS2 core was prepared using a one-pot aqueous synthesis stabilized by CMC at room temperature and physiological pH. Then, an outer layer of ZnS was grown and thermally annealed to improve their optical properties and split the emission range, leading to core-shell alloyed nanostructures. Their physicochemical and optical properties were characterized, demonstrating that luminescent monodispersed AIS and ZAIS QDs were produced with average sizes of 2.2 nm and 4.3 nm, respectively. Moreover, the results evidenced that they were cytocompatible using in vitro cell viability assays towards human embryonic kidney cell line (HEK 293T) and U-87 MG cells. These AIS and ZAIS successfully behaved as fluorescent nanoprobes (red and green, resp.) allowing multiplexed bioimaging and biolabeling of costained glioma cells using confocal microscopy

Pattern matching through Chaos Game Representation: bridging numerical and discrete data structures for biological sequence analysis

This work was partially supported by FCT through the PIDDAC Program funds (INESC-ID multiannual funding) and under grant PEst-OE/EEI/LA0008/2011 (IT multiannual funding). In addition, it was also partially funded by projects HIVCONTROL (PTDC/EEA-CRO/100128/2008, S. Vinga, PI), TAGS (PTDC/EIA-EIA/112283/2009) and NEUROCLINOMICS (PTDC/EIA-EIA/111239/2009) from FCT (Portugal).Background: Chaos Game Representation (CGR) is an iterated function that bijectively maps discrete sequences into a continuous domain. As a result, discrete sequences can be object of statistical and topological analyses otherwise reserved to numerical systems. Characteristically, CGR coordinates of substrings sharing an L-long suffix will be located within 2(-L) distance of each other. In the two decades since its original proposal, CGR has been generalized beyond its original focus on genomic sequences and has been successfully applied to a wide range of problems in bioinformatics. This report explores the possibility that it can be further extended to approach algorithms that rely on discrete, graph-based representations. Results: The exploratory analysis described here consisted of selecting foundational string problems and refactoring them using CGR-based algorithms. We found that CGR can take the role of suffix trees and emulate sophisticated string algorithms, efficiently solving exact and approximate string matching problems such as finding all palindromes and tandem repeats, and matching with mismatches. The common feature of these problems is that they use longest common extension (LCE) queries as subtasks of their procedures, which we show to have a constant time solution with CGR. Additionally, we show that CGR can be used as a rolling hash function within the Rabin-Karp algorithm. Conclusions: The analysis of biological sequences relies on algorithmic foundations facing mounting challenges, both logistic (performance) and analytical (lack of unifying mathematical framework). CGR is found to provide the latter and to promise the former: graph-based data structures for sequence analysis operations are entailed by numerical-based data structures produced by CGR maps, providing a unifying analytical framework for a diversity of pattern matching problems.publishersversionpublishe

Pattern matching through Chaos Game Representation: bridging numerical and discrete data structures for biological sequence analysis

BACKGROUND: Chaos Game Representation (CGR) is an iterated function that bijectively maps discrete sequences into a continuous domain. As a result, discrete sequences can be object of statistical and topological analyses otherwise reserved to numerical systems. Characteristically, CGR coordinates of substrings sharing an L-long suffix will be located within 2(-L )distance of each other. In the two decades since its original proposal, CGR has been generalized beyond its original focus on genomic sequences and has been successfully applied to a wide range of problems in bioinformatics. This report explores the possibility that it can be further extended to approach algorithms that rely on discrete, graph-based representations. RESULTS: The exploratory analysis described here consisted of selecting foundational string problems and refactoring them using CGR-based algorithms. We found that CGR can take the role of suffix trees and emulate sophisticated string algorithms, efficiently solving exact and approximate string matching problems such as finding all palindromes and tandem repeats, and matching with mismatches. The common feature of these problems is that they use longest common extension (LCE) queries as subtasks of their procedures, which we show to have a constant time solution with CGR. Additionally, we show that CGR can be used as a rolling hash function within the Rabin-Karp algorithm. CONCLUSIONS: The analysis of biological sequences relies on algorithmic foundations facing mounting challenges, both logistic (performance) and analytical (lack of unifying mathematical framework). CGR is found to provide the latter and to promise the former: graph-based data structures for sequence analysis operations are entailed by numerical-based data structures produced by CGR maps, providing a unifying analytical framework for a diversity of pattern matching problems

Amanita phalloides poisoning: Mechanisms of toxicity and treatment

Amanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially α-amanitin, are the main responsible for the toxic effects in humans. It is recognized that α-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms.This work was supported by the Fundação para a Ciência e Tecnologia (FCT ) – project PTDC/DTPFTO/4973/2014 – and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013. Juliana Garcia and Vera Marisa Costa thank FCT for their PhD grant (SFRH/BD/74979/2010) and Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015), respectively.info:eu-repo/semantics/publishedVersio

Oxygen defects in phosphorene

Physical Review Letters114404680

Corrosion and tribocorrosion behaviour of Ti6Al4V produced by selective laser melting and hot pressing in comparison with the commercial alloy

The corrosion and tribocorrosion behaviour of SLM-produced Ti6Al4V alloy was studied in comparison with its HP and commercial counterparts in 9 g/L NaClsolution at body temperature. Results showed that SLM processing route influenced the electrochemical response of the SLM-produced alloy by leading to a relatively lower quality for the passive film due to decreased beta phase and the formation of alpha' phase. However, after tribocorrosion, neither the total volume loss nor the volume loss under the influence of mechanical wear and wear accelerated corrosion showed any statistically significant difference between the processing routes.This study was supported by FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 - Program Operacional Competitividade e Internacionalizacao (POCI) with the reference project POCI-01-0145-FEDER-006941, together with projects NORTE-01-0145-FEDER-000018-HAMaBICo and PTDC/EMS-TEC/5422/2014. The authors would also like to acknowledge Prof. Grata Minas for the provision of the profilometry

Supply network science: Emergence of a new perspective on a classical field.

Supply networks emerge as companies procure goods from one another to produce their own products. Due to a chronic lack of data, studies on these emergent structures have long focussed on local neighbourhoods, assuming simple, chain-like structures. However, studies conducted since 2001 have shown that supply chains are indeed complex networks that exhibit similar organisational patterns to other network types. In this paper, we present a critical review of theoretical and model based studies which conceptualise supply chains from a network science perspective, showing that empirical data do not always support theoretical models that were developed, and argue that different industrial settings may present different characteristics. Consequently, a need that arises is the development and reconciliation of interpretation across different supply network layers such as contractual relations, material flow, financial links, and co-patenting, as these different projections tend to remain in disciplinary siloes. Other gaps include a lack of null models that show whether the observed properties are meaningful, a lack of dynamical models that can inform how layers evolve and adopt to changes, and a lack of studies that investigate how local decisions enable emergent outcomes. We conclude by asking the network science community to help bridge these gaps by engaging with this important area of research

Bacteriophage-receptor binding proteins for multiplex detection of Staphylococcus and Enterococcus in blood

Health care-associated infections (HCAIs) affect hundreds of millions of patients, representing a significant burden for public health. They are usually associated to multidrug resistant bacteria, which increases their incidence and severity. Bloodstream infections (BSIs) are among the most frequent and life-threatening HCAIs, with Enterococcus and Staphylococcus among the most common isolated pathogens. The correct and fast identification of the etiological agents is crucial for clinical decision-making, allowing to rapidly select the appropriate antimicrobial and to prevent from overuse and misuse of antibiotics and the consequent increase in antimicrobial resistance. Conventional culture methods are still the gold standard to identify these pathogens, however are time-consuming and may lead to erroneous diagnosis, which compromises an efficient treatment. (Bacterio)phage receptor binding proteins (RBPs) are the structures responsible for the high specificity conferred to phages against bacteria and thus are very attractive biorecognition elements with high potential for specific detection and identification of pathogens. Taking into account all these facts, we have designed and developed a new, fast, accurate, reliable and unskilled diagnostic method based on newly identified phage RBPs and spectrofluorometric techniques that allows the multiplex detection of Enterococcus and Staphylococcus in blood samples in less than 1.5 hours after an enrichment step.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the project “Phages‐on‐chip” PTDC/BTM‐SAL/32442/2017 (POCI‐01‐0145‐FEDER‐032442) and the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE‐01‐0145‐FEDER‐000004) funded by the European Regional Development Fund under the scope of Norte2020 − Programa Operacional Regional do Norte. Catarina Nogueira, Ana Brandão and Susana Costa were supported by the FCT grants PD/BD/143037/2018, SFRH/BD/133193/2017 and SFRH/BD/130098/2017, respectively. We would also like to acknowledge Professor Hermínia de Lencastre, Doctor Carina Almeida and Doctor Nuno Cerca for gently providing some of the strains used in this study. We acknowledge Professor Paulo Freitas for providing some of the infrastructures to perform the experiments.info:eu-repo/semantics/publishedVersio

Identification of Eschweilenol C in derivative of Terminalia fagifolia Mart. and green synthesis of bioactive and biocompatible silver nanoparticles

A green synthetic route was developed to prepare silver nanoparticles (AgNPs) in aqueous solution for biological applications. Eschweilenol C, a compound derivative ellagic acid was identified as the main constituent of the aqueous fraction of the ethanolic extract of Terminalia fagifolia Mart. by NMR analysis. In the green synthesis, the ethanolic extract of T. fagifolia and its aqueous fraction were used to promote silver reduction and nanoparticle stabilization. The synthesized AgNPs presented a spherical or polygonal morphology shape by TEM analysis and AgNPs showed high levels of antioxidant and considerable antibacterial and antifungal activities. Synthesized nanoparticles presented significant antioxidant activity by sequestration of DPPH and ABTS radicals, in addition to iron reduction (FRAP assay) and measurement of antioxidant capacity in ORAC units, in addition, AgNP synthesized with the aqueous fraction also demonstrated antioxidant potential in microglial cells. Gram-positive and Gram-negative bacteria were susceptible to growth inhibition by the nanoparticles, among which the AgNPs formed by the ethanolic extract was the most effective. The data obtained by AFM images suggested that AgNPs could lead to the lysis of bacteria and subsequent death. The antifungal assays showed high efficiency against yeasts and dermatophytes. This work represents the first description of antifungal activity by AgNPs against Fonsecaea pedrosoi, the etiologic agent of chromoblastomycosis. In relation to biocompatibility, the AgNPs induced lower haemolysis than AgNO3.We thank Herbert Kogler and Reinhard Wimmer for the identification of Eschweilenol C. The NMR laboratory at Aalborg University is supported by the Obel Family, SparNord and Carlsberg foundations.The authors are grateful to Carla Eiras (LIMAV/CT/UFPI) and to FCT and EU for financial support through project UID/QUI/50006/2013– POCI-01-0145-FEDER-007265 from COMPETE and projectNORTE-01-0145-FEDER-000011 from COMPETE. Thanks to Andreia Pinto for help with the TEM measurements at Instituto de Medicina Molecular (IMM). This work was supported by the Histology and Comparative Pathology Laboratory of the IMMinfo:eu-repo/semantics/publishedVersio

Atuação da comissão de farmácia e terapêutica em um hospital de ensino

The hospital activities are characterized by a highly dynamism as a result of new health technologies such as medicines. A hospital due its characteristics of teaching, research and high complexity care, has the highest concentration of different types of health technologies. The Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto – USP (HCFMRP-USP) is a hospital, with proven quality, inserted in the SUS as a tertiary/quaternary referral and has the Pharmaceutical Services Division (DAF) for development of actions of health care. To aid resource management, selection and standardizationof drugs, DAF adopted the strategy of Pharmacy and Therapeutics Committee (CFT). The CFT is a collegial, consultative and deliberative body, established by the World Health Organization as a strategy tool to monitor and promote the quality in the use of medicine, but studies of CFTs are incipient in Brazil. Thus, this study aims to present the CFT of HCFMRP–USP. Objectives: To introduce the composition, responsibilities and working methods of CFT, as well as a critical analysis of its current operation. Methods: A descriptive study aimed to describe the current functioning of the CFT of HCFMRP-USP was performed. Ordinances, internal regulations were surveyed and a bibliographic review of the CFT was performed. To the critical analysis of the current operating, was selected by the committee from the standard one that would fit classification as belonging to “A” and “V” items after the crossing of the curves ABC and VEN, whose selected item was the medicine Sevoflurane. Results: The CFT was established in 2010 to replace the defunct standardization committee. Since then, the CFT examined 134 requests and 41 of these were standardized. The Sevoflurane drug was incorporated into the HCFMRP-USP in 2010 and, starting that year, there was a gradual increase in the consumption of the same. However, after analyzing the requirements of the drug in 2012, it was observed that the dispensation of Sevoflurane does not follow the specifications of the patient profile as established in the protocol established at the time of standardization. Conclusions: We concluded that the implementation of CFT was a strategy that provided a rational standardization. However, it is observed that there is no control of dispensing and use of the product according to the protocol established at the time of standardization. We emphasize that control the use of Sevoflurane is not responsibility of the CFT and this assignment should be delegated to the responsible technical area.As atividades hospitalares caracterizam-se por um acentuado dinamismo em consequência do surgimento de novas tecnologias em saúde, tais como medicamentos. Uma unidade hospitalar, devido suas características de ensino, pesquisa e atendimentos de alta complexidade, possui maior concentração de diferentes tipos de tecnologias em saúde. O Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto –USP (HCFMRP-USP) é uma instituição hospitalar, de qualidade comprovada, inserido no SUS como referência terciária/quaternária e que conta com a Divisão de Assistência Farmacêutica (DAF) para desenvolvimento das ações de atenção a saúde. A DAF para auxílio da gestão de recursos, seleção e padronização de medicamentos adotou como estratégia a Comissão de Farmácia e Terapêutica (CFT). A CFT é uma instância colegiada, de caráter consultivo e deliberativo, estabelecida pela Organização Mundial de Saúde como ferramenta de estratégia para monitorar e promover a qualidade no uso do medicamento, porém estudos que sobre a atuação das CFTs no Brasil são incipientes. Desta forma, este estudo pretende apresentar a CFT do HCFMRP-USP. Objetivos: apresentar a composição, atribuições e metodologia de trabalho da CFT, bem como desenvolver uma análise crítica de seu atual funcionamento. Metodologia: Foi realizado estudo descritivo e exploratório com o objetivo de descrever o atual funcionamento da CFT do HCFMRP-USP. Foram buscadas portarias, regulamentações internas e foi realizada revisão bibliográfica sobre a CFT. Para Análise crítica do atual funcionamento, foi selecionado dentre os itens padronizados pela comissão aquele que se enquadrasse como pertencente a classificação A e V, após o cruzamento das curvas ABC e VEN, cujo item selecionado foi o medicamento Sevoflurano. Resultados: A CFT foi instituída no ano de 2010 em substituição a extinta comissão de padronização. Desde então, a CFT analisou 134 solicitações e destas 41 foram padronizadas. O medicamento sevoflurano foi incorporado no HCFMRP-USP em 2010 e, a partir deste ano, observa-se um aumento gradativo do consumo do mesmo. Entretanto, após análise das prescrições do referido medicamento no ano de 2012, foi observado que a dispensação do sevoflurano não segue as especificações do perfil de pacientes conforme estabelecido no protocolo instituído no momento da padronização. Conclusões: Portanto, concluímos que a implantação da CFT foi uma estratégia que proporcionou a padronização racional. Entretanto, observa-se que não há controle da dispensação e utilização do medicamento de acordo com o protocolo estabelecido no momento da padronização. Salientamos que o controle do uso do Sevoflurano não é atribuição da CFT devendo esta atribuição ser delegada à área técnica responsável