In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography

Background and aims: Positron emission tomography (PET) using 18F labelled 2-fluoro-2-deoxy-D-glucose (18FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine (18FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of 18FLT and 18FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). Patients and methods: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54–87), were evaluated. Patients underwent 18FDG and 18FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). Results: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both 18FLT and 18FDG. Three of the five resected liver metastases were also avid for 18FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of 18FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with 18FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with 18FDG avid lesions (r =0.4). Conclusions: 18FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy

Aging alters the production of iNOS, arginase and cytokines in murine macrophages

The limited amount of information on the primary age-related deficiencies in the innate immune system led us to study the production of inducible nitric oxide synthase (iNOS), arginase, and cytokines in macrophages of young (8 weeks old) and old (72 weeks old) female BALB/c mice. We first evaluated iNOS and arginase inducers on peritoneal (PM&#934;) and bone marrow-derived (BMM&#934;) macrophages of young BALB/c and C57BL/6 mice, and then investigated their effects on macrophages of old mice. Upon stimulation with lipopolysaccharide (LPS), resident and thioglycolate-elicited PM&#934; from young mice presented higher iNOS activity than those from old mice (54.4%). However, LPS-stimulated BMM&#934; from old mice showed the highest NO levels (50.1%). Identical NO levels were produced by PM&#934; and BMM&#934; of both young and old mice stimulated with interferon-&#947;. Arginase activity was higher in resident and elicited PM&#934; of young mice stimulated with LPS (48.8 and 32.7%, respectively) and in resident PM&#934; stimulated with interleukin (IL)-4 (64%). BMM&#934; of old mice, however, showed higher arginase activity after treatment with IL-4 (46.5%). In response to LPS, PM&#934; from old mice showed the highest levels of IL-1&#945; (772.3 ± 51.9 pg/mL), whereas, those from young mice produced the highest amounts of tumor necrosis factor (TNF)-&#945; (937.2 ± 132.1 pg/mL). Only TNF-&#945; was expressed in LPS-treated BMM&#934;, and cells from old mice showed the highest levels of this cytokine (994.1 ± 49.42 pg/mL). Overall, these results suggest that macrophages from young and old mice respond differently to inflammatory stimuli, depending on the source and maturity of the cell donors.67168

Sub-terahertz, microwaves and high energy emissions during the December 6, 2006 flare, at 18:40 UT

The presence of a solar burst spectral component with flux density increasing with frequency in the sub-terahertz range, spectrally separated from the well-known microwave spectral component, bring new possibilities to explore the flaring physical processes, both observational and theoretical. The solar event of 6 December 2006, starting at about 18:30 UT, exhibited a particularly well-defined double spectral structure, with the sub-THz spectral component detected at 212 and 405 GHz by SST and microwaves (1-18 GHz) observed by the Owens Valley Solar Array (OVSA). Emissions obtained by instruments in satellites are discussed with emphasis to ultra-violet (UV) obtained by the Transition Region And Coronal Explorer (TRACE), soft X-rays from the Geostationary Operational Environmental Satellites (GOES) and X- and gamma-rays from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI). The sub-THz impulsive component had its closer temporal counterpart only in the higher energy X- and gamma-rays ranges. The spatial positions of the centers of emission at 212 GHz for the first flux enhancement were clearly displaced by more than one arc-minute from positions at the following phases. The observed sub-THz fluxes and burst source plasma parameters were found difficult to be reconciled to a purely thermal emission component. We discuss possible mechanisms to explain the double spectral components at microwaves and in the THz ranges.Comment: Accepted version for publication in Solar Physic

On the statistical significance of the conductance quantization

Recent experiments on atomic-scale metallic contacts have shown that the quantization of the conductance appears clearly only after the average of the experimental results. Motivated by these results we have analyzed a simplified model system in which a narrow neck is randomly coupled to wide ideal leads, both in absence and presence of time reversal invariance. Based on Random Matrix Theory we study analytically the probability distribution for the conductance of such system. As the width of the leads increases the distribution for the conductance becomes sharply peaked close to an integer multiple of the quantum of conductance. Our results suggest a possible statistical origin of conductance quantization in atomic-scale metallic contacts.Comment: 4 pages, Tex and 3 figures. To be published in PR

Genetically engineered silk-based composite biomaterials functionalized with fibronectin type-II that promote cell adhesion

[Excerpt] Recombinant protein-based polymers (rPBPs) are an emerging class of biopolymers inspired by Nature and produced by synthetic protein biotechnology approaches. Due to their exceptional physical-chemical and biological characteristics, as well as their ability to be customized for specific applications, rPBPs have been explored for the development of advanced biomaterials [1]. Within rPBPs, silk-like polymers (SLP) are being utilized in a range of studies in materials science [2]. [...]This work was supported by FCT Funded Project “Chimera” (PTDC/EBB-EBI/109093/2008), by FCT/MEC through Portuguese funds (PIDDAC) – PEst-OE/BIA/UI4050/2014, by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). TC is thankful to the FCT for its support through Investigador FCT 2015. ARibeiro thanks FCT for the SFRH/BPD/98388/2013 grant. RMachado and AdaCosta acknowledge FCT for SFRH-BPD/86470/2012 and SFRH/BD/75882/2011 grants, respectively

Estimation of furrow irrigation sediment loss using an artificial neural network

The area irrigated by furrow irrigation in the U.S. has been steadily decreasing but still represents about 20% of the total irrigated area in the U.S. Furrow irrigation sediment loss is a major water quality issue and a method for estimating sediment loss is needed to quantify the environmental impacts and estimate effectiveness and economic value of conservation practices. Artificial neural network (NN) modeling was applied to furrow irrigation to predict sediment loss as a function of hydraulic and soil conditions. A data set consisting of 1926 furrow evaluations spanning three continents and a wide range of hydraulic and soil conditions was used to train and test a multilayer perceptron feed forward NN model. The final NN model consisted of 16 inputs, 19 hidden nodes in a single hidden layer and 1 output node. Prediction performance of the NN model was model efficiency (ME) = 0.66 for the training data set and ME = 0.80 for the testing data set. The prediction performance for the complete data set of 1926 furrow evaluations was ME= 0.70 with an absolute sediment loss prediction error of less than ±5, ±10, ±20, and ±30 kg per furrow for 35%, 53%, 72% and 85% of the data set values, respectively. The NN model is applicable to predicting sediment loss rates between 1 and 300 kg per furrow for furrow lengths between 30 m and 400 m, slopes between 0.1% and 4%, flow rates between 5 L/min-1 and 75 L/min-1, and silt or sand particle sized fractions between 0.1 and 0.75

A IMPORTÂNCIA DA INFORMAÇÃO FINANCEIRA NAS EMPRESAS PORTUGUESAS: O JUSTO VALOR DO ATIVO FIXO TANGÍVEL

RESUMO Motivação: A União Europeia preconizou, através do Regulamento 1606/2002, a obrigatoriedade da adoção das normas do IASB nas contas consolidadas de todas as empresas cotadas em bolsas europeias, a partir de 1 de Janeiro de 2005. A transição para as IAS/IFRS em 2005 na Europa proporciona uma oportunidade única para estudar forças e fatores explicativos das práticas contabilísticas, particularmente na adoção do justo valor. O modo de mensuração tradicionalmente adotado pelas empresas europeias, no relato financeiro, é o custo histórico, enquanto as normas do IASB apresentam-se mais próximas do critério do justo valor. Objetivo do estudo: O presente estudo investiga a importância da informação financeira para investidor, nomeadamente o justo valor nas empresas portuguesas cotadas em bolsa de valores, no que concerne aos ativos fixos tangíveis. Assumindo que as escolhas contabilísticas são influenciadas por um conjunto de variáveis e que as empresas ponderam e reconhecem a importância da informação financeira, procurou-se neste estudo identificar se a informação sobre o valor do ativo fixo tangível, endividamento, o resultado líquido e o ganho de revalorização está incorporado no preço das ações. Metodologia: O presente estudo empírico baseia-se em empresas cotadas portuguesas, incluídas na Bolsa de Valores de Lisboa, tendo sido analisado o período de 1995 a 2014. Para o efeito, utilizamos a base de dados Thomson Worldscope Database. Para identificar se a informação financeira está incorporada no preço das ações, utilizamos o modelo de avaliação de Ohlson (1995). Resultados / Contribuições: No geral, os resultados obtidos vão de encontro às nossas expectativas. Eles indicam que, tanto antes da adoção das IFRS, como após a adoção das IFRS, a informação representada no valor das ações pelas empresas, é influenciada, de modo significativo, pelo valor dos ativos, o nível de endividamento e o resultado líquido. Palavras-chave: Ativo Fixo Tangível, Justo Valor, IFRS, Portuga

UPLC-MS-ESI-QTOF analysis and antifungal activity of the spondias tuberosa arruda leaf and root hydroalcoholic extracts

The aim of this study was to identify and evaluate the chemical compositions and effects of the S. tuberosa leaf and root hydroalcoholic extracts (HELST and HERST) against different strains of Candida. Chemical analysis was performed by Ultra-Performance Liquid Chromatography Coupled to Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF). The Inhibitory Concentration of 50% of the growth (IC50) as well as the intrinsic and combined action of the extracts with the antifungal fluconazole (FCZ) were determined by the microdilution method while the minimum fungicidal concentrations (MFCs) and the effect on fungal morphological transitions were analyzed by subculture and in humid chambers, respectively. From the preliminary phytochemical analysis, the phenols and flavonoids were the most abundant. The intrinsic IC50 values for HELST ranged from 5716.3 to 7805.8 \ub5g/mL and from 6175.4 to 51070.9 \ub5g/mL for the HERST, whereas the combination of the extracts with fluconazole presented IC50 values from 2.65 to 278.41 \ub5g/mL. The MFC of the extracts, individually, for all the tested strains was 6516384 \ub5g/mL. When fluconazole was combined with each extract, the MFC against CA URM 5974 was reduced (HELST: 2048 and HERST: 4096 \ub5g/mL). Synergism was observed against standard C. albicans (CA) and C. tropicalis (CT) strains and with the root extract against the CT isolate. The leaf extract inhibited the morphological transition of all strains while the root extract inhibited only CT strains

Cellular and biochemical response of the human lung after intrapulmonary instillation of ferric oxide particles

Bronchoalveolar lavage (BAL) was used to sample lung cells and biochemical components in the lung air spaces at various times from 1 to 91 d after intrapulmonary instillation of 2.6 μm-diameter iron oxide particles in human subjects. The instillation of particles induced transient acute inflammation during the first day post instillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages as well as increased amounts of protein, lactate dehydrogenase, and interleukin-8 in BAL fluids. This response was subclinical and was resolved within 4 d PI. A similar dose-dependent response was seen in rats 1 d after intratracheal instillation of the same particles. The particles contained small amounts of soluble iron (240 ng/mg) and possessed the capacity to catalyze oxidant generation in vitro. Our findings indicate that the acute inflammation after particle exposure may, at least partially, be the result of oxidant generation catalyzed by the presence of residual amounts of ferric ion, ferric hydroxides, or oxyhydroxides associated with the particles. These findings may have relevance to the acute health effects associated with increased levels of ambient particulate air pollutants

Transfer learning for galaxy morphology from one survey to another

© 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society.Deep Learning (DL) algorithms for morphological classification of galaxies have proven very successful, mimicking (or even improving) visual classifications. However, these algorithms rely on large training samples of labelled galaxies (typically thousands of them). A key question for using DL classifications in future Big Data surveys is how much of the knowledge acquired from an existing survey can be exported to a new dataset, i.e. if the features learned by the machines are meaningful for different data. We test the performance of DL models, trained with Sloan Digital Sky Survey (SDSS) data, on Dark Energy survey (DES) using images for a sample of $\sim$5000 galaxies with a similar redshift distribution to SDSS. Applying the models directly to DES data provides a reasonable global accuracy ($\sim$ 90%), but small completeness and purity values. A fast domain adaptation step, consisting in a further training with a small DES sample of galaxies ($\sim$500-300), is enough for obtaining an accuracy > 95% and a significant improvement in the completeness and purity values. This demonstrates that, once trained with a particular dataset, machines can quickly adapt to new instrument characteristics (e.g., PSF, seeing, depth), reducing by almost one order of magnitude the necessary training sample for morphological classification. Redshift evolution effects or significant depth differences are not taken into account in this study.Peer reviewedFinal Accepted Versio