Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Enhanced PCA-based localization using depth maps with missing data

In this paper a new method for self-localization of mobile robots, based on a PCA positioning sensor to operate in unstructured environments, is proposed and experimentally validated. The proposed PCA extension is able to perform the eigenvectors computation from a set of signals corrupted by missing data. The sensor package considered in this work contains a 2D depth sensor pointed upwards to the ceiling, providing depth images with missing data. The positioning sensor obtained is then integrated in a Linear Parameter Varying mobile robot model to obtain a self-localization system, based on linear Kalman filters, with globally stable position error estimates. A study consisting in adding synthetic random corrupted data to the captured depth images revealed that this extended PCA technique is able to reconstruct the signals, with improved accuracy. The self-localization system obtained is assessed in unstructured environments and the methodologies are validated even in the case of varying illumination conditions.

XRCC3 THR241MET polymorphism influence on nuclear buds frequency in exposed to formaldehyde

Formaldehyde (FA), also known as formalin, formal and methyl aldehydes, is a colorless, flammable, strong-smelling gas. It has an important application in embalming tissues and that result in exposures for workers in the pathology anatomy laboratories and mortuaries. Occupational exposure to FA has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. Manifold in vitro studies clearly indicated that FA is genotoxic. FA induced various genotoxic effects in proliferating cultured mammalian cells. The cytokinesis-block micronucleus (CBMN) assay was originally developped as an ideal system form easuring micronucleus (MN), however it can also be used to measure nucleoplasmic bridges (NBP) and nuclear buds (NBUD). Over the past decade another unique mechanism of micronucleus formation, known as nuclear budding has emerged. NBUDS is considered as a marker of gene amplification and/or altered gene dosage because the nuclear budding process is the mechanism by which cells removed amplified and/excess DNA.

Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass Separator accelerator at the European Organization for Nuclear Research

A new circuit topology is proposed to replace the actual pulse transformer and thyratron based resonant modulator that supplies the 60 kV target potential for the ion acceleration of the On-Line Isotope Mass Separator accelerator, the stability of which is critical for the mass resolution downstream separator, at the European Organization for Nuclear Research. The improved modulator uses two solid-state switches working together, each one based on the Marx generator concept, operating as series and parallel switches, reducing the stress on the series stacked semiconductors, and also as auxiliary pulse generator in order to fulfill the target requirements. Preliminary results of a 10 kV prototype, using 1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx circuits, ten stages each, with an electrical equivalent circuit of the target, are presented, demonstrating both the improved voltage stability and pulse flexibility potential wanted for this new modulator.

Genotoxicity biomarkers micronucleus, nucleoplasmic bridges and nuclear buds

The increase of mortality from cancer brought urgency in identification and validation of predictive markers of risk and therefore early diagnosis. There is evidence that cytogenetic biomarkers are positively correlated with risk of cancer, and this is validated by studies of cohort and case-control. Cytokinesis-blocked micronucleus (CBMN) assay is used extensively in molecular epidemiology, and can be considered as a “cytome” assay covering cell proliferation, apoptosis, necrosis and chromosomal changes. The chromosomal alterations most reported and studied by the CBMN are: micronucleus (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUDS). The use of the MN assay in biomonitoring studies had a large increase in the last 15 years and international projects such as the HUMN have helped to increase the applicability and reliability of these tests.

A medicina nuclear no diagnóstico dos tumores gastroenteropancreáticos

Objectivo do estudo - Demonstrar o contributo, essencial, que a Medicina Nuclear apresenta no diagnóstico dos Tumores Gastroenteropancreáticos e demonstrar a importância da precocidade diagnóstica recorrendo, maioritariamente, aos exames de medicina nuclear.

Performance of microstrip antennas in the presence of EBG in an indoor localization system

Indoor localization systems in nowadays is a huge area of interest not only at academic but also at industry and commercial level. The correct location in these systems is strongly influenced by antennas performance which can provide several gains, bandwidths, polarizations and radiation patterns, due to large variety of antennas types and formats. This paper presents the design, manufacture and measurement of a compact microstrip antenna, for a 2.4 GHZ frequency band, enhanced with the use of Electromagnetic Band-Gap (EBG) structures, which improve the electromagnetic behavior of the conventional antennas. The microstrip antenna with an EBG structure integrated allows an improvement of the location system performance in about 25% to 30% relatively to a conventional microstrip antenna.

Viabilidade económica da implementação de um reactor nuclear para a produção de energia eléctrica em Portugal

O presente trabalho tem como objectivo avaliar economicamente e determinar a viabilidade da implementação de um reactor nuclear para produção de energia eléctrica. Faz-se uma abordagem a aspectos da energia nuclear no mundo e em particular a energia nuclear na união europeia, faz-se uma análise sobre a estrutura do sector nuclear em Espanha e o futuro da energia no mundo. É realizada uma análise sobre a energia nuclear em Portugal, são abordados aspectos como o planeamento energético, a localização da central nuclear, os recursos nacionais e internacionais, a inspecção e regulação nuclear e o impacto industrial. Por fim, faz-se uma análise sobre o mix energético português. Faz-se uma descrição do ciclo de combustível, isto é, um estudo a todas as fases pela qual o combustível nuclear passa desde a sua extracção, passando pela produção de energia e processamento dos resíduos. São descritos os principais componentes de uma central nuclear e o seu princípio de funcionamento. São analisados em detalhe os principais componentes de um reactor PWR (Objecto de estudo deste trabalho) e faz-se uma breve descrição de alguns modelos de reactores nucleares. É feita uma breve abordagem aos principais acidentes nucleares que ocorreram, e descrita a escala de ocorrências nucleares e as várias fases de desmantelamento de uma central. São apresentados os principais custos da central nuclear. Também é apresentado um estudo de viabilidade económica analisando três cenários diferentes e é apresentada uma análise de sensibilidade do VAL em função de algumas variáveis que têm grande influência na avaliação económica. São apresentadas as principais conclusões.

Mass spectrometry improvement on an high current ion implanter

The development of accurate mass spectrometry, enabling the identification of all the ions extracted from the ion source in a high current implanter is described. The spectrometry system uses two signals (x-y graphic), one proportional to the magnetic field (x-axes), taken from the high-voltage potential with an optic fiber system, and the other proportional to the beam current intensity (y-axes), taken from a beam-stop. The ion beam mass register in a mass spectrum of all the elements magnetically analyzed with the same radius and defined by a pair of analyzing slits as a function of their beam intensity is presented. The developed system uses a PC to control the displaying of the extracted beam mass spectrum, and also recording of all data acquired for posterior analysis. The operator uses a LabView code that enables the interfacing between an I/O board and the ion implanter. The experimental results from an ion implantation experiment are shown. (C) 2011 Elsevier B.V. All rights reserved.

Otimização do co-registo metabolismo-morfologia em estudos de PET/CT com 18F-DG de nódulos pulmonares: comparação de dois protocolos - 4D vs CT lento

Mestrado em Medicina Nuclear - Área de especialização: Tomografia por Emissão de Positrões.

Detection of FRET signals with a wavelength sensitive device based on a-SiC:H

Glucose sensing is an issue with great interest in medical and biological applications. One possible approach to glucose detection takes advantage of measuring changes in fluorescence resonance energy transfer (FRET) between a fluorescent donor and an acceptor within a protein which undergoes glucose-induced changes in conformation. This demands the detection of fluorescent signals in the visible spectrum. In this paper we analyzed the emission spectrum obtained from fluorescent labels attached to a protein which changes its conformation in the presence of glucose using a commercial spectrofluorometer. Different glucose nanosensors were used to measure the output spectra with fluorescent signals located at the cyan and yellow bands of the spectrum. A new device is presented based on multilayered a-SiC:H heterostructures to detect identical transient visible signals. The transducer consists of a p-i'(a-SiC:H)-n/p-i(a-Si:H)-n heterostructure optimized for the detection of the fluorescence resonance energy transfer between fluorophores with excitation in the violet (400 nm) and emissions in the cyan (470 nm) and yellow (588 nm) range of the spectrum. Results show that the device photocurrent signal measured under reverse bias and using appropriate steady state optical bias, allows the separate detection of the cyan and yellow fluorescence signals. (C) 2013 Elsevier B.V. All rights reserved.

Agentes fitoquímicos como radio-sensibilizadores na terapêutica em medicina nuclear

Mestrado em Medicina Nuclear. Área de especialização: Radiofarmácia.

A similarity measure for music signals

One of the goals in the field of Music Information Retrieval is to obtain a measure of similarity between two musical recordings. Such a measure is at the core of automatic classification, query, and retrieval systems, which have become a necessity due to the ever increasing availability and size of musical databases. This paper proposes a method for calculating a similarity distance between two music signals. The method extracts a set of features from the audio recordings, models the features, and determines the distance between models. While further work is needed, preliminary results show that the proposed method has the potential to be used as a similarity measure for musical signals.

Unveiling the Biometric Potential of Finger-Based ECG Signals

The ECG signal has been shown to contain relevant information for human identification. Even though results validate the potential of these signals, data acquisition methods and apparatus explored so far compromise user acceptability, requiring the acquisition of ECG at the chest. In this paper, we propose a finger-based ECG biometric system, that uses signals collected at the fingers, through a minimally intrusive 1-lead ECG setup recurring to Ag/AgCl electrodes without gel as interface with the skin. The collected signal is significantly more noisy than the ECG acquired at the chest, motivating the application of feature extraction and signal processing techniques to the problem. Time domain ECG signal processing is performed, which comprises the usual steps of filtering, peak detection, heartbeat waveform segmentation, and amplitude normalization, plus an additional step of time normalization. Through a simple minimum distance criterion between the test patterns and the enrollment database, results have revealed this to be a promising technique for biometric applications.

An Evaluation of Local Feature Combiners for Robot Visual Localization

In the last decade, local image features have been widely used in robot visual localization. To assess image similarity, a strategy exploiting these features compares raw descriptors extracted from the current image to those in the models of places. This paper addresses the ensuing step in this process, where a combining function must be used to aggregate results and assign each place a score. Casting the problem in the multiple classifier systems framework, we compare several candidate combiners with respect to their performance in the visual localization task. A deeper insight into the potential of the sum and product combiners is provided by testing two extensions of these algebraic rules: threshold and weighted modifications. In addition, a voting method, previously used in robot visual localization, is assessed. All combiners are tested on a visual localization task, carried out on a public dataset. It is experimentally demonstrated that the sum rule extensions globally achieve the best performance. The voting method, whilst competitive to the algebraic rules in their standard form, is shown to be outperformed by both their modified versions.