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.

Image quality of myocardial perfusion-gated studies: effect of ingestion of different fat content in the reduction of extra-myocardial abdominal signal

Myocardial perfusion-gated-SPECT (MP-gated-SPECT) imaging often shows radiotracer uptake in abdominal organs. This accumulation interferes frequently with qualitative and quantitative assessment of the infero-septal region of myocardium. The objective of this study is to evaluate the effect of ingestion of different fat content on the reduction of extra-myocardial uptake and to improve MP-gated-SPECT image quality. In this study, 150 patients (65 ^ 18 years) who were referred for MP-gated-SPECT underwent a 1-day-protocol including imaging after stress (physical or pharmacological) and resting conditions. All patients gave written informed consent. Patients were subdivided into five groups: GI, GII, GIII, GIV and GV. In the first four groups, patients ate two chocolate bars with different fat content. Patients in GV – control group (CG) – had just water. Uptake indices (UI) of myocardium (M)/liver(L) and M/stomach–proximal bowel(S) revealed lower UI of M/S at rest in all groups. Both stress and rest studies using different food intake indicate that patients who ate chocolate with different fat content showed better UI of M/L than the CG. The UI of M/L and M/S of groups obtained under physical stress are clearly superior to that of groups obtained under pharmacological stress. These differences are only significant in patients who ate high-fat chocolate or drank water. The analysis of all stress studies together (GI, GII, GIII and GIV) in comparison with CG shows higher mean ranks of UI of M/L for those who ate high-fat chocolate. After pharmacological stress, the mean ranks of UI of M/L were higher for patients who ate high- and low-fat chocolate. In conclusion, eating food with fat content after radiotracer injection increases, respectively, the UI of M/L after stress and rest in MP-gated-SPECT studies. It is, therefore, recommended that patients eat a chocolate bar after radiotracer injection and before image acquisition.

Pentagonal parch-excited sectorized antenna for localization systems

A pentagonal patch-excited sectorized antenna (SA) suitable for 2.4-2.5 GHz localization systems was studied and developed. The integration of six patch-excited structures converges into a sectorized antenna called Hive5 that provides gain improvement compared to a patch antenna, maximum variation of 3 dB beam width over the radiation pattern and circular polarization (CP). This antenna is presented and analyzed taking into account the tap length and the flare angle. The proposed antenna in combination with a RF-Switch provides a cost effective solution for localization based on Wireless Sensor Networks (WSN) and will be used for implementing angle of arrival (AoA) techniques combined with RF fingerprinting techniques.

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.

A two terminal optical signal and image processing p-i-n/p-i-n image and colour sensor

A two terminal optically addressed image processing device based on two stacked sensing/switching p-i-n a-SiC:H diodes is presented. The charge packets are injected optically into the p-i-n sensing photodiode and confined at the illuminated regions changing locally the electrical field profile across the p-i-n switching diode. A red scanner is used for charge readout. The various design parameters and addressing architecture trade-offs are discussed. The influence on the transfer functions of an a-SiC:H sensing absorber optimized for red transmittance and blue collection or of a floating anode in between is analysed. Results show that the thin a-SiC:H sensing absorber confines the readout to the switching diode and filters the light allowing full colour detection at two appropriated voltages. When the floating anode is used the spectral response broadens, allowing B&W image recognition with improved light-to-dark sensitivity. A physical model supports the image and colour recognition process.

New stacked photodevices for signal multiplexing and demultiplexing applications in the visible spectrum

Results on the use of a double a-SiC:H p-i-n heterostructure for signal multiplexing and demultiplexing applications in the visible range are presented. Pulsed monochromatic beams together (multiplexing mode), or a single polychromatic beam (demultiplexing mode) impinge on the device and are absorbed, accordingly to their wavelength. Red, green and blue pulsed input channels are transmitted together, each one with a specific transmission rate. The combined optical signal is analyzed by reading out, under different applied voltages, the generated photocurrent. Results show that in the multiplexing mode the output signal is balanced by the wavelength and transmission rate of each input channel, keeping the memory of the incoming optical carriers. In the demultiplexing mode the photocurrent is controlled by the applied voltage allowing regaining the transmitted information. A physical model supported by a numerical simulation gives insight into the device operation.

Implications of the LHC two-photon signal for two-Higgs-doublet models

We study the implications for two-Higgs-doublet models of the recent announcement at the LHC giving a tantalizing hint for a Higgs boson of mass 125 GeV decaying into two photons. We require that the experimental result be within a factor of 2 of the theoretical standard model prediction, and analyze the type I and type II models as well as the lepton-specific and flipped models, subject to this requirement. It is assumed that there is no new physics other than two Higgs doublets. In all of the models, we display the allowed region of parameter space taking the recent LHC announcement at face value, and we analyze the W+W-, ZZ, (b) over barb, and tau(+)tau(-) expectations in these allowed regions. Throughout the entire range of parameter space allowed by the gamma gamma constraint, the numbers of events for Higgs decays into WW, ZZ, and b (b) over bar are not changed from the standard model by more than a factor of 2. In contrast, in the lepton-specific model, decays to tau(+)tau(-) are very sensitive across the entire gamma gamma-allowed region.

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.

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.

Agentes fitoquímicos como radio-sensibilizadores na terapêutica em medicina nuclear

Mestrado em Medicina Nuclear. Área de especialização: Radiofarmácia.

Signal Subspace Identification in Hyperspectral Linear Mixtures

Chpater in Book Proceedings with Peer Review Second Iberian Conference, IbPRIA 2005, Estoril, Portugal, June 7-9, 2005, Proceedings, Part II