Via de sinalização mTOR no carcinoma urotelial da bexiga

Trabalho de Projeto apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Análises Laboratoriais Especializadas, área de especialização em Análise BiomédicaMundialmente, o cancro da bexiga (CB) é o 7º tipo de cancro mais frequente em homens e o 17 º mais frequente em mulheres. É uma doença com etiologia multifatorial associada a vários agentes ambientais e genéticos, dos quais o tabagismo é o fator de risco mais importante. Os carcinomas uroteliais da bexiga (CUBs) são geralmente superficiais em 70% a 80% dos pacientes e invasores em 20% a 30%. Os CUBs não-invasores têm uma alta taxa de recorrência e progressão e os invasores e metastáticos representam a principal causa de morbidade e mortalidade entre os pacientes com CB. A via fosfatidilinositol-3cinase (PI3K) /AKT (Proteína cinase b) -alvo da rapamicina em mamíferos (m-TOR) é uma importante via envolvida no crescimento celular, tumorogénese, invasão celular e resposta a drogas. Esta via é frequentemente ativada em muitas neoplasias e o descontrolo da sinalização PI3K-AKT-mTOR no CB pode contribuir para o crescimento do tumor, angiogénese e metastização. Neste trabalho, foram estudados 96 casos de tumores diagnosticados como CUBs de vários graus e estádios e foi avaliada a imunoexpressão do phospho-mTOR (Ser2448) e do phospho-S6 (Ser235/236). Em relação à expressão do p-mTOR verificou-se que mais de 50% dos casos de CUB não apresentavam ou apresentavam uma baixa expressão desta proteína sendo que não foi encontrada associação deste com estádio ou grau de diferenciação tumoral. Em relação à proteína p-S6 a sua expressão nos CUB foi igualmente nula ou baixa, no entanto encontrou-se uma associação estatisticamente significativa com o estádio e grau de diferenciação, em duas formas de avaliação qualitativa. Estes dois marcadores imunohistoquímicos, quando analisados em conjunto apresentaram uma correlação positiva moderada nos CUB, no entanto, estudos futuros são necessários para avaliar a sua validade como marcadores biológicos e, eventualmente, alvos terapêuticos. Worldwide, bladder cancer (BC) is the 7th most frequent type of cancer in men and the 17th most common in women. It is a disease with multifactorial etiology associated with multiple genetic and environmental agents, of which smoking is the most important risk factor. The urothelial carcinomas of the bladder (CUBs) are generally superficial in 70% to 80% of patients and invasive in 20% to 30%. The non-invasive CUBs have a high rate of recurrence and progression, and the metastatic and invaders ones are the leading cause of morbidity and mortality among patients with CB. The 3 cinase via phosphatidylinositol PI3K/AKT (cinase protein b) target of rapamycin in mammals (m-TOR) is an important pathway involved in cell growth, tumorigenesis, cell invasion and drug response. This pathway is frequently activated in many tumors and uncontrollable signaling PI3K/AKT/mTOR pathway in BC may contribute to tumor growth, angiogenesis and metastasis. In this study, 96 cases of tumors diagnosed as CUBs of various grades and stages were studied, and it was evaluated the immunoreactivity of phospho-mTOR (Ser2448) and phospho-S6 (Ser235/236). Concerning the p-mTOR expression, it was observed that more than 50% of CUB didn`t express or had a low expression of this protein, and it wasn`t found any association between this and the state or grade of the tumor. In what concerns the p-S6 protein, it was equally low or absent its expression in the CUB, although it was found a statistical association with the state and grade of the tumor, in two forms of qualitative evaluation. When analyzed, together, these two markers presented a positive moderated correlation in the CUB, however future studies are necessary to access its validity as biological markers and, eventually, therapeutic targets

práticas artísticas no ensino básico e secundário

Educação Artística: integrar a inovação. A educação artística apresenta-se como um território a re-cartografar, numa atualização tão rápida quanto aquela que ocorre no campo artístico. As propostas publicadas neste número 11 da Revista Matéria-Prima trazem essa diversidade de abordagens, com novidades conceptuais que estabelecem as devidas relações entre educação e cidadania, participação, sustentabilidade, cultura visual, e também com alguma atenção sobre os debates pós-coloniais e as questões de género. Os 16 artigos reunidos neste 11º número da Revista Matéria-Prima trazem a realidade operativa quer na formação de professores e quer na formulação dos discursos pedagógicos, suas justificações e suas propostas alternativas.As propostas apresentadas devolvem o debate ao terreno, e alargam-no. Provocam as periferias, convocam abordagens diferenciadas sobre o tema da arte e da educação. Em todas elas a proposta de crescimento através da arte, que hoje implica cada vez mais cidadania, crítica, criatividade, interligação, comprometimento, participação.info:eu-repo/semantics/publishedVersio

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data

Study of downward Terrestrial Gamma-ray Flashes with the surface detector of the Pierre Auger Observatory

The surface detector (SD) of the Pierre Auger Observatory, consisting of 1660 water-Cherenkov detectors (WCDs), covers 3000 km2 in the Argentinian pampa. Thanks to the high efficiency of WCDs in detecting gamma rays, it represents a unique instrument for studying downward Terrestrial Gamma-ray Flashes (TGFs) over a large area. Peculiar events, likely related to downward TGFs, were detected at the Auger Observatory. Their experimental signature and time evolution are very different from those of a shower produced by an ultrahigh-energy cosmic ray. They happen in coincidence with low thunderclouds and lightning, and their large deposited energy at the ground is compatible with that of a standard downward TGF with the source a few kilometers above the ground. A new trigger algorithm to increase the TGF-like event statistics was installed in the whole array. The study of the performance of the new trigger system during the lightning season is ongoing and will provide a handle to develop improved algorithms to implement in the Auger upgraded electronic boards. The available data sample, even if small, can give important clues about the TGF production models, in particular, the shape of WCD signals. Moreover, the SD allows us to observe more than one point in the TGF beam, providing information on the emission angle

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Investigating multiple elves and halos above strong lightning with the fluorescence detectors of the Pierre Auger Observatory

ELVES are being studied since 2013 with the twenty-four FD Telescopes of the Pierre Auger Observatory, in the province of Mendoza (Argentina), the world’s largest facility for the study of ultra-high energy cosmic rays. This study exploits a dedicated trigger and extended readout. Since December 2020, this trigger has been extended to the three High levation Auger Telescopes (HEAT), which observe the night sky at elevation angles between 30 and 60 degrees, allowing a study of ELVES from closer lightning. The high time resolution of the Auger telescopes allows us to upgrade reconstruction algorithms and to do detailed studies on multiple ELVES. The origin of multiple elves can be studied by analyzing the time difference and the amplitude ratio between flashes and comparing them with the properties of radio signals detected by the ENTLN lightning network since 2018. A fraction of multi-ELVES can also be interpreted as halos following ELVES. Halos are disc-shaped light transients emitted at 70-80 km altitudes, appearing at the center of the ELVES rings, due to the rearrangement of electric charges at the base of the ionosphere after a strong lightning event