The Delta Np63 Proteins Are Key Allies of BRCA1 in the Prevention of Basal-Like Breast Cancer

Little is known about the origin of basal-like breast cancers, an aggressive disease that is highly similar to BRCA1-mutant breast cancers. p63 family proteins that are structurally related to the p53 suppressor protein are known to function in stem cell regulation and stratified epithelia development in multiple tissues, and p63 expression may be a marker of basal-like breast cancers. Here we report that Delta Np63 isoforms of p63 are transcriptional targets for positive regulation by BRCA1. Our analyses of breast cancer tissue microarrays and BRCA1-modulated breast cancer cell lines do not support earlier reports that p63 is a marker of basal-like or BRCA1 mutant cancers. Nevertheless, we found that BRCA1 interacts with the specific p63 isoform Delta Np63 gamma along with transcription factor isoforms AP-2 alpha and AP-2 gamma. BRCA1 required Delta Np63 gamma and AP-2 gamma to localize to an intronic enhancer region within the p63 gene to upregulate transcription of the Delta Np63 isoforms. In mammary stem/progenitor cells, siRNA- mediated knockdown of Delta Np63 expression resulted in genomic instability, increased cell proliferation, loss of DNA damage checkpoint control, and impaired growth control. Together, our findings establish that transcriptional upregulation of Delta Np63 proteins is critical for BRCA1 suppressor function and that defects in BRCA1-Delta Np63 signaling are key events in the pathogenesis of basal-like breast cancer. Cancer Res; 71( 5); 1933-44. (c) 2011 AACR.

Degradation of carbon disulphide (CS2) in soils and groundwater from a CS2 -contaminated site

This study is the first investigation of biodegradation of carbon disulphide (CS₂) in soil that provides estimates of degradation rates and identifies intermediate degradation products and carbon isotope signatures of degradation. Microcosm studies were undertaken under anaerobic conditions using soil and groundwater recovered from CS₂-contaminated sites. Proposed degradation mechanisms were validated using equilibrium speciation modelling of concentrations and carbon isotope ratios. A first-order degradation rate constant of 1.25 × 10-2 h-1 was obtained for biological degradation with soil. Carbonyl sulphide (COS) and hydrogen sulphide (H₂S) were found to be intermediates of degradation, but did not accumulate in vials. A 13C/12C enrichment factor of -7.5 ± 0.8 ‰ was obtained for degradation within microcosms with both soil and groundwater whereas a 13C/12C enrichment factor of -23.0 ± 2.1 ‰ was obtained for degradation with site groundwater alone. It can be concluded that biological degradation of both CS2-contaminated soil and groundwater is likely to occur in the field suggesting that natural attenuation may be an appropriate remedial tool at some sites. The presence of biodegradation by-products including COS and H₂S indicates that biodegradation of CS₂ is occurring and stable carbon isotopes are a promising tool to quantify CS₂ degradation.

Opening the Frontier: The Gubbio-Perugia Frontier in the Course of History.

The frontier between Gubbio (ancient Umbria) and Perugia (ancient Etruria), in the northeast part of the modern region of Umbria, was founded in the late sixth century BC. The frontier endured in different forms, most notably in the late antique and medieval periods, as well as fleetingly in 1944, and is fossilized today in the local government boundaries. Archaeological, documentary and
philological evidence are brought together to investigate different scales of time that vary from millennia to single days in the representation of a frontier that captured a watershed of geological origins. The foundation of the frontier appears to have been a product of the active agency of the Etruscans, who projected new settlements across the Tiber in the course of the sixth century BC,
protected at the outer limit of their territory by the naturally defended farmstead of Col di Marzo. The immediate environs of the ancient abbey of Montelabate have been studied intensively by targeted, systematic and geophysical survey in conjunction with excavation, work that is still in progress. An overview of the development of the frontier is presented here, employing the data currently available.

AMBIGUITIES IN ADSORBATE SITE ASSIGNMENT FROM VIBRATIONAL FREQUENCIES - A TLEED STRUCTURAL STUDY OF (2X1)CO-PD(110)

The structure of the (2 X 1)CO-Pd(110) surface phase has been determined by LEED intensity analysis. The CO molecule is found to be adsorbed in an atop site, tilted by 11-degrees +/- 4-degrees with respect to the surface normal, with a C-O bond length of 1.16 +/- 0.04 angstrom. Interestingly, the C-O vibrational frequency for this system (2003 cm-1) is virtually identical to the frequency observed for the (2 X 1)CO-Ni(110) surface phase (1998 cm-1) which a previous LEED study has shown involves bridge bound CO molecules. The result indicates that care must be taken in assigning site symmetries on the basis of C-O stretching frequencies alone.

Guerre et exil chez Louis-Ferdinand Céline

O nosso estudo incide, primordialmente, sobre as polémicas de carácter político e consequentes acusações de que Louis-Ferdinand Céline foi – e continua a ser – alvo. Tais aspectos conduzem-nos a questionar, com alguma veemência e perplexidade, as razões da sua fuga através da Alemanha, bem como as relações que estabeleceu com os Nazis durante a segunda guerra mundial. Num primeiro momento, elaborámos uma contextualização de cariz temporal e factual, tentando perceber – quiçá explicar -, o sentido das posições assumidas por Céline aquando da composição dos seus pamphlets, marcada por uma reivindicação violenta do seu antisemitismo e que surge, omnipresente, sob forma de cartas, entrevistas e outros escritos. Contudo, a essência do nosso trabalho consistiu numa análise detalhada das diferentes etapas dos anos de exílio do escritor, primeiro numa Alemanha devastada pela guerra, onde se refugia a partir de 17 de Junho de 1944 e mais tarde, na Dinamarca (1945-1951), de onde terá de responder às acusações de traição que lhe são dirigidas pela justiça francesa, antes de um regresso sem glória, a França, e de uma reabilitação tardia e titubeante. Os escritos que constituem o corpus do nosso trabalho traduzem, de modo inequívoco, a experiência amarga e cruel dos anos de exílio e da lembrança feita de dor e ódio, que o escritor sentiu profundamente, como um espinho na própria carne. Apesar do caminho tortuoso, que lhe confere uma aura de escritor “maldito”, Céline permanece, ainda hoje, como um dos maiores génios da literatura francesa do século XX.

Aprendizagens em contexto de formação inicial : um estudo com futuros professores de ciências em Cabo Verde

Tese de mestrado, Educação (Didáctica das Ciências), Universidade de Lisboa, Instituto de Educação, 2010

A importância do estudo do conhecimento no ensino secundário : o despertar da curiosidade e o renascer da motivação

Relatório da prática de ensino supervisionada, Mestrado em Ensino da Filosofia, Universidade de Lisboa, 2011

A ética como criação de qualidade de vida : o apreço pela vida como pilar de sustentação da acção humana

Relatório da Prática de Ensino Supervisionada, Mestrado em Ensino da Filosofia, Universidade de Lisboa, 2011

Using genomics for drug discovery in medulloblastoma

Tese de doutoramento, Medicina (Neurocirurgia), Universidade de Lisboa, Faculdade de Medicina, 2014

Comportamentos autolesivos em adolescentes : características epidemiológicas e análise de fatores psicopatológicos, temperamento efetivo e estratégias de coping

Tese de doutoramento, Medicina (Psiquiatria e Saúde Mental), Universidade de Lisboa, Faculdade de Medicina, 2014

Poetizando a história nacional : ficcionalização da história e método historiográfico em José de Alencar

Tese de doutoramento, História (História e Cultura do Brasil), Universidade de Lisboa, Faculdade de Letras, 2014

Abordagem do tema da fundamentação moral no programa de filosofia do ensino secundário

Relatório da prática de ensino supervisionada, Mestrado em Ensino de Filosofia, Universidade de Lisboa, 2014

Agostinho da Silva : filosofia e espiritualidade, educação e pedagogia

Tese de doutoramento, Filosofia (Filosofia da Educação), Universidade de Lisboa, Faculdade de Letras, 2015

The Potential of Participedia as a Crowdsourcing Tool for Comparative Analysis of Democratic Innovations

For two reasons, our capacity for systematic comparison of innovative participatory democratic processes remains limited. First, the category of participatory democratic innovations remains relatively vague when compared to more traditional democratic institutions and practices. Second, until recently there existed no large-sample databases that captured relevant variables in the practice of democratic innovation. The lone exception to these patterns is the Participedia database, located online. Participedia is well placed to respond to the two obstacles to systematic comparative research on democratic innovation. First, its crowdsourced data collection strategy means that many of the cases on the platform are not well known and have not been the subject of sustained academic analysis. Second, the data captured in the articles provides the basis for systematic comparative analysis of democratic innovations both within type (e.g., participatory budgeting, mini-publics) and across types. The platform allows for systematic content analysis of text descriptions and/or statistical analysis of the datasets generated from the structured data fields. This article describes the data about innovative participatory democratic processes available from Participedia, and furnishes examples of the kinds of quantitative and qualitative insights about those processes that Participedia enables.

Nanofibers fabricated using triaxial electrospinning as zero order drug delivery systems

A new strategy for creating functional trilayer nanofibers through triaxial electrospinning is demonstrated. Ethyl cellulose (EC) was used as the filament-forming matrix in the outer, middle, and inner working solutions and was combined with varied contents of the model active ingredient ketoprofen (KET) in the three fluids. Triaxial electrospinning was successfully carried out to generate medicated nanofibers. The resultant nanofibers had diameters of 0.74 ± 0.06 μm, linear morphologies, smooth surfaces, and clear trilayer nanostructures. The KET concentration in each layer gradually increased from the outer to the inner layer. In vitro dissolution tests demonstrated that the nanofibers could provide linear release of KET over 20 h. The protocol reported in this study thus provides a facile approach to creating functional nanofibers with sophisticated structural features.