Phage display as a tool for generation of bio-therapeutic agents for breast cancer

Notch is a conserved signalling pathway, which plays a crucial role in a multiple cellular processes such as stem cell self-renewal, cell division, proliferation and apoptosis. In mammalian, four Notch receptors and five ligands are described, where interaction is achieved through their extracellular domains, leading to a transcription activation of different target genes. Increased expression of Notch ligands has been detected in several types of cancer, including breast cancer suggesting that these proteins represent possible therapeutic targets. The goal of this work was to generate quality protein targets and, by phage display technology, select function-blocking antibodies specific for Notch ligands. Phage display is a powerful technique that allows the generation of highly specific antibodies to be used for therapeutics, and it has also proved to be a reliable approach in identifying and validating new cancer-related targets. Also, we aimed at solving the tri-dimensional structure of the Notch ligands alone and in complex with selected antibodies. In this work, the initial phase focused on the optimization of the expression and purification of a human Delta-like 1 ligand mutant construct (hDLL1-DE3), by refolding from E. coli inclusion bodies. To confirm the biological activity of the produced recombinant protein cellular functional studies were performed, revealing that treatment with hDLL1-DE3 protein led to a modulation of Notch target genes. In a second stage of this study, Antibody fragments (Fabs) specific for hDLL1-DE3 were generated by phage display, using the produced protein as target, in which one good Fab candidate was selected to determine the best expression conditions. In parallel, multiple crystallization conditions were tested with hDLL1-DE3, but so far none led to positive results.

Complications of tracheobronchial foreign body aspiration in children: report of 5 cases and review of the literature

Foreign body aspiration (FBA) is one of leading causes of death in children, especially among those younger than 3 years of age. The inhalation of a foreign body may cause a wide variety of symptoms, and early diagnosis is highly associated with the successful removal of the inhaled foreign material. Despite the great advances in endoscopic procedures and anesthesia, a large number of difficulties and complications still result from foreign body aspiration. We describe 5 cases of serious acute complications following aspiration of foreign bodies that became lodged in the tracheobronchial tree, including pneumomediastinum, pneumothorax, total atelectasis, foreign body dislodgment, and need for thoracotomy in children admitted into our intensive care unit in 1999 and 2000; these were all situations that could have been prevented with early recognition and prompt therapeutic intervention.

Relatório de estágio no departamento central de investigação e acção penal

The means of obtaining evidence, the amount of evidence obtained, the number of defendants related to each criminal case and the gravity of the crimes for which the magistrates of the Department are holders of penal action, define its real importance to the Rule of Law. I have deeply studied the subject of the institution of hierarchical intervention required by the assistant and the application of an opening statement by the defendant, starting from a hypothetical case, provided when the query of an investigation with the subject of the crime of active corruption, where this institution was called as a reaction to the archiving dispatch delivered by the Public Ministry. I have study about the implementation of the institution of provisional suspension of the process, specifically in the scope of fiscal criminality, analyzing the effective satisfaction of the purposes of the sentences in two slopes: general prevention and special prevention. I went for my first time to a Central Court of Criminal Instruction, where I attended the measures of inquiry and instructive debate of a process that culminated with the prosecution and pronunciation of the defendants. In addition to this criminal experience, I have deepened and consolidated the academic knowledge with the study of various criminal cases from various fields in the scope of criminality investigated by the Department. I could therefore check the basis of procedural delays, regarding to our legal system, especially in this type of crime, raising issues that I analyzed and discussed, always in a critical and academic way. I had the opportunity to attend and witness a seminar in the Lisbon Directorate of Finance as well of entering the Centre for Judicial Studies to attend a conference on the International Anti-Corruption Day. Focus on the investigatory importance of the international judicial cooperation, through the various organs, with special interest to EUROJUST. I comprehended the organization and functioning of these communitarian organs and means of communication of procedural acts, in particular, the rogatory letters and european arrest warrants. This involvement is motivated by the moratorium factor of the investigations where rogatory letters are necessary for the acquisition of evidence or information relevant to the good continuation of the process. For this reason the judicial cooperation through the relevant communitarian organs, translates a streamlined response between the competent judicial authorities of the Member States, through the National Member that integrates EUROJUST. This report aims to highlight some of the difficulties and procedural issues that Public Prosecutors of DCIAP and criminal police bodies that assist them, face in combating violent and organized crime, of national and transnational nature, of particular complexity, according to the specifics of criminal types.

Prostate innervation and local anesthesia in prostate procedures

The nerve supply of the human prostate is very abundant, and knowledge of the anatomy contributes to successful administration of local anesthesia. However, the exact anatomy of extrinsic neuronal cell bodies of the autonomic and sensory innervation of the prostate is not clear, except in other animals. Branches of pelvic ganglia composed of pelvic (parasympathetic) and hypogastric (sympathetic) nerves innervate the prostate. The autonomic nervous system plays an important role in the growth, maturation, and secretory function of this gland. Prostate procedures under local anesthesia, such as transurethral prostatic resections or transrectal ultrasound-guided prostatic biopsy, are safe, simple, and effective. Local anesthesia can be feasible for many special conditions including uncomplicated prostate surgery and may be particularly useful for the high-risk group of patients for whom inhalation or spinal anesthesia is inadvisable.

Relatório de estágio curricular no Ministério Público na Comarca de Setúbal

This report represents four months of study on activities in the public prosecution service at the Local Instance of Setúbal judiciary district, started in September 2014 and completed of the same year. This report was prepared considering all the teachings of criminal law courses and criminal procedural law, doctrine, jurisprudence and all the practical experience experienced with prosecutors. In this context, their traineeship provided contact with different procedural stages: the investigation stage that allowed to understand better the progress of the processing of summary proceedings; the expedient distribution of urgent cases; the investigation stage, as regards the procedural impulse assistant and the accused; and the trial stage. This last phase allowed contact with different types of crimes especially road crimes and the crime of domestic violence. The analysis carried out the summary proceedings in the Public Ministry service would acquire relevant information to explain the incidence of road crimes. Topics will be addressed that were found on stage during the various procedural stages, as the implementation of new judicial map. The relationship between the prosecution and the Criminal Police Bodies was also an issue to be addressed. The work also raises awareness of the issue of archives in order to find out the position of assistant.

Cultural journalism in a digital environment : new models, practices and possibilities

Both culture coverage and digital journalism are contemporary phenomena that have undergone several transformations within a short period of time. Whenever the media enters a period of uncertainty such as the present one, there is an attempt to innovate in order to seek sustainability, skip the crisis or find a new public. This indicates that there are new trends to be understood and explored, i.e., how are media innovating in a digital environment? Not only does the professional debate about the future of journalism justify the need to explore the issue, but so do the academic approaches to cultural journalism. However, none of the studies so far have considered innovation as a motto or driver and tried to explain how the media are covering culture, achieving sustainability and engaging with the readers in a digital environment. This research examines how European media which specialize in culture or have an important cultural section are innovating in a digital environment. Specifically, we see how these innovation strategies are being taken in relation to the approach to culture and dominant cultural areas, editorial models, the use of digital tools for telling stories, overall brand positioning and extensions, engagement with the public and business models. We conducted a mixed methods study combining case studies of four media projects, which integrates qualitative web features and content analysis, with quantitative web content analysis. Two major general-interest journalistic brands which started as physical newspapers – The Guardian (London, UK) and Público (Lisbon, Portugal) – a magazine specialized in international affairs, culture and design – Monocle (London, UK) – and a native digital media project that was launched by a cultural organization – Notodo, by La Fábrica – were the four case studies chosen. Findings suggest, on one hand, that we are witnessing a paradigm shift in culture coverage in a digital environment, challenging traditional boundaries related to cultural themes and scope, angles, genres, content format and delivery, engagement and business models. Innovation in the four case studies lies especially along the product dimensions (format and content), brand positioning and process (business model and ways to engage with users). On the other hand, there are still perennial values that are crucial to innovation and sustainability, such as commitment to journalism, consistency (to the reader, to brand extensions and to the advertiser), intelligent differentiation and the capability of knowing what innovation means and how it can be applied, since this thesis also confirms that one formula doesn´t suit all. Changing minds, exceeding cultural inertia and optimizing the memory of the websites, looking at them as living, organic bodies, which continuously interact with the readers in many different ways, and not as a closed collection of articles, are still the main challenges for some media.

A importância da Polícia Municipal na segurança

The challenge of this work is to assess the importance of the municipal police in improving the safety of citizens, if gauging from this reality through contributions from the Municipal Police Guimarães. The IV Constitutional Review in 1997, enabled the Portuguese municipalities creating administrative police bodies. These services, known as Municipal Police, have gradually come up in several municipalities. Currently the Municipal Police have their fundamental legal regulations of Law No. 19/2004 of 20 May, which, according to the Portuguese Constitution provides that these must be seen as municipal services, which act in a space territorially delimited, which corresponds to the municipality that each belongs. Under Article 237, paragraph 3, of the Constitution, the Municipal Police are municipal services, which shall cooperate in the maintenance of public order and protection of local communities, acting in cooperation with the security forces, public security functions. The safety concept has been taking an increasingly significant importance within the population. Is also no doubt say that, currently, insecurity affects all of society and is a major concern of law enforcement authorities. To find suitable answers we found that there are several studies on these subjects. In order to be able to make our contribution, text looks us on this subject, having had the support of the Municipal Police Guimarães, in the preparation of this work. Thus, based on a survey, they were sounded out, as privileged actors, agents of the Municipal Police Guimarães, in order to know their perceptions with regard to security issues faced in the context of security. We understand ask them to answer in particular the following questions: What are the most facilitators situations of crime? How important is the Municipal Police Guimarães in crime prevention? What are the strategies for prevention of incivilities? What other skills that can be conferred upon the Municipal Police? The results obtained allowed us to conclude that incivilities facilitate the occurrence of crimes and that the Municipal Police may have a more active role in the security of the population. If you were given other duties, in addition to that already have, the Municipal Police could reach another level of effectiveness. However we understand that any change to the tasks of this police need a serious and profound reflection, to find complementary alternatives with the security forces, which does not conflict with current assignments of any of the parties or with the interests of citizens.

A minimal version of a Protein Tyrosine Phosphatase

Phosphatase and tensin homologue (PTEN) protein belongs to the family of protein tyrosine phos-phatase. Mutations on the phosphatase and tensin homologue (PTEN) protein are highly observed in diverse types of human tumors, being mostly identified on the phosphatase domain of the protein. Although PTEN is a modular protein composed by a phosphatase domain and a C2 domain for mem-brane anchoring, this work aimed at developing a minimal version of PTEN´s phosphatase domain. The minimal version (Small Domain) comprises a 28 residue peptide, with the PTEN 8-mer catalytic peptide accommodated between a α-helix and β-turn as observed in PTEN native structure. Firstly, a de novo prediction of the Small Domain´s secondary structure was carried out by molecular modeling tools. The stability of the predicted structures were then evaluated by Molecular Dynamics. Automated molecular docking of PTEN natural substrate PIP3, its analogue (Inositol) and a PTEN inhibitor (L-tar-tare) were performed with the modeled structure, and PTEN used as a positive control. The gene en-coding for Small Domain was designed and cloned into an expression vector at N-terminal of Green Fluorescence Protein (GFP) encoding gene. The fusion protein was then expressed in Escherichia coli cells. Different expression conditions have been explored for the production of the fusion protein to minimize the formation of inclusion bodies.

PT Multimedia

The purpose of the present case – and accompanying Teaching Notes – is to better understand the spin-off of PT Multimédia, by Portugal Telecom, after receiving a Public Takeover Offer from Sonaecom, in 2006. The Government and the Competition Authority had never looked in a serious way at PT’s dominant position and the lack of room for competition in the TMT sector – PT was the owner of both the cable and copper networks, having access to privileged information from its competitors with control over the wholesale and retail businesses. In 2006, the company received a takeover offer from Sonaecom, the TMT subsidiary from the Portuguese conglomerate Sonae. The offer was voted and rejected by a majority of PT shareholders, but the whole process triggered several recommendations from the regulatory bodies. As a result, PT divested its cable business with the spin-off of PT Multimédia, giving birth to a new competitor and a totally different landscape in the telecommunications sector in Portugal.

DISTRIBUTION AND FEEDING ECOLOGY OF THE AFRICAN TILAPIA Oreochromis mossambicus (TELEOSTEI, PERCIFORMES, CICHLIDAE) IN SURINAME (SOUTH AMERICA) WITH COMMENTS ON THE TILAPIA-KWIKWI (Hoplosternum littorale) (TELEOSTEI, SILURIFORMEs, CALLICHTHYIDAE) INTERACTION

The geographical distribution of the African Tilapia Oreochromis mossambicusin Suriname is restricted to a narrow strip of land along the Atlantic coast. Within the coastal plain, O. mossambicusoccurs in brackish lagoons, oligohaline canals, and shell-sand pit lakes. Physico-chemical characteristics and phytoplankton composition of representative Tilapia water bodies are described. Blue-green algae and fine flocculent detritus are dominant food items in the diet of the Tilapia, while Rotifera and microcrustacea are also important in the diet of larvae and juveniles. Intraspecific diet overlap among ontogenetic stages of the Tilapia did not differ significantly from 1, which means that these diets showed complete overlap. Interspecific diet overlap between the Tilapia and the indigenous armoured catfish Hoplosternum littoralewere moderate or low. The results are discussed in relation to recent developments in the Surinamese fisheries and aquaculture sector.

Reasons and benefits associated with ISO 9001 - Certification for sugar and ethanol companies

With increasing business competitiveness, companies have sought to adapt their processes and / or products to worldwide established quality standards in order to achieve a greater share of consumers having as favorable aspect the quality assurance of the products and/or services provided. It was observed that companies of different sizes have different challenges regarding the certification however, the degree of difficulty is the same for all of them. The objective of this paper is to verify the reasons for the implementation of ISO 9001, the obstacles encountered during the implementation, the benefits arising from the use of the quality management system and the degree of difficulty to implement this standard. This work was developed based on a survey involving companies certified with ISO 9001:2008 from the productive sector of sugar, ethanol and derivatives of sugarcane, located in all Brazilian states. It was observed that companies of different sizes have different challenges regarding the certification however the degree of difficulty is the same for all of them. Thus, we believe that expected results represent a very important contribution to examining the reasons, benefits and difficulties of the ISO 9001 to both, the companies and certification bodies, and to researchers.

O Esclavagismo dos Tempos Modernos e a Tutela Jurídica das suas Vítimas: os meios jurídicos ao serviço da recuperação psicológica das vítimas de tráfico de seres humanos

Dissertação de mestrado em Direitos Humanos

A (in)existência de apoio judiciário na arbitragem administrativa: o direito de acesso à tutela jurisdicional efetiva?

Dissertação de mestrado em Direito Administrativo

Da prova: na atuação policial e no âmbito da infração tributária

Relatório de atividade profissional de mestrado em Direito Judiciário

Alcohol sponsored events: the impact on attitudes and intentions, and the mitigating impact of persuasion knowledge

Doctor of Philosophy in Marketing and Strategy