Assessment of Notch1 ligands production - key protein targets in breast cancer

Cell-to-cell communication is required for many biological processes in development and adult life. One of the most common systems utilized by a wide range of eukaryotes is the Notch signalling pathway. Four Notch receptors and five ligands have been identified in mammals that interact via their extracellular domains leading to transcription activation. Studies have shown that the Notch ligands expression is undetectable in normal breast tissues, but moderate to high expression has been detected in breast cancer. Thus, any of the Notch1 ligands can be studied as possible therapeutic targets for breast cancer. To study Notch pathway proteins there is the need to obtain stable protein solutions. E. coli is the host of excellence for recombinant proteins for the ease of use, fast growth and high cell densities. However, the expression of mammalian proteins in such systems may overwhelm the bacterial cellular machinery, which does not possess the ability for post-translational modifications, or dedicated compartments for protein synthesis. Mammalian cells are therefore preferred, despite their technical and financial increased demands. We aim to determine the best expression and purification conditions for the different ligand protein constructs, to develop specific function-blocking antibodies using the Phage Display technology. Moreover, we propose to crystallize the Notch1 ligands alone and in complex with the phage display selected antibodies, unveiling molecular details. hJag2DE3 and hDll1DE6 proteins were purified from refolded inclusion bodies or mammalian cell culture supernatants, respectively, and purity was confirmed by SDS-PAGE (>95%). Protein produced in mammalian cells showed to be more stable, apparently with the physiological disulfide pattern, contrary to what was observed in the refolded protein. Several nano-scale crystallization experiments were set up in 96-well plates, but no positive result was obtained. We will continue to pursue for the best expression for the Notch ligand constructs in both expression systems.

The implementation of an Enterprise Geographical Information System to support Cadastre and Expropriation activities.

The processes of mobilization of land for infrastructures of public and private domain are developed according to proper legal frameworks and systematically confronted with the impoverished national situation as regards the cadastral identification and regularization, which leads to big inefficiencies, sometimes with very negative impact to the overall effectiveness. This project report describes Ferbritas Cadastre Information System (FBSIC) project and tools, which in conjunction with other applications, allow managing the entire life-cycle of Land Acquisition and Cadastre, including support to field activities with the integration of information collected in the field, the development of multi-criteria analysis information, monitoring all information in the exploration stage, and the automated generation of outputs. The benefits are evident at the level of operational efficiency, including tools that enable process integration and standardization of procedures, facilitate analysis and quality control and maximize performance in the acquisition, maintenance and management of registration information and expropriation (expropriation projects). Therefore, the implemented system achieves levels of robustness, comprehensiveness, openness, scalability and reliability suitable for a structural platform. The resultant solution, FBSIC, is a fit-for-purpose cadastre information system rooted in the field of railway infrastructures. FBSIC integrating nature of allows: to accomplish present needs and scale to meet future services; to collect, maintain, manage and share all information in one common platform, and transform it into knowledge; to relate with other platforms; to increase accuracy and productivity of business processes related with land property management.

Res Publica: Citizenship and Political Representation in Portugal, 1820-1926

The term res publica (literally “thing of the people”) was coined by the Romans to translate the Greek word politeia, which, as we know, referred to a political community organised in accordance with certain principles, amongst which the notion of the “good life” (as against exclusively private interests) was paramount. This ideal also came to be known as political virtue. To achieve it, it was necessary to combine the best of each “constitutional” type and avoid their worst aspects (tyranny, oligarchy and ochlocracy). Hence, the term acquired from the Greeks a sense of being a “mixed” and “balanced” system. Anyone that was entitled to citizenship could participate in the governance of the “public thing”. This implied the institutionalization of open debate and confrontation between interested parties as a way of achieving the consensus necessary to ensure that man the political animal, who fought with words and reason, prevailed over his “natural” counterpart. These premises lie at the heart of the project which is now being presented under the title of Res Publica: Citizenship and Political Representation in Portugal, 1820-1926. The fact that it is integrated into the centenary commemorations of the establishment of the Republic in Portugal is significant, as it was the idea of revolution – with its promise of rupture and change – that inspired it. However, it has also sought to explore events that could be considered the precursor of democratization in the history of Portugal, namely the vintista, setembrista and patuleia revolutions. It is true that the republican regime was opposed to the monarchic. However, although the thesis that monarchy would inevitably lead to tyranny had held sway for centuries, it had also been long believed that the monarchic system could be as “politically virtuous” as a republic (in the strict sense of the word) provided that power was not concentrated in the hands of a single individual. Moreover, various historical experiments had shown that republics could also degenerate into Caesarism and different kinds of despotism. Thus, when absolutism began to be overturned in continental Europe in the name of the natural rights of man and the new social pact theories, initiating the difficult process of (written) constitutionalization, the monarchic principle began to be qualified as a “monarchy hedged by republican institutions”, a situation in which not even the king was exempt from isonomy. This context justifies the time frame chosen here, as it captures the various changes and continuities that run through it. Having rejected the imperative mandate and the reinstatement of the model of corporative representation (which did not mean that, in new contexts, this might not be revived, or that the second chamber established by the Constitutional Charter of 1826 might not be given another lease of life), a new power base was convened: national sovereignty, a precept that would be shared by the monarchic constitutions of 1822 and 1838, and by the republican one of 1911. This followed the French example (manifested in the monarchic constitution of 1791 and in the Spanish constitution of 1812), as not even republicans entertained a tradition of republicanism based upon popular sovereignty. This enables us to better understand the rejection of direct democracy and universal suffrage, and also the long incapacitation (concerning voting and standing for office) of the vast body of “passive” citizens, justified by “enlightened”, property- and gender-based criteria. Although the republicans had promised in the propaganda phase to alter this situation, they ultimately failed to do so. Indeed, throughout the whole period under analysis, the realisation of the potential of national sovereignty was mediated above all by the individual citizen through his choice of representatives. However, this representation was indirect and took place at national level, in the hope that action would be motivated not by particular local interests but by the common good, as dictated by reason. This was considered the only way for the law to be virtuous, a requirement that was also manifested in the separation and balance of powers. As sovereignty was postulated as single and indivisible, so would be the nation that gave it soul and the State that embodied it. Although these characteristics were common to foreign paradigms of reference, in Portugal, the constitutionalization process also sought to nationalise the idea of Empire. Indeed, this had been the overriding purpose of the 1822 Constitution, and it persisted, even after the loss of Brazil, until decolonization. Then, the dream of a single nation stretching from the Minho to Timor finally came to an end.

A DSL for querying building data streams of energy, eeather and occupation data

The superfluous consumption of energy is faced by the modern society as a Socio-Economical and Environmental problem of the present days. This situation is worsening given that it is becoming clear that the tendency is to increase energy price every year. It is also noticeable that people, not necessarily proficient in technology, are not able to know where savings can be achieved, due to the absence of accessible awareness mechanisms. One of the home user concerns is to balance the need of reducing energy consumption, while producing the same activity with all the comfort and work efficiency. The common techniques to reduce the consumption are to use a less wasteful equipment, altering the equipment program to a more economical one or disconnecting appliances that are not necessary at the moment. However, there is no direct feedback from this performed actions, which leads to the situation where the user is not aware of the influence that these techniques have in the electrical bill. With the intension to give some control over the home consumption, Energy Management Systems (EMS) were developed. These systems allow the access to the consumption information and help understanding the energy waste. However, some studies have proven that these systems have a clear mismatch between the information that is presented and the one the user finds useful for his daily life, leading to demotivation of use. In order to create a solution more oriented towards the user’s demands, a specially tailored language (DSL) was implemented. This solution allows the user to acquire the information he considers useful, through the construction of questions about his energy consumption. The development of this language, following the Model Driven Development (MDD) approach, took into consideration the ideas of facility managers and home users in the phases of design and validation. These opinions were gathered through meetings with experts and a survey, which was conducted to the purpose of collecting statistics about what home users want to know.

Photochemical degradation of triclosan: a comparison between different light sources

New emerging contaminants could represent a danger to the environment and Humanity with repercussions not yet known. One of the major worldwide pharmaceutical and personal care productions are antimicrobials products, triclosan, is an antimicrobial agent present in most products. Despite the high removal rate of triclosan present in wastewater treatments, triclosan levels are on the rise in the environment through disposal of wastewater effluent and use of sewage sludge in land application. Regulated in the EC/1272/2008 (annex VI, table 3.1), this compound is considered very toxic to aquatic life and it has been reported that photochemical transformation of triclosan produces dioxins. In the current work it was defined three objectives; determination of the most efficient process in triclosan degradation, recurring to photochemical degradation methods comparing different sources of light; identification of the main by-products formed during the degradation and the study of the influence of the Fenton and photo-Fenton reaction. Photochemical degradation methods such as: photocatalysis under florescent light (UV), photocatalysis under visible light (sunlight), photocatalysis under LEDs, photo-Fenton and Fenton reaction have been compared in this work. The degradation of triclosan was visualized through gas chromatography/mass spectrometry (GC/MS). In this study photo-Fenton reaction has successfully oxidized triclosan to H2O and CO2 without any by-products within 2 hours. Photocatalysis by titanium dioxide (TiO2) under LEDs was possible, having a degradation rate of 53% in an 8 hours essay. The degradation rate of the Fenton reaction, UV light and sunlight showed degradation between 90% and 95%. The results are reported to the data observed without statistic support, since this was not possible during the work period. Hydroquinone specie and 2,4-dichlorophenol by-products were identified in the first hour of photocatalysis by UV. A common compound, possibly identified has C7O4H , was present at the degradation by UV, sunlight and LEDs and was concluded to be a contaminant. In the future more studies in the use of LEDs should be undertaken given the advantages of long durability and low consumption of energy of these lamps and that due to their negative impact on the environment fluorescent lamps are being progressively made unavailable by governments, requiring new solutions to be found. Fenton and photo-Fenton reactions can also be costly processes given the expensive reagents used.

Health-related quality of life in patients with Chagas disease

INTRODUCTION: Chagas disease (ChD) is a chronic illness related to significant morbidity and mortality that can affect the quality of life (QoL) of infected patients. However, there are few studies regarding QoL in ChD. The objectives of this study are to construct a health-related QoL (HRQoL) profile of ChD patients and compare this with a non-ChD (NChD) group to identify factors associated with the worst HRQoL scores in ChD patients. METHODS: HRQoL was investigated in 125 patients with ChD and 21 NChD individuals using the Medical Outcomes Study 36-item Short-Form (SF-36) and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Patients were submitted to a standard protocol that included clinical examination, ECG, Holter monitoring, Doppler echocardiogram and autonomic function tests. RESULTS: HRQoL scores were significantly worse among the ChD group compared to the NChD group in the SF-36 domains of physical functioning and role-emotional and in the MLWHFQ scale. For the ChD group, univariate analysis showed that HRQoL score quartiles were associated with level of education, sex, marital status, use of medication, functional classification and cardiovascular and gastrointestinal symptoms. In the multivariate analysis, female sex, fewer years of education, single status, worst functional classification, presence of cardiovascular and gastrointestinal symptoms, associated illnesses, Doppler echocardiographic abnormalities and ventricular arrhythmia detected during Holter monitoring were predictors of lower HRQoL scores. CONCLUSIONS: ChD patients showed worse HRQoL scores compared to NChD. For the ChD group, sociodemographic and clinical variables were associated with worst scores.

Rigid pavements distresses - pavement condition index evaluation

Pavements require maintenance in order to provide good service levels during their life period. Because of the significant costs of this operation and the importance of a proper planning, a pavement evaluation methodology, named Pavement Condition Index (PCI), was created by the U.S. Army Corps of Engineers. This methodology allows for the evaluation of the pavement condition along the life period, generally yearly, with minimum costs and, in this way, it is possible to plan the maintenance action and to adopt adequate measures, minimising the rehabilitation costs. The PCI methodology provides an evaluation based on visual inspection, namely on the distresses observed on the pavement. This condition index of the pavement is classified from 0 to 100, where 0 it is the worst possible condition and 100 the best possible condition. This methodology of pavement assessment represents a significant tool for management methods such as airport pavement management system (APMS) and life-cycle costs analysis (LCCA). Nevertheless, it has some limitations which can jeopardize the correct evaluation of the pavement behavior. Therefore the objective of this dissertation is to help reducing its limitations and make it easier and faster to use. Thus, an automated process of PCI calculation was developed, avoiding the abaci consultation, and consequently, minimizing the human error. To facilitate also the visual inspection a Tablet application was developed to replace the common inspection data sheet and thus making the survey easier to be undertaken. Following, an airport pavement condition was study accordingly with the methodology described at Standard Test Method for Airport Pavement Condition Index Surveys D5340, 2011 where its original condition level is compared with the condition level after iterate possible erroneous considered distresses as well as possible rehabilitations. Afterwards, the results obtained were analyzed and the main conclusions presented together with some future developments.

The impact of leprosy on health-related quality of life

INTRODUCTION: Leprosy is a potentially disabling infectious disease that evolves into emotional issues due to the prejudice that persists about the illness. The endemic has declined substantially with multidrug therapy (MDT) in the 80's; however, new demands associated with the reduction of stigma and the improvement of the affected people's quality of life have emerged. In Brazil, leprosy is still a public health problem. Piauí is the second state in the Northeast in prevalence and detection, and Teresina is a hyperendemic city. This study aimed to analyze the health-related quality of life (HRQoL) of people in treatment for leprosy in Teresina/PI. METHODS: An observational study was conducted using the SF-36 (a specific questionnaire for assessing quality of life), which sought the determinants of poor quality of life among people with leprosy, outlining the sociodemographic, clinical, and epidemiological characteristics of the 107 patients interviewed. RESULTS: The correlations between the variables showed five determinants of HRQoL: late diagnosis, multibacillary forms, reactions, disability diagnosis grade II, and prejudice. The profile of the participants showed that leprosy still affects the lower social classes in historically endemic areas, causing high percentages of secondary injuries that compromise the work capacity and quality of life of the affected people, perpetuating the stigma associated with the disease. CONCLUSIONS: The study reinforces the need to implement more effective strategies of disease control, due to the development of severe and disabling forms of leprosy is directly related to poor HRQoL in the same cured patient.

Quality of life of hypertensive and diabetic patients: Who suffers the most?

Objective: Quality of life was measured using the EQ-5D index for Portugal and a Self-Assessed Ranking of Health (SARH) to understand which patients suffer the most decrease in quality of life: diabetics or hypertensive. Method: Using the National Health Survey (NHS), two analyses were conducted on 5649 respondents. The EQ-5D index was calculated by matching questions in the NHS with its dimensions. The SARH was calculated based on a specific question in the NHS. Results: Differences between diseases do not occur using the EQ-5D index. Using the SARH, type 1 diabetics suffer the most while hypertensive suffers the least.

The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

Degree of disability, pain levels, muscle strength, and electromyographic function in patients with Hansen's disease with common peroneal nerve damage

INTRODUCTION: This study evaluated the degree of disability, pain levels, muscle strength, and electromyographic function (RMS) in individuals with leprosy. METHODS: We assessed 29 individuals with leprosy showing common peroneal nerve damage and grade 1 or 2 disability who were referred for physiotherapeutic treatment, as well as a control group of 19 healthy participants without leprosy. All subjects underwent analyses of degree of disability, electromyographic tests, voluntary muscle force, and the Visual Analog Pain Scale. RESULTS: McNemar's test found higher levels of grade 2 of disability (Δ = 75.9%; p = 0.0001) among individuals with leprosy. The Mann-Whitney test showed greater pain levels (Δ = 5.0; p = 0.0001) in patients with leprosy who had less extension strength in the right and left extensor hallucis longus muscles (Δ = 1.28, p = 0.0001; Δ = 1.55, p = 0.0001, respectively) and dorsiflexion of the right and left feet (Δ = 1.24, p = 0.0001; Δ = 1.45, p = 0.0001, respectively) than control subjects. The Kruskal-Wallis test showed that the RMS score for dorsiflexion of the right (Δ = 181.66 m·s-2, p = 0.001) and left (Δ = 102.57m·s-2, p = 0.002) feet was lower in patients with leprosy than in control subjects, but intragroup comparisons showed no difference. CONCLUSIONS: Leprosy had a negative influence on all of the study variables, indicating the need for immediate physiotherapeutic intervention in individuals with leprosy. This investigation opens perspectives for future studies that analyze leprosy treatment with physical therapeutic intervention.

O contrato de Project Finance

Currently, Angola portrays a notorious economic growth and due to recent innovative legislations, it has become the major investment attracting pole, especially in Sub-Saharan Africa, having, thus, an extraordinary potentiality for a rapid and sustainable development, likely to place her in outstanding positions in the world economic ranking. Yet, such economic growth entails demanding levels of intensive investment in infrastructure, what has been reported of the Angolan Government to be unable to respond to, save if recurring to very high index of external debt, poisoning, in this way, the future budgeting of the country. Due to these infrastructure investment shortages, the cost of production remains highly onerous and the cost of life extremely unaffordable. On this account, the current study disserts about the contract of Project Finance; an alternative finance resource given as a viable solution for the private financing of infrastructure, aiming to demonstrate that such contractual figure, likewise the experience of several emerging economies and others, is a contract bid framework to take into account in today’s world. It refers to a financing technique – through which the Government may satisfy a common need (for example, the construction of a public domain or public servicing), without having to pay neither offer any collateral – based on a complex legal-financial engineering, arranged throughout a coalition of typical and atypical agreements, whereby it is mandatory to look back at the basic concepts of corporate law. More than just a simple financial study, the dissertation at stake analyses the nature and legal framework of Project Finance, which is a legally atypical and innominate contract, concluding that there is a relevant need for regulating and devoting a special legal regime in the Angolan jurisdiction for this promising legal form in the contemporary corporate finance world.

As práticas comerciais desleais

The following study aims to examine a controversial and relatively unexplored subject within our system: the legal framework on unfair business-to-consumer commercial practices. Given the fact that this subject is based on the Directive 2005/29/EC, we considered to be appropriate to explore, firstly, the background and origin of such normative instrument. Nevertheless, we have centered our analysis on the interpretation of the set rules established by the Portuguese legal system (Law nr 57/2008, March 26th). For this dissertation, we have proposed a model of tripartite approach. Chapter V seeks to shed light on the general clause by analyzing a set of open concepts such as professional diligence, honest market practice, good faith or material distortion of the consumer’s economic behavior. In chapter VI, we will focus on two common types of unfair commercial practices: misleading and aggressive practices. Finally, due to the fact that chapter VII deals with the black list, we have illustrated the listed practices by giving real life examples. Taking into account the indefinite concepts used in the general prohibition and in the misleading and aggressive clauses, it is particularly difficult to demonstrate the unfairness of the professional’s behavior. In the light of this information, we have concluded that the regime fails on achieving its main goal: it does not protect proper and effectively the consumer’s interests.

Quality of life of patients with hepatitis C

INTRODUCTION: Self-report on the quality of life (QOL) is increasingly studied in the evaluation of various diseases, especially in chronic ones. However, there are few data in the literature focusing the QOL of patients living with chronic hepatitis C. The objective of this study was to evaluate the QOL in patients with hepatitis C assessed by the World Health Organization Quality of Life Assessment (WHOQOL)-bref scale. METHODS: One hundred and eight hepatitis C patients attending the Outpatient Healthcare Medical Specialties in Tubarão, State of Santa Catarina, Brazil, were contacted from May 2010 to February 2011. Patients answered the WHOQOL-bref scale and a questionnaire about their treatment and risk factors to hepatitis C virus (VHC) infection. RESULTS: Although most of patients with chronic hepatitis C considered their QoL good or very good (58.1%), 47 (44.8%) patients were poorly or very poorly satisfied with their health. About the WHOQOL answers, the environment domain had the highest score (25.15 + 5.77), while the lowest score was the social relationships domain (9.19 + 2.5). There was statistically significant association between household income and quality of life in all domains (p<0.001) and statistically significant association between education and the physical, psychological and social domains of quality of life (p<0.05). CONCLUSIONS: Based on the answers given in WHOQOL-bref, patients with chronic hepatitis C have a generally poor QOL, especially in social relationship domain. Household income and educational level were factors that interfered significantly with patients' QOL assessment.

Fatores de risco no patrulhamento da GNR em ambiente operacional

In the mid-twentieth century, Portugal took the first big step towards social awareness of the Safety and Health at Work. Still later, the International Labour Organization and the World Health Organization were responsible for setting global guidelines that clarified the States for the way forward in inguito of safeguarding the common interests of workers, businesses and the state. All workers should be covered by the rules governing matters relating to Safety, imperative requirements established in the Constitution of the Portuguese Republic. These also include those soldiers from National Guard who, in contemporary social conjecture face in their everyday life situations worthy of heightened risk aquidade. Ensure the identification of risk factors to which they are exposed, is, first, a big boost in the way of preserving the safety of these employees, who daily selflessly and under the most adverse working conditions fulfill the mission of the Guarda Nacional Republicana. Adverse weather conditions, and violence at work are two examples of risk factors to which the military Guard are daily exposed, and hence arise many days of absence from the workplace. The purpose of this study is to identify the main risk factors to which the military from GNR are exposed during dismounted patrols, and also provide solutions on ways to mitigate and manage the risks presented. The cognitive distance traveled, throughout this study led us to demonstrate that it has been done by the GNR chain of Command, a huge effort to ensure through various forms (including emphasize the new Regulation of Uniforms), the resolution of the main factors that may jeopardize the integrity of the patrolmen, betting this Institution in the protection of the military that compose it, and the prevention of accidents at work through training and systematic monitoring that superiors expend with its employees.