Critical analysis: Portuguese 9th grade exam results and socioeconomic factors

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA ��� School of Business and Economics

Why management consultants? : Between functionalist and critical perspectives

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA ��� School of Business and Economics

The effectiveness of the Media Smart Program on promoting the critical thinking of children towards the use of celebrities in television advertising

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA ��� School of Business and Economics

Interplay of Exoribonucleases, Hfq and Small RNAs Structural Determinants in the Control of Gene Expression

Dissertation presented to obtain the Ph.D degree in Biology

Interaction of malaria parasites with host late endocytic and autophagic pathways is essential for Plasmodium liver stage development

RESUMO: A Mal��ria �� causada por parasitas do g��nero Plasmodium, sendo a doen��a parasit��ria mais fatal para o ser humano. Apesar de, durante o s��culo passado, o desenvolvimento econ��mico e a implementa����o de diversas medidas de controlo, tenham permitido erradicar a doen��a em muitos pa��ses, a Mal��ria continua a ser um problema de sa��de grave, em particular nos pa��ses em desenvolvimento. A Mal��ria �� transmitida atrav��s da picada de uma f��mea de mosquito do g��nero Anopheles. Durante a picada, os esporozo��tos s��o injetados na pele do hospedeiro, seguindo-se a fase hep��tica e obrigat��ria do ciclo de vida. No f��gado, os esporozo��tos infetam os hepat��citos onde se replicam, dentro de um vac��olo parasit��rio (VP) e de uma forma imunit��ria silenciosa, em centenas de merozoitos. Estas novas formas do parasita s��o as respons��veis por infetar os eritr��citos, iniciando a fase sangu��nea da doen��a, onde se os primeiros sintomas se manifestam, tais como a caracter��stica febre c��clica. A fase hep��tica da doen��a �� a menos estudada e compreendida. Mais ainda, as intera����es entre o VP e os organelos da c��lulas hospedeira est��o ainda pouco caracterizados. Assim, neste estudo, as intera����es entre os organelos endoc��ticos e autof��gicos da c��lula hospedeira e o VP foram dissecados, observando-se que os anfisomas, que s��o organelos resultantes da intersec����o do dois processos de tr��fego intracelular, interagem com o parasita. Descobrimos que a autofagia tem tamb��m uma importante fun����o imunit��ria durante a fase hep��tica inicial, ao passo, que durante o desenvolvimento do parasita, j�� numa fase mais tardia, o parasita depende da intera����o com os endossomas tardios e anfisomas para crescer. Vesiculas de BSA, EGF e LC3, foram, tamb��m, observadas dentro do VP, sugerindo que os parasitas s��o capazes de internalizar material endoc��tico e autof��gico do hospedeiro. Mais ainda, mostramos que esta intera����o depende da cinase PIKfyve, respons��vel pela convers��o do fosfoinositidio-3-fosfato no fosfoinositidio-3,5-bifosfato, uma vez que inibindo esta cinase o parasita n��o �� capaz de crescer normalmente. Finalmente, mostramos que a prote��na TRPML1, uma prote��na efetora do fosfoinositidio-3,5-bifosfato, e envolvida no processo de fus��o das membranas dos organelos endoc��ticos e autof��gicos, tamb��m �� necess��ria para o crescimento do parasita. Desta forma, o nosso estudo sugere que a membrana do VP funde com vesiculas endoc��ticas e autof��gicas tardias, de uma forma dependente do fositidio-3,5-bifosfato e do seu effetor TRPML1, permitindo a troca de material com a c��lula hospedeira. Concluindo, os nossos resultados evidenciam que o processo autof��gico que ocorre na c��lula hospedeira tem um papel duplo durante a fase hep��tica da malaria. Enquanto numa fase inicial os hepat��citos usam o processo autof��gico como forma de defesa contra o parasita, j�� durante a fase de replica����o o VP funde com vesiculas autof��gicas e endoc��ticas de forma a obter os nutrientes necess��rios ao seu desenvolvimento.--------- ABSTRACT: Malaria, which is caused by parasites of the genus Plasmodium, is the most deadly parasitic infection in humans. Although economic development and the implementation of control measures during the last century have erradicated the disease from many areas of the world, it remains a serious human health issue, particularly in developing countries. Malaria is transmitted by female mosquitoes of the genus Anopheles. During the mosquito blood meal, Plasmodium spp. sporozoites are injected into the skin dermis of the vertebrate host, followed by an obligatory liver stage. Upon entering the liver, Plasmodium parasites infect hepatocytes and silently replicate inside a host cell-derived parasitophorous vacuole (PV) into thousands of merozoites. These new parasite forms can infect red blood cells initiating the the blood stage of the disease which shows the characteristic febrile malaria episodes. The liver stage is the least characterized step of the malaria infection. Moreover, the interactions between the Plasmodium spp. PV and the host cell trafficking pathways are poorly understood. We dissected the interaction between Plasmodium parasites and the host cell endocytic and autophagic pathways and we found that both pathways intersect and interconnect in the close vicinity of the parasite PV, where amphisomes are formed and accumulate. Interestingly, we observed a clearance function for autophagy in hepatocytes infected with Plasmodium berghei parasites at early infection times, whereas during late liver stage development late endosomes and amphisomes are required for parasite growth. Moreover, we found the presence of internalized BSA, EGF and LC3 inside parasite vacuoles, suggesting that the parasites uptake endocytic and autophagic cargo. Furthermore, we showed that the interaction between the PV and host traffic pathways is dependent on the kinase PIKfyve, which converts the phosphoinositide PI(3)P into PI(3,5)P2, since PIKfyve inhibition caused a reduction in parasite growth. Finally, we showed that the PI(3,5)P2 effector protein TRPML1, which is involved in late endocytic and autophagic membrane fusion, is also required for parasite development. Thus, our studies suggest that the parasite parasitophorous vacuole membrane (PVM) is able to fuse with late endocytic and autophagic vesicles in a PI(3,5)P2- and TRPML1-dependent manner, allowing the exchange of material between the host cell and the parasites, necessary for the rapid development of the latter that is seen during the liver stage of infection. In conclusion, we present evidence supporting a specific and essential dual role of host autophagy during the course of Plasmodium liver infection. Whereas in the initial hours of infection the host cell uses autophagy as a cell survival mechanism to fight the infection, during the replicative phase the PV fuses with host autophagic and endocytic vesicles to obtain nutrients required for parasite growth.

Using cilia mutants to study left-right asymmetry in zebrafish

A thesis submitted in fulfillment of the requirements for the degree of the Masters in Molecular Genetics and Biomedicine

Study of novel energy metabolism pathways in anaerobic bacteria

Energy conservation in chemotrophic anaerobic bacteria is achieved by two possible processes, substrate level phosphorylation (SLP) and electron transfer phosphorylation (ETP). This second mechanism, also known as respiration, involves chemiosmotic coupling. However, a third mechanism for energy coupling was recently proposed: the flavin-based electron bifurcation (FBEB). (...)

How effective is dog culling in controlling zoonotic visceral leishmaniasis? a critical evaluation of the science, politics and ethics behind this public health policy

INTRODUCTION: Zoonotic kala-azar, a lethal disease caused by protozoa of the genus Leishmania is considered out of control in parts of the world, particularly in Brazil, where transmission has spread to cities throughout most of the territory and mortality presents an increasing trend. Although a highly debatable measure, the Brazilian government regularly culls seropositive dogs to control the disease. Since control is failing, critical analysis concerning the actions focused on the canine reservoir was conducted. METHODS: In a review of the literature, a historical perspective focusing mainly on comparisons between the successful Chinese and Soviet strategies and the Brazilian approach is presented. In addition, analyses of the principal studies regarding the role of dogs as risk factors to humans and of the main intervention studies regarding the efficacy of the dog killing strategy were undertaken. Brazilian political reaction to a recently published systematic review that concluded that the dog culling program lacked efficiency and its effect on public policy were also reviewed. RESULTS: No firm evidence of the risk conferred by the presence of dogs to humans was verified; on the contrary, a lack of scientific support for the policy of killing dogs was confirmed. A bias for distorting scientific data towards maintaining the policy of culling animals was observed. CONCLUSIONS: Since there is no evidence that dog culling diminishes visceral leishmaniasis transmission, it should be abandoned as a control measure. Ethical considerations have been raised regarding distorting scientific results and the killing of animals despite minimal or absent scientific evidence

Design, implementation, and performance of a distributed and scalable sensor system for critical distance measurements in the CMS detector at LHC

The ���CMS Safety Closing Sensors System��� (SCSS, or CSS for brevity) is a remote monitoring system design to control safety clearance and tight mechanical movements of parts of the CMS detector, especially during CMS assembly phases. We present the different systems that makes SCSS: its sensor technologies, the readout system, the data acquisition and control software. We also report on calibration and installation details, which determine the resolution and limits of the system. We present as well our experience from the operation of the system and the analysis of the data collected since 2008. Special emphasis is given to study positioning reproducibility during detector assembly and understanding how the magnetic fields influence the detector structure.

Cutaneous leishmaniasis in northeastern Brazil: a critical appraisal of studies conducted in State of Pernambuco

American cutaneous leishmaniasis (ACL) is a complex disease with clinical and epidemiological features that may vary from region to region. In fact, at least seven different Leishmania species, including Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis, Leishmania (Viannia) lainsoni, Leishmania (Viannia) naiffi, Leishmania (Viannia) shawi, Leishmania (Viannia) lindenbergi, and Leishmania (Leishmania) amazonensis, have been implicated in the etiology of ACL in Brazil, and numerous phlebotomine sandfly species of the genus Lutzomyia have been regarded as putative or proven vectors. Because ACL is a focal disease, understanding the disease dynamics at the local level is essential for the implementation of more effective control measures. The present paper is a narrative review about the ACL epidemiology in Pernambuco, northeastern Brazil. Furthermore, the need for more effective diagnosis, treatment, control and prevention strategies for the affected populations is highlighted. This paper will provide researchers with a critical appraisal of ACL in Pernambuco. Hopefully, it will also be helpful for public health authorities to improve current control strategies against ACL at the state and country levels.

Southern Modernisms. Critical Stances through Regional Appropriations. Conference proceedings

The hegemonic definition of Modernism has been subjected to an intense critical revision process that began several decades ago. This process has contributed to the significant broadening of the modernist canon by challenging its primal essentialist assumptions and formalist interpretations in the fields of both the visual arts and architecture. This conference aims to further expand this revision, as it seeks to discuss the notion of ���Southern Modernisms��� by considering the hypothesis that regional appropriations, both in Southern Europe and the Southern hemisphere, entailed important critical stances that have remained unseen or poorly explored by art and architectural historians. In association with the Southern Modernisms research project (FCT ��� EXPL/CPC-HAT/0191/2013), we want to consider the entrenchment of southern modernisms in popular culture (folk art and vernacular architecture) as anticipating some of the premises of what would later become known as critical regionalism. It is therefore our purpose to explore a research path that runs parallel to key claims on modernism���s intertwinement with bourgeois society and mass culture, by questioning the idea that an aesthetically significant regionalism ��� one that resists to the colonization of international styles and is supported by critical awareness ��� occurred only in the field of architecture, and can only be represented as a postmodernist turn. (...)

Gold nanoprobes for assessing expression of critical genes in the infection pathway of MRSA

Staphylococcus aureus is an important opportunistic pathogen that can cause a wide variety of diseases from mild to life-threatening conditions. S. aureus can colonize many parts of the human body but the anterior nares are the primary ecological niche. Its clinical importance is due to its ability to resist almost all classes of antibiotics available together with its large number of virulence factores. MRSA (Methicillin-Resistant S. aureus) strains are particularly important in the hospital settings, being the major cause of nosocomial infections worldwide. MRSA resistance to ��-lactam antibiotics involves the acquisition of the exogenous mecA gene, part of the SCCmec cassette. Fast and reliable diagnostic techniques are needed to reduce the mortality and morbidity associated with MRSA infections, through the early identification of MRSA strains. The current identification techniques are time-consuming as they usually involves culturing steps, taking up to five days to determine the antibiotic resistance profile. Several amplification-based techniques have been developed to accelerate the diagnosis. The aim of this project was to develop an even faster methodology that bypasses the DNA amplification step. Gold-nanoprobes were developed and used to detect the presence of mecA gene in S. aureus genome, associated with resistance traits, for colorimetric assays based on non-crosslinking method. Our results showed that the mecA and mecA_V2 gold-nanoprobes were sensitive enough to discriminate the presence of mecA gene in PCR products and genomic DNA (gDNA) samples for target concentrations of 10 ng/��L and 20 ng/��L, respectively. As our main objective was to avoid the amplification step, we concluded that the best strategy for the early identification of MRSA infection relies on colorimetric assays based on non-crosslinking method with gDNA samples that can be extracted directly from blood samples.

Effects of continuous versus bolus infusion of enteral nutrition in critical patients

PURPOSE: Enteral alimentation is the preferred modality of support in critical patients who have acceptable digestive function and are unable to eat orally, but the advantages of continuous versus intermittent administration are surrounded by controversy. With the purpose of identifying the benefits and complications of each technique, a prospective controlled study with matched subjects was conducted. PATIENTS AND METHODS: Twenty-eight consecutive candidates for enteral feeding were divided into 2 groups (n = 14 each) that were matched for diagnosis and APACHE II score. A commercial immune-stimulating polymeric diet was administered via nasogastric tube by electronic pump in the proportion of 25 kcal/kg/day, either as a 1-hour bolus every 3 hours (Group I), or continuously for 24 hours (Group II), over a 3-day period. Anthropometrics, biochemical measurements, recording of administered drugs and other therapies, thorax X-ray, measurement of abdominal circumference, monitoring of gastric residue, and clinical and nutritional assessments were performed at least once daily. The principal measured outcomes of this protocol were frequency of abdominal distention and pulmonary aspiration, and efficacy in supplying the desired amount of nutrients. RESULTS: Nearly half of the total population (46.4%) exhibited high gastric residues on at least 1 occasion, but only 1 confirmed episode of pulmonary aspiration occurred (3.6%). Both groups displayed a moderate number of complications, without differences. Food input during the first day was greater in Group II (approximately 20% difference), but by the third day, both groups displayed similarly small deficits in total furnished volume of about 10%, when compared with the prescribed diet. CONCLUSIONS: Both administration modalities permitted practical and effective administration of the diet with frequent registered abnormalities but few clinically significant problems. The two groups were similar in this regard, without statistical differences, probably because of meticulous technique, careful monitoring, strict patient matching, and conservative amounts of diet employed in both situations. Further studies with additional populations, diagnostic groups, and dietetic prescriptions should be performed in order to elucidate the differences between these commonly used feeding modalities.

Modeling and optimization of extracellular polysaccharides production by Enterobacter A47

Polysaccharides are gaining increasing attention as potential environmental friendly and sustainable building blocks in many fields of the (bio)chemical industry. The microbial production of polysaccharides is envisioned as a promising path, since higher biomass growth rates are possible and therefore higher productivities may be achieved compared to vegetable or animal polysaccharides sources. This Ph.D. thesis focuses on the modeling and optimization of a particular microbial polysaccharide, namely the production of extracellular polysaccharides (EPS) by the bacterial strain Enterobacter A47. Enterobacter A47 was found to be a metabolically versatile organism in terms of its adaptability to complex media, notably capable of achieving high growth rates in media containing glycerol byproduct from the biodiesel industry. However, the industrial implementation of this production process is still hampered due to a largely unoptimized process. Kinetic rates from the bioreactor operation are heavily dependent on operational parameters such as temperature, pH, stirring and aeration rate. The increase of culture broth viscosity is a common feature of this culture and has a major impact on the overall performance. This fact complicates the mathematical modeling of the process, limiting the possibility to understand, control and optimize productivity. In order to tackle this difficulty, data-driven mathematical methodologies such as Artificial Neural Networks can be employed to incorporate additional process data to complement the known mathematical description of the fermentation kinetics. In this Ph.D. thesis, we have adopted such an hybrid modeling framework that enabled the incorporation of temperature, pH and viscosity effects on the fermentation kinetics in order to improve the dynamical modeling and optimization of the process. A model-based optimization method was implemented that enabled to design bioreactor optimal control strategies in the sense of EPS productivity maximization. It is also critical to understand EPS synthesis at the level of the bacterial metabolism, since the production of EPS is a tightly regulated process. Methods of pathway analysis provide a means to unravel the fundamental pathways and their controls in bioprocesses. In the present Ph.D. thesis, a novel methodology called Principal Elementary Mode Analysis (PEMA) was developed and implemented that enabled to identify which cellular fluxes are activated under different conditions of temperature and pH. It is shown that differences in these two parameters affect the chemical composition of EPS, hence they are critical for the regulation of the product synthesis. In future studies, the knowledge provided by PEMA could foster the development of metabolically meaningful control strategies that target the EPS sugar content and oder product quality parameters.

Critical analysis of the allocation policy for liver transplantation in Brazil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of S��o Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Sa��de de S��o Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.