Determinants of exchange rates: An empirical analysis

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

Synthesis of new enzyme stabilisers inspired by compatible solutes of hyperthermophilic microorganisms

Dissertation presented to obtain the Ph.D degree in Engineering Sciences and Technology.

Evaluation of intrathecal synthesis of specific IgG antibodies against Toxoplasma gondii in the diagnosis assessment of presumptive toxoplasma encephalitis in aids patients

The diagnosis of neurotoxoplasmosis in patients with acquired immunodeficiency syndrome is mainly based on tomographic or magnetic resonance findings and on the response to specific treatment. We studied 55 patients with AIDS and neurotoxoplasmosis according to these diagnostic criteria (group 1), 37 patients with AIDS and neurological involvement of other etiology (group 2), and 16 anti-HIV-negative individuals with neurological manifestations (group 3). Serum and cerebrospinal fluid were examined for the presence of anti-T. gondii IgG, by indirect immunofluorescence. In 72 of them, the total amounts of these antibodies were determined in order to assess local production of anti-T. gondii antibodies in the central nervous system and to correlate their titers with infection activity in patients with AIDS and neurotoxoplasmosis. IgG titers > 1/64 in cerebrospinal fluid reached 100% specificity for the diagnosis of neurotoxoplasmosis in AIDS. Evidence of local synthesis of these antibodies was detected in 42.8% of patients of group 1, in 29.1% of patients of group 2 and in no patient of group 3. The test showed 70.8% specificity and therefore was not useful in our study for the differential diagnosis of neurotoxoplasmosis in patients with AIDS.

Synthesis of Polymeric Nanoparticles for biomedical delivery applications

Polymeric nanoparticles (PNPs) have attracted considerable interest over the last few years due to their unique properties and behaviors provided by their small size. Such materials could be used in a wide range of applications such as diagnostics and drug delivery. Advantages of PNPs include controlled release, protection of drug molecules and its specific targeting, with concomitant increasing of the therapeutic index. In this work, novel sucrose and cholic acid based PNPs were prepared from different polymers, namely polyethylene glycol (PEG), poly(D,L-lactic-co-glycolic acid) (PLGA) and PLGA-co-PEG copolymer. In these PNP carriers, cholic acid will act as a drug incorporation site and the carbohydrate as targeting moiety. The uptake of nanoparticles into cells usually involves endocytotic processes, which depend primarily on their size and surface characteristics. These properties can be tuned by the nanoparticle preparation method. Therefore, the nanoprecipitation and the emulsion-solvent evaporation method were applied to prepare the PNPs. The influence of various parameters, such as concentration of the starting solution, evaporation method and solvent properties on the nanoparticle size, size distribution and morphology were studied. The PNPs were characterized by using atomic force microscopy (AFM), scanning electron microscopy (SEM) and dynamic light scattering (DLS) to assess their size distribution and morphology. The PNPs obtained by nanoprecipitation ranged in size between 90 nm and 130 nm with a very low polydispersity index (PDI < 0.3). On the other hand, the PNPs produced by the emulsion-solvent evaporation method revealed particle sizes around 300 nm with a high PDI value. More detailed information was found in AFM and SEM images, which demonstrated that all these PNPs were regularly spherical. ζ-potential measurements were satisfactory and evidenced the importance of sucrose moiety on the polymeric system, which was responsible for the obtained negative surface charge, providing colloidal stability. The results of this study show that sucrose and cholic acid based polymeric conjugates can be successfully used to prepare PNPs with tunable physicochemical characteristics. In addition, it provides novel information about the materials used and the methods applied. It is hoped that this work will be useful for the development of novel carbohydrate based nanoparticles for biomedical applications, specifically for targeted drug delivery.

Synanthropic triatomines (Hemiptera, Reduviidae) in the state of Pernambuco, Brazil: geographical distribution and natural Trypanosoma infection rates between 2006 and 2007

INTRODUCTION: The present study shows a descriptive analysis of triatomine occurrence and its natural Trypanosoma infection rates in the state of Pernambuco, Brazil, between 2006 and 2007. METHODS: Entomological data for the species, such as specimens captured in both intra and peridomiciles and natural infection index, were obtained via domiciliary capture in 147 municipalities from 11 Regional Managements of Health. The database was obtained from a sample of insects (100% infected and 20% non-infected) sent to the Central Laboratory of Pernambuco. RESULTS: A total of 18,029 triatomines were analyzed from 138 municipalities of the state. Triatoma pseudomaculata (35%), Triatoma brasiliensis (34%), and Panstrongylus lutzi (25%) were the most captured species. These species also showed a widespread geographical distribution in the state. Panstrongylus megistus, Triatoma petrocchiae, Triatoma melanocephala, Triatoma sordida, Rhodnius nasutus, Rhodnius neglectus, and Triatoma infestans showed more limited geographical distribution and lower relative abundance. The parasitological research showed that 8.8% of the triatomines were naturally infected with flagellates morphologically similar to Trypanosoma cruzi and 91.3% of them were captured inside houses in 113 municipalities. P. lutzi showed the highest rates of natural infection. CONCLUSIONS: After the control of T. infestans, synanthropic species, such as T. brasiliensis, T. pseudomaculata, and P. lutzi, maintain the risk of T. cruzi transmission to humans in the state of Pernambuco. These species are widely distributed, and infected specimens have been found inside houses. Thus, an enhanced surveillance and vector control of Chagas disease is recommended in Pernambuco.

Evaluation of the welfare impact of regulating mobile termination rates in Portugal

Following the European Commission’s 2009 Recommendation on the Regulatory Treatment of Fixed and Mobile Termination Rates in the EU, the Portuguese regulatory authority (ANACOM) decided to reduce termination prices in mobile networks to their long-run incremental cost (LRIC). Nevertheless, no serious quantitative assessment of the potential effects of this decision was carried out. In this paper, we adapt and calibrate the Harbord and Hoernig (2014) model of the UK mobile telephony market to the Portuguese reality, and simulate the likely impact on consumer surplus, profits and welfare of four different regulatory approaches: pure LRIC, reciprocal termination charges with fixed networks, “bill & keep”, and asymmetric termination rates. Our results show that reducing MTRs does increase social welfare, profits and consumer surplus in the fixed market, but mobile subscribers are seriously harmed by this decision.

Empirical evidence on the difference between the effective and the statutory tax rates for listed groups in Germany

The difference between the statutory and effective tax rate for listed groups is a complex variable influenced by a variety of factors. This paper aims to analyze whether this difference exists for listed groups in the German market and tests which factors have an impact on it. Thus the sample consists of 130 corporations listed in the three major German stock indices. The findings suggest that the companies that pay less than the statutory rate clearly outweigh the ones that pay more, and that the income earned from associated companies has a significant impact on this difference.

Phlebotomine sandfly fauna and natural Leishmania infection rates in a rural area of Cerrado (tropical savannah) in Nova Mutum, State of Mato Grosso in Brazil

Introduction American cutaneous leishmaniasis (ACL) has been reported in every municipality of the State of Mato Grosso, Brazil, but the transmission epidemiology remains poorly understood. Our study was developed in a rural area of the Nova Mutum municipality where four autochthonous cases of ACL were reported in 2009. Our aims were to describe the local phlebotomine sandfly fauna and to investigate the infection rates and infecting Leishmania species in the captured sandflies. Methods Entomological captures were performed bimonthly at 10 fixed sites close to the edge of a forested area between June 2011 and April 2012. Results A total of 3,743 phlebotomine sandflies belonging to 31 distinct species were captured. Approximately 75% of the specimens were females. The most abundant species (45.4%) was Lutzomyia antunesi, which was consistently captured at every site. Species that are epidemiologically important for ACL, such as L. flaviscutellata, L. whitmani and L. umbratilis, were also captured. L. antunesi and L. ubiquitalis were naturally infected by Leishmania braziliensis or Le. guyanensis, with minimum infection rates of 0.88% and 6.67%, respectively. Surprisingly, L. antunesi was infected by Le. infantum (synonym chagasi). Conclusions The natural infection of L. antunesi and L. ubiquitalis by Leishmania sp. suggests that these species might play a role in the zoonotic cycle of ACL in Nova Mutum. The presence of Le. infantum in L. antunesi suggests that there may be a risk of an outbreak of visceral leishmaniasis (VL) in Nova Mutum.

Genome-scale metabolic network reconstruction of Polaromonas sp. strain JS666: analysis of cDCE degradation rates and design of experiments for bioremediation improvement

Release of chloroethene compounds into the environment often results in groundwater contamination, which puts people at risk of exposure by drinking contaminated water. cDCE (cis-1,2-dichloroethene) accumulation on subsurface environments is a common environmental problem due to stagnation and partial degradation of other precursor chloroethene species. Polaromonas sp. strain JS666 apparently requires no exotic growth factors to be used as a bioaugmentation agent for aerobic cDCE degradation. Although being the only suitable microorganism found capable of such, further studies are needed for improving the intrinsic bioremediation rates and fully comprehend the metabolic processes involved. In order to do so, a metabolic model, iJS666, was reconstructed from genome annotation and available bibliographic data. FVA (Flux Variability Analysis) and FBA (Flux Balance Analysis) techniques were used to satisfactory validate the predictive capabilities of the iJS666 model. The iJS666 model was able to predict biomass growth for different previously tested conditions, allowed to design key experiments which should be done for further model improvement and, also, produced viable predictions for the use of biostimulant metabolites in the cDCE biodegradation.

Technical optimization of the synthesis of flavours

The goal of this thesis is the investigation and optimization of the synthesis of potential fragrances. This work is projected as collaboration between the University of Applied Sciences in Merseburg and the company Miltitz Aromatics GmbH in Bitterfeld‐Wolfen (Germany). Flavoured compounds can be synthesized in different ways and by various methods. In this work, methods like the phase transfer catalysis and the Cope‐rearrangement were investigated and applied, for getting a high yield and quantity of the desired substances and without any by‐products or side reactions. This involved the study of syntheses with different process parameters such as temperature, solvent, pressure and reaction time. The main focus was on Cope‐rearrangement, which is a common method in the synthesis of new potential fragrance compounds. The substances synthesized in this work have a hepta‐1,5‐diene‐structure and that is why they can easily undergo this [3,3]‐sigma tropic rearrangement. The lead compound of all research was 2,5‐dimethyl‐2‐vinyl‐4‐hexenenitrile (Neronil). Neronil is synthesized by an alkylation of 2‐methyl‐3‐butenenitrile with prenylchloride under basic conditions in a phase‐transfer system. In this work the yield of isolated Neronil is improved from about 35% to 46% by according to the execution conditions of the reaction. Additionally the amount of side product was decreased. This synthesized hexenenitrile involved not only the aforementioned 1,5‐diene‐structure, but also a cyano group, that makes this structure a suitable base for the synthesis of new potential fragrance compounds. It was observed that Neronil can be transferred into 2,5‐dimethyl‐2‐vinyl‐4‐hexenoic acid by a hydrolysis under basic conditions. After five hours the acid can be obtained with a yield of 96%. The following esterification is realized with isobutanol to produce 2,5‐dimethyl‐2‐vinyl‐4‐hexenoic acid isobutyl ester with quantitative conversion. It was observed that the Neronil and the corresponding ester can be converted into the corresponding Cope‐product, with a conversion of 30 % and 80%. Implementing the Cope‐rearrangement, the acid was heated and an unexpected decarboxylated product is formed. To achieve the best verification of reaction development and structure, scrupulous analyses were done using GC‐MS, 1H‐NMR and 13C‐ NMR.

Impact of the antipneumococcal conjugate vaccine on the occurrence of infectious respiratory diseases and hospitalization rates in children

INTRODUCTION: In 2010, to reduce the occurrence of serious pneumococcal disease, the Ministry of Health in Brazil incorporated the 10-valent pneumococcal vaccine in the immunization schedule of children younger than two years of age. The objective of this study was to evaluate the impact of vaccination on the incidence of infectious respiratory diseases in infants before and after the introduction of the 10-valent pneumococcal vaccine. METHODS: This cross-sectional study involved primary care and hospital networks from a city in Minas Gerais State, Brazil, between 2009 and 2012. RESULTS: A 40% reduction in the prevalence of community-acquired pneumonia (CAP) was observed after introducing the pneumococcal conjugate vaccine. Male children were 28% more likely to develop the disease. The prevalence ratio ([PR] = 1.96, 95% CI: 1.52 to 2.53, p < 0.05) suggested that not being vaccinated was associated with the occurrence of pneumonia. The prevalence of CAP was 70% lower (PR 0.30, 95% CI: 0.24 to 0.37, p<0.05) in children vaccinated as recommended compared to children with delayed vaccination, suggesting that the updated vaccine schedule improves protection. CONCLUSIONS: Immunization with the 10-valent pneumococcal vaccine appeared to reduce the number of pneumonia cases in children during the study period. Prospective studies are needed to confirm the efficacy of the vaccine against the occurrence of pneumococcal pneumonia.

The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

INTRODUCTION: Although urine is considered the gold-standard material for the detection of congenital cytomegalovirus (CMV) infection, it can be difficult to obtain in newborns. The aim of this study was to compare the efficiency of detection of congenital CMV infection in saliva and urine samples. METHODS: One thousand newborns were included in the study. Congenital cytomegalovirus deoxyribonucleic acid (DNA) was detected by polymerase chain reaction (PCR). RESULTS: Saliva samples were obtained from all the newborns, whereas urine collection was successful in only 333 cases. There was no statistically significant difference between the use of saliva alone or saliva and urine collected simultaneously for the detection of CMV infection. CONCLUSIONS: Saliva samples can be used in large-scale neonatal screening for CMV infection.

Synthesis of precursors of the rare 3-O-methylmannose polysaccharides present in Nontuberculous Mycobacteria

3-O-methylmannose polysaccharides (MMPs) are cytoplasmic carbohydrates synthesized by mycobacteria, which play important intracellular roles, such as for example in metabolism regulation. An important way to confirm if the inhibition of the synthesis of these polysaccharides will critically affect the survival of mycobacteria is the study of the biosynthetic pathways from these molecules on these microorganisms. The purpose of this work is the efficient synthesis of three saccharides, which are rare cellular precursors from the biosynthesis of the mycobacterial polysaccharides, allowing its study. In order to obtain these molecules, a chemical strategy to connect two precursors was used. This process is called chemical glycosylation and its importance will be highlighted as an important alternative to enzymatic glycosylation. The first objective was the synthesis of the disaccharides Methyl (3-O-methyl-α-D-mannopyranosyl)-(1→4)-3-O-methyl-α-D-mannopyranoside and (3-O-Methyl-α-D-mannopyra- nosyl)-(1→4)-3-O-methyl-(α/β)-D-mannopyranose. The mannose precursors were prepared before the glycosylation reaction. The same mannosyl donor was used in the preparation of both molecules and its efficient synthesis was achieved using a 8 step synthetic route from D-mannose. A different mannosyl acceptor was used in the synthesis of each disaccharide and their syntheses were also efficient, the first one a 4 step synthetic route from α-methyl-D-mannose and the second one as an intermediate from the synthesis of the mannosyl donor. The stereoselective preparation of these disaccharides was performed successfully. The second and last objective of the proposed work was the synthesis of the tetrasaccharide methyl (3-O-methyl-α-D-mannopyranosyl-(1→4)-3-O-methyl-α-D-mannopyra- nosyl-(1→4)-3-O-methyl-α-D-mannopyranosyl-(1→4)-3-O-methyl-α-D-mannopyranoside. The disaccharide acceptor and donor to be linked through a stereoselective glycosidic reaction had to be first synthesized. Several synthetic strategies were studied. Neither the precursors nor the tetrasaccharide were synthesized, but a final promising synthetic route for its preparation has been proposed.

Evaluation of human T-lymphotropic virus prevalence/co-infection rates for a four-year period in a non-metropolitan blood center in Southeast Brazil

Abstract: INTRODUCTION: Human T-lymphotropic virus types 1/2 (HTLV-1/2) are distributed worldwide and are endemic in specific regions. METHODS: Serological evaluation of the HTLV-1/2 prevalence and co-infection rate [human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Chagas disease, and syphilis)] for 2011-2014 was performed with volunteer blood donors from the western part of São Paulo State. RESULTS: Serrana and Araçatuba had higher HTLV seroprevalence rates (0.1%); while Franca, Olimpia, and Bebedouro had lower seroprevalences (0.04%). Co-infection (HBV and syphilis) was present in 12.3% of HTLV-infected blood donors. CONCLUSIONS: Our findings provide data for the prevalence of HTLV in Brazil and demonstrate the importance of regional and global hemovigilance.

Study of the role of wall teichoic acids in the localization Staphylococcus aureus cell wall synthesis protein PBP4

The cell wall of Staphylococcus aureus is a highly complex network mainly composed of highly cross-linked peptidoglycan (PG) and teichoic acids (TAs), both important for the maintenance of the integrity and viability of bacteria. The penicillin binding proteins (PBPs), which catalyse the final stage of PG biosynthesis, are targets of β-lactam antibiotics and have been a key focus of antibacterial research. S. aureus has four native PBPs, PBP1-4 carried by both methicillin-sensitive (MSSA) and –resistant (MRSA) strains. PBP4 is required for the synthesis of the highly cross-linked PG and, as shown in recent studies, is essential for the expression of β-lactam resistance in community-acquired strains (CA-MRSA). This protein has a septal localization that seems to be spatially and temporally regulated by an unknown intermediate of the wall teichoic acids (WTA) biosynthesis pathway. Therefore, if WTA synthesis is compromised, PBP4 becomes dispersed throughout the entire cell membrane. The aim of this project was to identify the WTA precursor responsible for the septal recruitment of PBP4. In order to do so, inducible mutants of tarB and tarL genes in the background of NCTCPBP4-YFP were constructed allowing for the study of PBP4 localization in the presence and absence of these specific tar genes.With this work we were able to show that the absence of TarB or TarL leads to the delocalization of PBP4, indicating that TarL or a protein/WTA precursor whose localization/synthesis is dependent on TarL is responsible for the recruitment of PBP4.