Characterization of molecular damage induced by UV photons and carbon ions on biomimetic heterostructures

The study of the effect of radiation on living tissues is a rather complex task to address mainly because they are made of a set of complex functional biological structures and interfaces. Particularly if one is looking for where damage is taking place in a first stage and what are the underlying reaction mechanisms. In this work a new approach is addressed to study the effect of radiation by making use of well identified molecular hetero-structures samples which mimic the biological environment. These were obtained by assembling onto a solid support deoxyribonucleic acid (DNA) and phospholipids together with a soft water-containing polyelectrolyte precursor in layered structures and by producing lipid layers at liquid/air interface with DNA as subphase. The effects of both ultraviolet (UV) radiation and carbon ions beams were systematically investigated in these heterostructures, namely damage on DNA by means vacuum ultraviolet (VUV), infrared (IR), X-Ray Photoelectron (XPS) and impedance spectroscopy. Experimental results revealed that UV affects furanose, PO2-, thymines, cytosines and adenines groups. The XPS spectrometry carried out on the samples allowed validate the VUV and IR results and to conclude that ionized phosphate groups, surrounded by the sodium counterions, congregate hydration water molecules which play a role of UV protection. The ac electrical conductivity measurements revealed that the DNA electrical conduction is arising from DNA chain electron hopping between base-pairs and phosphate groups, with the hopping distance equal to the distance between DNA base-pairs and is strongly dependent on UV radiation exposure, due loss of phosphate groups. Characterization of DNA samples exposed to a 4 keV C3+ ions beam revealed also carbon-oxygen bonds break, phosphate groups damage and formation of new species. Results from radiation induced damage carried out on biomimetic heterostructures having different compositions revealed that damage is dependent on sample composition, with respect to functional targeted groups and extent of damage. Conversely, LbL films of 1,2-dipalmitoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (Sodium Salt) (DPPG) liposomes, alternated with poly(allylamine hydrochloride) (PAH) revealed to be unaffected, even by prolonged UV irradiation exposure, in the absence of water molecules. However, DPPG molecules were damaged by the UV radiation in presence of water with cleavage of C-O, C=O and –PO2- bonds. Finally, the study of DNA interaction with the ionic lipids at liquid/air interfaces revealed that electrical charge of the lipid influences the interaction of phospholipid with DNA. In the presence of DNA in the subphase, the effects from UV irrladiation were seen to be smaller, which means that ionic products from biomolecules degradation stabilize the intact DPPG molecules. This mechanism may explain why UV irradiation does not cause immediate cell collapse, thus providing time for the cellular machinery to repair elements damaged by UV.

Flexible multivariate GARCH modeling with an application to international stock markets

This paper offers a new approach to estimating time-varying covariance matrices in the framework of the diagonal-vech version of the multivariate GARCH(1,1) model. Our method is numerically feasible for large-scale problems, produces positive semidefinite conditional covariance matrices, and does not impose unrealistic a priori restrictions. We provide an empirical application in the context of international stock markets, comparing the nev^ estimator with a number of existing ones.

The role of pneumococcal carbon metabolism in colonisation and invasive disease

Streptococcus pneumoniae is a common asymptomatic commensal of the human nasopharynx. However, it is better known as a threatening pathogen that causes serious diseases such as pneumonia, meningitis and sepsis, as well as other less severe but more prevalent infections (e.g. otitis media). With the increase of antibiotic resistance and the limited efficacy of vaccines, pneumococcal infections remain a major problem. Therefore, the discovery of new therapeutic targets and preventive drugs are in high demand.(...)

Predictability of stock market returns: Evidence from Eurozone's banking sectors

This paper analyzes the in-, and out-of sample, predictability of the stock market returns from Eurozone’s banking sectors, arising from bank-specific ratios and macroeconomic variables, using panel estimation techniques. In order to do that, I set an unbalanced panel of 116 banks returns, from April, 1991, to March, 2013, to constitute equal-weighted country-sorted portfolios representative of the Austrian, Belgian, Finish, French, German, Greek, Irish, Italian, Portuguese and Spanish banking sectors. I find that both earnings per share (EPS) and the ratio of total loans to total assets have in-sample predictive power over the portfolios’ monthly returns whereas, regarding the cross-section of annual returns, only EPS retain significant explanatory power. Nevertheless, the sign associated with the impact of EPS is contrarian to the results of past literature. When looking at inter-yearly horizon returns, I document in-sample predictive power arising from the ratios of provisions to net interest income, and non-interest income to net income. Regarding the out-of-sample performance of the proposed models, I find that these would only beat the portfolios’ historical mean on the month following the disclosure of year-end financial statements. Still, the evidence found is not statistically significant. Finally, in a last attempt to find significant evidence of predictability of monthly and annual returns, I use Fama and French 3-Factor and Carhart models to describe the cross-section of returns. Although in-sample the factors can significantly track Eurozone’s banking sectors’ stock market returns, they do not beat the portfolios’ historical mean when forecasting returns.

Modeling and forecasting value-at-risk for the Portuguese stock market

The aim of this work project is to find a model that is able to accurately forecast the daily Value-at-Risk for PSI-20 Index, independently of the market conditions, in order to expand empirical literature for the Portuguese stock market. Hence, two subsamples, representing more and less volatile periods, were modeled through unconditional and conditional volatility models (because it is what drives returns). All models were evaluated through Kupiec’s and Christoffersen’s tests, by comparing forecasts with actual results. Using an out-of-sample of 204 observations, it was found that a GARCH(1,1) is an accurate model for our purposes.

Financial depth, stock markets and economic growth in the EU-15 countries

The aim of this paper is to assess the impact of financial depth on economic growth in the EU-15 countries from 1970 until 2012, using the two-step System GMM estimator. Even though it might be expected a positive impact, the results show it is negative and sometimes even negative and statistically significant. Among the reasons presented for this, the existence of banking crises seems to better explain these results. In tranquil periods, financial deepening appears to have a positive impact, whereas in banking crises it is persistently negative and statistically significant. Also, after an assessment of the impact of stock markets on economic growth, it appears that more developed countries in the EU-15 have an economy more reliant on this segment of the financial system rather than in bank intermediation.

The accuracy of the escrowed dividend model on the value of European options on a stock paying discrete dividend

This project characterizes the accuracy of the escrowed dividend model on the value of European options on a stock paying discrete dividend. A description of the escrowed dividend model is provided, and a comparison between this model and the benchmark model is realized. It is concluded that options on stocks with either low volatility, low dividend yield, low ex-dividend to maturity ratio or that are deep in or out of the money are reasonably priced with the escrowed dividend model.

Non-cell autonomous neuroprotective effect of carbon monoxide : microglia-to-neuron communication

RESUMO: A isquémia cerebral é uma das doenças mais predominantes a nivel mundial, sendo uma das principais causas de mortalidade e invalidez. Parte da propagação de dano no cérebro é causado por inflamação descontrolada, causada principalmente por disfunção da microglia. Desta forma, existe a necessidade de tentar desenvolver estratégias para melhor compreender e modular as acções destas células. O monóxido de carbono (CO), é uma molécula endógena com provas dadas como anti-neuroinflamatório em vários modelos. Assim, o principal objectivo do trabalho foi o estudo do CO como um modulador da acção da microglia, com principal foco dado à comunicação entre estas células e neurónios, tentando entender se existe um efeito neuroprotector por inibição da inflamação. Um protocolo de meio condicionado foi estabelecido usando as linhas celulares BV2 e SH-SY5Y, de microglia e neurónio. A molécula CORM-A1, que liberta expontaniamente CO, foi usada como método de entrega da molécula às celulas. Demonstrámos que o pre-tratamento de células BV2 com CORM-A1 gera neuroprotecção já que reduz a morte celular de neurónios SH-SY5Y quando são incubados com meio condicionado de microglia activada em conjunto com o pró-oxidante t-BHP (tert-butil hidroperóxido). Assim, considerámos que o CO promove neuroprotecção ao inibir as acções inflamatórias da microglia. O papel anti-inflamatório da molécula CORM-A1 foi confirmado quando se verificou que pré-tratamento desta molécula em microglia BV2 limita a secreção de TNF-α mas estimula a secreção de IL-10. Por último, a CORM-A1 induziu a expressão do receptor da microglia CD200R1, molécula que participa na comunicação neurónio-microglia e fundamental para a modulação das acções inflamatórias destas últimas. Em suma, o nosso trabalho reforçou as propriedades anti-neuroinflamatórias do CO e uma capacidade de modular viabilidade neuronal através do seu efeito a nível de comunicação célula-célula. ---------------------------- ABSTRACT: Brain ischemia is a widespread disease worldwide, being one of the main causes of mortality and permanent disability. A portion of the damage that ensues following the ischemic event is caused by unrestrained inflammation, which is mainly orchestrated by exacerbated microglial activity. Hence, developing strategies for modulating microglial inflammation is a major concern nowadays. The endogenous molecule carbon monoxide (CO) has been shown to possess anti-neuroinflammatory properties using in vitro and in vivo approaches. Thus, our objective was to study CO as modulator of microglial activity, in particular in what concerns their communication with neurons, by promoting neuronal viability and limiting inflammatory output of activated microglia. A conditioned media strategy was established with BV2 microglia and SH-SY5Y neurons as cell models. CO-releasing molecule A1 (CORM-A1), a compound that releases CO spontaneously, was used as method of CO delivery to cells. We found that CORM-A1 pre-treatment in BV2 cells yields neuroprotective results, as it limits cell death when SH-SY5Y neurons are challenged with conditioned media from LPS-activated microglia and the pro-oxidant t-BHP (tert-butyl-hydroperoxide). Thus, we assumed carbon monoxide promotes neuroprotection via inhibition of microglial inflammation, displaying a non-cell autonomous role. CORM-A1 pre-treatment limited inflammation by inhibiting BV2 secretion of TNF-α and stimulating IL-10 production. These results reinforce that CO’s anti-inflammatory role confers neuroprotection, as the alterations in these cytokines occur concurrently with the increase in SH-SY5Y viability. Finally, we showed for the first time that carbon monoxide promotes the expression of CD200R1, a microglial receptor involved in neuron-glia communication and modulation of microglia inflammation. Further studies are necessary to clarify this role. Altogether, other than just highlighting CO as an anti-inflammatory and neuroprotective molecule, this work set the foundation for disclosing its involvement in cell-to-cell communication.

Overstock and stock-out in Volkswagen Autoeuropa

The following work is a case study of overstock and stock-out problems at Volkswagen Autoeuropa (VWAE). It introduces the supply chain of Autoeuropa and specializes then on failures connected to inventory problems. Having a successful supply chain is important in a world where products become more and more similar as it can give to companies an edge over their competitors. The case shows three practices that VWAE uses to prevent and to overcome stock problems. Information was gathered by doing interviews with different managers, by analyzing the company’s key processes and by literature research related to the topics of supply chain management and flexibility in the supply chain. Three practices were further investigated: the use of alternative parts, support of the supplier and a rating system of suppliers. In the question section of this work the importance of flexibility and Supplier Relationship Management (SRM) when connected to supply chain management are explained. The described different practices are numerically analyzed and it is concluded that each practice brings both cost savings and the possibility of achieving target numbers to the company, showing the company’s flexibility to react to supply chain disturbances. Because of confidentiality reasons, persons in the case are fictionalized and numbers are wherever possible equalized to 100 in order to display true proportions.

Impact of carbon/nitrogen feeding strategy on polyhydroxyalkanoates production using mixed microbial cultures

Polyhydroxyalkanoates (PHA) production using mixed microbial cultures (MMC) requires a multi-stage process involving the microbial selection of PHA-storing microorganisms, typically operated in sequencing batch reactors (SBR), and an accumulation reactor. Since low-cost renewable feedstocks used as process feedstock are often nitrogen-deficient, nutrient supply in the selection stage is required to allow for microbial growth. In this context, the possibility to uncouple nitrogen supply from carbon feeding within the SBR cycle has been investigated in this study. Moreover, three different COD:N ratios (100:3.79, 100:3.03 and 100:2.43) were tested in three different runs which also allowed the study of COD:N ratio on the SBR performance. For each run, a synthetic mixture of acetic and propionic acids at an overall organic load rate of 8.5 gCOD L-1 d-1 was used as carbon feedstock, whereas ammonium sulfate was the nitrogen source in a lab-scale sequence batch reactor (SBR) with 1 L of working volume. Besides, a sludge retention time (SRT) of 1 d was used as well as a 6 h cycle length. The uncoupled feeding strategy significantly enhanced the selective pressure towards PHA-storing microorganisms, resulting in a two-fold increase in the PHA production (up to about 1.3 gCOD L-1). A high storage response was observed for the two runs with the COD:N ratios (gCOD:gN) of 100:3.79 and 100:3.03, whereas the lowest investigated nitrogen load resulted in very poor performance in terms of polymer production. In fact, strong nitrogen limitation caused fungi to grow and a very poor storage ability by microorganisms that thrived in those conditions. The COD:N ratio also affected the polymer composition, indeed the produced poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) showed a variable HV content (1-20 %, w/w) among the three runs, lessening as the COD:N increased. This clearly suggests the possibility to use the COD:N ratio as a tool for tuning polymer properties regardless the composition of the feedstock.

The impact of credit conditions on market liquidity – a case for European stock markets

The recent financial crisis has drawn the attention of researchers and regulators to the importance of liquidity for stock market stability and efficiency. The ability of market-makers and investors to provide liquidity is constrained by the willingness of financial institutions to supply funding capital. This paper sheds light on the liquidity linkages between the Central Bank, Monetary Financial Institutions and market-makers as crucial elements to the well-functioning of markets. Results suggest the existence of causality between credit conditions and stock market liquidity for the Eurozone between 2003 and 2015. Similar evidence is found for the UK during the post-crisis period. Keywords: stock

Trading the changes of stock market index composition: Evidence from European markets

This paper studies the changes in European stock market indexes composition from 1995 to 2015. It was found that there are mixed price effects producing abnormal returns around the effective replacement of added and deleted stocks. The price pressure hypothesis seems to hold for added stocks in some indexes but not for deleted stocks as there is not a clear inversion of behaviour after the replacement. Finally, the building and back testing of a trading strategy aiming to capture some of those abnormal returns shows it yields a Sharpe Ratio of 1.4 and generates an annualised alpha of 11%.

Hybrid investment strategy active portfolio management – US stock market

This thesis aims to develop an alternative active managed portfolio strategy based on companies‟ Fundamental and Technical Analysis and analyze its finals results. There is a big distinction between the two approaches and the main objective is to understand if it is possible to take advantage of both. With this in mind a Hybrid investment strategy for the US stock market, due to its dimension and liquidity, which was able to outperform the S&P 500 index, the benchmark, during both Bear and Bull Markets between 2000 and 2015.

Anatomy of the portuguese stock market risk and return in the 1977-2012 period

This paper analyses the Portuguese stock market since it reopened in 1977, with a special focus on the evolution of the statistic and stochastic characteristics of the market return throughout this 36 year period. The market return for the period of time between 1977 and 2012 (September 28th) is estimated and then compared with the return that would have been achieved with Government bonds and treasury bills, which allows us to confirm that the hierarchy of return / risk across the different financial instruments is verified. The market risk premium for this 36 year period is also estimated and a comparison with other markets is performed, suggesting that the Portuguese market’s risk has not been compensated by an adequate return. The study also examines the evolution of the Portuguese market’s volatility in the 1977-2012 period and compares it with other markets, showing the existence of extremely high peaks during the first 11 years, but indicating a downwards trend throughout the whole period under analysis. Finally, the correlation between market returns for Portugal and for other countries and the degree of integration are estimated and their evolution throughout time is assessed, leading to the conclusion that the performance of the Portuguese stock market has become increasingly correlated with major European markets – correlation with some markets close to 0.70 from 2000 onwards-, but that country-specific risk factors are still relevant.