«A Responsabilidade das Empresas pelo Crime de Corrupção», «Direito Penal § Fundamentos Dogmáticos e Político-Criminais»

Resumo: 1- Introdução: algumas notícias da comunicação social; 2 – O designado «Conselho de Prevenção de Corrupção»; 3 – Procuradoria-Geral da República (P.G.R.) e o Departamento Central de Investigação e Acção Penal (D.I.A.P.); 4 – Alguns sítios com relevo; 5 – Alguns dos problemas que podem ser colocados em relação à Responsabilidade das Empresas pelo Crime de Corrupção; 5.1 – Âmbito dos problemas a serem falados; 6 – Qual a noção de «empresas que vamos utilizar»?; 6.1 – A noção de «empresa» em sentido geral objectivo e penal; 7 – Mas que tipo de crimes de corrupção vamos falar?; 8 – O art. 11º do Código Penal e os crimes de corrupção no contexto do ordenamento jurídico português; 8.1 – No contexto do art. 11º do Código Penal, o que significa «em nome da pessoa colectiva»?; 8.2 – No contexto do art. 11º do Código Penal, o que significa «no interesse da pessoa colectiva»?; 8.2.1 – No contexto do art. 11º do Código Penal, o que significa «quando não há interesse colectivo»?; 9 – E haverá diferenças, por exemplo, entre o modo de funcionamento técnico-jurídico do art. 11º do Código Penal e o art. 3º do Regime das Infracções Anti-Económicas e Contra a Saúde Pública (R.I.A.E.C.S.P.)?; 10 – E como é que a Jurisprudência portuguesa, a que tivemos acesso - dado não haver ainda fartura de decisões neste campo -, estabelece o nexo de imputação de responsabilidade penal a uma pessoa colectiva e/ou organização?; 10.1 – Uma primeira pré-conclusão dentro do objectivo que pretendemos demonstrar na totalidade deste trabalho; 11 – Uma segunda pré-conclusão: será que as diferenças acima assinaladas, por exemplo, entre o modo de funcionamento técnico-jurídico do art. 11º do Código Penal e o art. 3º do Regime das Infracções Anti-Económicas e Contra a Saúde Pública (R.I.A.E.C.S.P.), são as únicas? Veja-se o caso, v.g., do art. 7º do Regime Geral das Infracções Tributárias (R.G.I.T.); 12 – Em face das duas pré-conclusões anteriores, faça-se aqui, neste breve ensaio, uma primeira grande conclusão; 13 – Uma (primeira) hipótese de solução; 14 – Que tipo de «empresa» podemos enquadrar no art. 11º do Código Penal?; 14.1 – De acordo com o referido anteriormente, podemos dizer que todas as «empresas» podem praticar os crimes previstos e punidos no Código Penal português?; 14.2 – De acordo com o referido antes, quais são as «empresas» que não podem praticar os crimes de corrupção que estão previstos e punidos no Código Penal português?; 14.3 – Uma outra pré-conclusão: 14.4 – Um esboço de um dos possíveis problemas; 14.4.1 – Mas, afinal, o que são Entidades Públicas Empresariais (E.P.E.)?; 14.5 – Outra hipótese de esboço de um outro dos possíveis problemas que aqui podemos encontrar; 14.6 – Nova pré-conclusão; 14.7 – Uma outra importante pergunta a fazer e a responder desde já; 14.7.1 - Alarguemos, pois, um pouco a nossa investigação para além do Código Penal português; 14.7.2 – O problema da responsabilidade penal das organizações e/ou «pessoas colectivas», rectius, neste breve ensaio, empresas, pela prática de crimes de corrupção previstos e punidos na mencionada Lei n.º 20/2008, de 21 de Abril («Responsabilidade penal por crimes de corrupção no comércio internacional e na actividade privada»); 14.7.3 – Mais algumas pré-conclusões; 15 - Em face das duas pré-conclusões anteriores, faça-se aqui, neste breve ensaio, uma segunda grande conclusão; 16 - O que também apresenta outras implicações como por exemplo na aplicação do crime de «branqueamento» quando nos fala em «corrupção» como «crime primário»; 17 – Outras interrogações; 18 – Conclusão final, mas não última, como nenhuma o pode ser em ciência; 19 – Hipótese de solução. § Abstract: 1 - Introduction: some news media; 2 - The so-called "Council for the Prevention of Corruption”, 3 – “Attorney General's Office” (PGR) and the Central Bureau of Investigation and Penal Action (DIAP) 4 - Some sites with relief , 5 - Some of the problems that can be placed in relation to the Corporate Responsibility of the Crime of Corruption; 5.1 - Scope of issues to be spoken, 6 - What is the concept of "companies that we will use"?; 6.1 - The term “business” in a general purpose and criminal matters; 7 - What kind of crimes of corruption we talking about?; 8 - Art. 11 of the Penal Code and the crimes of corruption in the context of the Portuguese legal system; 8.1 - In the context of art. 11 of the Penal Code, which means "in the name of the legal person"?; 8.2 - In the context of art. 11 of the Penal Code, which means “in the interests of the legal person"?; 8.2.1 - In the context of art. 11 of the Penal Code, which means "where there is no collective interest"?; 9 - There will be differences, for example, between the operating mode of the Art. 11 of the Criminal Code and Art. 3 of the Legal Infractions Anti-Economic and Against Public Health (RIAECSP)?; 10 - And how does the case law of Portugal, we had access - as there still plenty of decisions in this field - makes a connection of allocating criminal liability to a legal person and / or organization?; 10.1 - A first pre-completion within the objective that we intend to demonstrate in all of this work; 11 - A second pre-conclusion: that the differences will be noted above, for example, between operating mode of the Art. 11 of the Criminal Code and Art. 3 of the Rules of the Offences Against Anti-Economics and Public Health (RIAECSP) are the only ones? Take the case v.g. of art. 7 of the Legal Framework of Tax Offences (RGIT) 12 - In view of the two pre-earlier conclusions, do it here, in this brief essay, a first major conclusion; 13 - A (first) chance for a solution, 14 - What kind “undertaking” we can frame the art. 11 of the Penal Code?; 14.1 - According to the above, we can say that all "companies" can practice the crimes defined and punished in the Portuguese Penal Code?; 14.2 - According to the mentioned before, what are the "business" who cannot practice corruption crimes that are planned and punished the Portuguese Penal Code?; 14.3 - Another pre-completion: 14.4 - A sketch of one of the possible problems; 14.4.1 - But after all the entities that are Public Enterprise (EPE)?; 14.5 - Another chance to draft another one of the possible problems that can be found here; 14.6 - New pre-completion; 14.7 - Another important question to ask and answer now; 14.7.1 - Let us expand, then, a little beyond our investigation of the Portuguese Penal Code; 14.7.2 - The problem of criminal liability of organizations and / or "legal persons", rectius, this brief essay, companies, for crimes of corruption provided for and punished mentioned in Law No. 20/2008 of 21 April ("Criminal liability for crimes of corruption in international trade and private activities"); 14.7.3 - Some more pre-conclusions; 15 - In view of the two pre-earlier conclusions, let it be here in this brief essay, a second major conclusion, 16 - Who also has other implications such as the application of the crime of "money laundering" when we talk about “corruption” as “primary crime”, 17 - Other questions; 18 - Bottom line, but not last, as the can be no science; 19 - Hypothesis solution. Abstract como no livro.

A Responsabilidade das Empresas pelo Crime de Corrupção: o Caso Português a partir de uma Perspectiva de Direito Penal, mas também de Criminologia

1- Introdução: algumas notícias da comunicação social; 2 – O designado «Conselho de Prevenção de Corrupção»; 3 – Procuradoria-Geral da República (P.G.R.) e o Departamento Central de Investigação e Acção Penal (D.I.A.P.); 4 – Alguns sítios com relevo; 5 – Alguns dos problemas que podem ser colocados em relação à Responsabilidade das Empresas pelo Crime de Corrupção; 5.1 – Âmbito dos problemas a serem falados; 6 – Qual a noção de «empresas que vamos utilizar»?; 6.1 – A noção de «empresa» em sentido geral objectivo e penal; 7 – Mas que tipo de crimes de corrupção vamos falar?; 8 – O art. 11º do Código Penal e os crimes de corrupção no contexto do ordenamento jurídico português; 8.1 – No contexto do art. 11º do Código Penal, o que significa «em nome da pessoa colectiva»?; 8.2 – No contexto do art. 11º do Código Penal, o que significa «no interesse da pessoa colectiva»?; 8.2.1 – No contexto do art. 11º do Código Penal, o que significa «quando não há interesse colectivo»?; 9 – E haverá diferenças, por exemplo, entre o modo de funcionamento técnico-jurídico do art. 11º do Código Penal e o art. 3º do Regime das Infracções Anti-Económicas e Contra a Saúde Pública (R.I.A.E.C.S.P.)?; 10 – E como é que a Jurisprudência portuguesa, a que tivemos acesso - dado não haver ainda fartura de decisões neste campo -, estabelece o nexo de imputação de responsabilidade penal a uma pessoa colectiva e/ou organização?; 10.1 – Uma primeira pré-conclusão dentro do objectivo que pretendemos demonstrar na totalidade deste trabalho; 11 – Uma segunda pré-conclusão: será que as diferenças acima assinaladas, por exemplo, entre o modo de funcionamento técnico-jurídico do art. 11º do Código Penal e o art. 3º do Regime das Infracções Anti-Económicas e Contra a Saúde Pública (R.I.A.E.C.S.P.), são as únicas? Veja-se o caso, v.g., do art. 7º do Regime Geral das Infracções Tributárias (R.G.I.T.); 12 – Em face das duas pré-conclusões anteriores, faça-se aqui, neste breve ensaio, uma primeira grande conclusão; 13 – Uma (primeira) hipótese de solução; 14 – Que tipo de «empresa» podemos enquadrar no art. 11º do Código Penal?; 14.1 – De acordo com o referido anteriormente, podemos dizer que todas as «empresas» podem praticar os crimes previstos e punidos no Código Penal português?; 14.2 – De acordo com o referido antes, quais são as «empresas» que não podem praticar os crimes de corrupção que estão previstos e punidos no Código Penal português?; 14.3 – Uma outra pré-conclusão: 14.4 – Um esboço de um dos possíveis problemas; 14.4.1 – Mas, afinal, o que são Entidades Públicas Empresariais (E.P.E.)?; 14.5 – Outra hipótese de esboço de um outro dos possíveis problemas que aqui podemos encontrar; 14.6 – Nova pré-conclusão; 14.7 – Uma outra importante pergunta a fazer e a responder desde já; 14.7.1 - Alarguemos, pois, um pouco a nossa investigação para além do Código Penal português; 14.7.2 – O problema da responsabilidade penal das organizações e/ou «pessoas colectivas», rectius, neste breve ensaio, empresas, pela prática de crimes de corrupção previstos e punidos na mencionada Lei n.º 20/2008, de 21 de Abril («Responsabilidade penal por crimes de corrupção no comércio internacional e na actividade privada»); 14.7.3 – Mais algumas pré-conclusões; 15 - Em face das duas pré-conclusões anteriores, faça-se aqui, neste breve ensaio, uma segunda grande conclusão; 16 - O que também apresenta outras implicações como por exemplo na aplicação do crime de «branqueamento» quando nos fala em «corrupção» como «crime primário»; 17 – Outras interrogações; 18 – Conclusão final, mas não última, como nenhuma o pode ser em ciência; 19 – Hipótese de solução; 20 – Novos desenvolvimentos. § 1 - Introduction: some news media; 2 - The so-called "Council for the Prevention of Corruption”, 3 – “Attorney General's Office” (PGR) and the Central Bureau of Investigation and Penal Action (DIAP) 4 - Some sites with relief , 5 - Some of the problems that can be placed in relation to the Corporate Responsibility of the Crime of Corruption; 5.1 - Scope of issues to be spoken, 6 - What is the concept of "companies that we will use"?; 6.1 - The term “business” in a general purpose and criminal matters; 7 - What kind of crimes of corruption we talking about?; 8 - Art. 11 of the Penal Code and the crimes of corruption in the context of the Portuguese legal system; 8.1 - In the context of art. 11 of the Penal Code, which means "in the name of the legal person"?; 8.2 - In the context of art. 11 of the Penal Code, which means “in the interests of the legal person"?; 8.2.1 - In the context of art. 11 of the Penal Code, which means "where there is no collective interest"?; 9 - There will be differences, for example, between the operating mode of the Art. 11 of the Criminal Code and Art. 3 of the Legal Infractions Anti-Economic and Against Public Health (RIAECSP)?; 10 - And how does the case law of Portugal, we had access - as there still plenty of decisions in this field - makes a connection of allocating criminal liability to a legal person and / or organization?; 10.1 - A first pre-completion within the objective that we intend to demonstrate in all of this work; 11 - A second pre-conclusion: that the differences will be noted above, for example, between operating mode of the Art. 11 of the Criminal Code and Art. 3 of the Rules of the Offences Against Anti-Economics and Public Health (RIAECSP) are the only ones? Take the case v.g. of art. 7 of the Legal Framework of Tax Offences (RGIT) 12 - In view of the two pre-earlier conclusions, do it here, in this brief essay, a first major conclusion; 13 - A (first) chance for a solution, 14 - What kind “undertaking” we can frame the art. 11 of the Penal Code?; 14.1 - According to the above, we can say that all "companies" can practice the crimes defined and punished in the Portuguese Penal Code?; 14.2 - According to the mentioned before, what are the "business" who cannot practice corruption crimes that are planned and punished the Portuguese Penal Code?; 14.3 - Another pre-completion: 14.4 - A sketch of one of the possible problems; 14.4.1 - But after all the entities that are Public Enterprise (EPE)?; 14.5 - Another chance to draft another one of the possible problems that can be found here; 14.6 - New pre-completion; 14.7 - Another important question to ask and answer now; 14.7.1 - Let us expand, then, a little beyond our investigation of the Portuguese Penal Code; 14.7.2 - The problem of criminal liability of organizations and / or "legal persons", rectius, this brief essay, companies, for crimes of corruption provided for and punished mentioned in Law No. 20/2008 of 21 April ("Criminal liability for crimes of corruption in international trade and private activities"); 14.7.3 - Some more pre-conclusions; 15 - In view of the two pre-earlier conclusions, let it be here in this brief essay, a second major conclusion, 16 - Who also has other implications such as the application of the crime of "money laundering" when we talk about “corruption” as “primary crime”, 17 - Other questions; 18 - Bottom line, but not last, as the can be no science; 19 - Hypothesis solution; 20 - New developments.

Can power laws help us understand gene and proteome information?

Proteins are biochemical entities consisting of one or more blocks typically folded in a 3D pattern. Each block (a polypeptide) is a single linear sequence of amino acids that are biochemically bonded together. The amino acid sequence in a protein is defined by the sequence of a gene or several genes encoded in the DNA-based genetic code. This genetic code typically uses twenty amino acids, but in certain organisms the genetic code can also include two other amino acids. After linking the amino acids during protein synthesis, each amino acid becomes a residue in a protein, which is then chemically modified, ultimately changing and defining the protein function. In this study, the authors analyze the amino acid sequence using alignment-free methods, aiming to identify structural patterns in sets of proteins and in the proteome, without any other previous assumptions. The paper starts by analyzing amino acid sequence data by means of histograms using fixed length amino acid words (tuples). After creating the initial relative frequency histograms, they are transformed and processed in order to generate quantitative results for information extraction and graphical visualization. Selected samples from two reference datasets are used, and results reveal that the proposed method is able to generate relevant outputs in accordance with current scientific knowledge in domains like protein sequence/proteome analysis.

On the use of IEEE 802.15.4/Zigbee for time-sensitive wireless sensor network applications

Mestrado em Engenharia Electrotécnica e de Computadores

Estudo exploratório dos comportamentos interativos mãe – filho(a) e pai – filho(a) aos 15 meses de vida.

Dissertação apresentada à Escola Superior de Educação de Lisboa para obtenção do grau de Mestre em Intervenção Precoce

A comparação da qualidade dos momentos de interação em jogo livre entre mãe/ filho - pai /filho e mãe/criança – técnica/criança entre os 13 e 15 meses de idade

Dissertação apresentada para obtenção do grau de Mestre em Ciências da Educação Área de especialização em Intervenção Precoce

Spectroscopic Studies and Characterization of a Novel Electron-Transfer Chain

A novel two-component enzyme system from Escherichia coli involving a flavorubredoxin (FlRd) and its reductase was studied in terms of spectroscopic, redox, and biochemical properties of its constituents. FlRd contains one FMN and one rubredoxin (Rd) center per monomer. To assess the role of the Rd domain, FlRd and a truncated form lacking the Rd domain (FlRd¢Rd), were characterized. FlRd contains 2.9 ( 0.5 iron atoms/subunit, whereas FlRd¢Rd contains 2.1 ( 0.6 iron atoms/subunit. While for FlRd one iron atom corresponds to the Rd center, the other two irons, also present in FlRd¢Rd, are most probably due to a di-iron site. Redox titrations of FlRd using EPR and visible spectroscopies allowed us to determine that the Rd site has a reduction potential of -140 ( 15 mV, whereas the FMN undergoes reduction via a red-semiquinone, at -140 ( 15 mV (Flox/Flsq) and -180 ( 15 mV (Flsq/Flred), at pH 7.6. The Rd site has the lowest potential ever reported for a Rd center, which may be correlated with specific amino acid substitutions close to both cysteine clusters. The gene adjacent to that encoding FlRd was found to code for an FAD-containing protein, (flavo)rubredoxin reductase (FlRd-reductase), which is capable of mediating electron transfer from NADH to DesulfoVibrio gigas Rd as well as to E. coli FlRd. Furthermore, electron donation was found to proceed through the Rd domain of FlRd as the Rd-truncated protein does not react with FlRd-reductase. In vitro, this pathway links NADH oxidation with dioxygen reduction. The possible function of this chain is discussed considering the presence of FlRd homologues in all known genomes of anaerobes and facultative aerobes.

Service-oriented mobility of java code in web services-based architectures

Dissertação apresentada na Faculdade de Ciências e Tecnologias da Universidade Nova de Lisboa para a obtenção do Grau de Mestre em Engenharia Informática

Calcificações vasculares nos doentes em diálise : elo de ligação entre doença óssea e doença vascular

RESUMO: A presente dissertação para tese de doutoramento apresenta o desenvolvimento e a validação de um método simples e original para o diagnóstico de calcificações vasculares em doentes em diálise, utilizando um score semiquantitativo criado por nós e obtido em RX simples da bacia e das mãos, denominado score de calcifi cação vascular simples. Demonstramos que este score vascular simples é preditor de risco cardiovascular nos doentes em diálise. O score de calcificação vascular simples associou-se ainda à baixa densidade mineral óssea avaliada por dual energy X -ray absortiometry (DXA) no colo do fémur. Verifi camos igualmente que, em doentes em diálise, as calcifi cações coronárias quantifi cadas pelo score de Agatston e o score de calcifi cação vascular simples se associaram a um menor volume ósseo avaliado em biopsias ósseas. Estes trabalhos corroboram a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular nos doentes em diálise, e um dos elementos que contribuem para este elo de ligação podem ser as calcificações vasculares. Este score de calcificação vascular simples avalia calcifi cações em artérias de grande, médio e pequeno calibre, e inclui os dois padrões radiológicos de calcificação: calcificação linear, associada à calcifi cação da camada média da parede arterial, e calcificação irregular, associada à calcifi cação da camada íntima arterial1. Nos diferentes trabalhos por nós publicados demonstramos que as calcificações vasculares avaliadas por este método simples e barato permitem a identificação de indivíduos com elevado risco cardiovascular. Este score vascular associa -se a maior risco de mortalidade cardiovascular2, de mortalidade de causa global3, de internamentos cardiovasculares2, de doença ardiovascular2, de doença arterial periférica2,4,de calcifi cações valvulares5 e de rigidez arterial3. As guidelines KDIGO (Kidney disease: improving global outcomes), publicadas em 2009,sugerem que os doentes renais crónicos nos estadios 3 a 5, com calcificações vasculares e valvulares, devem ser considerados como apresentando o mais elevado risco cardiovascular6. A elevada mortalidade dos doentes renais crónicos não é totalmente explicada pelos fatores de risco tradicionais7. A organização KDIGO defende, desde 2006, a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular8. Esta ligação pode ser explicada pelas alterações do metabolismo mineral e ósseo e pela sua interação com as calcificações vasculares. Verificamos, nos nossos trabalhos, uma associação entre calcifi cações vasculares e doença óssea. O baixo volume ósseo diagnosticado por análise histomorfométrica de biopsias ósseas foi preditor de maior risco de calcificações vasculares avaliadas pelo score de calcifi cação vascular simples (dados apresentados nesta dissertação, no capítulo 6) e pelo score coronário de Agatston num grupo de doentes em diálise9. A contribuição original deste artigo9 foi considerada merecedora de um editorial feito pelo Dr. Gérard London10, investigador líder na área da calcificação vascular dos doentes renais crónicos e actual Presidente da EDTA (European Dialysis and Transplantation Association). Fomos também os primeiros a descrever uma associação independente e inversa entre a densidade mineral avaliada no colo do fémur por DXA (dual energy X -ray absortiometry) com calcificações vasculares avaliadas pelo score de calcificação vascular simples, com rigidez arterial avaliada por velocidade de onda de pulsocarotidofemoral e com doença arterial periférica diagnosticada por critérios clínicos11. Fomos igualmente os primeiros a mostrar uma correlação signifi cativa entre a densidade mineral óssea avaliada por DXA no colo do fémur, mas não na coluna lombar, com a espessura cortical avaliada por análise histomorfométrica em biopsia óssea12. O nosso estudo atribui pela primeira vez à DXA um papel no diagnóstico de porosidade cortical nos doentes em diálise. A utilidade da avaliação diferencial da densidade mineral óssea cortical e trabecular necessita ainda de ser confirmada em estudos prospectivos. Este achado inovador do nosso estudo foi mencionado pela ERBP (European Renal Best Practice) no comentário feito à posição da KDIGO que considera ser reduzida a utilidade da densidade mineral óssea nos doentes em diálise13. Dois dos trabalhos incluídos nesta dissertação foram referenciados nas guidelines KDIGO 2009 para avaliar a prevalência das calcificações vasculares (KDIGO 2009: Tabela suplementar 10, Fig. 3.6) e para validar a associação entre calcificações vasculares e mortalidade cardiovascular (KDIGO 2009: Tabela suplementar 12, Fig. 3.7)6. A inclusão destes nossos dois estudos nas referências destas guidelines, que utilizaram o exigente sistema GRADE (Grades of recommendation, assessment, development, and evaluation) na classificação e selecção dos estudos, valida o interesse científico dos nossos trabalhos. O diagnóstico de calcificações vasculares tem um interesse prático para os doentes renais crónicos. A presença de calcifi cações vasculares é um sinal de alerta para a existência de um elevado risco cardiovascular, e esta informação pode ser utilizada para modificar a terapêutica nestes doentes6. Diferentes métodos podem ser usados para diagnosticar calcificações vasculares nos doentes em diálise14,15. O score de calcificação vascular simples tem a vantagem da simplicidade e de poder ser facilmente interpretado pelo nefrologista, sem necessidade de um radiologista. A reprodutibilidade deste score já foi demonstrada por diferentes grupos em estudos nacionais e internacionais16-24. Nestes estudos foi demonstrado que as calcifi cações vasculares avaliadas pelo método criado por nós são preditoras de maior risco de eventos cardiovasculares16, de amputações dos membros inferiores17, de velocidade de onda de pulso18,19, de calcificações corneanas e conjuntivais20 e de calcifi cações coronárias21. Também foi demonstrada uma associação inversa entre o score de calcificação vascular simples com os níveis séricos de PTH21, com os níveis de 25(OH)vitamina D 22,23 e com os níveis de fetuína A19,24. Todos estes estudos, realizados por diferentes grupos, que utilizaram o score de calcificação vascular simples na sua metodologia, comprovam a facilidade de utilização deste score e a concordância de resultados atestam a sua reprodutibilidade e a utilidade na avaliação dos doentes renais crónicos. ---------------------------ABSTRACT: This thesis presents the development and validation of a simple and original method to identify vascular calcifications in dialysis patients, using a semi -quantitative score that we have created and that is obtained in plain X -ray of pelvis and hands. This score was named in different publications as “simple vascular calcifi cation score”. We have demonstrated that this score is a predictor of higher cardiovascular risk in dialysis patients. The simple vascular calcification score was also associated with lower mineral bone density evaluated by DXA in femoral neck. In hemodialysis patients coronary calcifications evaluated by the coronary Agatston score and by the simple vascular calcification score were associated with lower bone volume analysed in bone biopsies. These studies corroborate the hypothesis of the existence of a link between bone disease and vascular disease in dialysis patients and one of the elements of this link may be vascular calcifications. This simple vascular calcification score identifi es calcifications in large, medium and small calibre arteries and includes the two radiological patterns of arterial calcifi cation: linear calcification which has been associated with the calcifi cation of the media layer of the arterial wall and irregular and patchy calcification which has been associated with the calcifi cation of the intima layer of the arterial wall1. In the several studies that we have published we have demonstrated that vascular calcifications evaluated by this simple and inexpensive method allow the identification of patients with high cardiovascular risk. This simple vascular calcification score is an independent predictor of cardiovascular mortality2, all -cause mortality3, cardiovascular hospitalizations2, cardiovascular disease2, peripheral artery disease2,4, valvular calcifi cations5 and arterial stiffness3.KDIGO (Kidney Disease: Improving Global Outcomes) guidelines published in 2009 suggest that chronic kidney disease patients in stages 3 to 5, with vascular and valvular calcifications should be considered to be at the highest cardiovascular risk6. The high mortality of chronic kidney disease patients is not completely explained by the traditional risk factors7 and KDIGO group supports, since 2006, the hypothesis of the existence of a link between bone disease and vascular disease8.This link may be explained by the alterations of the bone and mineral metabolism and their interaction with development and progression of vascular calcifications. We have also verifi ed in our studies the existence of an association between vascular calcifications and bone disease. Low bone volume diagnosed by histomorphometric analysis of bone biopsies, in a group of dialysis patients, was independently associated with the simple vascular calcification score (data presented in this thesis,chapter 6) and with coronary calcifications evaluated by the Agatston score9. The original contribution of this article published in CJASN9 deserved a commentary in an Editorial written by Prof. Gérard London10 leader investigator in this area and current EDTA (European Dialysis and Transplantation Association) President. We were also the fi rst group to describe an independent and inverse association between bone mineral density evaluated in the femoral neck by DXA (dual energy X -ray absortiometry) with vascular calcifications evaluated by the simple vascular calcification score, with arterial stiffness evaluated by carotid-femoral pulse wave velocity and with peripheral artery disease diagnosed by clinical criteria11. We were also the first group to demonstrate a significant correlation between bone mineral density evaluated by DXA in femoral neck but not in lumbar spine, with cortical thickness evaluated by histomorphometric analysis of bone biopsy12. Our study has attributed to DXA, for the first time, a role in the diagnosis of cortical porosity in dialysis patients. The clinical utility of the differential evaluation of bone mineral density in cortical or trabecular bone needs, however, to be confi rmed in prospective studies. This original fi nding of our study was mentioned by ERBP (European Renal Best Practice) commenting the KDIGO position in relation with the reduced utility of bone mineral density evaluation in dialysis patients13. Two of the studies included in this thesis have been integrated in a group of studies selected as references by the KDIGO guidelines published in 2009 to evaluate the prevalence of vascular calcifications in CKD patients (KDIGO 2009: Supplementary Table 10, Fig. 3.6) and to corroborate the association between vascular calcifications and cardiovascular mortality (KDIGO 2009: Supplementary Table 12, Fig. 3.7)6. The inclusion of both studies as references in the KDIGO guidelines that have used the exigent GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation) in the classifi cation and selection of studies, validates the scientifi c value of our studies. The diagnosis of vascular calcifi cations has a practical interest for chronic kidney disease patients. The presence of vascular calcifications is an alert sign to the existence of a high cardiovascular risk and this information may be used to modify the treatment of these patients6. Different methods may be used to detect the presence of vascular calcifications in dialysis patients14,15. The simple vascular calcifi cation score has the advantage of being simple, inexpensive and easily evaluated by the Nephrologist without the need for a Radiologist interpretation. The reproducibility of this method has already been demonstrated by other groups in national and international studies16 -24. It was demonstrated in those studies that vascular calcifi cations evaluated by the method created by us, predict higher risk of cardiovascular events16, higher risk of lower limbs amputations17, higher pulse wave velocity18,19, corneal and conjuntival calcifi cations 20 and coronary calcifi cations21. A negative association between the simple vascular calcification score and PTH levels21, 25(OH) vitamin D levels22,23 and Fetuin A levels19,24 has also been demonstrated. All these studies performed by different groups that have used the simple vascular calcifi cation score in their methods demonstrate that this score is simple, useful and reproducible in the evaluation of chronic kidney disease patients simple, useful and reproducible in the evaluation of chronic kidney disease patients.

15

Developing a predictive understanding of subsurface flow and transport is complicated by the disparity of scales across which controlling hydrological properties and processes span. Conventional techniques for characterizing hydrogeological properties (such as pumping, slug, and flowmeter tests) typically rely on borehole access to the subsurface. Because their spatial extent is commonly limited to the vicinity near the wellbores, these methods often cannot provide sufficient information to describe key controls on subsurface flow and transport. The field of hydrogeophysics has evolved in recent years to explore the potential that geophysical methods hold for improving the quantification of subsurface properties and processes relevant for hydrological investigations. This chapter is intended to familiarize hydrogeologists and water-resource professionals with the state of the art as well as existing challenges associated with hydrogeophysics. We provide a review of the key components of hydrogeophysical studies, which include: geophysical methods commonly used for shallow subsurface characterization; petrophysical relationships used to link the geophysical properties to hydrological properties and state variables; and estimation or inversion methods used to integrate hydrological and geophysical measurements in a consistent manner. We demonstrate the use of these different geophysical methods, petrophysical relationships, and estimation approaches through several field-scale case studies. Among other applications, the case studies illustrate the use of hydrogeophysical approaches to quantify subsurface architecture that influence flow (such as hydrostratigraphy and preferential pathways); delineate anomalous subsurface fluid bodies (such as contaminant plumes); monitor hydrological processes (such as infiltration, freshwater-seawater interface dynamics, and flow through fractures); and estimate hydrological properties (such as hydraulic conductivity) and state variables (such as water content). The case studies have been chosen to illustrate how hydrogeophysical approaches can yield insights about complex subsurface hydrological processes, provide input that improves flow and transport predictions, and provide quantitative information over field-relevant spatial scales. The chapter concludes by describing existing hydrogeophysical challenges and associated research needs. In particular, we identify the area of quantitative watershed hydrogeophysics as a frontier area, where significant effort is required to advance the estimation of hydrological properties and processes (and their uncertainties) over spatial scales relevant to the management of water resources and contaminants.

Three Essays on the Formation and Impact of Economic Policy

Introduction In my thesis I argue that economic policy is all about economics and politics. Consequently, analysing and understanding economic policy ideally has at least two parts. The economics part, which is centered around the expected impact of a specific policy on the real economy both in terms of efficiency and equity. The insights of this part point into which direction the fine-tuning of economic policies should go. However, fine-tuning of economic policies will be most likely subject to political constraints. That is why, in the politics part, a much better understanding can be gained by taking into account how the incentives of politicians and special interest groups as well as the role played by different institutional features affect the formation of economic policies. The first part and chapter of my thesis concentrates on the efficiency-related impact of economic policies: how does corporate income taxation in general, and corporate income tax progressivity in specific, affect the creation of new firms? Reduced progressivity and flat-rate taxes are in vogue. By 2009, 22 countries are operating flat-rate income tax systems, as do 7 US states and 14 Swiss cantons (for corporate income only). Tax reform proposals in the spirit of the "flat tax" model typically aim to reduce three parameters: the average tax burden, the progressivity of the tax schedule, and the complexity of the tax code. In joint work, Marius Brülhart and I explore the implications of changes in these three parameters on entrepreneurial activity, measured by counts of firm births in a panel of Swiss municipalities. Our results show that lower average tax rates and reduced complexity of the tax code promote firm births. Controlling for these effects, reduced progressivity inhibits firm births. Our reading of these results is that tax progressivity has an insurance effect that facilitates entrepreneurial risk taking. The positive effects of lower tax levels and reduced complexity are estimated to be significantly stronger than the negative effect of reduced progressivity. To the extent that firm births reflect desirable entrepreneurial dynamism, it is not the flattening of tax schedules that is key to successful tax reforms, but the lowering of average tax burdens and the simplification of tax codes. Flatness per se is of secondary importance and even appears to be detrimental to firm births. The second part of my thesis, which corresponds to the second and third chapter, concentrates on how economic policies are formed. By the nature of the analysis, these two chapters draw on a broader literature than the first chapter. Both economists and political scientists have done extensive research on how economic policies are formed. Thereby, researchers in both disciplines have recognised the importance of special interest groups trying to influence policy-making through various channels. In general, economists base their analysis on a formal and microeconomically founded approach, while abstracting from institutional details. In contrast, political scientists' frameworks are generally richer in terms of institutional features but lack the theoretical rigour of economists' approaches. I start from the economist's point of view. However, I try to borrow as much as possible from the findings of political science to gain a better understanding of how economic policies are formed in reality. In the second chapter, I take a theoretical approach and focus on the institutional policy framework to explore how interactions between different political institutions affect the outcome of trade policy in presence of special interest groups' lobbying. Standard political economy theory treats the government as a single institutional actor which sets tariffs by trading off social welfare against contributions from special interest groups seeking industry-specific protection from imports. However, these models lack important (institutional) features of reality. That is why, in my model, I split up the government into a legislative and executive branch which can both be lobbied by special interest groups. Furthermore, the legislative has the option to delegate its trade policy authority to the executive. I allow the executive to compensate the legislative in exchange for delegation. Despite ample anecdotal evidence, bargaining over delegation of trade policy authority has not yet been formally modelled in the literature. I show that delegation has an impact on policy formation in that it leads to lower equilibrium tariffs compared to a standard model without delegation. I also show that delegation will only take place if the lobby is not strong enough to prevent it. Furthermore, the option to delegate increases the bargaining power of the legislative at the expense of the lobbies. Therefore, the findings of this model can shed a light on why the U.S. Congress often practices delegation to the executive. In the final chapter of my thesis, my coauthor, Antonio Fidalgo, and I take a narrower approach and focus on the individual politician level of policy-making to explore how connections to private firms and networks within parliament affect individual politicians' decision-making. Theories in the spirit of the model of the second chapter show how campaign contributions from lobbies to politicians can influence economic policies. There exists an abundant empirical literature that analyses ties between firms and politicians based on campaign contributions. However, the evidence on the impact of campaign contributions is mixed, at best. In our paper, we analyse an alternative channel of influence in the shape of personal connections between politicians and firms through board membership. We identify a direct effect of board membership on individual politicians' voting behaviour and an indirect leverage effect when politicians with board connections influence non-connected peers. We assess the importance of these two effects using a vote in the Swiss parliament on a government bailout of the national airline, Swissair, in 2001, which serves as a natural experiment. We find that both the direct effect of connections to firms and the indirect leverage effect had a strong and positive impact on the probability that a politician supported the government bailout.

Dibenzofuran degradation by Sphingomonas wittichii RW1 under environmental stresses

Sphingomonas wittichii is a gram-negative Alpha-proteobacterium, capable of degrading xenobiotic compounds such as dibenzofuran (DBF), dibenzo-p-dioxin, carbazole, 2-hydroxybiphenyl or nitro diphenyl ether herbicides. The metabolism of strain RW1 has been the subject of previous studies and a number of genes involved in DBF degradation have been characterized. It is known that RW1 posseses a unique initial DBF dioxygenase (encoded by the dxnAl gene) that catalyzes the first step in the degradation pathway. None of the organisms known to be able to degrade DBF have a similar dioxygenase, the closest match being the DBF dioxygenase from Rhodococcus sp. with an overall amino acid similarity of 45%. Genes participating in the conversion of the metabolite salicylate via the ortho-cleavage pathway to TCA cycle intermediates were identified as well. Apart from this scarce information, however, there is a lack of global knowledge on the genes that are involved in DBF degradation by strain RW1 and the influence of environmental stresses on DBF-dependent global gene expression. A global analysis is necessary, because it may help to better understand the behaviour of the strain under field conditions and suggest improvements for the current bioaugmentation practice. Chapter 2 describes the results of whole-genome analysis to characterize the genes involved in DBF degradation by RW1. Micro-array analysis allowed us to detect differences in gene transcription when strain RW1 was exposed to DBF. This was complemented by ultra-high throughput sequencing of mutants no longer capable of growing on salicylate and DBF. Some of the genes of the ortho-cleavage pathway were induced 2 to 4 times in the presence of DBF, as well as the initial DBF dioxygenase. However two gene clusters, named 4925 and 5102 were induced up to 19 times in response to DBF induction. The cluster 4925 is putatively participating in a meta-cleavage pathway while the cluster 5102 might be part of a gentisate pathway. The three pathways, ortho-cleavage, meta-cleavage and gentisate pathway seem to be active in parallel when strain RW1 is exposed to DBF, presenting evidence for a redundancy of genes for DBF degradation in the genome of RW1. Chapter 3 focuses on exploiting genetic tools to construct bioreporters representative for DBF degradation in RW1. A set of basic tools for genetic manipulation in Sphingomonas wittichii RW1 was tested and optimized. Both plasmids and mini-transposons were evaluated for their ability to be maintained in RW1 with or without antibiotic selection pressure, and for their ability to lead to fluorescent protein expression in strain RW1 from a constitutive promoter. Putative promoter regions of three of the previously found DBF-induced genes (Swit_4925, Swit_5102 and Swit_4897-dxnAl) were then used to construct eg/^-bioreporters in RW1. Chapter 4 describes the use of the constructed RW1-based bioreporter strains for examining the expression of the DBF degradation pathway genes under microcosm conditions. The bioreporter strains were first exposed to different carbon sources in liquid culture to calibrate the egfp induction. Contrary to our expectations from micro-array analysis only the construct with the promoter from gene cluster 4925 responded to DBF, whereas the other two constructs did not show specific induction with DBF. The response from the bioreporters was subsequently tested for sensitivity to water stress, given that this could have an important impact in soils. Exposure to liquid cultures with decreasing water potential, achieved by NaCl or PEG addition to the growth media, showed that eGFP expression in RW1 from the promoter regions 4925 and 5102 was not directly influenced by water stress, but only through an overall reduction in growth rate. In contrast, expression of eGFP from the dxnAl or an uspA promoter was also directly dependent on the extent of water stress. The RW1 with the 4925 construct was subsequently used in soil microcosms to evaluate DBF bioavailability to the cells in presence or absence of native microbiota or other contaminated material. We found that RW1 could grow on DBF added to soil, but bioreporter expression suggested that competition with native microbiota for DBF intermediates may limit its ability to proliferate to a maximum. Chapter 5 describes the results from the experiments carried out to more specifically detect genes of RW1 that might be implicated in water stress resistance. Hereto we created transposon mutagenesis libraries in RW1, either with a classical mini-Tn5 or with a variant that would express egfp when the transposon would insert in a gene induced under water stress. Classical mutant libraries were screened by replica plating under high and low water stress conditions (achieved by adding NaCl to the agar medium). In addition, we screened for smaller microcolonies formed by mutants in agarose beads that could be analized with flow cytometry. A number of mutants impaired to grow on NaCl-supplemented media were recovered and the transposon insertion sites sequenced. In a second procedure we screened by flow cytometry for mutants with a higher eGFP production after exposure to growth medium with higher NaCl concentrations. Mutants from both libraries rarely overlapped. Discovered gene functions of the transposon insertions pointed to compatible solute synthesis (glutamate and proline), cell membrane synthesis and modification of cell membrane composition. The results obtained in the present study give us a more complete picture of the mechanisms of DBF degradation by S. wittichii RW1, how it reacts to different DBF availability and how the DBF catabolic activity may be affected by the conditions found in contaminated environments. - Sphingomonas wittichii est une alpha-protéobactérie gram-négative, capable de dégrader des composés xénobiotiques tels que le dibenzofurane (DBF), la dibenzo-p-dioxine, le carbazole, le 2-hydroxybiphényle ou les herbicides dérivés du nitro-diphényléther. Le métabolisme de la souche RW1 a fait l'objet d'études antérieures et un certain nombre de gènes impliqués dans la dégradation du DBF ont été caractérisés. Il est connu que RW1 possède une unique dioxygénase DBF initiale (codée par le gène dxnAl) qui catalyse la première étape de la voie de dégradation. Aucun des organismes connus pour être capables de dégrader le DBF n'a de dioxygénase similaire. L'enzyme la plus proche étant la DBF dioxygénase de Rhodococcus sp. avec 45% d'acides aminés conservés. Les gènes qui participent à la transformation du salicylate en métabolites intermédiaires du cycle de Krebs par la voie ort/io-cleavage ont aussi été identifiés. Outre ces informations lacunaires, il y a un manque de connaissances sur l'ensemble des gènes impliqués dans la dégradation du DBF par la souche RW1 ainsi que l'effet des stress environnementaux sur l'expression génétique globale, en présence du DBF. Une analyse globale est nécessaire, car elle peut aider à mieux comprendre le comportement de la souche dans les conditions de terrain et de proposer des améliorations pour l'utilisation de la bio-augmentation comme technique de bio-remédiation. Le chapitre 2 décrit les résultats de l'analyse du génome pour caractériser les gènes impliqués dans la dégradation du DBF par RW1. Une analyse de micro-arrays nous a permis de détecter des différences dans la transcription des gènes lorsque la souche RW1 a été exposée au DBF. L'analyse a été complétée par le criblage à ultra-haut débit de mutants qui n'étaient plus capables de croître avec le salicylate ou le DBF comme seule source de carbone. Certains des gènes de la voie ortho-cleavage, dont la DBF dioxygénase initiale, ont xî été induits 2 à 4 fois, en présence du DBF. Cependant, deux groupes de gènes, nommés 4925 et 5102 ont été induits jusqu'à 19 fois en réponse au DBF. Le cluster 4925 participe probablement dans une voie de meta-cleavage tandis que le cluster 5102 pourrait faire partie d'une voie du gentisate. Les trois voies, ortho-cleavage, meta-cleavage et la voie du gentisate semblent être activées en parallèle lorsque la souche RW1 est exposée au DBF, ce qui représente une redondance de voies pour la dégradation du DBF dans le génome de RW1. Le chapitre 3 se concentre sur l'exploitation des outils génétiques pour la construction de biorapporteurs de la dégradation du DBF par RW1. Un ensemble d'outils de base pour la manipulation génétique dans Sphingomonas wittichii RW1 a été testé et optimisé. Deux plasmides et mini-transposons ont été évalués pour leur capacité à être maintenu dans RW1 avec ou sans pression de sélection par des antibiotiques, et pour leur capacité à exprimer la protéine fluorescente verte (eGFP) dans la souche RW1. Les trois promoteurs des gènes Swit_4925, Swit_5102 et Swit_4897 (dxnAl), induits en réponse au DBF, ont ensuite été utilisés pour construire des biorapporteurs dans RW1. Le chapitre 4 décrit l'utilisation des souches biorapportrices construites pour l'analyse de l'expression des gènes de la voie de dégradation du DBF dans des microcosmes avec différents types de sols. Les souches biorapportrices ont d'abord été exposées à différentes sources de carbone en cultures liquides afin de calibrer l'induction de la eGFP. La construction avec le promoteur du gène 4925 a permis une réponse au DBF. Mais contrairement à nos attentes, basées sur les résultats de l'analyse des micro-arrays, les deux autres constructions n'ont pas montré d'induction spécifique au DBF. La réponse des biorapporteurs a ensuite été testée pour la sensibilité au stress hydrique, étant donné que cela pourrait avoir un impact important dans les microcosmes. La diminution du potentiel hydrique en culture liquide est obtenue par addition de NaCl ou de PEG au milieu de croissance. Nous avons montré que l'expression de la eGFP contrôlée par les promoteurs 4925 et 5102 n'était pas directement influencée par le stress hydrique, mais seulement par une réduction globale des taux de croissance. En revanche, l'expression de la eGFP dépendante des promoteurs dxnAl et uspA était aussi directement dépendante de l'ampleur du stress hydrique. La souche avec la construction 4925 a été utilisée par la suite dans des microcosmes avec différents types de sols pour évaluer la biodisponibilité du DBF en présence ou absence des microbes indigènes et d'autres composés contaminants. Nous avons constaté que RW1 pouvait se développer si le DBF a été ajouté au sol, mais l'expression de la eGFP par le biorapporteur suggère que la compétition avec la microbiota indigène pour les métabolites intermédiaires du DBF peut limiter sa capacité à proliférer de manière optimale. Le chapitre 5 décrit les résultats des expériences réalisées afin de détecter spécifiquement les gènes de RW1 qui pourraient être impliquées dans la résistance au stress hydrique. Ici on a crée des bibliothèques de mutants de RW1 par transposon, soit avec un mini-Tn5 classique ou avec une variante qui exprime la eGFP lorsque le transposon s'insère dans un gène induit par le stress hydrique. Les bibliothèques de mutants ont été criblées par la méthode classique de repiquage sur boîtes, dans des conditions de stress hydrique élevé (obtenu par l'addition de NaCl dans les boîtes). En outre, nous avons criblé des micro¬colonies dans des billes d'agarose qui ont pu être analysées par cytométrie de flux. Un certain nombre de mutants déficients à croître sur des milieux supplémentés avec du NaCl ont été isolés et les sites d'insertion du transposon séquencés. Dans une deuxième procédure nous avons criblé par cytométrie de flux des mutants avec une production de eGFP supérieure, après exposition à un milieu de croissance avec une concentration élevée de NaCl. Les mutants obtenus dans les deux bibliothèques n'étaient pas similaires. Les fonctions des gènes où se trouvent les insertions de transposons sont impliqués dans la synthèse de solutés compatibles (glutamate et de la proline), dans la synthèse de la membrane cellulaire et dans la modification de la composition de la membrane cellulaire. Les résultats obtenus dans la présente étude nous donnent une image plus complète des mécanismes de dégradation du DBF par S. wittichii RW1, comment cette souche réagit à la disponibilité du DBF et comment l'activité catabolique peut être affectée par les conditions rencontrées dans des environnements contaminés.