Is there a case to be made for a global patent system? The example of plant biotechnology

The assessment of patterns of patentability in plant biotechnology on the basis of existing statistics shows a considerable concentration of patents to a few countries, in particular the United States, Australia, Japan, China, Mexico, Brazil, Germany, Canada, New Zealand, South Korea, India, Spain and Hungary. These patterns suggest that there is a clear relationship between the choice of patent jurisdictions and the biotechnology regulatory framework. This observation of the geographic distribution of biotechnology patents lends credence to maintaining a system of territorial rights that allow for regulatory competition, but continuing the process of substantive patent law harmonization which potentially minimize trade barriers.

Fluxo de Informação Financeira entre o Território Nacional e os Teatros de Operaçõe s: Abordagem Sociocrítica em contexto de mudança

O presente Trabalho de Investigação Aplicada encontra-se subordinado ao tema “Fluxo de Informação Financeira entre o Território Nacional e os Teatros de Operações: Abordagem Sociocrítica em contexto de mudança.”. Tendo em conta o contexto económico que o país atravessa, e que indiretamente afeta as organizações do Estado, através das consequentes reduções orçamentais, torna-se imprescindível que exista um aproveitamento dos recursos muito mais eficiente e eficaz. Neste contexto e face à existência em Território Nacional do Sistema Integrado de Gestão nas Instituições do Ministério de Defesa Nacional, nomeadamente no Exército, revelou-se indispensável a implementação desta ferramenta de gestão nas Forças Nacionais Destacadas dos Teatros de Operações. Desta forma, o objetivo geral desta investigação é identificar as limitações e potencialidades que a recente implementação do Sistema Integrado de Gestão nos Teatros de Operações provocou no desempenho das funções dos Oficiais de Finanças. Neste trabalho procuramos ainda identificar o impacto da harmonização dos procedimentos contabilísticos na execução orçamental, as melhorias do processo de tomada de decisão, a harmonização na realização do relato financeiro, e consequentes alterações nos procedimentos de mudança de contingente, bem como as alterações na execução das diferentes fases do Registo Contabilístico do Fundo de Maneio. Para a elaboração desta investigação aplicou-se o método hipotético-dedutivo, sendo desenvolvida segundo objetivos descritivos e exploratórios com o intuito de identificar, explorar e descrever as limitações e potencialidades da implementação do Sistema Integrado de Gestão na Força Nacional Destacada do Kosovo, recorrendo ao estudo exploratório/descritivo, enquadrando-se ainda na categoria do Estudo de Caso. No sentido de atingir os objetivos propostos inicialmente foram elaborados e aplicados diferentes inquéritos por entrevista. Após a análise e discussão dos resultados foi possível concluir que a informação contabilística disponível em tempo real, de forma imediata e oportuna, permite aos Oficiais de Finanças serem mais eficazes e assertivos no aconselhamento ao Comandante, assim como origina uma melhor e mais célere tomada de decisão em Teatro de Operações e para toda cadeia de comando em Território Nacional. Outra grande mais-valia foi a possibilidade de reduzir significativamente o Fundo de Maneio. Alcançado o final desta investigação, foi possível concluir que não existem limitações do Sistema Integrado de Gestão nos Teatros de Operações que não existam em Território Nacional, sendo dessa forma possível constatar que as possíveis melhorias são a implementação da contabilidade analítica e a integração de todas as áreas desta ferramenta, permitindo tirar total partido da mesma.

A novel method to determine new potent angiotensin inhibitor, azilsartan, in human plasma via micelle-enhanced spectrofluorimetry using cremophor RH 40

Purpose: To develop a micelle-enhanced spectrofluorimetric method for the assay of azilsartan (AZL) in bulk form and spiked human plasma without the need for derivatization procedure. Method: The proposed method was based on studying the fluorescence behavior of AZL in Cremophor RH 40 (Cr RH 40) micellar system. The fluorescence intensity was measured at 371 nm after excitation at 264 nm. The proposed procedure was validated according to International Council on Harmonization (ICH) guidelines. Results: In aqueous solution, the fluorescence intensity of AZL was greatly enhanced by more than 3- fold in the presence of Cr RH 40. The fluorescence –concentration plot was linear over the range of 10 – 500 ng.mL-1, with a limit of detection of 3.287 ngmL-1. The proposed method was successfully applied to the determination of AZL in pure powder form and spiked human plasma. The mean recovery of AZL in spiked human plasma using the proposed method was 90.54 ± 1.17 %. Conclusion: The suggested method is highly sensitive and simple, and can easily be applied for the quantification of AZL in pure powder form as well as in biological fluids such as plasma.

Étude sur la sécurité dynamique : le cas de Cité-des-Prairies

Travail dirigé présenté à la Faculté des études supérieures en vue de l’obtention du grade de maître ès sciences (M.Sc.) en criminologie option sécurité intérieure

Étude sur la sécurité dynamique : le cas de Cité-des-Prairies

Travail dirigé présenté à la Faculté des études supérieures en vue de l’obtention du grade de maître ès sciences (M.Sc.) en criminologie option sécurité intérieure

Mental health and human rights in forensic psychiatry in the European Union

One of the most important events which characterizes the process of transitioning to the European Union is the ratification of the Convention for the Protection of Human Rights and Fundamental Freedoms by the European Council in 1950. Since then, the topic of human rights has become the inspiring principle in the construction of the European Community and afterwards the institutional apparatus which constitutes the Union. The primary objective of the European Union States currently is to promote a harmonization of the national legislations on mental health, favoring a central health policy which reduces inequalities amongst the member States. For this reason Europe is a region of the world in which is more abundant the normative one about mental health, especially in form of Recommendations directed to the States by the Council of Europe, although norms of direct application also exist. Special interest has the sentences dictated by the European Court of Human Rights and the conclusions of the European Committee for the Prevention of Torture and Inhuman or Degrading Treatment or Punishment. It should be mentioned the work of European Union equally and of the Office for Europe of the World Organization of the Health. This group of juridical instruments configures the most complete regulation on the mental patient's rights.

Aplicaciones del Caos y la Complejidad en la Cadena de Suministros del Sector Agroindustrial

La presente investigación consiste en determinar las aplicaciones existentes de las teorías del caos y las teorías de la complejidad en la cadena de suministro del sector agroindustrial colombiano. Además, tiene como propósito describir el sector de la agroindustria y la cadena de suministro, identificar los modelos de caos y complejidad y posteriormente determinar cuáles de éstos son aplicables al sector. Se define el caos como una sub-disciplina de las matemáticas que estudia sistemas complejos o dinámicos y tiene inmerso implicaciones filosóficas; por otra parte complejidad es la cualidad que adquiere un sistema en el que hay diversos componentes relacionados. Se ha identificado que en el ámbito colombiano existen diferentes estudios enfocados en la construcción de modelos agroindustriales, donde se adopta el concepto de complejidad para calificar el atributo de dichos modelos que involucran la armonización e integración de diferentes actores, desde los productores hasta los consumidores. En este estudio se emplea un estudio monográfico de tipo documental teniendo como unidad de análisis la cadena de suministro del sector agroindustrial. Los resultados indican que las teorías del caos y complejidad se encuentran presentes dentro de la cadena de suministros del sector agroindustrial colombiano, ya que en ella se ocurre la interconexión entre productores, procesadores y comercializadores, interactuando entre ellos y presentando alteraciones en su comportamiento económico a lo largo del tiempo en función de variaciones de las condiciones iniciales influenciadas por variables macroeconómicas, ambientales, sociales y políticas.

Reasonableness in European and Chinese Contract Law. A Comparative Law Study

Contemporary private law, in teh last few decades, TEMPhas been increasingly characterized by teh spread of general clauses and standards and by teh growing role of interpreters in teh framework of teh sources of law. dis process TEMPhas also consistently effected those systems dat are not typically centered on judge-made law. In particular in contract law general clauses and standards has assumed a leading role and has become protagonists of processes of integration and harmonization of teh law. Wifin dis context, teh reasonableness clause TEMPhas come to teh attention of scholars, emerging as a new element of connection between different legal systems -first of all between common law and civil law – and even between different legal traditions. dis research aims at reconstructing teh patterns of emersion and evolution of teh TEMPprincipal of reasonableness in contract law both wifin European Union Law and in teh Chinese legal system, in order to identify evolutionary trends, processes of emersion and circulation of legal models and teh scope of operation of teh TEMPprincipal in teh two contexts. In view of teh increasingly intense economic relations between Europe and China, wifin teh framework of teh new project called Belt and Road Initiative, a comparative survey of dis type can foster mutual understanding and make communications more TEMPeffective, at teh level of legal culture and commercial relations, and to support teh processes of supranational harmonization of contract law rules.

The Financial Services Regime in International Economic Law: on the Difficult Relationship between Trade Liberalization and Prudential Measures

The PhD thesis analyses the financial services regime in international economic law from the perspective of the difficult relationship between trade liberalisation and prudential measures. Financial stability plays a fundamental role for the well-being and well-functioning of the global economy, but, it is at the same time a complex sector to regulate and supervise and, especially after the 2007-08 economic crisis, States have tightened up their regulation of financial services, introducing more severe and protectionist prudential measures. However, in an increasingly interconnected global economy, the harmonization of prudential regulation at the international level is an essential step to guarantee integrity, fairness and stability of financial markets and trade. The research analyses the tools at disposition to achieve this aim, the related problematic issues and the perspectives and possible solutions for the future, starting from the World Trade Organization (WTO) legal framework and its General Agreement on Trade in Services (GATS), devoted to discipline trade in services among the WTO Members. Then, the research moves to a second legal instrument, the Free Trade Agreements (FTAs), which has witnessed a remarkable spread in the last decades. Finally, the research addresses the international standards, developed by supranational entities and implemented by an increasing number of States, as they offer rules and guidelines adequate to update the international financial scenario. Nevertheless, the international standards alone cannot be the solution because, first, they are not mandatory, as governments decide voluntarily to apply them and, second, their decision-making process do not respect the requirements of transparency and representative membership. In light of this analysis, the thesis aims at providing an answer to its research question: how to give more certainty to States and economic operators in the planning of the domestic disciplines and business activities in order to provide a sound and stable international financial system.

Fondamento e limiti costituzionali del potere punitivo nel sistema di legalità integrata

La ricerca affronta la questione della punizione nella prospettiva del diritto costituzionale nazionale integrata con quella del diritto europeo dei diritti dell’uomo. Nella Parte I è sostenuta la tesi secondo cui la trasformazione della Costituzione penale avviata sotto l’influsso della giurisprudenza CEDU rappresenta complessivamente un avanzamento nel processo di costituzionalizzazione del potere punitivo. Questa conclusione è supportata attraverso un confronto della filosofia costituzionale classica sulla punizione con i diversi approcci interpretativi alla Costituzione penale sviluppati durante il XX secolo (approcci tradizionale, costituzionalistico ed EDU). Nella Parte II è invece sostenuta la tesi secondo cui, nonostante gli effetti positivi dell’armonizzazione sovranazionale, lo statuto costituzionale della punizione dovrebbe comunque rimanere formalmente autonomo dal diritto EDU. Non solo, infatti, nessun paradigma dei rapporti interordinamentali finora sviluppato può giustificarne un’integrazione totale, ma essa rischierebbe anche di diminuire la normatività dell’aspetto sociale della Costituzione penale, già ipocostituzionalizzato rispetto a quello liberale. Nella Conclusione sono quindi sviluppati gli elementi fondamentali di un approccio interpretativo alternativo alla Costituzione penale che risponda meglio di quelli esistenti alle esigenze sia di garantire la massima costituzionalizzazione della punizione sia di facilitare l’integrazione sovranazionale. In base a un simile approccio costituzionalmente fondato, sostanzialista, rights-based e inclusivo di tutte le ideologie costituenti, la Costituzione potrebbe essere letta nel senso di prevedere un modello di disciplina unitario per tutte le forme di esercizio del potere punitivo (salvo quello disciplinare, distinguibile sotto l’aspetto istituzionale) caratterizzato da: una riserva di legge a intensità variabile; uno scrutinio stretto della Corte sulla giustificabilità costituzionale della pena; l’estensione dell’ambito di applicazione dei principi di colpevolezza e rieducazione; un pieno sviluppo degli aspetti di garanzia collettiva dei classici principi costituzionalpenalistici (obblighi di tutela penale e garanzia dell’effettiva collocazione della pena in capo al soggetto colpevole), nonché derivabili dall’art. 3 Cost. (proporzionalità della pena alle condizioni materiali del soggetto punito).

Cross-sensors analysis of multispectral Earth observation data for environmental monitoring

Time Series Analysis of multispectral satellite data offers an innovative way to extract valuable information of our changing planet. This is now a real option for scientists thanks to data availability as well as innovative cloud-computing platforms, such as Google Earth Engine. The integration of different missions would mitigate known issues in multispectral time series construction, such as gaps due to clouds or other atmospheric effects. With this purpose, harmonization among Landsat-like missions is possible through statistical analysis. This research offers an overview of the different instruments from Landsat and Sentinel missions (TM, ETM, OLI, OLI-2 and MSI sensors) and products levels (Collection-2 Level-1 and Surface Reflectance for Landsat and Level-1C and Level-2A for Sentinel-2). Moreover, a cross-sensors comparison was performed to assess the interoperability of the sensors on-board Landsat and Sentinel-2 constellations, having in mind a possible combined use for time series analysis. Firstly, more than 20,000 pairs of images almost simultaneously acquired all over Europe were selected over a period of several years. The study performed a cross-comparison analysis on these data, and provided an assessment of the calibration coefficients that can be used to minimize differences in the combined use. Four of the most popular vegetation indexes were selected for the study: NDVI, EVI, SAVI and NDMI. As a result, it is possible to reconstruct a longer and denser harmonized time series since 1984, useful for vegetation monitoring purposes. Secondly, the spectral characteristics of the recent Landsat-9 mission were assessed for a combined use with Landsat-8 and Sentinel-2. A cross-sensor analysis of common bands of more than 3,000 almost simultaneous acquisitions verified a high consistency between datasets. The most relevant discrepancy has been observed in the blue and SWIRS bands, often used in vegetation and water related studies. This analysis was supported with spectroradiometer ground measurements.

Green approach to Palladium Cross-Coupling reactions and development of new methodologies based on highly abundant metals

Transition metal catalyzed cross-coupling reactions represent among the most versatile and useful tools in organic synthesis for the carbon-carbon (C-C) bond formation and have a prominent role in both the academic and pharmaceutical segments. Among them, palladium catalyzed cross-coupling reactions are currently the most versatile. In this thesis, the applications, impact and development of green palladium cross-coupling reactions are discussed. Specifically, we discuss the translation of the Twelve Principles of Green Chemistry and their applications in pharmaceutical organometallic chemistry to stimulate the development of cost-effective and sustainable catalytic processes for the synthesis of active pharmaceutical ingredients (API). The Heck-Cassar-Sonogashira (HCS) and the Suzuki-Miyaura (SM) protocols, using HEP/H2O as green mixture and sulfonated phosphine ligands, allowed to recycle and recover the catalyst, always guaranteeing high yields and fast conversion under mild conditions, with aryl iodides, bromides, triflates and chlorides. No catalyst leakage or metal contamination of the final product were observed during the HCS and SM reactions, respecting the very low limits for metal impurities in medicines established by the International Conference of Harmonization Guidelines Q3D (ICH Q3D). In addition, a deep understanding of the reaction mechanism is very important if the final target is to develop efficient protocols that can be applied at industrial level. Experimental and theoretical studies pointed out the presence of two catalytic cycles depending on the counterion, shedding light on the role of base in catalyst reduction and acetylene coordination in the HCS coupling. Finally, the development of a cross-coupling reaction to form aryldifluoronitriles in the presence of copper is discussed, highlighting the importance of inserting fluorine atoms within biological structures and the use of readily available metals such as copper as an alternative to palladium.

TiMMing: developing an innovative suite of bioinformatic tools to harmonize and track the origin of copy number alterations in the evolutive history of multiple myeloma

Multiple Myeloma (MM) is a hematologic cancer with heterogeneous and complex genomic landscape, where Copy Number Alterations (CNAs) play a key role in the disease's pathogenesis and prognosis. It is of biological and clinical interest to study the temporal occurrence of early alterations, as they play a disease "driver" function by deregulating key tumor pathways. This study presents an innovative bioinformatic tools suite created for harmonizing and tracing the origin of CNAs throughout the evolutionary history of MM. To this aim, large cohorts of newly-diagnosed MM (NDMM, N=1582) and Smoldering-MM (SMM, N=282) were aggregated. The tools developed in this study enable the harmonization of CNAs as obtained from different genomic platforms in such a way that a high statistical power can be obtained. By doing so, the high numerosity of those cohorts was harnessed for the identification of novel genes characterized as "driver" (NFKB2, NOTCH2, MAX, EVI5 and MYC-ME2-enhancer), and the generation of an innovative timing model, implemented with a statistical method to introduce confidence intervals in the CNAs-calls. By applying this model on both NDMM and SMM cohorts, it was possible to identify specific CNAs (1q(CKS1B)amp, 13q(RB1)del, 11q(CCND1)amp and 14q(MAX)del) and categorize them as "early"/ "driver" events. A high level of precision was guaranteed by the narrow confidence intervals in the timing estimates. These CNAs were proposed as critical MM alterations, which play a foundational role in the evolutionary history of both SMM and NDMM. Finally, a multivariate survival model was able to identify the independent genomic alterations with the greatest effect on patients’ survival, including RB1-del, CKS1B-amp, MYC-amp, NOTCH2-amp and TRAF3-del/mut. In conclusion, the alterations that were identified as both "early-drivers” and correlated with patients’ survival were proposed as biomarkers that, if included in wider survival models, could provide a better disease stratification and an improved prognosis definition.

Transatlantic regulatory divergence in pharmaceuticals: exploring economic and cultural explanations

The analysis delves into the regulatory divergence between the EU and the US in the pharmaceutical sector. Through law and economics, political science, and cultural theory perspectives, the study explores how collective preferences within each jurisdiction shape regulations. By identifying cultural orientations such as individualism in the US and hierarchy in the EU, the research suggests that underlying cultural factors play a significant role in regulatory decisions. Despite calls for regulatory harmonization, the recognition of legitimate differences in preferences due to cultural diversity emphasizes that uniformity may not always be the best solution, showcasing the importance of understanding cultural influences in shaping regulatory landscapes.