Toward the therapeutic editing of mutated RNA sequences.

If RNA editing could be rationally directed to mutated RNA sequences, genetic diseases caused by certain base substitutions could be treated. Here we use a synthetic complementary RNA oligonucleotide to direct the correction of a premature stop codon mutation in dystrophin RNA. The complementary RNA oligonucleotide was hybridized to a premature stop codon and the hybrid was treated with nuclear extracts containing the cellular enzyme double-stranded RNA adenosine deaminase. When the treated RNAs were translated in vitro, a dramatic increase in expression of a downstream luciferase coding region was observed. The cDNA sequence data are consistent with deamination of the adenosine in the UAG stop codon to inosine by double-stranded RNA adenosine deaminase. Injection of oligonucleotide-mRNA hybrids into Xenopus embryos also resulted in an increase in luciferase expression. These experiments demonstrate the principle of therapeutic RNA editing.

Study of interaction between Si(O,C) nanowires and the biological system

Nanomedicine is a new branch of medicine, based on the potentiality and intrinsic properties of nanomaterials. Indeed, the nanomaterials ( i.e. the materials with nano and under micron size) can be suitable to different applications in biomedicine. The nanostructures can be used by taking advantage of their properties (for example superparamagnetic nanoparticles) or functionalized to deliver the drug in a specific target, thanks the ability to cross biological barriers. The size and the shape of 1D-nanostructures (nanotubes and nanowires) have an important role on the cell fate: their morphology plays a key role on the interaction between nanostructure and the biological system. For this reason the 1D nanostructure are interesting for their ability to mime the biological system. An implantable material or device must therefore integrate with the surrounding extracellular matrix (ECM), a complex network of proteins with structural and signaling properties. Innovative techniques allow the generation of complex surface patterns that can resemble the structure of the ECM, such as 1D nanostructures. NWs based on cubic silicon carbide (3C-SiC), either bare (3C-SiC NWs) or surrounded by an amorphous shell (3C-SiC/SiO2 core/shell NWs), and silicon oxycarbide nanowires (SiOxCy NWs) can meet the chemical, mechanical and electrical requirements for tissue engineering and have a strong potential to pave the way for the development of a novel generation of implantable nano-devices. Silicon oxycarbide shows promising physical and chemical properties as elastic modulus, bending strength and hardness, chemical durability superior to conventional silicate glasses in aggressive environments and high temperature stability up to 1300 °C. Moreover, it can easily be engineered through functionalization and decoration with macro-molecules and nanoparticles. Silicon carbide has been extensively studied for applications in harsh conditions, as chemical environment, high electric field and high and low temperature, owing to its high hardness, high thermal conductivity, chemical inertness and high electron mobility. Also, its cubic polytype (3C) is highly biocompatible and hemocompatible, and some prototypes of biomedical applications and biomedical devices have been already realized starting from 3C-SiC thin films. Cubic SiC-based NWs can be used as a biomimetic biomaterial, providing a robust and novel biocompatible biological interface . We cultured in vitro A549 human lung adenocarcinoma epithelial cells and L929 murine fibroblast cells over core/shell SiC/SiO2, SiOxCy and bare 3C-SiC nanowire platforms, and analysed the cytotoxicity, by indirect and direct contact tests, the cell adhesion, and the cell proliferation. These studies showed that all the nanowires are biocompatible according to ISO 10993 standards. We evaluated the blood compatibility through the interaction of the nanowires with platelet rich plasma. The adhesion and activation of platelets on the nanowire bundles, assessed via SEM imaging and soluble P-selectin quantification, indicated that a higher platelet activation is induced by the core/shell structures compared to the bare ones. Further, platelet activation is higher with 3C-SiC/SiO2 NWs and SiOxCyNWs, which therefore appear suitable in view of possible tissue regeneration. On the contrary, bare 3C-SiC NWs show a lower platelet activation and are therefore promising in view of implantable bioelectronics devices, as cardiovascular implantable devices. The NWs properties are suitable to allow the design of a novel subretinal Micro Device (MD). This devices is based on Si NWs and PEDOT:PSS, though the well know principle of the hybrid ordered bulk heterojunction (OBHJ). The aim is to develop a device based on a well-established photovoltaic technology and to adapt this know-how to the prosthetic field. The hybrid OBHJ allows to form a radial p–n junction on a nanowire/organic structure. In addition, the nanowires increase the light absorption by means of light scattering effects: a nanowires based p-n junction increases the light absorption up to the 80%, as previously demonstrated, overcoming the Shockley-Queisser limit of 30 % of a bulk p-n junction. Another interesting employment of these NWs is to design of a SiC based epicardial-interacting patch based on teflon that include SiC nanowires. . Such contact patch can bridge the electric conduction across the cardiac infarct as nanowires can ‘sense’ the direction of the wavefront propagation on the survival cardiac tissue and transmit it to the downstream surivived regions without discontinuity. The SiC NWs are tested in terms of toxicology, biocompatibility and conductance among cardiomyocytes and myofibroblasts.

Influence of Religious Institutions in the Creation and Implementation of Public Policy: The Case of Roman Catholic Argentina and Secular Uruguay

The strong presence of religious institutions in Latin America, especially the Roman Catholic Church, and their participation in the creation and implementation of public policy within a sovereign state can be counter-productive for the social development and progress of that specific country. Argentina and Uruguay and the social controversy of social issues of abortion and same-sex marriage are used as examples to establish the accuracy of the above statement. Historical, statistical, and legislative information about both topics in both countries show that the political power that the Roman Catholic Church has in the region is more an outdated influence than a reality, and the principle of secularization appears to be the most stabilizing philosophy for modern nations.

Erosion of universal health coverage in Spain

Whereas the recent UN resolution urges governments to accelerate progress towards universal access to affordable and quality health-care services, the Spanish Government, bypassing the parliamentary procedure, enacted a Royal Decree to limit access to free services at the point of delivery for all-undermining the principle of universal coverage. Spanish health and social service budgets have been subjected to large cuts (13,7% in 2012 and 16,2% in 2013) with some regions imposing additional budget cuts.

Performance Assessment of a Polymer Electrolyte Membrane Electrochemical Reactor under Alkaline Conditions – A Case Study with the Electrooxidation of Alcohols

A novel polymer electrolyte membrane electrochemical reactor (PEMER) configuration has been employed for the direct electrooxidation of propargyl alcohol (PGA), a model primary alcohol, towards its carboxylic acid derivatives in alkaline medium. The PEMER configuration comprised of an anode and cathode based on nanoparticulate Ni and Pt electrocatalysts, respectively, supported on carbonaceous substrates. The electrooxidation of PGA was performed in 1.0 M NaOH, where a cathode based on a gas diffusion electrode was manufactured for the reduction of oxygen in alkaline conditions. The performance of a novel alkaline anion-exchange membrane based on Chitosan (CS) and Poly(vinyl) alcohol (PVA) in a 50:50 composition ratio doped with a 5 wt.% of poly (4-vinylpyridine) organic ionomer cross-linked, methyl chloride quaternary salt resin (4VP) was assessed as solid polymer electrolyte. The influence of 4VP anionic ionomer loading of 7, 12 and 20 wt.% incorporated into the electrocatalytic layers was examined by SEM and cyclic voltammetry (CV) upon the optimisation of the electroactive area, the mechanical stability and cohesion of the catalytic ink onto the carbonaceous substrate for both electrodes. The performance of the 4VP/CS:PVA membrane was compared with the commercial alkaline anion-exchange membrane FAA −a membrane generally used in direct alcohol alkaline fuel cells- in terms of polarisation plots in alkaline conditions. Furthermore, preparative electrolyses of the electrooxidation of PGA was performed under alkaline conditions of 1 M NaOH at constant current density of 20 mA cm−2 using a PEMER configuration to provide proof of the principle of the feasibility of the electrooxidation of other alcohols in alkaline media. PGA conversion to Z isomers of 3-(2-propynoxy)-2-propenoic acid (Z-PPA) was circa 0.77, with average current efficiency of 0.32. Alkaline stability of the membranes within the PEMER configuration was finally evaluated after the electrooxidation of PGA.

The autonomy of the EU legal order and the law-making activities of international organizations. Some examples regarding the Council most recent practice. Research Papers in Law 03/2012

[Introduction.] It is generally believed that while the principle of the autonomy of the EU legal order, in the sense of constitutional and institutional autonomy that is to say what concerns the autonomous decision-making of the EU, has been clearly strengthened by the most recent jurisprudence of the Court of Justice (eg. Moxplant3, Intertanko or the Kadi/Al Baraakat judgements or the Opinion 1/2009 of the CJEU etc.) as well as, in my opinion, in many aspects by the Treaty of Lisbon, it is still valid to add that the principle of a favourable approach, stemming from the Court jurisprudence, for the enhanced openness of the EU legal order to international law has remained equally important for the EU4. On the other hand, it should be also seen that in a globalized world, and following the increased role of the EU as an international actor, its indispensable and crucial role concerning the creation of world (legal) order in many policy fields ( for example let's think about the G20 issues, the global economic and financial crisis, the role of the EU in promoting and protecting human rights worldwide, the implementation of the multilateral or regional conventional law, developed in the framework the UN (e.g. in the field of agriculture or environment etc) or what concerns the Kyoto process on climate change or the conservation of marine biological resources at international level etc), it seems reasonable and justified to submit that the influence, for example, of the law-making activities of the main stakeholder international organizations in the mentioned policy-areas on the EU (especially on the development of its constantly evolving legal order) or vice-versa the influence of the EU law-making practice on these international organizations is significant, in many aspects mutually interdependent and more and more remarkable. This tendency of the 21st century doesn't mean, however, in my view, that the notion of the autonomy of the EU legal order would have been weakened by this increasing interaction between international law and EU law over the passed years. This contribution is going to demonstrate and prove these departuring points by giving some concrete examples from the most recent practice of the Council (all occuring either in the second half of 2009 or after the entry into force of the Lisbon Treaty), and which relate to two very important policy areas in the EU, namely the protection of human rights and the Common Fishery Policy.

The future of the Eurozone and the role of the German Constitutional Court. Research Papers in Law, 05/2012

[Introduction.] Necessary reforms towards a deepened and increased European shaped economic, financial and budgetary policy, paraphrased with the term “fiscal union”, could possibly reach constitutional limits. In its EFSF judgment1, the German Constitutional Court, following the Lisbon judgment in which certain government tasks were determined as being part of the “constitutional identity”2, connected the budget right of the parliament via the principle of democracy to the eternity clause of Art. 79 para 3 Basic Law. A transfer of essential parts of the budget right of the German Bundestag, which would be in conflict with the German constitution, is said to exist when the determination of the nature and amount of the tax affecting the citizens is largely regulated on the supranational level and thereby deprived of the Bundestag’s right to disposition. A reform of the Economic and Monetary Union that touches the core of the budget right can, according to the German Federal Court, with regard to Art. 79 (3) of the Basic Law only be realized by way of Art. 146 of the Basic Law, thus with a new constitution given by the people that replaces the Basic Law.3

The concept of 'economic activity' in the EU treaty: from ideological dead-ends to workable judicial concepts. Research Paper in Law 06/2011

[From the Introduction]. The economic rules, or put more ambitiously, the economic constitution of the Treaty,1 only apply to economic activities. This general principle remains valid, even if some authors strive to demonstrate that certain Treaty rules also apply in the absence of an economic activity,2 and despite the fact that non-economic (horizontal) Treaty provisions (e.g. principle of nondiscrimination, rules on citizenship) are also applicable in the absence of any economic activity.3 Indeed, the exercise of some economic activity transcends the concepts of ‘goods’ (having positive or negative market value),4 workers (even if admitted in an extensive manner),5 and services (offered for remuneration).6 It is also economic activity or ‘the activity of offering goods and services into the market’7 that characterises an ‘undertaking’ thus making the competition rules applicable. Further, it is for regulating economic activity that Article 115 TFEU, Article 106(3) TFEU and most other legal bases in the TFEU provide harmonisation powers in favour of the EU. Last but not least, Article 14 TFEU on the distinction between services of general economic interest (SGEIs) and non-economic services of general interest (NESGIs), as well as Protocol n. 26 on Services of General Interest (SGIs) confirm the constitutional significance of the distinction between economic and non-economic: a means of dividing competences between the EU and the member states. The distinction between economic and non-economic activities is fraught with legal and technical intricacies – the latter being generated by dynamic technological advances and regulatory experimentation. More importantly, however, the distinction is overcharged with political and ideological significations and misunderstandings and, even, terminological confusions.8

The European Court of Justice and the Draft Constitution: A Supreme Court for the Union? Research Paper in Law 8/2003

[Introduction]. The purpose of this paper is twofold. First, it examines selectively the provisions of the draft Constitution pertaining to the Court of Justice and assesses the ways in which the draft Constitution is likely to affect the jurisdiction and the function of the Court. Secondly, it discusses the challenges faced by the Court in relation to the protection of human rights by reference to the recent judgment in Schmidberger.1 Both aspects of the discussion serve to underlie that the Court is assuming the function of the Supreme Court of the Union whose jurisdiction is fundamentally constitutional in character. It has a central role to play not only in relation to matters of economic integration but also in deciding issues of political governance, defining democracy at European and national level, and contributing through the process of judicial harmonisation to the emergence of a European demos. This constitutional jurisdiction of the ECJ is not new but has acquired more importance in recent years and is set to be enhanced under the provisions of the new Constitution. The paper is divided as follows: The first section provides an overview of the way the new Constitution affects the ECJ. The subsequent sections examine respectively Article 28(1) of the draft Constitution, the appointment and tenure of the judiciary, locus standi for private individuals, sanctions against Member States, jurisdiction under the CFSP and the Chapter on freedom, security and justice, preliminary references, other provisions o f the Constitution pertaining to the Court, the principle of subsidiarity, and the judgment in Schmidberger. The final section contains some concluding remarks.

National Parliaments and their Role in European Integration: The EU’s Democratic Deficit in Times of Economic Hardship and Political Insecurity. Bruges Political Research Paper 28/2013

The article describes and assesses the role of national parliaments in EU legislation considering the reforms introduced by the Lisbon Treaty. This is closely connected with the understanding and (political) application of the principle of subsidiarity. After an analysis of the possibilities and limitations of the relevant legal regulations in the post-Lisbon age, alternative ways for participation of national legislators on the European level are being scrutinized and proposed. The issue of democratic legitimization is also interconnected with the current political reforms being discussed in order to overcome the Euro Crisis. Finally, the authors argue that it does not make sense to include national parliaments in the existing legislative triangle of the EU, but instead to promote the creation of a new kind of supervisory body.

Il lavoro a termine nella giurisprudenza della Corte di giustizia [Jurisprudence in the Court of Justice]. WP C.S.D.L.E. "Massimo D'Antona" .INT - 93/2012

The paper analyzes the ECJ case law on fixed-term work, with specific regard to non-regression clause, measures to prevent abuses and the principle of non-discrimination. In particular, the Author points out that the principle of non-discrimination is to be regarded as being the core of the fixed-term work regulation; in this respect, especially in more recent judgments, the Court seems to maximize the scope of such principle.

European Criminal Law and General Principles of Union Law. Research Papers in Law, 5/2005

From the Introduction. The European Court of Justice, partly followed in this by the European legislator, has regulated Community law and policy through a set of general principles of law. For the Community legal order in the first pillar, general legal principles have developed from functional policy areas such as the internal market, the customs union, the monetary union, the common agricultural policy, the European competition policy, etc., which are of great importance for the quality and legitimacy of Community law. The principles in question are not so much general legal principles of an institutional character, such as the priority of Community law, direct effect or Community loyalty, but rather principles of law which shape the fundamental rights and basic rights of the citizen. I refer to the principle of legality, of nulla poena, the inviolability of the home, the nemo tenetur principle, due process, the rights of the defence, etc. Many of these legal principles have been elevated to primary Community law status by the European Court of Justice, often as a result of preliminary questions. Nevertheless, a considerable number of them have also been elaborated in the context of contentious proceedings before the Court of Justice, such as in the framework of European competition law and European public servants law.

Not Making the Lists: The Underrepresentation of Women in EU Politics and Business. EPIN Commentary No. 12, 22 August 2013

The EU has recently been pushing for legislation to strengthen the gender balance on company boards in its member states and indeed, the principle of gender equality is enshrined in the European treaties. Yet, as Vilde Renman points out, women are clearly underrepresented in top positions within EU institutions themselves. The upcoming European Parliament elections are an opportunity for the EU to appoint more women at the highest levels of administration and legislature, thereby setting an example for companies, member states and citizens alike.

The Social Impact of Migration and the Notion of Citizenship for the EU. Ensuing challenges and opportunities for the Union. CEPS Commentaries, 13 March 2014

Documenting the unwelcoming treatment extended by government officials to the poorest EU citizens from other member states, including denying them their EU rights, Elspeth Guild censures these officials for shattering the principle of equality of citizens and of disaggregating Europe into nationals of the member states who can be treated differently simply on the basis of their origins.

How much does EU citizenship cost? The Maltese citizenship-for-sale affair: A breakthrough for sincere cooperation in citizenship of the union? CEPS Liberty and Security in Europe No. 64, April/2014

How much does European citizenship cost in the EU? This was the question that has raised so much controversy over the Maltese citizenship-for-sale programme. The outright selling of Maltese nationality to rich foreigners led to unprecedented responses by the European Parliament and European Commission. This paper examines the affair and its relevance for current and future configurations of citizenship of the EU. It studies the extent to which member states are still free to lay down the grounds for the acquisition and loss of nationality without any EU supervision and accountability. It provides a comparative overview of member state schemes and the exact price for buying citizenship and a residency permit in the EU. It is argued that the EU’s intervention on the Maltese citizenship-for-sale affair constitutes a legal precedent for assessing the lawfulness of passport-for-sale or golden migration programmes in other EU member states. The affair has also revealed the increasing relevance of a set of European and international legal principles limiting member states’ discretion over citizenship matters and providing a supranational constellation of accountability venues scrutinising the impact of their decisions over citizenship of the Union. The Maltese citizenship-for-sale affair has placed at the forefront the EU general principle of sincere cooperation in nationality matters. Member states’ actions in the citizenship domain cannot negatively affect in substance the concept and freedoms of European citizenship. That notwithstanding, the European institutions’ insistence on the need for Maltese nationality law to require a ‘genuine link’ in the form of an effective residence criteria for any rich applicants to benefit from the fast-track naturalisation poses a fundamental dilemma from the angle of Union citizenship: what is this genuine link really about? And what is precisely ‘habitual’, ‘effective’ or ‘functional’ residence? It is argued that by supporting the ‘real connections’ as the most relevant standard, the European institutions may be paradoxically fuelling nationalistic misuses by member states of the ‘genuine link’ as a way to justify restrictive integration policies on the acquisition of nationality.