Extending Citizenship Rights to Third Country Nationals: The Correlation between Migration and Integration: A Sample from South Europe. CEPS Working Document No. 175, October 2001

Various issues arise in the European context with respect to the boundaries of citizenship; one of the main questions is to what extent the division between the European Union citizens and third country nationals will increase, especially if "deepening" of the Union leads to more tightening of its external borders. This paper addresses the question of how far citizenship rights can be extended to third country migrants in the EU? The paper is divided into two parts; the first is a brief theoretical approach to questions about the parameters of citizenship in the EU. The second part focuses on Italy and Spain as new receiving states affected by North\South migration in the Mediterranean (their policies, people's attitudes, internal distribution of migrants, etc.) and compares their current position with the countries who have had a tradition of labour immigration since the1960s. It contrasts policy and practice vis-à-vis Maghrebi nationals in these two countries, although both are Mediterranean states in close geographical proximity to North Africa. The analysis suggests that the problems encountered by the different Mediterreanean EU members have, in some respects, to be treated on an individual basis. My empirical focus is mainly centred on labour immigration from the Maghreb countries (Morocco, Algeria and Tunisia) and the public policy implications for the EU as a supranational Community rather than as a group of individual member states. I have chosen the Maghrebi immigrants not only because they constitute a high percentage of immigrants residing and working at present in the EU (about 2.5 million), but because their numbers have increased significantly (for both economic and political reasons). The empirical material largely relates to legally resident migrant workers in the EU and their families. The conclusion attempts to show why the EU cannot avoid dealing with this issue at least to some extent. The development of the EU's principles of the free movement of persons within the Community in order to work in another member state, equal treatment and social justice will be tested as they apply to the position of legally resident third country nationals

Striking a Balance between Freedom, Security and Justice. CEPS Paperback. October 2002

This monograph surveys the achievements of the European Union in the field of Justice and Home Affairs and analyses the pro’s and con’s of setting up an area of freedom, security and justice. The inter-connections between internal and external security issues are carefully examined - both from a practical and institutional point of view-and consideration is given to how to avoid excessive “securitisation” of society. It argues for the need to take an integrated approach towards these issues in order to ensure that the right balance is actually being struck between these three dimensions

In vivo delivery of transcription factors with multifunctional oligonucleotides.

Therapeutics based on transcription factors have the potential to revolutionize medicine but have had limited clinical success as a consequence of delivery problems. The delivery of transcription factors is challenging because it requires the development of a delivery vehicle that can complex transcription factors, target cells and stimulate endosomal disruption, with minimal toxicity. Here, we present a multifunctional oligonucleotide, termed DARTs (DNA assembled recombinant transcription factors), which can deliver transcription factors with high efficiency in vivo. DARTs are composed of an oligonucleotide that contains a transcription-factor-binding sequence and hydrophobic membrane-disruptive chains that are masked by acid-cleavable galactose residues. DARTs have a unique molecular architecture, which allows them to bind transcription factors, trigger endocytosis in hepatocytes, and stimulate endosomal disruption. The DARTs have enhanced uptake in hepatocytes as a result of their galactose residues and can disrupt endosomes efficiently with minimal toxicity, because unmasking of their hydrophobic domains selectively occurs in the acidic environment of the endosome. We show that DARTs can deliver the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) to the liver, catalyse the transcription of Nrf2 downstream genes, and rescue mice from acetaminophen-induced liver injury

Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.

Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that would manage spatiotemporal heterogeneity sufficiently to enable meeting two new target attributes and conducted virtual experiments to explore different ideas for model mechanism improvement at intrahepatocyte and multihepatocyte levels. For the latter, evidence supports intercellular communication via exosomes, gap junctions, and connexin hemichannels playing essential roles in the toxic effects of chemicals, including facilitating or counteracting cell death processes. Logic requiring hepatocytes to obtain current information about whether downstream and lateral neighbors have triggered necrosis enabled virtual hepatocytes to achieve both new target attributes. A virtual hepatocyte that is glutathione-depleted uses that information to determine if it will initiate necrosis. When a less-stressed hepatocyte is flanked by at least two neighbors that have triggered necrosis, it too will initiate necrosis. We hypothesize that the resulting intercellular communication-enabled model mechanism is analogous to the actual explanation for APAP-induced hepatotoxicity at comparable levels of granularity

Antidote application: an educational system for treatment of common toxin overdose

Poisonings account for almost 1% of emergency room visits each year. Time is a critical factor in dealing with a toxicologic emergency. Delay in dispensing the first antidote dose can lead to life-threatening sequelae. Current toxicological resources that support treatment decisions are broad in scope, time-consuming to read, or at times unavailable. Our review of current toxicological resources revealed a gap in their ability to provide expedient calculations and recommendations about appropriate course of treatment. To bridge the gap, we developed the Antidote Application (AA), a computational system that automatically provides patient-specific antidote treatment recommendations and individualized dose calculations. We implemented 27 algorithms that describe FDA (the US Food and Drug Administration) approved use and evidence-based practices found in primary literature for the treatment of common toxin exposure. The AA covers 29 antidotes recommended by Poison Control and toxicology experts, 19 poison classes and 31 poisons, which represent over 200 toxic entities. To the best of our knowledge, the AA is the first educational decision support system in toxicology that provides patient-specific treatment recommendations and drug dose calculations. The AA is publicly available at http://projects.met- hilab.org/antidote/

Estimation of the Hurst and the stability indices of a HH-self-similar stable process

In this paper we estimate both the Hurst and the stable indices of a H-self-similar stable process. More precisely, let $X$ be a $H$-sssi (self-similar stationary increments) symmetric $\alpha$-stable process. The process $X$ is observed at points $\frac{k}{n}$, $k=0,\ldots,n$. Our estimate is based on $\beta$-variations with $-\frac{1}{2}<\beta<0$. We obtain consistent estimators, with rate of convergence, for several classical $H$-sssi $\alpha$-stable processes (fractional Brownian motion, well-balanced linear fractional stable motion, Takenaka's processes, L\'evy motion). Moreover, we obtain asymptotic normality of our estimators for fractional Brownian motion and L\'evy motion. Keywords: H-sssi processes; stable processes; self-similarity parameter estimator; stability parameter estimator

Asymptotic Pad\'e Approximants and the SQCD β\beta-function

We present a prediction for the four loop $\beta$-function for SQCD based on the method of Asymptotic Pad\'e Approximants.Comment: 8 pages, including 2 figures. Plain TeX. Uses Harvmac and eps

Paradoxical roles of antioxidant enzymes:Basic mechanisms and health implications

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways

Combined Effect of Ethanol and Acetaminophen on the Central Nervous System of Daphnia magna

The combined consumption of acetaminophen (APAP) and ethanol (EtOH) has been an issue with clinical implications. Previous findings regarding the simultaneous consumption of APAP and EtOH have reported harmful effects on the liver and stomach; however, little is known about the effects on the central nervous system (CNS). We hypothesized that EtOH and APAP will have a synergistic effect on the CNS of Daphnia magna (D. magna), causing a pronounced decrease in heart rate at a toxic dose of EtOH. To better understand the effects of the combined consumption of EtOH and APAP on the CNS, the heart rates of D. magna were measured under a dissection microscope after exposure to EtOH, APAP, or a combined EtOH-APAP solution. Interestingly, the average heart rates of D. magna exposed to the EtOH-APAP solution and D. magna exposed only to APAP were approximately the same. Although our results did not support our original hypothesis, the data demonstrated that APAP exerted a dominant effect over EtOH. APAP and EtOH are known to have inhibitory effects on the CNS. Therefore, these findings suggest that APAP and EtOH may compete against each other on similar pathways to be the substance that exerts an inhibitory effect in the CNS