Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

Orthogonal protection of peptides and peptoids for cyclization by the thiol-ene reaction and conjugation

Cyclic peptides and peptoids were prepared using the thiolene Michael-type reaction. The linear precursors were provided with additional functional groups allowing for subsequent conjugation: an orthogonally protected thiol, a protected maleimide, or an alkyne. The functional group for conjugation was placed either within the cycle or in an external position. The click reactions employed for conjugation with suitably derivatized nucleoside or oligonucleotides were either cycloadditions (Diels-Alder, Cu(I)-catalyzed azide-alkyne) or the same Michael-type reaction as for cyclization.

Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

Mujeres víctimas de trata en prisión en España

La trata de seres humanos constituye uno de los fenómenos criminales emergentes en la sociedad globalizada. La comunidad internacional emprendió una estrategia global contra este fenómeno a comienzos de los 2000, adoptando una política esencialmente criminalizadora. Más contemporáneamente, las políticas emprendidas contra este fenómeno pretenden abordarlo integralmente, incidiendo también en la prevención y esencialmente en la protección de las víctimas, que pasa por su identificación como tales. El Estado español ha efectuado en los últimos dos años esfuerzos para alcanzar los estándares internacionalmente establecidos para luchar contra este fenómeno. Sin embargo, el estudio empírico que aquí se presenta muestra como en el plano aplicativo queda todavía mucho por hacer. Se trata de un estudio cualitativo efectuado con 45 mujeres recluidas en dos Centros penitenciarios españoles algunas de las cuales han sido objeto de una grave victimización institucional. En el caso de 10 de estas mujeres, identificadas como víctimas de trata en este estudio, al padecimiento del proceso victimizador propio de haber sufrido los efectos de la trata de seres humanos, se suma la victimización integrada no sólo por no haber sido detectadas como víctimas de este fenómeno por el sistema, sino además por haber sido condenadas y hallarse recluidas cumpliendo condena por la comisión de un delito producida en fase de explotación del proceso de trata.

Factors affecting hospital admission and recovery stay duration of in-patient motor victims in Spain

Hospital expenses are a major cost driver of healthcare systems in Europe, with motor injuries being the leading mechanism of hospitalizations. This paper investigates the injury characteristics which explain the hospitalization of victims of traffic accidents that took place in Spain. Using a motor insurance database with 16.081 observations a generalized Tobit regression model is applied to analyse the factors that influence both the likelihood of being admitted to hospital after a motor collision and the length of hospital stay in the event of admission. The consistency of Tobit estimates relies on the normality of perturbation terms. Here a semi-parametric regression model was fitted to test the consistency of estimates, concluding that a normal distribution of errors cannot be rejected. Among other results, it was found that older men with fractures and injuries located in the head and lower torso are more likely to be hospitalized after the collision, and that they also have a longer expected length of hospital recovery stay.

Discrete distributions when modeling the disability severity score of motor victims

Many European states apply score systems to evaluate the disability severity of non-fatal motor victims under the law of third-party liability. The score is a non-negative integer with an upper bound at 100 that increases with severity. It may be automatically converted into financial terms and thus also reflects the compensation cost for disability. In this paper, discrete regression models are applied to analyze the factors that influence the disability severity score of victims. Standard and zero-altered regression models are compared from two perspectives: an interpretation of the data generating process and the level of statistical fit. The results have implications for traffic safety policy decisions aimed at reducing accident severity. An application using data from Spain is provided.

The European Union Perception of Cuba: From Frustation to Irritation

On Friday May 16, the Ministry of Foreign Affairs of Cuba summoned the newly-appointed charged’affairs of the European Commission in Havana and announced the withdrawal of the application procedure for membership in the Cotonou Agreement of the Africa, Caribbean, and Pacific (ACP) countries, and in fact renouncing to benefit from European development aid.1 In a blistering note published in the Granma official newspaper of the Cuban Communist Party, the government blamed the EU Commission for exerting undue pressure, its alleged alignment with the policies of the United States, and censure for the measures taken by Cuba during the previous weeks.2 In reality, Cuba avoided an embarrasin flat rejection for its application. This was the anti-climatic ending for a long process that can be traced back to the end of the Cold War, in a context where Cuba has been testing alternative grounds to substitute for the overwhelming protection of the Soviet Union

La tutela cautelar de les víctimes de violència de gènere

Aquest projecte de recerca té com a objecte l'anàlisi de les línies bàsiques de la Llei orgànica 1/2004, de 28 de desembre, de mesures de protecció integral contra la violència de gènere i, més concretament, de la regulació de la tutela cautelar de les víctimes d'aquest tipus de violència. Quant a la regulació de les mesures de protecció que podrà adoptar el Jutge de violència de gènere, s'ha optat per la seva inclusió expressa, ja que no es troben recollides com a mesures cautelars a la Llei d'enjudiciament criminal, que només regula la prohibició de residència i la de poder anar a un determinat lloc pels delictes recollits a l'art. 57 del Codi penal (article 544 bis LECrim, introduït per la Llei orgànica 14/1999). Malgrat els dubtes envers la naturalesa jurídica d'aquestes mesures, és clar que també persegueixen el fi típic de les mesures cautelars clàssiques, encara que de forma tangencial: assegurar el desenvolupament amb èxit del judici oral, mantenint allunyada a la víctima tan de nous actes violents com d'amenaces dirigides a assolir una retractació del seu inicial testimoni. Es tracta, doncs, de "mesures cautelars" (personals) que incideixen sobre la llibertat de l'imputat (restringint la seva llibertat de circulació i de residència), que tenen com a pressupostos tant el fumus boni iuris (judici de probabilitat del jutge), com el periculum in mora (entès més aviat com a periculum libertatis o periculum in damno), i que responen a les característiques d'instrumentalitat, provisionalitat, jurisdiccionalitat, oficialitat, revocabilitat i homogeneïtat (però no identitat) amb les mesures executives. D'altra banda, també s'afegeix la possibilitat que qualsevol d'aquestes mesures de protecció pugui ser utilitzada com a mesura de seguretat, des del principi o al llarg de l'execució de la sentència, incrementant-se així la llista de l'art. 105 del Codi penal, i possibilitant al jutge la garantia de protecció de les víctimes més enllà de la finalització del procés.

The externalisation of the asylum function in the European Union

This paper aims to identify and assess the main items in the strategy followed by the EU and its member states on the externalisation of their asylum function. First, it analyses the European harmonisation of the return to safe third countries and to countries of first asylum, which is carried out by means of readmission agreements. Second, it refers to the strategies defined by the Hague and the Stockholm programs concerning the External Aspects of the European Union Asylum Policy, on the detention centres for illegal immigrants abroad, and on the proposals for delocalisation of asylum applications processing centres beyond the EU borders. Finally, this paper considers whether the strategy of externalisation of the function of asylum sometimes lacks legitimacy, and to what extent there is a fair balance between the interests of the states and the protection of the human rights of refugees and asylum seekers.

Federalism and democracy. The case of minority nations: a federalist deficit

In this chapter, after pointing out the different logics that lie behind the familiar ideas of democracy and federalism, I have dealt with the case of plurinational federal democracies. Having put forward a double criterion of an empirical nature with which to differentiate between the existence of minority nations within plurinational democracies (section 2), I suggest three theoretical criteria for the political accommodation of these democracies. In the following section, I show the agonistic nature of the normative discussion of the political accommodation of this kind of democracies, which bring monist and pluralist versions of the demos of the polity into conflict (section 3.1), as well as a number of conclusions which are the result of a comparative study of 19 federal and regional democracies using four analytical axes: the uninational/plurinational axis; the unitarianism-federalism axis; the centralisation-decentralisation axis; and the symmetry-asymmetry axis (section 3.2). This analysis reveals shortcomings in the constitutional recognition of national pluralism in federal and regional cases with a large number of federated units/regions with political autonomy; a lower degree of constitutional federalism and a greater asymmetry in the federated entities or regions of plurinational democracies. It also reveals difficulties to establish clear formulas in these democracies in order to encourage a “federalism of trust” based on the participation and protection of national minorities in the shared government of plurinational federations/regional states. Actually, there is a federal deficit in this kind polities according to normative liberal-democratic patterns and to what comparative analysis show. Finally, this chapter advocates the need for a greater normative and institutional refinement in plurinational federal democracies. In order to achieve this, it is necessary to introduce a deeper form of “ethical” pluralism -which displays normative agonistic trends, as well as a more “confederal/asymmetrical” perspective, congruent with the national pluralism of these kind of polities.

Competing engines of growth: Innovation and standardization

We study a dynamic general equilibrium model where innovation takes theform of the introduction of new goods whose production requires skilled workers.Innovation is followed by a costly process of standardization, whereby these newgoods are adapted to be produced using unskilled labor. Our framework highlightsa number of novel results. First, standardization is both an engine of growth anda potential barrier to it. As a result, growth is an inverse U-shaped function ofthe standardization rate (and of competition). Second, we characterize the growthand welfare maximizing speed of standardization. We show how optimal protection of intellectual property rights affecting the cost of standardization vary withthe skill-endowment, the elasticity of substitution between goods and other parameters. Third, we show that, depending on how competition between innovatingand standardizing firms is modelled and on parameter values, a new type of multiplicity of equilibria may arise. Finally, we study the implications of our model forthe skill-premium and we illustrate novel reasons for linking North-South trade tointellectual property rights protection.

Caution, children crossing: Heterogeneity of victim's cost of care and negligence rule

The paper deals with a bilateral accident situation in which victims haveheterogeneous costs of care. With perfect information,efficient care bythe injurer raises with the victim's cost. When the injurer cannot observeat all the victim's type, and this fact can be verified by Courts, first-bestcannot be implemented with the use of a negligence rule based on thefirst-best levels of care. Second-best leads the injurer to intermediate care,and the two types of victims to choose the best response to it. This second-bestsolution can be easily implemented by a negligence rule with second-best as duecare. We explore imperfect observation of the victim's type, characterizing theoptimal solution and examining the different legal alternatives when Courts cannotverify the injurers' statements. Counterintuitively, we show that there is nodifference at all between the use by Courts of a rule of complete trust and arule of complete distrust towards the injurers' statements. We then relate thefindings of the model to existing rules and doctrines in Common Law and Civil Lawlegal systems.

The colonial origins of Civil War

The dominant hypothesis in the literature that studies conflict is that poverty is the main cause of civil wars. We instead analyze the effect of institutions on civil war, controlling for income per capita. In our set up, institutions are endogenous and colonial origins affect civil wars through their legacy on institutions. Our results indicate that institutions, proxied by the protection of property rights, rule of law and the efficiency of the legal system, are a fundamental cause of civil war. In particular, an improvement in institutions from the median value in the sample to the 75th percentile is associated with a 38 percentage points reduction in the incidence of civil wars. Moreover, once institutions are included as explaining civil wars, income does not have any effect on civil war, either directly or indirectly.

Testing the response of macroinvertebrate functional structure and biodiversity to flooding and confinement

The aim of the present study was to investigate the relative importance of flooding- and confinement-related environmentalfeatures in explaining macroinvertebrate trait structure and diversity in a pool of wetlands located in a Mediterranean riverfloodplain. To test hypothesized trait-environment relationships, we employed a recently implemented statistical procedure, thefourth-corner method. We found that flooding-related variables, mainly pH and turbidity, were related to traits that confer an abilityof the organism to resist flooding (e.g., small body-shape, protection of eggs) or recuperate faster after flooding (e.g., short life-span, asexual reproduction). In contrast, confinement-related variables, mainly temperature and organic matter, enhanced traits that allow organisms to interact and compete with other organisms (e.g., large size, sexual reproduction) and to efficiently use habitat and resources (e.g., diverse locomotion and feeding strategies). These results are in agreement with predictions made under the River Habitat Templet for lotic ecosystems, and demonstrate the ability of the fourth-corner method to test hypothesis that posit traitenvironment relationships. Trait diversity was slightly higher in flooded than in confined sites, whereas trait richness was not significantly different. This suggests that although trait structure may change in response to the main environmental factors, as evidenced by the fourth-corner method, the number of life-history strategies needed to persist in the face of such constraints remains more or less constant; only their relative dominance differs

1,2-Dimethylindole-3-sulfonyl (MIS) as protecting group for the side chain of arginine

The protection of arginine (Arg) side chains is a crucial issue in peptide chemistry because of the propensity of the basic guanidinium group to produce side reactions. Currently, sulfonyl-type protecting groups, such as 2,2,5,7,8-pentamethylchroman (Pmc) and 2,2,4,6,7-pentamethyldihydrobenzofurane (Pbf), are the most widely used for this purpose. Nevertheless, Arg side chain protection remains problematic as a result of the acid stability of these two compounds. This issue is even more relevant in Arg-rich sequences, acid-sensitive peptides and large-scale syntheses. The 1,2-dimethylindole-3-sulfonyl (MIS) group is more acid-labile than Pmc and Pbf and can therefore be a better option for Arg side chain protection. In addition, MIS is compatible with tryptophan-containing peptides.