An Unemployment Insurance Scheme for the Euro Area: A simulation exercise of two options. CEPS Special Report No. 98/December 2014

This study offers an in-depth economic analysis of the two main proposals for the creation of a European unemployment insurance scheme. One proposes the creation of a harmonised European unemployment benefit scheme that would apply automatically to every eligible unemployed person. The alternative, termed ‘reinsurance’ here, would transfer funds to national unemployment insurance schemes to finance benefits from the centre to the periphery when unemployment is measurably higher than normal. The rationale behind these proposals is to set up an EU-level shock absorber to overcome coordination failures and the crisis-budget constraints of individual countries. The authors consider the possible trade-offs and challenges of, for example, the definition of the trigger, the fiscal rule and the harmonisation of national benefits. They conclude that while both options are viable, ‘reinsurance’ offers a stronger stabilisation effect for the same amount of European distribution.

Interactions métaboliques entre le bisphénol A et le naproxène dans un modèle de foie de rat isolé et perfusé

L'exposition aux mélanges de contaminants (environnementaux, alimentaires ou thérapeutiques) soulève de nombreuses interrogations et inquiétudes vis-à-vis des probabilités d'interactions toxicocinétiques et toxicodynamiques. Une telle coexposition peut influencer le mode d’action des composants du cocktail et donc de leur toxicité, suite à un accroissement de leurs concentrations internes. Le bisphénol A (4 dihydroxy-2,2-diphenylpropane) est un contaminant chimique répandu de manière ubiquitaire dans notre environnement, largement utilisé dans la fabrication des plastiques avec l’un des plus grands volumes de production à l’échelle mondiale. Il est un perturbateur endocrinien par excellence de type œstrogèno-mimétique. Cette molécule est biotransformée en métabolites non toxiques par un processus de glucuronidation. L'exposition concomitante à plusieurs xénobiotiques peut induire à la baisse le taux de glucuronidation du polluant chimique d'intérêt, entre autres la co-exposition avec des médicaments. Puisque la consommation de produits thérapeutiques est un phénomène grandissant dans la population, la possibilité d’une exposition simultanée est d’autant plus grande et forte. Sachant que l'inhibition métabolique est le mécanisme d'interaction le plus plausible pouvant aboutir à une hausse des niveaux internes ainsi qu’à une modulation de la toxicité prévue, la présente étude visait d'abord à confirmer et caractériser ce type d'interactions métaboliques entre le bisphénol A et le naproxène, qui est un anti-inflammatoire non stéroïdiennes (AINS), sur l'ensemble d'un organe intact en utilisant le système de foie de rat isolé et perfusé (IPRL). Elle visait ensuite à déterminer la cinétique enzymatique de chacune de ces deux substances, seule puis en mélange binaire. Dans un second temps, nous avons évalué aussi l’influence de la présence d'albumine sur la cinétique métabolique et le comportement de ces deux substances étudiées en suivant le même modèle de perfusion in vivo au niveau du foie de rat. Les constantes métaboliques ont été déterminées par régression non linéaire. Les métabolismes du BPA et du NAP seuls ont montré une cinétique saturable avec une vélocité maximale (Vmax) de 8.9 nmol/min/ mg prot de foie et une constante d'affinité de l'enzyme pour le substrat (Km) de 51.6 μM pour le BPA et de 3 nmol/min/mg prot de foie et 149.2 μM pour le NAP. L'analyse des expositions combinées suggère une inhibition compétitive partielle du métabolisme du BPA par le NAP avec une valeur de Ki estimée à 0.3542 μM. Les résultats obtenus montrent que l’analyse de risque pour les polluants environnementaux doit donc prendre en considération la consommation des produits pharmaceutiques comme facteur pouvant accroitre le niveau interne lors d’une exposition donnée. Ces données in vivo sur les interactions métaboliques pourraient être intégrées dans un modèle pharmacocinétique à base physiologique (PBPK) pour prédire les conséquences toxicococinétique (TK) de l'exposition d'un individu à ces mélanges chimiques.

La agenda de la seguridad en revisión : casos conmocionantes, temas y problemas públicos en el actual período democrático argentino (1983-2016)

El trabajo explora la emergencia de temas y la constitución de problemas públicos que integran la agenda de la seguridad en Argentina en la etapa democrática a partir de procesos vinculados a la problematización pública de muertes violentas constituidas como casos conmocionantes. Con estos fines, el análisis integra la reconstrucción en el registro de la acción pública de casos conmocionantes con una revisión de trabajos que desde las ciencias sociales abordan dimensiones de la muerte violenta y problemas vinculados a la agenda nacional de la seguridad. Como punto de llegada del análisis destacamos la capacidad que en la actualidad manifiesta la inseguridad para absorber e integrar dimensiones en tanto problema que se constituye como un guion cultural privilegiado para la comprensión de la violencia, que sintetiza sentidos sociales circulantes sobre el riesgo y que sirve de plataforma para la demanda política de amplios sectores de la ciudadanía.

Total cross sections of nuclei for 280 Mev neutrons.

The measurement of 28O-Mev neutron cross sections of various nuclei is described. The neutron beam used results from 340-Mev protons in the 184-in. cyclotron striking a 2-in. Be target. The neutron detector consists of a double coincidence anthracene scintillation counter telescope which counts recoil protons scattered at 15 deg from a paraffin cylinder placed in the collimated neutron beam. A 2-in. Cu absorber placed between the counters assures that only protons of energy greater than 250 Mev are counted. The cross sections for all nuclei measured from Li to Pb are smaller than the corresponding cross sections measured at 90 Mev by factors between 0.5 and 0.6.

The molecular basis for the lack of immunostimulatory activity of vertebrate DNA

Macrophages and B cells are activated by unmethylated CpG-containing sequences in bacterial DNA. The lack of activity of self DNA has generally been attributed to CpG suppression and methylation, although the role of methylation is in doubt. The frequency of CpG in the mouse genome is 12.5% of Escherichia coli, with unmethylated CpG occurring at similar to3% the frequency of E. coli. This suppression of CpG alone is insufficient to explain the inactivity of self DNA; vertebrate DNA was inactive at 100 mug/ml, 3000 times the concentration at which E. coli DNA activity was observed. We sought to resolve why self DNA does not activate macrophages. Known active CpG motifs occurred in the mouse genome at 18% of random occurrence, similar to general CpG suppression. To examine the contribution of methylation, genomic DNAs were PCR amplified. Removal of methylation from the mouse genome revealed activity that was 23-fold lower than E. coli DNA, although there is only a 7-fold lower frequency of known active CpG motifs in the mouse genome. This discrepancy may be explained by G-rich sequences such as GGAGGGG, which potently inhibited activation and are found in greater frequency in the mouse than the E. coli genome. In summary, general CpG suppression, CpG methylation, inhibitory motifs, and saturable DNA uptake combined to explain the inactivity of self DNA. The immunostimulatory activity of DNA is determined by the frequency of unmethylated stimulatory sequences within an individual DNA strand and the ratio of stimulatory to inhibitory sequences.

GLUT4 overexpression or deficiency in adipocytes of transgenic mice alters the composition of GLUT4 vesicles and the subcellular localization of GLUT4 and insulin-responsive aminopeptidase

The majority of GLUT4 is sequestered in unique intracellular vesicles in the absence of insulin. Upon insulin stimulation GLUT4 vesicles translocate to, and fuse with, the plasma membrane. To determine the effect of GLUT4 content on the distribution and subcellular trafficking of GLUT4 and other vesicle proteins, adipocytes of adipose-specific, GLUT4-deficient (aP2-GLUT4-/-) mice and adipose-specific, GLUT4-overexpressing (aP2GLUT4- Tg) mice were studied. GLUT4 amount was reduced by 80 - 95% in aP2-GLUT4-/- adipocytes and increased similar to10-fold in aP2-GLUT4-Tg adipocytes compared with controls. Insulin-responsive aminopeptidase ( IRAP) protein amount was decreased 35% in aP2-GLUT4-/- adipocytes and increased 45% in aP2-GLUT4-Tg adipocytes. VAMP2 protein was also decreased by 60% in aP2-GLUT4-/- adipocytes and increased 2-fold in aP2GLUT4- Tg adipocytes. IRAP and VAMP2 mRNA levels were unaffected in aP2-GLUT4-Tg, suggesting that overexpression of GLUT4 affects IRAP and VAMP2 protein stability. The amount and subcellular distribution of syntaxin4, SNAP23, Munc-18c, and GLUT1 were unchanged in either aP2-GLUT4-/- or aP2-GLUT4-Tg adipocytes, but transferrin receptor was partially redistributed to the plasma membrane in aP2-GLUT4-Tg adipocytes. Immunogold electron microscopy revealed that overexpression of GLUT4 in adipocytes increased the number of GLUT4 molecules per vesicle nearly 2-fold and the number of GLUT4 and IRAP-containing vesicles per cell 3-fold. In addition, the proportion of cellular GLUT4 and IRAP at the plasma membrane in unstimulated aP2-GLUT4-Tg adipocytes was increased 4- and 2-fold, respectively, suggesting that sequestration of GLUT4 and IRAP is saturable. Our results show that GLUT4 overexpression or deficiency affects the amount of other GLUT4-vesicle proteins including IRAP and VAMP2 and that GLUT4 sequestration is saturable.

The BeWo choriocarcinoma cell line as a model of iodide transport by placenta

Cultured human choriocarcinoma cells of the BeWo line exhibited saturable accumulation of radioiodide. Inhibition by competing anions followed the affinity series perchlorate >= iodide >= thiocyanate, consistent with uptake through the thyroid iodide transporter, NIS, whose messenger RNA was found in BeWo cells, and whose protein was distributed towards the apical pole of the cells. Efflux obeyed first order kinetics and was inhibited by DIDS, an antagonist of anion exchangers including pendrin, whose messenger RNA was also present. In cultures where iodide uptake through NIS was blocked with excess perchlorate, radiolodide accumulation was stimulated by exposure to medium in which physiological anions were replaced by 2-morpholinoethanesulfonic acid (MES), consistent with the operation of an anion exchange mechanism taking up iodide. Chloride in the medium was more effective than sulfate at inhibiting this uptake, matching the ionic specificity of pendrin. These studies provide evidence that the trophoblast accumulates iodide through NIS and releases it to the fetal compartment through pendrin. (c) 2004 Elsevier Ltd. All rights reserved.

Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells

The uptake and metabolism profiles of ginsenoside Rh2 and its aglycon protopanaxadiol (ppd) were studied in the human epithelial Caco-2 cell line. High-performance liquid chromatography-mass spectrometry was applied to determine Rh2 and its aglycon ppd concentration in the cells at different pH, temperature, concentration levels and in the presence or absence of inhibitors. Rh2 uptake was time and concentration dependent, and its uptake rates were reduced by metabolic inhibitors and influenced by low temperature, thus indicating that the absorption process was energy-dependent. Drug uptake was maximal when the extracellular pH was 7.0 for Rh2 and 8.0 for ppd. Rh2 kinetic analysis showed that a non-saturable component (K-d 0.17 nmol (.) h(-1) (.) mg(-1) protein) and an active transport system with a K-m of 3.95 mumol (.) l(-1) and a V-max of 4.78 nmol(.)h(-1) (.)mg(-1) protein were responsible for the drug uptake. Kinetic analysis of ppd showed a non-saturable component (K-d 0.78 nmol (.) h(-1) (.) mg(-1) protein). It was suggested that active extrusion of P-glycoprotein and drug degradation in the intestine may influence Rh2 bioavailability.

Unidirectional inversion of ibuprofen in Caco-2 cells: Developing a suitable model for presystemic chiral inversion study

Intestinal chiral inversion of ibuprofen is still lacking direct evidence. In a preliminary experiment, ibuprofen was found to undergo inversion in Caco-2 cells. This investigation was thus conducted to determine the characteristics and influence of some biochemical factors on the chiral inversion of ibuprofen in Caco-2 cells. The effects of substrate concentration (2.5-40 mu g/ml), cell density (0.5-2 x 10(6) cells/ well), content of serum (0-20%), coexistence of S ibuprofen (corresponding doses), sodium azide (10mm), exogenous Coenzyme A (CoA) (0.1 - 0.4 mm),. and palmitic acid (5-25 mu m) on inversion were examined. A stereoselective HPLC method based on the Chromasil-CHI-TBB column was developed for quantitative analysis of the drug in cell culture medium. The inversion ratio (F-i) and elimination rate constant were calculated as the indexes of inversion extent. Inversion of ibuprofen in Caeo-2 cells was found to be both dose and cell density dependent, indicating saturable characteristics. Addition of serum significantly inhibited the inversion, to an extent of 2.7 fold decrease at 20% content. Preexistence of S enantiomer exerted a significant inhibitory effect (p < 0.01 for all tests). Sodium azide decreased the inversion ratio from 0.43 to 0.32 (p < 0.01). Exogenous CoA and palmitic acid significantly promoted the inversion at all tested doses (p < 0.01 for all tests). This research provided strong evidence to the capacity and capability of intestinal chiral inversion. Although long incubation times up to 120 h were required, Caco-2 cells should be a suitable model for chiral inversion research of 2-APAs considering the human-resourced and well-defined characteristics from the present study.

Identification of a novel inositol phosphate recognition site: specific [3H]inositol hexakisphosphate binding to brain regions and cerebellar membranes

[3H]Inositol hexakisphosphate (InsP6) binds with a heterogeneous distribution to frozen sections of unfixed rat brain and is displaced by unlabelled InsP6. The pattern of binding correlates with binding to neuronal cell bodies. [3H]InsP6 binding to cerebellar membranes has been further characterised, is reversible, and saturable, and exhibits high specificity for inositol polyphosphates. The IC50 for competition by unlabelled InsP6 is approximately 100nM, whereas inositol 1,3,4,5,6 pentakisphosphate (Ins(13456)P5), inositol 1,3,4,5 tetrakisphosphate (Ins(1345)P4), and inositol 1,4,5 trisphosphate (Ins(145)P3) bind with an affinity at least one order of magnitude lower. [3H]InsP6 binding is clearly distinct from previously characterised Ins(145)P3 (ref. 1, 2) and Ins(1345)P4 (ref. 3) binding, both in terms of pharmacology and brain distribution.

A study in the application of domestic solar assisted heat pumps for heating and cooling

In the present work, the more important parameters of the heat pump system and of solar assisted heat pump systems were analysed in a quantitative way. Ideal and real Rankine cycles applied to the heat pump, with and without subcooling and superheating were studied using practical recommended values for their thermodynamics parameters. Comparative characteristics of refrigerants here analysed looking for their applicability in heat pumps for domestic heating and their effect in the performance of the system. Curves for the variation of the coefficient of performance as a function of condensing and evaporating temperatures were prepared for R12. Air, water and earth as low-grade heat sources and basic heat pump design factors for integrated heat pumps and thermal stores and for solar assisted heat pump-series, parallel and dual-systems were studied. The analysis of the relative performance of these systems demonstrated that the dual system presents advantages in domestic applications. An account of energy requirements for space and hater heating in the domestic sector in the O.K. is presented. The expected primary energy savings by using heat pumps to provide for the heating demand of the domestic sector was found to be of the order of 7%. The availability of solar energy in the U.K. climatic conditions and the characteristics of the solar radiation here studied. Tables and graphical representations in order to calculate the incident solar radiation over a tilted roof were prepared and are given in this study in section IV. In order to analyse and calculate the heating load for the system, new mathematical and graphical relations were developed in section V. A domestic space and water heating system is described and studied. It comprises three main components: a solar radiation absorber, the normal roof of a house, a split heat pump and a thermal store. A mathematical study of the heat exchange characteristics in the roof structure was done. This permits to evaluate the energy collected by the roof acting as a radiation absorber and its efficiency. An indication of the relative contributions from the three low-grade sources: ambient air, solar boost and heat loss from the house to the roof space during operation is given in section VI, together with the average seasonal performance and the energy saving for a prototype system tested at the University of Aston. The seasonal performance as found to be 2.6 and the energy savings by using the system studied 61%. A new store configuration to reduce wasted heat losses is also discussed in section VI.

Low jitter, long distance pulse transmission near net fibre dispersion zero wavelength

The authors study experimentally ~10 ps return-to-zero pulse propagation near the net dispersion zero of an optical fibre transmission line. Stable near-jitter-free propagation was observed over 70 Mm. Pulse stabilisation and ASE suppression were achieved through the saturable aborber mechanism of nonlinear polarisation rotation.

Picosecond soliton transmission using concatenated nonlinear optical loop mirror intensity filters

We investigate the use of nonlinear optical loop mirrors as saturable absorbers in picosecond soliton transmission systems. It is found that they allow short (1–5-ps) pulses to be propagated through chains of optical amplifiers spaced at intervals of typically 10 km. The loop mirror removes dispersive waves and stabilizes the peak amplitude of the soliton. An additional advantage is that the self-frequency shift of the soliton may be suppressed by bandwidth filtering without causing growth of dispersive waves at the center of the passband. The timing jitter and soliton interactions present in the scheme are also described.

Cost-exergy optimisation of linear Fresnel reflectors

This paper presents a new method for the optimisation of the mirror element spacing arrangement and operating temperature of linear Fresnel reflectors (LFR). The specific objective is to maximise available power output (i.e. exergy) and operational hours whilst minimising cost. The method is described in detail and compared to an existing design method prominent in the literature. Results are given in terms of the exergy per total mirror area (W/m2) and cost per exergy (US $/W). The new method is applied principally to the optimisation of an LFR in Gujarat, India, for which cost data have been gathered. It is recommended to use a spacing arrangement such that the onset of shadowing among mirror elements occurs at a transversal angle of 45°. This results in a cost per exergy of 2.3 $/W. Compared to the existing design approach, the exergy averaged over the year is increased by 9% to 50 W/m2 and an additional 122 h of operation per year are predicted. The ideal operating temperature at the surface of the absorber tubes is found to be 300 °C. It is concluded that the new method is an improvement over existing techniques and a significant tool for any future design work on LFR systems

Experimental transmission of dispersion managed solitons

This thesis investigates the feasibility of soliton transmission at 1150nm over standard fibre. This is done using a dispersion compensating fibre module in each amplifier span to compensate for the high dispersion. The basic principles of soliton propagation in optical fibre are discussed within this thesis, followed by an introduction to advantages of dispersion management. In the experimental chapter single channel transmission results are presented in 10Gbit/s and 40Gbit/s. At 10Gbit/s the effects of dispersion management on the power dispersion relationship for solitons are investigated. The detrimental effects of soliton-soliton interactions, which are increased due to the greater overlap breathing solitons are discussed. A technique for reducing the soliton-soliton interactions through amplifier positioning is presented as a solution to this problem. The experiments demonstrate the feasibility of using standard fibre for transmission over trans-oceanic distances at 10Gbit/s. The 40Gbit/s experiment demonstrates transmission over sufficient distance for an terrestrial system. Also contained within this thesis are experimental results showing transmission of solitons over dispersion shifted fibre using a novel technique that makes use of the non-linear polarisation rotation of the soliton in the fibre. This is used to generate the effect of saturable absorption, allowing transmission distances of 200,000km to be achieved.