Distribution of esterase activity in porcine ear skin, and the effects of freezing and heat separation

Porcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin. Using an esterase staining kit, esterase activity was found to be localised in the stratum corneum and viable epidermis. Under frozen storage and a common heating protocol of epidermal sheet separation, esterase staining in the skin visibly diminished. This was confirmed by a quantitative assay using HPLC to monitor the hydrolysis of aspirin, in freshly excised, frozen or heated porcine ear skin. Compared to vehicle-only control, the rate of aspirin hydrolysis was approximately three-fold higher in the presence of freshly excised skin, but no different in the presence of frozen or heated skin. Therefore, frozen and heat-separated porcine ear skin should not be used to study the permeation of ester-containing permeants, in particular co-drugs and pro-drugs, whose hydrolysis or degradation can be modulated by skin esterases.

The paradox of nationalism: the common denominator of radical right and radical left euroscepticism

What can explain the strong euroscepticism of radical parties of both the right and the left? This article argues that the answer lies in the paradoxical role of nationalism as a central element in both party families, motivating opposition towards European integration. Conventionally, the link between nationalism and euroscepticism is understood solely as a prerogative of radical right-wing parties, whereas radical left-wing euroscepticism is associated with opposition to the neoliberal character of the European Union.This article contests this view. It argues that nationalism cuts across party lines and constitutes the common denominator of both radical right-wing and radical left-wing euroscepticism. It adopts a mixed-methods approach, combining intensive case study analysis with quantitative analysis of party manifestos. First, it traces the link between nationalism and euroscepticism in Greece and France in order to demonstrate the internal validity of the argument. It then undertakes a cross-country statistical estimation to assess the external validity of the argument and its generalisability across Europe.

Effect of shear rupture on aggregate scale formation in sea ice

A discrete element model is used to study shear rupture of sea ice under convergent wind stresses. The model includes compressive, tensile, and shear rupture of viscous elastic joints connecting floes that move under the action of the wind stresses. The adopted shear rupture is governed by Coulomb’s criterion. The ice pack is a 400 km long square domain consisting of 4 km size floes. In the standard case with tensile strength 10 times smaller than the compressive strength, under uniaxial compression the failure regime is mainly shear rupture with the most probable scenario corresponding to that with the minimum failure work. The orientation of cracks delineating formed aggregates is bimodal with the peaks around the angles given by the wing crack theory determining diamond-shaped blocks. The ice block (floe aggregate) size decreases as the wind stress gradient increases since the elastic strain energy grows faster leading to a higher speed of crack propagation. As the tensile strength grows, shear rupture becomes harder to attain and compressive failure becomes equally important leading to elongation of blocks perpendicular to the compression direction and the blocks grow larger. In the standard case, as the wind stress confinement ratio increases the failure mode changes at a confinement ratio within 0.2–0.4, which corresponds to the analytical critical confinement ratio of 0.32. Below this value, the cracks are bimodal delineating diamond shape aggregates, while above this value failure becomes isotropic and is determined by small-scale stress anomalies due to irregularities in floe shape.

A paradoxical presidency: Nicolas Sarkozy, 2007-2012

The Sarkozy presidency is shot through with paradox and contrast: between a well-elected president swiftly loathed by most voters; a ‘hyper-president’ who probably weakened the office; a talented party leader who lost effective control of his party; a right-wing president who was readily compared to Tony Blair; and an ambitious reformer who promised a clean break with the indecision of his two predecessors but whose record was more timid than his rhetoric. This article interprets Sarkozy’s record in the context of the presidential office, the specific circumstances of his presidency, and of the president’s own personality, skills and shortcomings.

Listening behind the Curtain: BBC broadcasting to East Germany and its Cold War echo

This article considers the BBC External Service's East German wing, which broadcast from 1949 on, focusing on the continuities in broadcast techniques between wartime anti-Nazi programming and slots such as 'Two Comrades' and 'The Bewildered Newspaper Reader', both of which replicated pre-1945 formats. The role of the Foreign Office, both as cold warrior in the 1940s and force for detente in the 1970s is included. The article also investigates the response from German listeners to the BBC's external service broadcasting in the 1950s and 1960s. The BBC paid special attention to its German listeners, and has preserved a large number of original letters at the Written Archive at Caversham, as well as conducting regular listener surveys. These considered whether Britain's democratic agenda was getting across in the late 1940s and 50s, but the author also considers to what extent German listeners were pressing for a harder stance in the Cold War or were urging caution on the great powers deciding their fate.

Design, synthesis and in vitro degradation of a novel co-drug for the treatment of psoriasis

Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 μM/min and Km = 65.1 μM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis.

Mixing apples with oranges? Partisanship and active labour market policies in Europe

There are competing theoretical expectations and conflicting empirical results concerning the impact of partisanship on spending on active labour market policies (ALMPs). This paper argues that one should distinguish between different ALMPs. Employment incentives and rehabilitation programmes incentivize the unemployed to accept jobs. Direct job creation reduces the supply of labour by creating non-commercial jobs. Training schemes raise the human capital of the unemployed. Using regression analysis this paper shows that the positions of political parties towards these three types of ALMPs are different. Party preferences also depend on the welfare regime in which parties are located. In Scandinavia, left-wing parties support neither employment incentives nor direct job creation schemes. In continental and Liberal welfare regimes, left-wing parties oppose employment incentives and rehabilitation programmes to a lesser extent and they support direct job creation. There is no impact of partisanship on training. These results reconcile the previously contradictory findings concerning the impact of the Left on ALMPs.

Species 2000 & ITIS Catalogue of Life, 2013 Annual Checklist

This release of the Catalogue of Life contains contributions from 132 databases with information on 1,352,112 species, 114,069 infraspecific taxa and also includes 928,147 synonyms and 408,689 common names covering the following groups: Viruses • Viruses and Subviral agents from ICTV_MSL UPDATED! Bacteria and Archaea from BIOS Chromista • Chromistan fungi from Species Fungorum Protozoa • Major groups from ITIS Regional, • Ciliates from CilCat, • Polycystines from WoRMS Polycystina UPDATED!, • Protozoan fungi from Species Fungorum and Trichomycetes database • Slime moulds from Nomen.eumycetozoa.com Fungi • Various taxa in whole or in part from CABI Bioservices databases (Species Fungorum, Phyllachorales, Rhytismatales, Saccharomycetes and Zygomycetes databases) and from three other databases covering Xylariaceae, Glomeromycota, Trichomycetes, Dothideomycetes • Lichens from LIAS UPDATED! Plantae (Plants) • Mosses from MOST • Liverworts and hornworts from ELPT • Conifers from Conifer Database • Cycads and 6 flowering plant families from IOPI-GPC, and 99 families from WCSP • Plus individual flowering plants families from AnnonBase, Brassicaceae, ChenoBase, Droseraceae Database, EbenaBase, GCC UPDATED!, ILDIS UPDATED!, LecyPages, LHD, MELnet UPDATED!, RJB Geranium, Solanaceae Source, Umbellifers. Animalia (Animals) • Marine groups from URMO, ITIS Global, Hexacorals, ETI WBD (Euphausiacea), WoRMS: WoRMS Asteroidea UPDATED!, WoRMS Bochusacea UPDATED!, WoRMS Brachiopoda UPDATED!, WoRMS Brachypoda UPDATED!, WoRMS Brachyura UPDATED!, WoRMS Bryozoa UPDATED!, WoRMS Cestoda NEW!, WoRMS Chaetognatha UPDATED!, WoRMS Cumacea UPDATED!, WoRMS Echinoidea UPDATED!, WoRMS Gastrotricha NEW!, WoRMS Gnathostomulida NEW!, WoRMS Holothuroidea UPDATED!, WoRMS Hydrozoa UPDATED!, WoRMS Isopoda UPDATED!, WoRMS Leptostraca UPDATED!, WoRMS Monogenea NEW!, WoRMS Mystacocarida UPDATED!, WoRMS Myxozoa NEW!, WoRMS Nemertea UPDATED!, WoRMS Oligochaeta UPDATED!, WoRMS Ophiuroidea UPDATED!, WoRMS Phoronida UPDATED!, WoRMS Placozoa NEW!, WoRMS Polychaeta UPDATED!, WoRMS Polycystina UPDATED!, WoRMS Porifera UPDATED!, WoRMS Priapulida NEW!, WoRMS Proseriata and Kalyptorhynchia UPDATED!, WoRMS Remipedia UPDATED!, WoRMS Scaphopoda UPDATED!, WoRMS Tanaidacea UPDATED!, WoRMS Tantulocarida UPDATED!, WoRMS Thermosbaenacea UPDATED!, WoRMS Trematoda NEW!, WoRMS Xenoturbellida UPDATED! • Rotifers, mayflies, freshwater hairworms, planarians from FADA databases: FADA Rotifera UPDATED!, FADA Ephemeroptera NEW!, FADA Nematomorpha NEW! & FADA Turbellaria NEW! • Entoprocts, water bears from ITIS Global • Spiders, scorpions, ticks & mites from SpidCat via ITIS UPDATED!, SalticidDB , ITIS Global, TicksBase, SpmWeb BdelloideaBase UPDATED! & Mites GSDs: OlogamasidBase, PhytoseiidBase, RhodacaridBase & TenuipalpidBase • Diplopods, centipedes, pauropods and symphylans from SysMyr UPDATED! & ChiloBase • Dragonflies and damselflies from Odonata database • Stoneflies from PlecopteraSF UPDATED! • Cockroaches from BlattodeaSF UPDATED! • Praying mantids from MantodeaSF UPDATED! • Stick and leaf insects from PhasmidaSF UPDATED! • Grasshoppers, locusts, katydids and crickets from OrthopteraSF UPDATED! • Webspinners from EmbiopteraSF UPDATED! • Bark & parasitic lices from PsocodeaSF NEW! • Some groups of true bugs from ScaleNet, FLOW, COOL, Psyllist, AphidSF UPDATED! , MBB, 3i Cicadellinae, 3i Typhlocybinae, MOWD & CoreoideaSF NEW!• Twisted-wing parasites from Strepsiptera Database UPDATED! • Lacewings, antlions, owlflies, fishflies, dobsonflies & snakeflies from LDL Neuropterida • Some beetle groups from the Scarabs UPDATED!, TITAN, WTaxa & ITIS Global • Fleas from Parhost • Flies, mosquitoes, bots, midges and gnats from Systema Dipterorum, CCW & CIPA • Butterflies and moths from LepIndex UPDATED!, GloBIS (GART) UPDATED!, Tineidae NHM, World Gracillariidae • Bees & wasps from ITIS Bees, Taxapad Ichneumonoidea, UCD, ZOBODAT Vespoidea & HymIS Rhopalosomatidae NEW!• Molluscs from WoRMS Mollusca NEW!, FADA Bivalvia NEW!, MolluscaFW NEW! & AFD (Pulmonata) • Fishes from FishBase UPDATED! • Reptiles from TIGR Reptiles • Amphibians, birds and mammals from ITIS Global PLUS additional species of many groups from ITIS Regional, NZIB and CoL China NEW!

Modelling the reorientation of sea-ice faults as the wind changes direction

A discrete-element model of sea ice is used to study how a 90° change in wind direction alters the pattern of faults generated through mechanical failure of the ice. The sea-ice domain is 400km in size and consists of polygonal floes obtained through a Voronoi tessellation. Initially the floes are frozen together through viscous–elastic joints that can break under sufficient compressive, tensile and shear deformation. A constant wind-stress gradient is applied until the initially frozen ice pack is broken into roughly diamond-shaped aggregates, with crack angles determined by wing-crack formation. Then partial refreezing of the cracks delineating the aggregates is modelled through reduction of their length by a particular fraction, the ice pack deformation is neglected and the wind stress is rotated by 90°. New cracks form, delineating aggregates with a different orientation. Our results show the new crack orientation depends on the refrozen fraction of the initial faults: as this fraction increases, the new cracks gradually rotate to the new wind direction, reaching 90° for fully refrozen faults. Such reorientation is determined by a competition between new cracks forming at a preferential angle determined by the wing-crack theory and at old cracks oriented at a less favourable angle but having higher stresses due to shorter contacts across the joints

Essays on labour market dualisation in Western Europe: active labour market policies, temporary work regulation and inequality

European labour markets are increasingly divided between insiders in full-time permanent employment and outsiders in precarious work or unemployment. Using quantitative as well as qualitative methods, this thesis investigates the determinants and consequences of labour market policies that target these outsiders in three separate papers. The first paper looks at Active Labour Market Policies (ALMPs) that target the unemployed. It shows that left and right-wing parties choose different types of ALMPs depending on the policy and the welfare regime in which the party is located. These findings reconcile the conflicting theoretical expectations from the Power Resource approach and the insider-outsider theory. The second paper considers the regulation and protection of the temporary work sector. It solves the puzzle of temporary re-regulation in France, which contrasts with most other European countries that have deregulated temporary work. Permanent workers are adversely affected by the expansion of temporary work in France because of general skills and low wage coordination. The interests of temporary and permanent workers for re-regulation therefore overlap in France and left governments have an incentive to re-regulate the sector. The third paper then investigates what determines inequality between median and bottom income workers. It shows that non-inclusive economic coordination increases inequality in the absence of compensating institutions such as minimum wage regulation. The deregulation of temporary work as well as spending on employment incentives and rehabilitation also has adverse effects on inequality. Thus, policies that target outsiders have important economic effects on the rest of the workforce. Three broader contributions can be identified. First, welfare state policies may not always be in the interests of labour, so left parties may not always promote them. Second, the interests of insiders and outsiders are not necessarily at odds. Third, economic coordination may not be conducive to egalitarianism where it is not inclusive.

En attendant Sarko? France’s mainstream Right and Centre, 2012-2014

In winning the municipal elections of March 2014, France’s mainstream opposition – the Centrists and the Union pour un Mouvement Populaire (UMP) – benefited not only from the unpopularity of the Left in power, but also from its own (partial) reconstruction. The Centrists had reorganised; the UMP had reaffirmed its right-wing programme and drawn strength from the opposition social movements launched in 2013. The European elections of 2014, however, demonstrated the limitations of this reconstruction. Their weak institutionalisation – the original sin of France’s Right and centre-Right – left internal ideological differences and (above all) personal rivalries unchecked within both forces. These tensions were compounded, in the UMP, by a series of financial scandals. At their heart was former president Nicolas Sarkozy, still the activists’ darling, ever more clearly a candidate for 2017, but also more hobbled by judicial investigations.

The rise of the far right in debtor and creditor European countries: the case of European Parliament elections

While the 2014 European Parliament elections were marked by the rise of far right-wing parties, the different patterns of support that we observe across Europe and across time are not directly related to the economic crisis. Indeed, economic hardship seems neither sufficient nor necessary for the rise of such parties to occur. Using the cross-national results for the 2004, 2009 and 2014 EP elections in order to capture time and country variations, we posit the economy affects the rise of far right-wing parties in more complex ways. Specifically, we compare the experience of high debt countries (the ‘debtors’) and the others (the ‘creditors’) and explore the relationship between far right-wing party success on the one hand, and unemployment, inequality, immigration, globalization and the welfare state on the other hand. Our discussion suggests there might be a trade off between budgetary stability and far right-wing party support, but the choice between Charybdis and Scylla may be avoided if policy makers carefully choose which policies should bear the brunt of the fiscal adjustment.

Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: evidence from randomised controlled trials

Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. METHODS AND RESULTS: One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). CONCLUSION: Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Immunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation. A novel detection method is also proposed. It enables signal detection specifically at microneedle tips and therefore may aid the construction of depth profiles of skin biomarkers. The detection method can be coupled with computerised densitometry for signal quantitation. The antigen specificity, sensitivity and functional stability of the device were assessed against a number of model biomarkers. Detection and analysis of endogenous antigens (interleukins 1α and 6) from the skin using the device was demonstrated. The results were verified using conventional enzyme-linked immunosorbent assays. The detection limit of the microneedle device, at ≤10 pg/mL, was at least comparable to conventional plate-based solid-phase enzyme immunoassays.

Selecting object pairs for action: is the active object always first?

Perception is linked to action via two routes: a direct route based on affordance information in the environment and an indirect route based on semantic knowledge about objects. The present study explored the factors modulating the recruitment of the two routes, in particular which factors affecting the selection of paired objects. In Experiment 1, we presented real objects among semantically related or unrelated distracters. Participants had to select two objects that can interact. The presence of distracters affected selection times, but not the semantic relations of the objects with the distracters. Furthermore, participants first selected the active object (e.g. teaspoon) with their right hand, followed by the passive object (e.g. mug), often with their left hand. In Experiment 2, we presented pictures of the same objects with no hand grip, congruent or incongruent hand grip. Participants had to decide whether the two objects can interact. Action decisions were faster when the presentation of the active object preceded the presentation of the passive object, and when the grip was congruent. Interestingly, participants were slower when the objects were semantically but not functionally related; this effect increased with congruently gripped objects. Our data showed that action decisions in the presence of strong affordance cues (real objects, pictures of congruently gripped objects) relied on sensory-motor representation, supporting the direct route from perception-to-action that bypasses semantic knowledge. However, in the case of weak affordance cues (pictures), semantic information interfered with action decisions, indicating that semantic knowledge impacts action decisions. The data support the dual-route account from perception-to-action.