Rousseau on the Tourist Trail

This essay looks at the post-Napoleonic tourist trail associated with Rousseau in Switzerland, reconstructing the tourist sentiment which the figure of the philosopher elicited. This was a complex meld of the biographical and the fictional, which solicited the self-conscious and performative occupation by the visitor of a Rousseauistic sensibility. By comparing and contrasting early nineteenth-century travellers’ accounts of visiting Voltaire’s chateau at Ferney and Rousseau’s homes, especially his farmhouse refuge on the Ile St Pierre in the Lac de Bienne, this paper traces the emergence and contours of a new, romantic type of tourist sensibility and matching practices created by and around Rousseau before considering the way in which this model was subsumed within the exilic appeal of the Byronic

Catalytic amidation of unactivated ester derivatives mediated by trifluoroethanol

A catalytic amidation method has been developed, employing 2,2,2-trifluoroethanol to facilitate condensation of unactivated esters and amines, enabling the synthesis of a range of amide products in good to excellent yields. Mechanistic studies indicate the reaction proceeds through a trifluoroethanol-derived active ester intermediate

Hässeldala – a key site for Last Termination climate events in northern Europe

The Last Termination (19 000–11 000 a BP) with its rapid and distinct climate shifts provides a perfect laboratory to study the nature and regional impact of climate variability. The sedimentary succession from the ancient lake at Hässeldala Port in southern Sweden with its distinct Lateglacial/early Holocene stratigraphy (>14.1–9.5 cal. ka BP) is one of the few chronologically well‐constrained, multi‐proxy sites in Europe that capture a variety of local and regional climatic and environmental signals. Here we present Hässeldala's multi‐proxy records (lithology, geochemistry, pollen, diatoms, chironomids, biomarkers, hydrogen isotopes) in a refined age model and place the observed changes in lake status, catchment vegetation, summer temperatures and hydroclimate in a wider regional context. Reconstructed mean July temperatures increased between c. 14.1 and c. 13.1 cal. ka BP and subsequently declined. This latter cooling coincided with drier hydroclimatic conditions that were probably associated with a freshening of the Nordic Seas and started a few hundred years before the onset of Greenland Stadial 1 (c. 12.9 cal. ka BP). Our proxies suggest a further shift towards colder and drier conditions as late as c. 12.7 cal. ka BP, which was followed by the establishment of a stadial climate regime (c. 12.5–11.8 cal. ka BP). The onset of warmer and wetter conditions preceded the Holocene warming over Greenland by c. 200 years. Hässeldala's proxies thus highlight the complexity of environmental and hydrological responses across abrupt climate transitions in northern Europe

Characterisation of the contribution of the GABA-benzodiazepine α1 receptor subtype to [11C]Ro15-4513 PET images

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume (VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant VT decrease (∼10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands

Fibrinogenolysis and fibrinolysis in Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT)

Acknowledgements The authors would like to thank all the patients whose samples were used as part of this study, and all the NHS Scotland staff who collected patient samples and looked after these patients. We thank Aberdeen Royal Infirmary Haematology laboratory for conducting the anti-platelet factor 4 antibody testing and Dr Sue Pavord, Consultant Haematologist at Oxford Teaching Hospitals for help in gathering clinical data on the patients. Funding This research was supported by The University of Aberdeen Development Trust (RG16009). CSW and NJM are supported by the British Heart Foundation (PG/15/82/31721; PG/20/17/35050).Peer reviewedPublisher PD

Fennoscandian freshwater control on Greenland hydroclimate shifts at the onset of the Younger Dryas

Sources and timing of freshwater forcing relative to hydroclimate shifts recorded in Greenland ice cores at the onset of Younger Dryas, ∼12,800 years ago, remain speculative. Here we show that progressive Fennoscandian Ice Sheet (FIS) melting 13,100–12,880 years ago generates a hydroclimate dipole with drier–colder conditions in Northern Europe and wetter–warmer conditions in Greenland. FIS melting culminates 12,880 years ago synchronously with the start of Greenland Stadial 1 and a large-scale hydroclimate transition lasting ∼180 years. Transient climate model simulations forced with FIS freshwater reproduce the initial hydroclimate dipole through sea-ice feedbacks in the Nordic Seas. The transition is attributed to the export of excess sea ice to the subpolar North Atlantic and a subsequent southward shift of the westerly winds. We suggest that North Atlantic hydroclimate sensitivity to FIS freshwater can explain the pace and sign of shifts recorded in Greenland at the climate transition into the Younger Dryas

Amidation of unactivated ester derivatives mediated by trifluoroethanol

A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity

Effect of bee venom and its fractions on the release of pro-inflammatory cytokines in PMA-differentiated U937 cells co-stimulated with LPS

The venom of Apis mellifera (honey bee) has been reported to play a role in immunotherapy, but existing evidence to support its immuno-modulatory claims is insufficient. Four fractions from whole bee venom (BV) were separated using medium pressure liquid chromatography. Their ability to induce the production of cytokines TNFα, IL-1β and IL-6 in phorbol-12-myristate-13-acetate (PMA)-treated U937 cells was assessed. The levels of the three cytokines produced by stimulation with the four fractions and crude BV without LPS were not significantly different from negative control values. However, co-stimulation of the cells with LPS and Fraction 4 (F-4) induced a 1.6-fold increase in TNF-α level (p < 0.05) compared to LPS alone. Likewise, LPS-induced IL-1β production was significantly synergised in the presence of F-1 (nine-fold), F-2 (six-fold), F-3 (four-fold) and F-4 (two-fold) fractions, but was only slightly enhanced with crude BV (1.5-fold) relative to LPS. Furthermore, the LPS-stimulated production of IL-6 was not significantly increased in cells co-treated with F-2 and F-3, but the organic fraction (F-4) showed an inhibitory effect (p < 0.05) on IL-6 production. The latter was elucidated by NMR spectroscopy and found to contain(Z)-9-eicosen-1-ol. The effects observed with the purified BV fractions were more marked than those obtained with the crude sample

Chiral dynamics of p-wave in K^- p and coupled states

We perform an evaluation of the p-wave amplitudes of meson-baryon scattering in the strangeness S=-1 sector starting from the lowest order chiral Lagrangians and introducing explicitly the Sigma^* field with couplings to the meson-baryon states obtained using SU(6) symmetry. The N/D method of unitarization is used, equivalent, in practice, to the use of the Bethe-Salpeter equation with a cut-off. The procedure leaves no freedom for the p-waves once the s-waves are fixed and thus one obtains genuine predictions for the p-wave scattering amplitudes, which are in good agreement with experimental results for differential cross sections, as well as for the width and partial decay widths of the Sigma^*(1385).Comment: LaTeX, 18 pages, 6 figure

Comparison of two modern vaccines and previous influenza infection against challenge with an equine influenza virus from the Australian 2007 outbreak

During 2007, large outbreaks of equine influenza (EI) caused by Florida sublineage Clade 1 viruses affected horse populations in Japan and Australia. The likely protection that would be provided by two modern vaccines commercially available in the European Union (an ISCOM-based and a canarypox-based vaccine) at the time of the outbreaks was determined. Vaccinated ponies were challenged with a representative outbreak isolate (A/eq/Sydney/2888-8/07) and levels of protection were compared. A group of ponies infected 18 months previously with a phylogenetically-related isolate from 2003 (A/eq/South Africa/4/03) was also challenged with the 2007 outbreak virus. After experimental infection with A/eq/Sydney/2888-8/07, unvaccinated control ponies all showed clinical signs of infection together with virus shedding. Protection achieved by both vaccination or long-term immunity induced by previous exposure to equine influenza virus (EIV) was characterised by minor signs of disease and reduced virus shedding when compared with unvaccinated control ponies. The three different methods of virus titration in embryonated hens’ eggs, EIV NP-ELISA and quantitative RT-PCR were used to monitor EIV shedding and results were compared. Though the majority of previously infected ponies had low antibody levels at the time of challenge, they demonstrated good clinical protection and limited virus shedding. In summary, we demonstrate that vaccination with current EIV vaccines would partially protect against infection with A/eq/Sydney/2888-8/07-like strains and would help to limit the spread of disease in our vaccinated horse population