The role of metaphor in shaping the identity and agenda of the United Nations: the imagining of an international community and international threat

This article examines the representation of the United Nations in speeches delivered by its Secretary General. It focuses on the role of metaphor in constructing a common ‘imagining’ of international diplomacy and legitimising an international organisational identity. The SG legitimises the organisation, in part, through the delegitimisation of agents/actions/events constructed as threatening to the international community and to the well-being of mankind. It is a desire to combat the forces of menace or evil which are argued to motivate and determine the organisational agenda. This is predicated upon an international ideology of humanity in which difference is silenced and ‘working towards the common good’ is emphasised. This is exploited to rouse emotions and legitimise institutional power. Polarisation and antithesis are achieved through the employment of metaphors designed to enhance positive and negative evaluations. The article further points to the constitutive, persuasive and edifying power of topic and situationally-motivated metaphors in speech-making

Dewetting of thin polymer films near the glass transition

Dewetting of ultra-thin polymer films near the glass transition exhibits unexpected front morphologies [G. Reiter, Phys. Rev. Lett., 87, 186101 (2001)]. We present here the first theoretical attempt to understand these features, focusing on the shear-thinning behaviour of these films. We analyse the profile of the dewetting film, and characterize the time evolution of the dry region radius, $R_{d}(t)$, and of the rim height, $h_{m}(t)$. After a transient time depending on the initial thickness, $h_{m}(t)$ grows like $\sqrt{t}$ while $R_{d}(t)$ increases like $\exp{(\sqrt{t})}$. Different regimes of growth are expected, depending on the initial film thickness and experimental time range.Comment: 4 pages, 5 figures Revised version, published in Physical Review Letters: F. Saulnier, E. Raphael and P.-G. de Gennes, Phys. Rev. Lett. 88, 196101 (2002

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals

Diquat Derivatives: Highly Active, Two-Dimensional Nonlinear Optical Chromophores with Potential Redox Switchability

In this article, we present a detailed study of structure−activity relationships in diquaternized 2,2′-bipyridyl (diquat) derivatives. Sixteen new chromophores have been synthesized, with variations in the amino electron donor substituents, π-conjugated bridge, and alkyl diquaternizing unit. Our aim is to combine very large, two-dimensional (2D) quadratic nonlinear optical (NLO) responses with reversible redox chemistry. The chromophores have been characterized as their PF_6^− salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. Their visible absorption spectra are dominated by intense π → π^* intramolecular charge-transfer (ICT) bands, and all show two reversible diquat-based reductions. First hyperpolarizabilities β have been measured by using hyper-Rayleigh scattering with an 800 nm laser, and Stark spectroscopy of the ICT bands affords estimated static first hyperpolarizabilities β_0. The directly and indirectly derived β values are large and increase with the extent of π-conjugation and electron donor strength. Extending the quaternizing alkyl linkage always increases the ICT energy and decreases the E_(1/2) values for diquat reduction, but a compensating increase in the ICT intensity prevents significant decreases in Stark-based β_0 responses. Nine single-crystal X-ray structures have also been obtained. Time-dependent density functional theory clarifies the molecular electronic/optical properties, and finite field calculations agree with polarized HRS data in that the NLO responses of the disubstituted species are dominated by ‘off-diagonal’ β_(zyy) components. The most significant findings of these studies are: (i) β_0 values as much as 6 times that of the chromophore in the technologically important material (E)-4′-(dimethylamino)-N-methyl-4-stilbazolium tosylate; (ii) reversible electrochemistry that offers potential for redox-switching of optical properties over multiple states; (iii) strongly 2D NLO responses that may be exploited for novel practical applications; (iv) a new polar material, suitable for bulk NLO behavior

Jupiter's X-Ray and UV Dark Polar Region

Abstract: We present 14 simultaneous Chandra X‐ray Observatory (CXO)‐Hubble Space Telescope (HST) observations of Jupiter's Northern X‐ray and ultraviolet (UV) aurorae from 2016 to 2019. Despite the variety of dynamic UV and X‐ray auroral structures, one region is conspicuous by its persistent absence of emission: the dark polar region (DPR). Previous HST observations have shown that very little UV emission is produced by the DPR. We find that the DPR also produces very few X‐ray photons. For all 14 observations, the low level of X‐ray emission from the DPR is consistent (within 2‐standard deviations) with scattered solar emission and/or photons spread by Chandra's Point Spread Function from known X‐ray‐bright regions. We therefore conclude that for these 14 observations the DPR produced no statistically significant detectable X‐ray signature

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty