Phonological Iconicity

The arbitrariness of the linguistic sign is a fundamental assumption in modern linguistic theory. In recent years, however, a growing amount of research has investigated the nature of non-arbitrary relations between linguistic sounds and semantics. This review aims at illustrating the amount of findings obtained so far and to organize and evaluate different lines of research dedicated to the issue of phonological iconicity. In particular, we summarize findings on the processing of onomatopoetic expressions, ideophones, and phonaesthemes, relations between syntactic classes and phonology, as well as sound-shape and sound-affect correspondences at the level of phonemic contrasts. Many of these findings have been obtained across a range of different languages suggesting an internal relation between sublexical units and attributes as a potentially universal pattern

Immigration and recommended care after a suicide attempt in Europe: equity or bias?

This report describes the investigation of care recommendations in the medical system across European countries to immigrants who attempted suicide. Data from seven European countries with 8865 local and 2921 immigrant person-cases were derived from the WHO/EURO Multicentre Study on Suicidal Behaviour and ensuing MONSUE (Monitoring Suicidal Behaviour in Europe) project. The relationship between immigrant status and type of aftercare recommended was analysed with binary logistic regression, adjusting for gender, age, method of attempt and the Centre collecting the data. Clear disparities were identified in the care recommendation practices toward immigrants, compared with hosts, over and above differing policies by the European Centres

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

The first binary star evolution model producing a Chandrasekhar mass white dwarf

Today, Type Ia supernovae are essential tools for cosmology, and recognized as major contributors to the chemical evolution of galaxies. The construction of detailed supernova progenitor models, however, was so far prevented by various physical and numerical difficulties in simulating binary systems with an accreting white dwarf component, e.g., unstable helium shell burning which may cause significant expansion and mass loss. Here, we present the first binary evolution calculation which models both stellar components and the binary interaction simultaneously, and where the white dwarf mass grows up to the Chandrasekhar limit by mass accretion. Our model starts with a 1.6 Msun helium star and a 1.0 Msun CO white dwarf in a 0.124 day orbit. Thermally unstable mass transfer starts when the CO core of the helium star reaches 0.53 Msun, with mass transfer rates of 1...8 times 10^{-6} Msun/yr. The white dwarf burns the accreted helium steadily until the white dwarf mass has reached ~ 1.3 Msun and weak thermal pulses follow until carbon ignites in the center when the white dwarf reaches 1.37 Msun. Although the supernova production rate through this channel is not well known, and this channel can not be the only one as its progenitor life time is rather short (~ 10^7 - 10^8 yr), our results indicate that helium star plus white dwarf systems form a reliable route for producing Type Ia supernovae.Comment: 4 pages, 5 figure

Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5MBq labelled antibody conjugate (1.11GBq/mg) 2 days after an intravenous graft of 5·106 Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300µg unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%±4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%±2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with 149Tb is worthy of consideration as a new-generation radio-immunotherapeutic approac

The LMC supersoft X-ray binary RX J0513.9-6951

A detailed analysis of simultaneous photometric and spectroscopic observations of the optical counterpart of the LMC "supersoft" X-ray source RX J0513.9-6951 (identified with HV 5682) is presented. The spectrum is dominated by He II emission lines and H + He II blends; no He I is observed but several higher ionization emission features, especially O VI (3811, 3834, and 5290A) are prominent. Radial velocity measurements suggest a binary period of 0.76 days. If the small velocity amplitude, K~11 km/s, is interpreted as orbital motion, this implies that the binary system contains a somewhat evolved star plus a relatively massive compact object, viewed nearly pole-on. No orbital photometric variations were found, although irregular brightness changes of ~0.3 mag occurred. Unusual emission lines are observed which cannot be identified except as high velocity (4000 km/s) bipolar outflows or jets. These outflows are seen in H and He II at the same positive and negative velocities. They were relatively stable for periods of ~5 days, but their velocities appear to have been ~250 km/s smaller in 1992 than in 1993 or 1994

Explanation in typology: Diachronic sources, functional motivations and the nature of the evidence

This volume provides an up-to-date discussion of a foundational issue that has recently taken centre stage in linguistic typology and which is relevant to the language sciences more generally: To what extent can cross-linguistic generalizations, i.e. statistical universals of linguistic structure, be explained by the diachronic sources of these structures? Everyone agrees that typological distributions are the result of complex histories, as “languages evolve into the variation states to which synchronic universals pertain” (Hawkins 1988). However, an increasingly popular line of argumentation holds that many, perhaps most, typological regularities are long-term reflections of their diachronic sources, rather than being ‘target-driven’ by overarching functional-adaptive motivations. On this view, recurrent pathways of reanalysis and grammaticalization can lead to uniform synchronic results, obviating the need to postulate global forces like ambiguity avoidance, processing efficiency or iconicity, especially if there is no evidence for such motivations in the genesis of the respective constructions. On the other hand, the recent typological literature is equally ripe with talk of "complex adaptive systems", "attractor states" and "cross-linguistic convergence". One may wonder, therefore, how much room is left for traditional functional-adaptive forces and how exactly they influence the diachronic trajectories that shape universal distributions. The papers in the present volume are intended to provide an accessible introduction to this debate. Covering theoretical, methodological and empirical facets of the issue at hand, they represent current ways of thinking about the role of diachronic sources in explaining grammatical universals, articulated by seasoned and budding linguists alike