Retromer controls planar polarity protein levels and asymmetric localization at intercellular junctions

The coordinated polarization of cells in the plane of a tissue, termed planar polarity, is a characteristic feature of epithelial tissues [1]. In the fly wing, trichome positioning is dependent on the core planar polarity proteins adopting asymmetric subcellular localizations at apical junctions, where they form intercellular complexes that link neighboring cells [1-3]. Specifically, the seven-pass transmembrane protein Frizzled and the cytoplasmic proteins Dishevelled and Diego localize to distal cell ends, the four-pass transmembrane protein Strabismus and the cytoplasmic protein Prickle localize proximally, and the seven-pass transmembrane spanning atypical cadherin Flamingo localizes both proximally and distally. To establish asymmetry, these core proteins are sorted from an initially uniform distribution; however, the mechanisms underlying this polarized trafficking remain poorly understood. Here, we describe the identification of retromer, a master controller of endosomal recycling [4-6], as a key component regulating core planar polarity protein localization in Drosophila. Through generation of mutants, we verify that loss of the retromer-associated Snx27 cargo adaptor, but notably not components of the Wash complex, reduces junctional levels of the core proteins Flamingo and Strabismus in the developing wing. We establish that Snx27 directly associates with Flamingo via its C-terminal PDZ binding motif, and we show that Snx27 is essential for normal Flamingo trafficking. We conclude that Wash-independent retromer function and the Snx27 cargo adaptor are important components in the endosomal recycling of Flamingo and Strabismus back to the plasma membrane and thus contribute to the establishment and maintenance of planar polarization

Intra-operative Raman spectroscopy and mapping for assessment of cartilage degradation

The development of a label-free, non-destructive and safe analytical method such as Raman spectroscopy for assessing cartilage degradation is highly desirable. Compared to non-optical imaging modalities, Raman mapping offers a more sensitive means of directly assessing the chemical composition of cartilage in three-dimensional space and the potential to monitor cartilage degeneration to inform intervention and treatment strategies. Herein, we report the application of Raman spectroscopic methods ex vivo and at arthroscopy to identify molecular alterations in cartilage specimens containing minor focal lesions characteristic of the early disease phase. Our initial ex vivo analysis, obtained by single-point Raman spectroscopy of cartilage samples, supports previous findings based on S-O stretching vibration bands associated with sulphated glycosaminoglycans (sGAGs). We extended the analyses to the high-wavenumber region where we observed that vibrational bands assigned to C-H and O-H stretching modes discriminated early cartilage alterations from healthy cartilage samples. Furthermore, we performed a proof-of-concept in-clinic study using a custom-built optical probe to acquire Raman spectral measurements for the first time in patients undergoing arthroscopy of knee joints. Spectra were obtained with adequate signal-to-noise ratios that similarly discriminated between lesion and adjacent cartilage sites and identified reductions in sGAGs in apparently healthy cartilage. Building on this, we present initial results from Raman mapping to spatially resolve the molecular constituents of cartilage through its depth and across a lesion. Mapping revealed a non-uniform and reduced sGAG distribution within the lesion and peripheral cartilage that was otherwise visually normal, similar to the in-clinic observations, showing that the degradative influence of the lesion extended beyond its border. This was accompanied by a decreased fluorescence signal intensity, which suggests that fluorescence may provide valuable information as an adjunct to the Raman signal in discriminating normal and degenerating cartilage. This work demonstrates the value of Raman mapping over single-point Raman measurements for the analysis of the anisotropy of articular cartilage and highlights the potential of the technology for in vivo articular joint arthroscopy applications

Self-consistent scattering description of transport in normal-superconductor structures

We present a scattering description of transport in several normal-superconductor structures. We show that the related requirements of self-consistency and current conservation introduce qualitative changes in the transport behavior when the current in the superconductor is not negligible. The energy thresholds for quasiparticle propagation in the superconductor are sensitive to the existence of condensate flow ($v_s\neq 0$). This dependence is responsible for a rich variety of transport regimes, including a voltage range in which only Andreev transmission is possible at the interfaces, and a state of gapless superconductivity which may survive up to high voltages if temperature is low. The two main effects of current conservation are a shift towards lower voltages of the first peak in the differential conductance and an enhancement of current caused by the greater availability of charge transmitting scattering channels.Comment: 31 pages, 10 PS figures, Latex file, psfig.sty file is added. To appear in Phys. Rev. B (Jan 97

The ZEPLIN II dark matter detector: data acquisition system and data reduction

ZEPLIN-II is a two-phase (liquid/gas) xenon dark matter detector searching for WIMP-nucleon interactions. In this paper we describe the data acquisition system used to record the data from ZEPLIN-II and the reduction procedures which parameterise the data for subsequent analysis.Comment: 11 pages, 10 figure

The ZEPLIN II dark matter detector: data acquisition system and data reduction

ZEPLIN-II is a two-phase (liquid/gas) xenon dark matter detector searching for WIMP-nucleon interactions. In this paper we describe the data acquisition system used to record the data from ZEPLIN-II and the reduction procedures which parameterise the data for subsequent analysis.Comment: 11 pages, 10 figure

Limits on spin-dependent WIMP-nucleon cross-sections from the first ZEPLIN-II data

The first underground data run of the ZEPLIN-II experiment has set a limit on the nuclear recoil rate in the two-phase xenon detector for direct dark matter searches. In this paper the results from this run are converted into the limits on spin-dependent WIMP-proton and WIMP-neutron cross-sections. The minimum of the curve for WIMP-neutron cross-section corresponds to 0.07 pb at a WIMP mass of around 65 GeV.Comment: 12 pages, 2 figures, to be published in Physics Letters

Superhard Phases of Simple Substances and Binary Compounds of the B-C-N-O System: from Diamond to the Latest Results (a Review)

The basic known and hypothetic one- and two-element phases of the B-C-N-O system (both superhard phases having diamond and boron structures and precursors to synthesize them) are described. The attention has been given to the structure, basic mechanical properties, and methods to identify and characterize the materials. For some phases that have been recently described in the literature the synthesis conditions at high pressures and temperatures are indicated.Comment: Review on superhard B-C-N-O phase

Experimental study and critical review of structural, thermodynamic and mechanical properties of superhard refractory boron suboxide, B6O

In the present paper we performed the analysis of available data on structural, thermodynamic and mechanical properties of B6O. Although the compound is known for half a century and has been extensively studied, many properties of this boron-rich solid remain unknown or doubtful. Semi-empirical analysis of our experimental and literature data allowed us to choose the best values of main thermodynamic and mechanical characteristics among previously reported data, to predict the thermoelastic equation of state of B6O, and dependence of its hardness on non-stoichiometry and temperature

Thermodynamic model of hardness: Particular case of boron-rich solids

A number of successful theoretical models of hardness have been developed recently. A thermodynamic model of hardness, which supposes the intrinsic character of correlation between hardness and thermodynamic properties of solids, allows one to predict hardness of known or even hypothetical solids from the data on Gibbs energy of atomization of the elements, which implicitly determine the energy density per chemical bonding. The only structural data needed is the coordination number of the atoms in a lattice. Using this approach, the hardness of known and hypothetical polymorphs of pure boron and a number of boron-rich solids has been calculated. The thermodynamic interpretation of the bonding energy allows one to predict the hardness as a function of thermodynamic parameters. In particular, the excellent agreement between experimental and calculated values has been observed not only for the room- temperature values of the Vickers hardness of stoichiometric compounds, but also for its temperature and concentration dependencies