Biliverdin Reductase: More than a Namesake – The Reductase, Its Peptide Fragments, and Biliverdin Regulate Activity of the Three Classes of Protein Kinase C

The expanse of human biliverdin reductase (hBVR) functions in the cells is arguably unmatched by any single protein. hBVR is a Ser/Thr/Tyr-kinase, a scaffold protein, a transcription factor, and an intracellular transporter of gene regulators. hBVR is an upstream activator of the insulin/IGF-1 signaling pathway and of protein kinase C (PKC) kinases in the two major arms of the pathway. In addition, it is the sole means for generating the antioxidant bilirubin-IXα. hBVR is essential for activation of ERK1/2 kinases by upstream MAPKK-MEK and by PKCδ, as well as the nuclear import and export of ERK1/2. Small fragments of hBVR are potent activators and inhibitors of the ERK kinases and PKCs: as such, they suggest the potential application of BVR-based technology in therapeutic settings. Presently, we have reviewed the function of hBVR in cell signaling with an emphasis on regulation of PKCδ activity

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

Anomalous layering at the liquid Sn surface

X-ray reflectivity measurements on the free surface of liquid Sn are presented. They exhibit the high-angle peak, indicative of surface-induced layering, also found for other pure liquid metals (Hg, Ga and In). However, a low-angle peak, not hitherto observed for any pure liquid metal, is also found, indicating the presence of a high-density surface layer. Fluorescence and resonant reflectivity measurements rule out the assignment of this layer to surface-segregation of impurities. The reflectivity is modelled well by a 10% contraction of the spacing between the first and second atomic surface layers, relative to that of subsequent layers. Possible reasons for this are discussed.Comment: 8 pages, 9 figures; to be submitted to Phys. Rev. B; updated references, expanded discussio

Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy

Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employees’ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention

The Chandra Source Catalog

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <~ 30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1 sigma uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of <~ 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages, 27 figure

Diffuse-interface model for rapid phase transformations in nonequilibrium systems

A thermodynamic approach to rapid phase transformations within a diffuse interface in a binary system is developed. Assuming an extended set of independent thermodynamic variables formed by the union of the classic set of slow variables and the space of fast variables, we introduce finiteness of the heat and solute diffusive propagation at the finite speed of the interface advancing. To describe the transformation within the diffuse interface, we use the phase-field model which allows us to follow the steep but smooth change of phases within the width of diffuse interface. The governing equations of the phase-field model are derived for the hyperbolic model, model with memory, and for a model of nonlinear evolution of transformation within the diffuse-interface. The consistency of the model is proved by the condition of positive entropy production and by the outcomes of the fluctuation-dissipation theorem. A comparison with the existing sharp-interface and diffuse-interface versions of the model is given.Comment: 15 pages, regular article submitted to Physical Review

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Vortex imaging in unconventional superconductors

The real space imaging of vortices in unconventional superconductors not only provides important information about the effectiveness of flux pinning that can inform high current applications, but also yields crucial insights into the form of the superconducting order parameter. For example, the structure of the vortex lattice reflects effective mass and order parameter anisotropies within the material, and profiles of isolated vortices provide a local measure of the magnetic penetration depth that can be used to infer the superfluid density. We describe here the analysis of recent studies whereby state-of-the-art scanning Hall probe microscopy (SHPM) has been used to perform vortex-resolved magnetic imaging on two distinct families of unconventional superconductors. Two sets of results will be analysed in detail; (i) vortex lattice structural transitions in the p-wave superconductor Sr2RuO4 that reflect underlying anisotropies in the system and (ii) a quantitative analysis of vortex profiles in Co-doped 122 pnictide superconductors (SrFe2-xCoxAs2 &amp; BaFe2-xCoxAs2) that allows one to infer the temperature-dependent superfluid density. The latter has then been compared with predictions for different order parameter models for a multiband superconductor.</p

Limitations of student-driven formative assessment in a clinical clerkship. A randomised controlled trial

Background Teachers strive to motivate their students to be self-directed learners. One of the methods used is to provide online formative assessment material. The concept of formative assessment and use of these processes is heavily promoted, despite limited evidence as to their efficacy.Methods Fourth year medical students, in their first year of clinical work were divided into four groups. In addition to the usual clinical material, three of the groups were provided with some form of supplementary learning material. For two groups, this was provided as online formative assessment. The amount of time students spent on the supplementary material was measured, their opinion on learning methods was surveyed, and their performance in summative exams at the end of their surgical attachments was measured.Results The performance of students was independent of any educational intervention imposed by this study. Despite its ready availability and promotion, student use of the online formative tools was poor.Conclusion Formative learning is an ideal not necessarily embraced by students. If formative assessment is to work students need to be encouraged to participate, probably by implementing some form of summative assessment.Edward J Palmer and Peter G Devit

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.