Order matters: How altering the sequence of performance events shapes perceived quality formation

Reputation research often employs rankings which combine both the prominence and perceived quality dimensions of reputation. Though this approach has merit, it neglects nuances in the formation of perceived firm quality – i.e., how stakeholders perceive a firm’s capabilities. Since perceptions are influenced by how information is presented, we posit that the patterns of a firm’s performances – their order and interval – explain variance in perceived quality beyond valence (absolute performance level), alone. We employ two experiments and an archival study to manipulate product ratings and collect perceived quality scores (experimentally), and use trajectory of performance outcomes to predict market valuation as a perceived quality proxy (archivally). Results suggest that while valence matters most for a firm’s perceived quality, presenting identical performance events with distinct orders and intervals changes perceived quality impressions, at least until new information is presented. We enumerate our findings and outline areas for future research on stakeholder perceptions

Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA

HGF (hepatocyte growth factor) is a pleiotropic cytokine homologous to the serine protease zymogen plasminogen that requires canonical proteolytic cleavage to gain functional activity. The activating proteases are key components of its regulation, but controversy surrounds their identity. Using quantitative analysis we found no evidence for activation by uPA (urokinase plasminogen activator), despite reports that this is a principal activator of pro-HGF. This was unaffected by a wide range of experimental conditions, including the use of various molecular forms of both HGF and uPA, and the presence of uPAR (uPA receptor) or heparin. In contrast the catalytic domains of the TTSPs (type-II transmembrane serine proteases) matriptase and hepsin were highly efficient activators (50% activation at 0.1 and 3.4 nM respectively), at least four orders of magnitude more efficient than uPA. PS-SCL (positional-scanning synthetic combinatorial peptide libraries) were used to identify consensus sequences for the TTSPs, which in the case of hepsin corresponded to the pro-HGF activation sequence, demonstrating a high specificity for this reaction. Both TTSPs were also found to be efficient activators at the cell surface. Activation of pro-HGF by PC3 prostate carcinoma cells was abolished by both protease inhibition and matriptase-targeting siRNA (small interfering RNA), and scattering of MDCK (Madin–Darby canine kidney) cells in the presence of pro-HGF was abolished by inhibition of matriptase. Hepsin-transfected HEK (human embryonic kidney)-293 cells also activated pro-HGF. These observations demonstrate that, in contrast with the uPA/uPAR system, the TTSPs matriptase and hepsin are direct pericellular activators of pro-HGF, and that together these proteins may form a pathway contributing to their involvement in pathological situations, including cancer

Sorting of chromosomes by magnetic separation

Chromosomes were isolated from Chinese hamster x human hybrid cell lines containing four and nine human chromosomes. Human genomic DNA was biotinylated by nick translation and used to label the human chromosomes by in situ hybridization in suspension. Streptavidin was covalently coupled to the surface of magnetic beads and these were incubated with the hybridized chromosomes. The human chromosomes were bound to the magnetic beads through the strong biotin-streptavidin complex and then rapidly separated from nonlabeled Chinese hamster chromosomes by a simple permanent magnet. The hybridization was visualized by additional binding of avidin-FITC (fluorescein) to the unoccupied biotinylated human DNA bound to the human chromosomes. After magnetic separation, up to 98% of the individual chromosomes attached to magnetic beads were classified as human chromosomes by fluorescence microscopy

The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis

Rationale:Idiopathic pulmonaryfibrosis (IPF)isa progressivelung disease of unknown cause that leads to respiratory failure and death within 5 years of diagnosis. Overt respiratory infection and immunosuppression carry a high morbidity and mortality, and polymorphisms in genes related to epithelial integrity and host defense predispose to IPF. Objectives: To investigate the role of bacteria in the pathogenesis and progression of IPF. Methods: We prospectively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, nonsmokers, and subjectswithmoderate chronic obstructive pulmonary disease as control subjects. Subjects underwent bronchoalveolar lavage (BAL), from which genomic DNA was isolated. The V3–V5 region of the bacterial 16S rRNA gene was amplified, allowing quantification of bacterial load and identification of communities by 16S rRNA quantitative polymerase chain reaction and pyrosequencing. Measurements and Main Results: Sixty-five patients with IPF had double the burden of bacteria in BAL fluid compared with 44 control subjects. Baseline bacterial burden predicted the rate of decline in lung volume and risk of death and associated independently with the rs35705950 polymorphism of the MUC5B mucin gene, a proven host susceptibilityfactorfor IPF. Sequencing yielded912,883 high-quality reads from all subjects.WeidentifiedHaemophilus, Streptococcus,Neisseria, and Veillonella spp. to be more abundant in cases than control subjects. Regression analyses indicated that these specific operational taxonomic units as well as bacterial burden associated independently with IPF. Conclusions: IPF is characterized by an increased bacterial burden in BAL that predicts decline in lung function and death. Trials of antimicrobial therapy are needed to determine if microbial burden is pathogenic in the disease

Incubation of ovine scrapie with environmental matrix results in biological and biochemical changes of PrPSc over time

Ovine scrapie can be transmitted via environmental reservoirs. A pool of ovine scrapie isolates were incubated on soil for one day or thirteen months and eluted prion was used to challenge tg338 mice transgenic for ovine PrP. After one-day incubation on soil, two PrPSc phenotypes were present: G338 or Apl338ii. Thirteen months later some divergent PrPSc phenotypes were seen: a mixture of Apl338ii with either G338 or P338, and a completely novel PrPSc deposition, designated Cag338. The data show that prolonged ageing of scrapie prions within an environmental matrix may result in changes in the dominant PrPSc biological/biochemical properties

Identification of complex health interventions suitable for evaluation: development and validation of the 8-step scoping framework

Background: There is extensive literature on the methodology of evaluation research and the development and evaluation of complex interventions but little guidance on the formative stages before evaluation and how to work with partner organizations that wish to have their provision evaluated. It is important to be able to identify suitable projects for evaluation from a range of provision and describe the steps required, often with academic institutions working in partnership with external organizations, in order to set up an evaluation. However, research evaluating programs or interventions rarely discusses these stages. Objective: This study aimed to extend work on evaluability assessment and pre-evaluation planning by proposing an 8-Step Scoping Framework to enable the appraisal of multiple programs in order to identify interventions suitable for evaluation. We aimed to add to the literature on evaluability assessment and more recent evaluation guidance by describing the processes involved in working with partner organizations. Methods: This paper documents the steps required to identify multiple complex interventions suitable for process and outcome evaluation. The steps were developed using an iterative approach by working alongside staff in a local government organization, to build an evidence base to demonstrate which interventions improve children’s outcomes. The process of identifying suitable programs for evaluation, thereby establishing the pre-evaluation steps, was tested using all Flying Start provision. Results: The 8-Step Scoping Framework was described using the example of the local government organization Flying Start to illustrate how each step contributes to finding projects suitable for process and outcome evaluation: (1) formulating overarching key questions that encompass all programs offered by an organization, (2) gaining an in-depth understanding of the work and provision of an organization and engaging staff, (3) completing a data template per project/program offered, (4) assessing the robustness/validity of data across all programs, (5) deciding on projects suitable for evaluation and those requiring additional data, (6) negotiating with chosen project leads, both within and outside the organization, (7) developing individual project evaluation protocols, and (8) applying for ethical approval from the university and partner organization. Conclusions: This paper describes the processes involved in identifying suitable projects for evaluation. It adds to the existing literature on the assessment of specific programs suitable for evaluation and guidance for conducting evaluations by establishing the formative steps required to identify suitable programs from a range of provision. This scoping framework particularly relates to academic partners and organizations tasked with delivering evidence-based services designed to meet local needs. The steps identified have been described in the context of early years provision but can be applied to a range of community-based evaluations, or more generally, to cases where an academic partner is working with external stakeholders to identify projects suitable for academic evaluation

Global tropospheric ozone trends, attributions, and radiative impacts in 1995–2017: an integrated analysis using aircraft (IAGOS) observations, ozonesonde, and multi-decadal chemical model simulations

Quantification and attribution of long-term tropospheric ozone trends are critical for understanding the impact of human activity and climate change on atmospheric chemistry but are also challenged by the limited coverage of long-term ozone observations in the free troposphere where ozone has higher production efficiency and radiative potential compared to that at the surface. In this study, we examine observed tropospheric ozone trends, their attributions, and radiative impacts from 1995–2017 using aircraft observations from the In-service Aircraft for a Global Observing System database (IAGOS), ozonesondes, and a multi-decadal GEOS-Chem chemical model simulation. IAGOS observations above 11 regions in the Northern Hemisphere and 19 of 27 global ozonesonde sites have measured increases in tropospheric ozone (950–250 hPa) by 2.7 ± 1.7 and 1.9 ± 1.7 ppbv per decade on average, respectively, with particularly large increases in the lower troposphere (950–800 hPa) above East Asia, the Persian Gulf, India, northern South America, the Gulf of Guinea, and Malaysia/Indonesia by 2.8 to 10.6 ppbv per decade. The GEOS-Chem simulation driven by reanalysis meteorological fields and the most up-to-date year-specific anthropogenic emission inventory reproduces the overall pattern of observed tropospheric ozone trends, including the large ozone increases over the tropics of 2.1–2.9 ppbv per decade and above East Asia of 0.5–1.8 ppbv per decade and the weak tropospheric ozone trends above North America, Europe, and high latitudes in both hemispheres, but trends are underestimated compared to observations. GEOS-Chem estimates an increasing trend of 0.4 Tg yr−1 of the tropospheric ozone burden in 1995–2017. We suggest that uncertainties in the anthropogenic emission inventory in the early years of the simulation (e.g., 1995–1999) over developing regions may contribute to GEOS-Chem's underestimation of tropospheric ozone trends. GEOS-Chem sensitivity simulations show that changes in global anthropogenic emission patterns, including the equatorward redistribution of surface emissions and the rapid increases in aircraft emissions, are the dominant factors contributing to tropospheric ozone trends by 0.5 Tg yr−1. In particular, we highlight the disproportionately large, but previously underappreciated, contribution of aircraft emissions to tropospheric ozone trends by 0.3 Tg yr−1, mainly due to aircraft emitting NOx in the mid-troposphere and upper troposphere where ozone production efficiency is high. Decreases in lower-stratospheric ozone and the stratosphere–troposphere flux in 1995–2017 contribute to an ozone decrease at mid-latitudes and high latitudes. We estimate the change in tropospheric ozone radiative impacts from 1995–1999 to 2013–2017 is +18.5 mW m−2, with 43.5 mW m−2 contributed by anthropogenic emission changes (20.5 mW m−2 alone by aircraft emissions), highlighting that the equatorward redistribution of emissions to areas with strong convection and the increase in aircraft emissions are effective for increasing tropospheric ozone's greenhouse effect.</p

No evidence for association between polymorphisms in GRM3 and schizophrenia

BACKGROUND: Three studies have previously reported data that were interpreted by the authors as supportive of association between schizophrenia and polymorphisms in the gene encoding the metabotropic glutamate receptor GRM3. METHODS: In a bid to examine this hypothesis, we examined seven SNPs spanning GRM3 in a UK case-control sample (schizophrenic cases n = 674, controls n = 716). These included all SNPs previously reported to be associated, alone or in haplotypes, with schizophrenia in European or European American samples. RESULTS: Our data showed no evidence for association with single markers, or 2, 3, 4 and 5 marker haplotypes, nor did any specific haplotypes show evidence for association according to previously observed patterns. CONCLUSION: Examination of our own data and those of other groups leads us to conclude that at present, GRM3 should not be viewed as a gene for which there is replicated evidence for association with schizophrenia

Potential implication of IL-24 in lymphangiogenesis of human breast cancer

Lymphangiogenesis is involved in the dissemination of malignant cells from solid tumours to regional lymph nodes and possibly to various distant sites. Lymphangiogenesis is regulated by vascular endothelial growth factor (VEGF)-C and VEGF-D. Interleukin (IL)-24 is known as a cytokine with potent antitumour and tumour-suppressive activity which functions through its receptor (IL-22R). Expression of IL-24 has been shown to be reduced in breast cancer, and the reduced expression is associated with lymphatic metastases and a poor prognosis. However, the involvement of IL-24 in lymphangiogenesis during lymphatic metastasis remains unclear. The aim of the present study was to determine whether there is an association between IL-24, IL-22R and lymphangiogenic factors and markers in breast cancer. Analysis of IL-24, IL-22R and lymphangiogenic factors in malignant breast tissue samples (n=127) revealed a correlation between increased expression of lymphangiogenic markers (podoplanin, Prox-1 and LYVE-1) and reduced levels of IL-24 and IL-22R. Samples stained with a high degree of positivity for lymphangiogenic factors and markers whereas staining for IL-24 was weak. In vitro assays showed that the average perimeter length of microtubules formed by endothelial cells treated with IL-24 was significantly reduced compared to the control. The growth of endothelial cells was significantly reduced when exposed to a high concentration of IL-24 (250 ng/ml). Treatment of HECV cells with IL-24 resulted in significantly reduced expression of VEGF-C (P<0.05) and VEGF-D (P<0.001). In conclusion, reduced expression of IL-24 and IL-22R in breast cancer is correlated with increased expression of specific lymphangiogenic markers. IL-24 suppressed in vitro growth and microtubule formation of endothelial cells. IL-24 may downregulate the expression of lymphangiogenic markers and factors although further research is required. This suggests that IL-24 plays a profound role in suppressing tumour lymphangiogenesis, thereby, reducing the likelihood of cancer metastasis via the lymphatic route

Ambipolar Electric Field and Potential in the Solar Wind Estimated from Electron Velocity Distribution Functions

The solar wind escapes from the solar corona and is accelerated, over a short distance, to its terminal velocity. The energy balance associated with this acceleration remains poorly understood. To quantify the global electrostatic contribution to the solar wind dynamics, we empirically estimate the ambipolar electric field (E∥) and potential (Φr,∞). We analyze electron velocity distribution functions (VDFs) measured in the near-Sun solar wind between 20.3 RS and 85.3 RS by the Parker Solar Probe. We test the predictions of two different solar wind models. Close to the Sun, the VDFs exhibit a suprathermal electron deficit in the sunward, magnetic-field-aligned part of phase space. We argue that the sunward deficit is a remnant of the electron cutoff predicted by collisionless exospheric models. This cutoff energy is directly linked to Φr,∞. Competing effects of E∥ and Coulomb collisions in the solar wind are addressed by the Steady Electron Runaway Model (SERM). In this model, electron phase space is separated into collisionally overdamped and underdamped regions. We assume that this boundary velocity at small pitch angles coincides with the strahl break-point energy, which allows us to calculate E∥. The obtained Φr,∞ and E∥ agree well with theoretical expectations. They decrease with radial distance as power-law functions with indices αΦ = −0.66 and αE = −1.69. We finally estimate the velocity gained by protons from electrostatic acceleration, which equals 77% calculated from the exospheric models, and 44% from the SERM model