Regulation of alpha 2,6-sialylation in B-cells and the role of sialylation in the pathogenesis of Rheumatoid Arthritis

Sialylation is a common post-translational modification involving the addition of sialic acid to glycoprotein chains. Sialic acid within the Fc fragment of IgG molecules can influence binding to Fc receptors. In rheumatoid arthritis (RA) and other autoimmune conditions, in disease specific auto-antibodies, Fc fragment sialylation is reduced compared to total IgG. Furthermore, plasmablasts from patients with RA display reduced cell surface sialylation compared to cells from healthy donors. Factors which determine B-cell surface sialylation and consequences of altered sialylation are not well understood. α2,6-sialylation was measured in B-cells isolated from healthy donors (HD), patients with pre-RA (PRA) or early RA (ERA) using SNA lectin flow cytometry. Sialylation and markers of activation were measured at baseline or following stimulation with TLR ligands or anti-IgM/G ± CD40L; treatment with neuraminidase (Neu) to digest sialic acid; or culture with serum from HD or patients with ERA. B-cells were differentiated to plasma cells in vitro and sialylation measured at each stage of differentiation. Furthermore, Neu activity in serum was measured by fluorescent assay. Sialylation was confirmed to be decreased in patients with ERA and PRA at baseline compared with HD B-cells. Upon stimulation with TLR ligands, sialylation was increased in HD cells but not cells from patients with ERA or PRA. Differentiated cells showed an initial increase in sialylation before decreasing in terminally differentiated cells. Exposure to serum in culture led to reduced B-cell sialylation and Neu activity was highest in serum from patients with ERA. Exposure to serum in culture as well as direct treatment with Neu led to reduced B-cell activation potential. These results suggest that B-cell sialylation influences activation and function, and control of surface sialylation may be disrupted in RA

A Precise Cluster Mass Profile Averaged from the Highest-Quality Lensing Data

We outline our methods for obtaining high precision mass profiles, combining independent weak-lensing distortion, magnification, and strong-lensing measurements. For massive clusters the strong and weak lensing regimes contribute equal logarithmic coverage of the radial profile. The utility of high-quality data is limited by the cosmic noise from large scale structure along the line of sight. This noise is overcome when stacking clusters, as too are the effects of cluster asphericity and substructure, permitting a stringent test of theoretical models. We derive a mean radial mass profile of four similar mass clusters of high-quality HST and Subaru images, in the range R=40kpc/h to 2800kpc/h, where the inner radial boundary is sufficiently large to avoid smoothing from miscentering effects. The stacked mass profile is detected at 58-sigma significance over the entire radial range, with the contribution from the cosmic noise included. We show that the projected mass profile has a continuously steepening gradient out to beyond the virial radius, in remarkably good agreement with the standard Navarro-Frenk-White form predicted for the family of CDM-dominated halos in gravitational equilibrium. The central slope is constrained to lie in the range, -dln{\rho}/dln{r}=0.89^{+0.27}_{-0.39}. The mean concentration is c_{vir}=7.68^{+0.42}_{-0.40} (at a mean virial mass 1.54^{+0.11}_{-0.10}\times 10^{15} M_{sun}/h), which is high for relaxed, high-mass clusters, but consistent with LCDM when a sizable projection bias estimated from N-body simulations is considered. This possible tension will be more definitively explored with new cluster surveys, such as CLASH, LoCuSS, Subaru HSC, and XXM-XXL, to construct the c-M relation over a wider mass range.Comment: Accepted by ApJ, minor text changes (10 pages, 3 figures

Beyond Environmental Regulatory Fragmentation: Signs of Integration in the Case of the Great Lakes Basin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72007/1/j.1468-0491.1995.tb00197.x.pd

Marketing as a means to transformative social conflict resolution: lessons from transitioning war economies and the Colombian coffee marketing system

Social conflicts are ubiquitous to the human condition and occur throughout markets, marketing processes, and marketing systems.When unchecked or unmitigated, social conflict can have devastating consequences for consumers, marketers, and societies, especially when conflict escalates to war. In this article, the authors offer a systemic analysis of the Colombian war economy, with its conflicted shadow and coping markets, to show how a growing network of fair-trade coffee actors has played a key role in transitioning the country’s war economy into a peace economy. They particularly draw attention to the sources of conflict in this market and highlight four transition mechanisms — i.e., empowerment, communication, community building and regulation — through which marketers can contribute to peacemaking and thus produce mutually beneficial outcomes for consumers and society. The article concludes with a discussion of implications for marketing theory, practice, and public policy

Cluster Lensing And Supernova survey with Hubble (CLASH): An Overview

The Cluster Lensing And Supernova survey with Hubble (CLASH) is a 524-orbit multi-cycle treasury program to use the gravitational lensing properties of 25 galaxy clusters to accurately constrain their mass distributions. The survey, described in detail in this paper, will definitively establish the degree of concentration of dark matter in the cluster cores, a key prediction of CDM. The CLASH cluster sample is larger and less biased than current samples of space-based imaging studies of clusters to similar depth, as we have minimized lensing-based selection that favors systems with overly dense cores. Specifically, twenty CLASH clusters are solely X-ray selected. The X-ray selected clusters are massive (kT > 5 keV; 5 - 30 x 10^14 M_solar) and, in most cases, dynamically relaxed. Five additional clusters are included for their lensing strength (Einstein radii > 35 arcsec at z_source = 2) to further quantify the lensing bias on concentration, to yield high resolution dark matter maps, and to optimize the likelihood of finding highly magnified high-redshift (z > 7) galaxies. The high magnification, in some cases, provides angular resolutions unobtainable with any current UVOIR facility and can yield z > 7 candidates bright enough for spectroscopic follow-up. A total of 16 broadband filters, spanning the near-UV to near-IR, are employed for each 20-orbit campaign on each cluster. These data are used to measure precise (sigma_phz < 0.02(1+z)) photometric redshifts for dozens of newly discovered multiply-lensed images per cluster. Observations of each cluster are spread over 8 epochs to enable a search, primarily in the parallel fields, for Type Ia supernovae at z > 1 to improve constraints on the time dependence of the dark energy equation of state and the evolution of such supernovae in an epoch when the universe is matter dominated.Comment: Accepted for publication in the Astrophysical Journal Supplements, 22 pages, 16 figures. Updated Tables 3,4,8 and figures 6 and 8 to reflect replacement of Abell 963 with Abell 1423 in CLASH survey. A963 cannot be observed with WFC3 due to the lack of usable guide star

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Caffeine and Memory - Friends or Foes?

Previous studies have shown that caffeine decreases the number of items recalled in a memory task (Terry & Phifer, 1986). The current study examined the effect of caffeine on the recall of words as well as factual and conceptual memory. Undergraduate college students were asked to complete three memory tasks after taking either a placebo or a 200mg caffeine pill. The first memory task included a version of the Auditory Verbal Learning Test (AVLT), where students were asked to recall as many words from a 16-item list. Additionally, students also watched a TED talk and answered nine factual and conceptual questions on the talk. The results failed to find a significant effect between the caffeine or placebo groups and their memory task scores. Future studies should evaluate the effect of caffeine on immediate recall and investigate the potential difference of caffeine on gender