A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function.

The integrin αIIbβ3 on resting platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. αIIbβ3 is known to interact with the general integrin-recognition motif RGD (arginine-glycine-aspartate) as well as the fibrinogen-specific γ-chain dodecapeptide; however, it is not known how fibrinogen binding triggers platelet activation. NGR (asparagine-glycine-arginine) is another integrin-recognition sequence present in fibrinogen and this study aims to determine if it plays a role in the interaction between fibrinogen and αIIbβ3. NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC50 of 175 µM but failed to inhibit the adhesion of activated platelets to fibrinogen (IC50\u3e 500 µM). Resting platelet adhesion to mutant fibrinogens lacking the NGR sequences was reduced compared to normal fibrinogen under both static and shear conditions (200 s⁻¹). However, pre-activated platelets were able to fully spread on all types of fibrinogen. Thus, the NGR motif in fibrinogen is the site that is primarily responsible for the interaction with resting αIIbβ3 and is responsible for triggering platelet activation

Masses of Neutron Stars in High-Mass X-ray Binaries with Optical Astrometry

Determining the type of matter that is inside a neutron star (NS) has been a long-standing goal of astrophysics. Despite this, most of the NS equations of state (EOS) that predict maximum masses in the range 1.4-2.8 solar masses are still viable. Most of the precise NS mass measurements that have been made to date show values close to 1.4 solar masses, but a reliable measurement of an over-massive NS would constrain the EOS possibilities. Here, we investigate how optical astrometry at the microarcsecond level can be used to map out the orbits of High-Mass X-ray Binaries (HMXBs), leading to tight constraints on NS masses. While previous studies by Unwin and co-workers and Tomsick and co-workers discuss the fact that the future Space Interferometry Mission should be capable of making such measurements, the current work describes detailed simulations for 6 HMXB systems, including predicted constraints on all orbital parameters. We find that the direct NS masses can be measured to an accuracy of 2.5% (1-sigma) in the best case (X Per), to 6.5% for Vela X-1, and to 10% for two other HMXBs.Comment: 8 pages, Accepted by Ap

Semisimplicity of the quantum cohomology for smooth Fano toric varieties associated with facet symmetric polytopes

The degree zero part of the quantum cohomology algebra of a smooth Fano toric symplectic manifold is determined by the superpotential function, W, of its moment polytope. In particular, this algebra is semisimple, i.e. splits as a product of fields, if and only if all the critical points of W are non-degenerate. In this paper we prove that this non-degeneracy holds for all smooth Fano toric varieties with facet-symmetric duals to moment polytopes.Comment: 16 pages; corrected version, published in Electron. Res. Announc. Math. Sc

Implementation of the LANS-alpha turbulence model in a primitive equation ocean model

This paper presents the first numerical implementation and tests of the Lagrangian-averaged Navier-Stokes-alpha (LANS-alpha) turbulence model in a primitive equation ocean model. The ocean model in which we work is the Los Alamos Parallel Ocean Program (POP); we refer to POP and our implementation of LANS-alpha as POP-alpha. Two versions of POP-alpha are presented: the full POP-alpha algorithm is derived from the LANS-alpha primitive equations, but requires a nested iteration that makes it too slow for practical simulations; a reduced POP-alpha algorithm is proposed, which lacks the nested iteration and is two to three times faster than the full algorithm. The reduced algorithm does not follow from a formal derivation of the LANS-alpha model equations. Despite this, simulations of the reduced algorithm are nearly identical to the full algorithm, as judged by globally averaged temperature and kinetic energy, and snapshots of temperature and velocity fields. Both POP-alpha algorithms can run stably with longer timesteps than standard POP. Comparison of implementations of full and reduced POP-alpha algorithms are made within an idealized test problem that captures some aspects of the Antarctic Circumpolar Current, a problem in which baroclinic instability is prominent. Both POP-alpha algorithms produce statistics that resemble higher-resolution simulations of standard POP. A linear stability analysis shows that both the full and reduced POP-alpha algorithms benefit from the way the LANS-alpha equations take into account the effects of the small scales on the large. Both algorithms (1) are stable; (2) make the Rossby Radius effectively larger; and (3) slow down Rossby and gravity waves.Comment: Submitted to J. Computational Physics March 21, 200

The Prevalence and Clinical Implications of Comorbid Back Pain in Shoulder Instability: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.

Background:Understanding predictors of pain is critical, as recent literature shows that comorbid back pain is an independent risk factor for worse functional and patient-reported outcomes (PROs) as well as increased opioid dependence after total joint arthroplasty. Purpose/Hypothesis:The purpose of this study was to evaluate whether comorbid back pain would be predictive of pain or self-reported instability symptoms at the time of stabilization surgery. We hypothesized that comorbid back pain will correlate with increased pain at the time of surgery as well as with worse scores on shoulder-related PRO measures. Study Design:Cross-sectional study; Level of evidence, 3. Methods:As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients consented to participate in pre- and intraoperative data collection. Demographic characteristics, injury history, preoperative PRO scores, and radiologic and intraoperative findings were recorded for patients undergoing surgical shoulder stabilization. Patients were also asked, whether they had any back pain. Results:The study cohort consisted of 1001 patients (81% male; mean age, 24.1 years). Patients with comorbid back pain (158 patients; 15.8%) were significantly older (28.1 vs 23.4 years; P < .001) and were more likely to be female (25.3% vs 17.4%; P = .02) but did not differ in terms of either preoperative imaging or intraoperative findings. Patients with self-reported back pain had significantly worse preoperative pain and shoulder-related PRO scores (American Shoulder and Elbow Surgeons score, Western Ontario Shoulder Instability Index) (P < .001), more frequent depression (22.2% vs 8.3%; P < .001), poorer mental health status (worse scores for the RAND 36-Item Health Survey Mental Component Score, Iowa Quick Screen, and Personality Assessment Screener) (P < .01), and worse preoperative expectations (P < .01). Conclusion:Despite having similar physical findings, patients with comorbid back pain had more severe preoperative pain and self-reported symptoms of instability as well as more frequent depression and lower mental health scores. The combination of disproportionate shoulder pain, comorbid back pain and mental health conditions, and inferior preoperative expectations may affect not only the patient's preoperative state but also postoperative pain control and/or postoperative outcomes

Factors that are associated with the risk of acquiring Plasmodium knowlesi malaria in Sabah, Malaysia: a case-control study protocol

Introduction Plasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission.Methods and analysis A population-based case–control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.Ethics This study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK

ISO LWS Spectroscopy of M82: A Unified Evolutionary Model

We present the first complete far-infrared spectrum (43 to 197 um) of M82, the brightest infrared galaxy in the sky, taken with the Long Wavelength Spectrometer of the Infrared Space Observatory (ISO). We detected seven fine structure emission lines, [OI] 63 and 145 um, [OIII] 52 and 88 um, [NII] 122 um, [NIII] 57 um and [CII] 158 um, and fit their ratios to a combination starburst and photo-dissociation region (PDR) model. The best fit is obtained with HII regions with n = 250 cm^{-3} and an ionization parameter of 10^{-3.5} and PDRs with n = 10^{3.3} cm^{-3} and a far-ultraviolet flux of G_o = 10^{2.8}. We applied both continuous and instantaneous starburst models, with our best fit being a 3-5 Myr old instantaneous burst model with a 100 M_o cut-off. We also detected the ground state rotational line of OH in absorption at 119.4 um. No excited level OH transitions are apparent, indicating that the OH is almost entirely in its ground state with a column density ~ 4x10^{14} cm^{-2}. The spectral energy distribution over the LWS wavelength range is well fit with a 48 K dust temperature and an optical depth, tau_{Dust} proportional to lambda^{-1}.Comment: 23 pages, 4 figures, accepted by ApJ, Feb. 1, 199

Asymptomatic and Submicroscopic Carriage of Plasmodium knowlesi Malaria in Household and Community Members of Clinical Cases in Sabah, Malaysia

Although asymptomatic carriage of human malaria species has been widely reported, the extent of asymptomatic, submicroscopic Plasmodium knowlesi parasitemia is unknown. In this study, samples were obtained from individuals residing in households or villages of symptomatic malaria cases with the aim of detecting submicroscopic P. knowlesi in this population. Four published molecular assays were used to confirm the presence of P. knowlesi. Latent class analysis revealed that the estimated proportion of asymptomatic individuals was 6.9% (95% confidence interval, 5.6%-8.4%). This study confirms the presence of a substantial number of asymptomatic monoinfections across all age groups; further work is needed to estimate prevalence in the wider community