Impact of loss of high-molecular-weight von Willebrand factor multimers on blood loss after aortic valve replacement

Background Severe aortic stenosis is associated with loss of the largest von Willebrand factor (vWF) multimers, which could affect primary haemostasis. We hypothesized that the altered multimer structure with the loss of the largest multimers increases postoperative bleeding in patients undergoing aortic valve replacement. Methods We prospectively included 60 subjects with severe aortic stenosis. Before and after aortic valve replacement, vWF antigen, activity, and multimer structure were determined and platelet function was measured by impedance aggregometry. Blood loss from mediastinal drainage and the use of blood and haemostatic products were evaluated perioperatively. Results Before operation, the altered multimer structure was present in 48 subjects (80%). Baseline characteristics and laboratory data were similar in all subjects. The median blood loss after 6 h was 250 (105-400) and 145 (85-240) ml in the groups with the altered and normal multimer structures, respectively (P=0.182). After 24 h, the cumulative loss was 495 (270-650) and 375 (310-600) ml in the groups with the altered and normal multimer structures, respectively (P=0.713). Multivariable analysis revealed no significant influence of multimer structure and platelet function on bleeding volumes after 6 and 24 h. After 24 h, there was no obvious difference in vWF antigen, activity, and multimer structure in subjects with and without the altered multimer structure before operation or in subjects with and without perioperative plasma transfusion. Conclusions The altered vWF multimer structure before operation was not associated with increased bleeding after aortic valve replacement. Our findings might be explained by perioperative release of vWF and rapid recovery of the largest vWF multimer

Geant4-related R&D for new particle transport methods

A R&D project has been launched in 2009 to address fundamental methods in radiation transport simulation and revisit Geant4 kernel design to cope with new experimental requirements. The project focuses on simulation at different scales in the same experimental environment: this set of problems requires new methods across the current boundaries of condensed-random-walk and discrete transport schemes. An exploration is also foreseen about exploiting and extending already existing Geant4 features to apply Monte Carlo and deterministic transport methods in the same simulation environment. An overview of this new R&D associated with Geant4 is presented, together with the first developments in progress.Comment: 4 pages, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

Origins and composition of fine atmospheric carbonaceous aerosol in the Sierra Nevada Mountains, California

In this paper we report chemically resolved measurements of organic aerosol (OA) and related tracers during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX) at the Blodgett Forest Research Station, California from 15 August–10 October 2007. OA contributed the majority of the mass to the fine atmospheric particles and was predominately oxygenated (OOA). The highest concentrations of OA were during sporadic wildfire influence when aged plumes were impacting the site. In situ measurements of particle phase molecular markers were dominated by secondary compounds and along with gas phase compounds could be categorized into six factors or sources: (1) aged biomass burning emissions and oxidized urban emissions, (2) oxidized urban emissions (3) oxidation products of monoterpene emissions, (4) monoterpene emissions, (5) anthropogenic emissions and (6) local methyl chavicol emissions and oxidation products. There were multiple biogenic components that contributed to OA at this site whose contributions varied diurnally, seasonally and in response to changing meteorological conditions, e.g. temperature and precipitation events. Concentrations of isoprene oxidation products were larger when temperatures were higher during the first half of the campaign (15 August–12 September) due to more substantial emissions of isoprene and enhanced photochemistry. The oxidation of methyl chavicol, an oxygenated terpene emitted by ponderosa pine trees, contributed similarly to OA throughout the campaign. In contrast, the abundances of monoterpene oxidation products in the particle phase were greater during the cooler conditions in the latter half of the campaign (13 September–10 October), even though emissions of the precursors were lower, although the mechanism is not known. OA was correlated with the anthropogenic tracers 2-propyl nitrate and carbon monoxide (CO), consistent with previous observations, while being comprised of mostly non-fossil carbon (>75%). The correlation between OA and an anthropogenic tracer does not necessarily identify the source of the carbon as being anthropogenic but instead suggests a coupling between the anthropogenic and biogenic components in the air mass that might be related to the source of the oxidant and/or the aerosol sulfate. Observations of organosulfates of isoprene and α-pinene provided evidence for the likely importance of aerosol sulfate in spite of neutralized aerosol although acidic plumes might have played a role upwind of the site. This is in contrast to laboratory studies where strongly acidic seed aerosols were needed in order to form these compounds. These compounds together represented only a minor fraction (<1%) of the total OA mass, which may be the result of the neutralized aerosol at the site or because only a small number of organosulfates were quantified. The low contribution of organosulfates to total OA suggests that other mechanisms, e.g. NO_x enhancement of oxidant levels, are likely responsible for the majority of the anthropogenic enhancement of biogenic secondary organic aerosol observed at this site

Statistical evaluation of the flux cross-calibration of the XMM-Newton EPIC cameras

The second XMM-Newton serendipitous source catalogue, 2XMM, provides the ideal data base for performing a statistical evaluation of the flux cross-calibration of the XMM-Newton European Photon Imaging Cameras (EPIC). We aim to evaluate the status of the relative flux calibration of the EPIC cameras on board XMM-Newton (MOS1, MOS2, and pn) and investigate the dependence of the calibration on energy, position in the field of view of the X-ray detectors, and lifetime of the mission. We compiled the distribution of flux percentage differences for large samples of 'good quality' objects detected with at least two of the EPIC cameras. The mean offset of the fluxes and dispersion of the distributions was then found by Gaussian fitting. Count rate to flux conversion was performed with a fixed spectral model. The impact on the results of varying this model was investigated. Excellent agreement was found between the two EPIC MOS cameras to better than 4% from 0.2 keV to 12.0 keV. MOS cameras register 7-9% higher flux than pn below 4.5 keV and 10-13% flux excess above 4.5 keV. No evolution of the flux ratios is seen with time, except at energies below 0.5 keV, where we found a strong decrease in the MOS to pn flux ratio with time. This effect is known to be due to a gradually degrading MOS redistribution function. The flux ratios show some dependence on distance from the optical axis in the sense that the MOS to pn flux excess increases with off-axis angle. Furthermore, in the 4.5-12.0 keV band there is a strong dependence of the MOS to pn excess flux on the azimuthal-angle. These results strongly suggest that the calibration of the Reflection Grating Array (RGA) blocking factors is incorrect at high energies. Finally, we recommend ways to improve the calculation of fluxes in future versions of XMM-Newton source catalogues.Comment: 11 pages, 10 figures, 3 tables. Abridged Abstract. Accepted for publication in Astronomy and Astrophysic

Research in Geant4 electromagnetic physics design, and its effects on computational performance and quality assurance

The Geant4 toolkit offers a rich variety of electromagnetic physics models; so far the evaluation of this Geant4 domain has been mostly focused on its physics functionality, while the features of its design and their impact on simulation accuracy, computational performance and facilities for verification and validation have not been the object of comparable attention yet, despite the critical role they play in many experimental applications. A new project is in progress to study the application of new design concepts and software techniques in Geant4 electromagnetic physics, and to evaluate how they can improve on the current simulation capabilities. The application of a policy-based class design is investigated as a means to achieve the objective of granular decomposition of processes; this design technique offers various advantages in terms of flexibility of configuration and computational performance. The current Geant4 physics models have been re-implemented according to the new design as a pilot project. The main features of the new design and first results of performance improvement and testing simplification are presented; they are relevant to many Geant4 applications, where computational speed and the containment of resources invested in simulation production and quality assurance play a critical role.Comment: 4 pages, 4 figures and images, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

Laser-microdissection unravels cell-type specific transcription in > arbuscular mycorrhizal roots, including CAAT-box TF gene expression correlating with fungal contact and spread

Arbuscular mycorrhizae (AM) are the most widespread symbioses on Earth, promoting nutrient supply of most terrestrial plant species. To unravel gene expression in defined stages of Medicago truncatula root colonization by AM fungi, we here combined genome-wide transcriptome profiling based on whole mycorrhizal roots with real-time RT-PCR experiments that relied on characteristic cell-types obtained via laser-microdissection. Our genome-wide approach delivered a core set of 512 genes significantly activated by the two mycorrhizal fungi Glomus intraradices and Glomus mossae. Focussing on 62 of these genes being related to membrane transport, signaling, and transcriptional regulation, we distinguished whether they are activated in arbuscule-containing or the neighbouring cortical cells harbouring fungal hyphae. In addition, cortical cells from non-mycorrhizal roots served as a reference for gene expression under non-colonized conditions. Our analysis identified 25 novel arbuscule-specific genes and 37 genes expressed both in the arbuscule-containing and the adjacent cortical cells colonized by fungal hyphae. Amongst the AM-induced genes specifying transcriptional regulators were two members encoding CAAT-box binding transcription factors (CBF), designated MtCbf1 and MtCbf2. Promoter analyses demonstrated that both genes were already activated by the first physical contact between the symbionts. Subsequently, and corresponding to our cell-type expression patterns, they were progressively up-regulated in those cortical areas colonized by fungal hyphae, including the arbuscule-containing cells. The encoded CBFs thus represent excellent candidates for regulators that mediate a sequential reprogramming of root tissues during the establishment of an AM symbiosi

Analyzing X-Ray Pulsar Profiles: Geometry and Beam Pattern of Her X-1

We report on our analysis of a large sample of energy dependent pulse profiles of the X-ray binary pulsar Hercules X-1. We find that all data are compatible with the assumption of a slightly distorted magnetic dipole field as sole cause of the asymmetry of the observed pulse profiles. Further the analysis provides evidence that the emission from both poles is equal. We determine an angle of 20 deg between the rotation axis and the local magnetic axis. One pole has an offset of 5 deg from the antipodal position of the other pole. The beam pattern shows structures that can be interpreted as pencil- and fan-beam configurations. Since no assumptions on the polar emission are made, the results can be compared with various emission models. A comparison of results obtained from pulse profiles of different phases of the 35-day cycle indicates different attenuation of the radiation from the poles being responsible for the change of the pulse shape during the main-on state. These results also suggest the resolution of an ambiguity within a previous analysis of pulse profiles of Cen X-3, leading to a unique result for the beam pattern of this pulsar as well. The analysis of pulse profiles of the short-on state indicates that a large fraction of the radiation cannot be attributed to the direct emission from the poles. We give a consistent explanation of both the evolution of the pulse profile and the spectral changes with the 35-day cycle in terms of a warped precessing accretion disk.Comment: 24 pages, 12 figures. To appear in ApJ 529 #2, 1 Feb 200

Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes

Quantifying sources of methane using light alkanes in the Los Angeles basin, California

Methane (CH4), carbon dioxide (CO2), carbon monoxide (CO), and C2-C5 alkanes were measured throughout the Los Angeles (L.A.) basin in May and June 2010. We use these data to show that the emission ratios of CH4/CO and CH4/CO2 in the L.A. basin are larger than expected from population-apportioned bottom-up state inventories, consistent with previously published work. We use experimentally determined CH4/CO and CH4/CO2 emission ratios in combination with annual State of California CO and CO2 inventories to derive a yearly emission rate of CH4 to the L.A. basin. We further use the airborne measurements to directly derive CH4 emission rates from dairy operations in Chino, and from the two largest landfills in the L.A. basin, and show these sources are accurately represented in the California Air Resources Board greenhouse gas inventory for CH4. We then use measurements of C2-C5 alkanes to quantify the relative contribution of other CH4 sources in the L.A. basin, with results differing from those of previous studies. The atmospheric data are consistent with the majority of CH4 emissions in the region coming from fugitive losses from natural gas in pipelines and urban distribution systems and/or geologic seeps, as well as landfills and dairies. The local oil and gas industry also provides a significant source of CH4 in the area. The addition of CH4 emissions from natural gas pipelines and urban distribution systems and/or geologic seeps and from the local oil and gas industry is sufficient to account for the differences between the top-down and bottom-up CH4 inventories identified in previously published work. Key PointsTop-down estimates of CH4 emissions in L.A. are greater than inventory estimatesEstimates of CH4 emissions from landfills in L.A. agree with CARB inventoryPipeline natural gas and/or seeps, and landfills are main sources of CH4 in L.A. ©2013. American Geophysical Union. All Rights Reserved