bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased platelet aggregation and in vivo platelet activation after granulocyte colony-stimulating factor administration
Authors: Spiel Alexander , Bartko Johann , Schwameis Michael , Firbas Christa , Siller-Matula Jolanta , Schuetz Matthias , Weigl Manuela , Jilma Bernd 
Published: February 2011

SummaryGranulocyte colony-stimulating factor (G-CSF) stimulates the bone marrow to produce granulocytes and stem cells and is widely used to accelerate neutrophil recovery after chemotherapy. Interestingly, specific G-CSF receptors have been demonstrated not only on myeloid cells, but also on platelets. Data on the effects of G-CSF on platelet function are limited and partly conflicting. The objective of this study was to determine the effect of G-CSF on platelet aggregation and in vivo platelet activation. Seventy-eight, healthy volunteers were enrolled into this randomised, placebo-controlled trial. Subjects received 5 μg/kg methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) or placebo subcutaneously for four days. We determined platelet aggregation with a whole blood impedance aggregometer with various, clinically relevant platelet agonists (adenosine diphosphate [ADP], collagen, arachidonic acid [AA], ristocetin and thrombin receptor activating peptide 6 [TRAP]). Filgrastim injection significantly enhanced ADP (+40%), collagen (+60%) and AA (+75%) -induced platelet aggregation (all p<0.01 as compared to placebo and p<0.001 as compared to baseline). In addition, G-CSF enhanced ristocetin-induced platelet aggregation (+18%) whereas TRAP-induced platelet aggregation decreased slightly (-14%) in response to filgrastim. While baseline aggregation with all agonists was only slightly but insignificantly higher in women than in men, this sex difference was enhanced by G-CSF treatment, and became most pronounced for ADP after five days (p<0.001). Enhanced platelet aggregation translated into a 75% increase in platelet activation as measured by circulating soluble P-selectin. G-CSF enhances platelet aggregation and activation in humans. This may put patients suffering from cardiovascular disease and cancer at risk for thrombotic events.
An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma
Authors: Roy Sebastien , Lavisse Melanie , Brasseur Denis , Schofield Joe , Touchard Nathalie Delesque , Savi Pierre , Bremond Nicolas , Rouchon Marie-Claude , Hurbin Fabrice , Sultan Eric , Tuffal Gilles 
Published: February 2011

SummaryPharmacokinetic analyses of clopidogrel are hampered by the existence of multiple active metabolite isomers (H1 to H4) and their instability in blood. We sought to retest the pharmacodynamic activities of the four individual active metabolite isomers in vitro, with the ultimate aim of determining the isomers responsible for clopidogrel activity in vivo. In vitro activity was evaluated by measuring binding of [33P]-2-methylthio-ADP on P2Y12-expressing Chinese hamster ovary (CHO) cells and human platelets in platelet-rich plasma (PRP). A stereoselective method that used reverse-phase ultra high-performance liquid chromatography (UHPLC) and tandem mass spectrometry (MS) was developed to measure individual concentrations of the stable 3’-methoxyacetophe-none (MP) derivatives of H1–H4. The new method was used to analyze plasma samples from clopidogrel-treated subjects enrolled in a phase I clinical trial. In vitro binding assays confirmed the previously observed biological activity of H4 (IC50: CHO-P2Y12: 0.12 μM; PRP: 0.97 μM) and inactivity of H3, and demonstrated that H1 was also inactive. Furthermore, H2 demonstrated approximately half of the biological activity in vitro compared with H4. Optimisation of UHPLC conditions and MS collision parameters allowed the resolution and detection of the four derivatised active metabolite isomers (MP-H1 to MP-H4). The stereoselective assay was extensively validated, and was accurate and precise over the concentration range 0.5–250 ng/ml. Only MP-H3 and MP-H4 were quantifiable in incurred clinical samples. Based on in vitro pharmacodynamic data and found concentrations, the active metabolite isomer H4 is the only diastereoisomer of clinical relevance for documenting the pharmacokinetic profile of the active metabolite of clopidogrel.
Characterisation of factor IX with a glycine-to-valine missense mutation at residue 190 in a patient with severe haemophilia B
Authors: Kao Chung-Yang , Lin Chia-Ni , Yang Yung-Li , Hamaguchi Nobuko , Yang Shu-Jhu , Shen Ming-Ching , Kao Jau-Tsuen , Lin Shu-Wha 
Published: February 2011

SummaryA patient with severe haemophilia B with a glycine-to-valine missense mutation at residue 190 (c25, chymotrypsin numbering) in factor IX (FIX; FIX-G190V or FIX-FuChou) had <1% of normal FIX clotting activity and 36% of normal FIX antigen levels (cross-reacting material-reduced, CRMr). Residue 190 in the C-terminal protease domain of human FIX is highly conserved in mammalian species and the serine protease family, suggesting that it has an indispensable role in protein function. To explore the pathological mechanism by which this mutation contributes to dysfunction of the FIX molecule, we functionally characterised FIX-G190V in vitro and in vivo. Liver-specific FIX-G190V gene expression following hydrodynamic plasmid delivery into haemophilia B mice revealed a 5.7-fold reduction in specific clotting activity compared with FIX-WT (wild type) and a two-fold decrease in plasma FIX-G190V concentration. Pulse-chase analysis demonstrated that FIX-G190V was secreted at a significantly slower rate than was FIX-WT. Purified FIX-G190V and FIX-WT displayed normal calcium-dependent conformational changes as shown by intrinsic fluorescence quenching. The in vivo half-lives of FIX-G190V and FIX-WT were indistinguishable. FIX-G190V was, however, more readily degraded than FIX-WT, especially after being activated by the active form of FXI. The vulnerable sites were mapped to the peptide bonds at Arg116-Leu117, Lys265-Tyr266, Arg327-Val328, and Arg338-Ser339, which are in the exposed loops of the FIX molecule. Also, failure of FXIa-activated FIX-G190V to bind p-aminobenzamidine indicated an abnormal conformation of the active-site pocket. Thus, the mutation at residue 190 of FIX may result in protein misfolding that affects secretion, clotting function, and hydrolysis.
IScore
Authors: Saposnik Gustavo , Kapral Moira K. , Liu Ying , Hall Ruth , O'Donnell Martin , Raptis Stavroula , Tu Jack V. , Mamdani Muhammad , Austin Peter C. 
Published: February 2011

Background—
A predictive model of stroke mortality may be useful for clinicians to improve communication with and care of hospitalized patients. Our aim was to identify predictors of mortality and to develop and validate a risk score model using information available at hospital presentation.

Methods and Results—
This retrospective study included 12 262 community-based patients presenting with an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003 and 2008 who had been identified from the Registry of the Canadian Stroke Network (8223 patients in the derivation cohort, 4039 in the internal validation cohort) and the Ontario Stroke Audit (3720 for the external validation cohort). The mortality rates for the derivation and internal validation cohorts were 12.2% and 12.6%, respectively, at 30 days and 22.5% and 22.9% at 1 year. Multivariable predictors of 30-day and 1-year mortality included older age, male sex, severe stroke, nonlacunar stroke subtype, glucose ≥7.5 mmol/L (135 mg/dL), history of atrial fibrillation, coronary artery disease, congestive heart failure, cancer, dementia, kidney disease on dialysis, and dependency before the stroke. A risk score index stratified the risk of death and identified low- and high- risk individuals. The c statistic was 0.850 for 30-day mortality and 0.823 for 1-year mortality for the derivation cohort, 0.851 for the 30-day model and 0.840 for the 1-year mortality model in the internal validation set, and 0.790 for the 30-day model and 0.782 for the 1-year model in the external validation set.

Conclusion—
Among patients with ischemic stroke, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The predictive score may assist clinicians in estimating stroke mortality risk and policymakers in providing a quantitative tool to compare facilities.
Tropical Oceanic Response to Extratropical Thermal Forcing in a Coupled Climate Model: A Comparison between the Atlantic and Pacific Oceans*
Authors: Yang Haijun , Wang Lu 
Published: February 2011

Abstract
The tropical oceanic response to the extratropical thermal forcing is quantitatively estimated in a coupled climate model. This work focuses on comparison of the responses between the tropical Atlantic and Pacific. Under the same extratropical forcing, the tropical sea surface temperature responses are comparable. However, the responses in the tropical subsurface in the two oceans are distinct. The tropical subsurface response in the Atlantic can be twice of that in the Pacific. The maximum subsurface temperature change in the tropical Pacific occurs in the eastern lower thermocline, while that in the tropical Atlantic occurs in the west and well below the lower thermocline. The different responses in the tropical Atlantic and Pacific are closely related to the different changes in the meridional overturning circulations. The Pacific shallow overturning circulation, or the subtropical cell, tends to slow down (speed up) in response to the extratropical warming (cooling) forcing. The changes in the upwelling in the eastern equatorial Pacific as well as the shallow subduction from the extratropical southern Pacific along the eastern boundary are accountable for the eastern Pacific temperature change. The Atlantic overturning circulation consists of the shallow subtropical cell and the deep thermohaline circulation. A weakened thermohaline circulation will result in a strengthened northern subtropical cell, in which the change in the lower branch, or the low-latitude North Brazil Current, can cause strong response below the western tropical thermocline. Here the coastal Kelvin wave along the western boundary on the intermediate isopycnal level also plays an important role in the equatorward conveying of the climate anomalies in the mid-to-high-latitude Atlantic, particularly during the initial stage of the extratropical forcing.
Verification and Intercomparison of Multimodel Simulated Land Surface Hydrological Datasets over the United States
Authors: Fan Yun , van den Dool Huug M. , Wu Wanru 
Published: February 2011

Abstract
Several land surface datasets, such as the observed Illinois soil moisture dataset; three retrospective offline run datasets from the Noah land surface model (LSM), Variable Infiltration Capacity (VIC) LSM, and Climate Prediction Center leaky bucket soil model; and three reanalysis datasets (North American Regional Reanalysis, NCEP/Department of Energy Global Reanalysis, and 40-yr ECMWF Re-Analysis), are used to study the spatial and temporal variability of soil moisture and its response to the major components of land surface hydrologic cycles: precipitation, evaporation, and runoff. Detailed analysis was performed on the evolution of the soil moisture vertical profile. Over Illinois, model simulations are compared to observations, but for the United States as a whole some impressions can be gained by comparing the multiple soil moisture–precipitation–evaporation–runoff datasets to one another. The magnitudes and partitioning of major land surface water balance components on seasonal–interannual time scales have been explored. It appears that evaporation has the most prominent annual cycle but its interannual variability is relatively small. For other water balance components, such as precipitation, runoff, and surface water storage change, the amplitudes of their annual cycles and interannual variations are comparable. This study indicates that all models have a certain capability to reproduce observed soil moisture variability on seasonal–interannual time scales, but offline runs are decidedly better than reanalyses (in terms of validation against observations) and more highly correlated to one another (in terms of intercomparison) in general. However, noticeable differences are also observed, such as the degree of simulated drought severity and the locations affected—this is due to the uncertainty in model physics, input forcing, and mode of running (interactive or offline), which continue to be major issues for land surface modeling.
Erosion of a Surface Vortex by a Seamount
Authors: Herbette Steven , Morel Yves , Arhan Michel 
Published: February 2011

Abstract
Numerical experiments are carried out on the f plane, using a shallow-water isopycnal model, to analyze the behavior of a surface-intensified anticyclonic vortex when it encounters an isolated seamount. The advection by the vortex of deep fluid parcels across the isobaths is known to generate deep anticyclonic and cyclonic circulations above and near the bathymetry, respectively. These circulations are shown to exert a strong shear on the upper layers, which causes an erosion of the initial vortex by filamentation. The erosion often results in a subdivision of the eddy. While the eroded original structure forms a dipole with the deep cyclone and is advected away, the filaments torn off from the original core aggregate into a new eddy above the seamount. Splitting in more than two structures is sometimes observed. The erosion process is quantified by the bulk volume integral of the eddy potential vorticity anomaly. A sensitivity study to different parameters of the configuration (distance between vortex and seamount, vortex radius, seamount radius, seamount height, or stratification) shows that the intensities of the deep anticyclonic and cyclonic circulations and the vortex erosion are governed both by the reservoir of positive potential vorticity associated with the seamount and by the strength of the cross-isobath flow induced by the eddy.
Influence of Vertical Mixing on the Thermohaline Hysteresis: Analyses of an OGCM
Authors: Prange Matthias , Lohmann Gerrit , Paul André 
Published: February 2011

Abstract
The thermohaline hysteresis response to varying North Atlantic freshwater forcing is studied by means of a three-dimensional global ocean general circulation model (OGCM). The influence of vertical diffusivity is examined using a wide range of mixing coefficients. For sufficiently large vertical diffusivity the model shows a pronounced hysteresis behavior, so that two equilibrium states of the thermohaline circulation are found: one mode with intense deep-water formation in the North Atlantic (“on” mode) and one mode with strongly reduced convective activity (“off” mode). By decreasing the diffusivity, the two branches of the hysteresis merge. In addition, the effect of numerical diffusion is analyzed by applying different advection schemes. A positive feedback between overturning strength and the numerical diffusivity of upstream advection is found, resulting in a reduced stability of the “on” mode. Comparing the results with those from zonally averaged models exhibits substantial differences regarding the stability properties of the thermohaline circulation. Freshwater transports by horizontal gyres have an important effect on the overturning circulation in the OGCM.
The M2 Internal Tide off Oregon: Inferences from Data Assimilation
Authors: Kurapov Alexander L. , Egbert Gary D. , Allen J. S. , Miller Robert N. , Erofeeva Svetlana Y. , Kosro P. M. 
Published: February 2011

Abstract
A linearized baroclinic, spectral-in-time tidal inverse model has been developed for assimilation of surface currents from coast-based high-frequency (HF) radars. Representer functions obtained as a part of the generalized inverse solution show that for superinertial flows information from the surface velocity measurements propagates to depth along wave characteristics, allowing internal tidal flows to be mapped throughout the water column. Application of the inverse model to a 38 km × 57 km domain off the mid-Oregon coast, where data from two HF radar systems are available, provides a uniquely detailed picture of spatial and temporal variability of the M2 internal tide in a coastal environment. Most baroclinic signal contained in the data comes from outside the computational domain, and so data assimilation (DA) is used to restore baroclinic currents at the open boundary (OB). Experiments with synthetic data demonstrate that the choice of the error covariance for the OB condition affects model performance. A covariance consistent with assumed dynamics is obtained by nesting, using representers computed in a larger domain. Harmonic analysis of currents from HF radars and an acoustic Doppler profiler (ADP) mooring off Oregon for May–July 1998 reveals substantial intermittence of the internal tide, both in amplitude and phase. Assimilation of the surface current measurements captures the temporal variability and improves the ADP/solution rms difference. Despite significant temporal variability, persistent features are found for the studied period; for instance, the dominant direction of baroclinic wave phase and energy propagation is always from the northwest. At the surface, baroclinic surface tidal currents (deviations from the depth-averaged current) can be 10 cm s–1, 2 times as large as the depth-averaged current. Barotropic-to-baroclinic energy conversion is generally weak within the model domain over the shelf but reaches 5 mW m–2 at times over the slopes of Stonewall Bank.
Numerical Simulation of Sea Surface Directional Wave Spectra under Hurricane Wind Forcing
Authors: Moon Il-Ju , Ginis Isaac , Hara Tetsu , Tolman Hendrik L. , Wright C. W. , Walsh Edward J. 
Published: February 2011

Abstract
Numerical simulation of sea surface directional wave spectra under hurricane wind forcing was carried out using a high-resolution wave model. The simulation was run for four days as Hurricane Bonnie (1998) approached the U.S. East Coast. The results are compared with buoy observations and NASA Scanning Radar Altimeter (SRA) data, which were obtained on 24 August 1998 in the open ocean and on 26 August when the storm was approaching the shore. The simulated significant wave height in the open ocean reached 14 m, agreeing well with the SRA and buoy observations. It gradually decreased as the hurricane approached the shore. In the open ocean, the dominant wavelength and wave direction in all four quadrants relative to the storm center were simulated very accurately. For the landfall case, however, the simulated dominant wavelength displays noticeable overestimation because the wave model cannot properly simulate shoaling processes. Direct comparison of the model and SRA directional spectra in all four quadrants of the hurricane shows excellent agreement in general. In some cases, the model produces smoother spectra with narrower directional spreading than do the observations. The spatial characteristics of the spectra depend on the relative position from the hurricane center, the hurricane translation speed, and bathymetry. Attempts are made to provide simple explanations for the misalignment between local wind and wave directions and for the effect of hurricane translation speed on wave spectra.
Reconciling the Stommel Box Model with the Stommel–Arons Model: A Possible Role for Southern Hemisphere Wind Forcing?
Authors: Greatbatch Richard J. , Lu Jian 
Published: February 2011

Abstract
In the Stommel box model, the strength of the overturning circulation is parameterized in terms of the density (and hence the pressure) difference between the two boxes. Straub has pointed out that this parameterization is not consistent with the Stommel–Arons model for the abyssal circulation. In particular, the zonally averaged density field implied by the Stommel–Arons model is unrelated to the strength or the direction of the meridional overturning circulation. Here, the inconsistency is examined using the abyssal circulation model of Kawase and a variant to include the effect of Southern Hemisphere wind forcing. The important parameter is R, the ratio of two timescales: the timescale for a perturbation to the density field to propagate, by either wave or advective processes, from a high-latitude source to the equator and the timescale for the dissipation of a perturbation to the density field by diapycnal mixing. If the model is forced only by a deep water source in the northern basin, it is found that the model behaves like the Stommel–Arons model when R ≪ 1 (the “weak” damping regime) and like the Stommel box model when R ≫ 1 (the “strong” damping regine). Estimates of R suggest that coarse-resolution models generally reside in or near the Stommel box model regime (R ≫ 1), which is probably why these models generally support the Stommel box model hypothesis and corroborate the momentum-based closure used in zonally averaged models. On the other hand, it is not clear that the real world is also in the strong damping regime. Indeed, it is easy to obtain estimates for R, using realistic parameter values, that sit in the weak damping regime. It is shown that, even in the weak damping regime (R ≪ 1), adding forcing by the Southern Hemisphere circumpolar westerlies generally moves the model into the Stommel box model regime. It therefore is concluded that, at least in the context of the Kawase model, the inconsistency noted by Straub can be removed by including the effect of Southern Hemisphere wind forcing and that the Stommel box model approach probably has wider applicability than is suggested by estimates of R alone.
Annual ENSO
Authors: Tozuka Tomoki , Yamagata Toshio 
Published: February 2011

Abstract
Using various observational data, the seasonal cycle of the tropical Pacific is investigated, suggesting the existence of an “annual El Niño–Southern Oscillation (ENSO).” A positive sea surface temperature anomaly (SSTA) appearing off Peru in boreal winter triggers a series of air–sea interactions that consist of westward propagations of positive SSTA, westerly wind anomalies, and negative outgoing longwave radiation anomalies. At the same time, the westerly wind anomaly generates cold temperature anomalies in the off-equatorial region, and they propagate westward as a “cold” Rossby wave, reaching the western tropical Pacific in boreal summer to autumn. A semiresonant condition between the westward propagating component of winds and the first-meridional-mode Rossby wave plays an important role in the amplification. The evolution of cold phase in the latter half of the year is almost a mirror image of the warm phase. From a new viewpoint of the annual ENSO, the ENSO is interpreted as the interaction between two distinct modes of air–sea interaction: the annual ENSO mode and an “interannual ENSO” mode. The eastward-propagating interannual ENSO mode is an air–sea coupled mode, which is triggered by the westerly wind stress anomaly in the western equatorial Pacific and leads to the deepening of the thermocline and the warming of SST in the central and eastern equatorial Pacific. This results in a modulation of the annual ENSO mode with a weaker cold season and stronger warm season owing to less effective upwelling of the cold subsurface water. The decadal variation of ENSO is explained by changes in the relative phase and amplitude of these two modes. The increase in the amplitude of the interannual ENSO mode after the late 1970s favors the appearance of the eastward propagation of ENSO signals.