bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of plasminogen activator inhibitor-1 on adipogenesis in vivo
Authors: Scroyen Ilse , Jacobs Frank , Cosemans Leen , Geest Bart De , Lijnen Roger 
Published: January 2009

SummaryTo study the functional role of plasminogen activator inhibitor-1 (PAI-1) in obesity, the effect of its overexpression on de novo adipogenesis was evaluated in murine models in vivo. Therefore, 3T3-F442A preadipocytes expressing murine PAI-1 (mPAI-1) or control cells were injected in the back of male NUDE mice, which were fed a high-fat diet (HFD) for four weeks. De novo fat pads that formed from the PAI-1 expressing cells were larger (21 ± 2.4 mg vs. 14 ± 1.4 mg; p = 0.017) and showed a higher adipocyte density (373 ± 28 mm-2 vs. 301 ± 12 mm-2; p = 0.03) as compared to those formed from control cells. In a second model, male NUDE mice were injected in the tail vein with an adenoviral construct expressing mPAI-1 or with the empty vector, and three days later with 3T3-F442A cells. After four weeks of HFD, total body weight and de novo fat pad weight were comparable for both groups. Mild adipocyte hypotrophy was observed in the de novo fat pads of the PAI-1 overexpressing mice (1180 ± 33 µm2 vs. 1285 ± 32 µm2; p= 0.024), whereas the blood vessel size was significantly smaller than in controls (30 ± 1.8 µm2 vs. 63 ± 3.6 µm2; p < 0.0001). Thus, the effect of local or systemic PAI-1 (over)expression on adipocyte or blood vessel size and density of de novo formed fat pads appears to be different, and concentration-dependent. Whereas local expression resulted in larger fat pads, systemic overexpression had no effect on de novo adipogenesis, although angiogenesis appeared to be impaired.
Vulnerable atherosclerotic plaque metalloproteinases and foam cell phenotypes
Authors: George Sarah , Ismail Yasmin , Johnson Jason , Sala-Newby Graciela , Thomas Anita , Newby Andrew 
Published: January 2009

SummaryPlaque rupture underlies most myocardial infarctions. Plaques vulnerable to rupture have thin fibrous caps, an excess of macrophages over vascular smooth muscle cells, large lipid cores, and depletion of collagen and other matrix proteins form the cap and lipid core. Production of matrix metalloproteinases from macrophages is prominent in human plaques, and studies in genetically modified mice imply a causative role for metallopro teinases in plaque vulnerability. Recent in-vitro studies on human monocyte-derived macrophages and on foam-cell macrophages generated in vivo suggest the existence of several macrophage phenotypes with distinct patterns of metalloproteinase expression. These phenotypes could play differing roles in cap, core and aneurysm formation.
Microsatellite (GT)n repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions
Authors: Daidone Viviana , Cattini Maria Grazia , Pontara Elena , Sartorello Francesca , Gallinaro Lisa , Marotti Alberto , Scaroni Carla , Pagnan Antonio , Casonato Alessandra 
Published: January 2009

SummaryVon Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)n modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)n of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions. (GT)n proved highly polymorphic, with alleles from 15 to 24 repeats long. (GT)21 and (GT)19 were the most common variants (37.4% and 34.4%, respectively). Short GT repeats (15–19) segregated mainly with haplotype 1, long GT repeats (20–24) with haplotype 2 (p<0.0001). The number of GT repeats did not correlate with VWF levels, nor did such levels correlate with haplotypes 1 and 2, considered alone or in association with the (GT)n locus. We conclude that (GT)n and -3268/-2709/-2661/-2527 loci are in strong linkage disequilibrium. This polymorphic region of the VWF promoter does not affect VWF levels under normal conditions, though it might represent an environmentally activable VWF regulation site.
Hereditary and acquired complement dysregulation in membranoproliferative glomerulonephritis
Authors: Fremeaux-Bacchi Veronique , Licht Christoph 
Published: January 2009

SummaryMembranoproliferative glomerulonephritis (MPGN) is a chronic progressive renal disease that is diagnosed on the basis of renal histological features. Several MPGN subtypes have been defined by the localization and composition of glomerular deposits (electron dense, Ig and C3). MPGN II or dense deposit disease (DDD) which is defined by the occurrence of electron dense deposits within the lamina densa of the glomerular basement membrane (GBM) is strongly associated with dysregulation of the alternative complement pathway (AP). However, C3 Nephritic Factor (C3NeF), an autoantibody against the alternative C3 convertase C3bBb, and mutations in regulatory proteins of the AP have also been identified in other subtypes of MPGN and even in glomerulonephritis with mesangial C3 deposits. Clinically, MPGN is characterized by proteinuria (up to nephrotic range) and hypertension, frequent progression to end-stage kidney disease and disease recurrence after renal transplantation. The age of onset varies from childhood to adulthood. In the following we will review our current knowledge of pathogenesis of MPGN and will present a novel classification system of the disease based on pathogenesis rather than on morphology. A better understanding of the pathogenesis of MPGN is crucial for the development of novel, specific treatment strategies.
Bivalirudin reduces platelet and monocyte activation after elective percutaneous coronary intervention
Authors: Busch Gabriele , Steppich Birgit , Sibbing Dirk , Braun Siegmund-Lorenz , Stein Andreas , Groha Philipp , Schömig Albert , Kastrati Adnan , Beckerath Nicolas von , Ott Ilka 
Published: January 2009

Summarylating platelets and CD11b, CD14 and CD15 on circulating leukocytes were evaluated by flow cytometry. Cytokine levels of IL-12p70, tumour necrosis factor (TNF), IL-8, IL-6, IL-1β and IL-10 were determined by cytometric bead array. Platelet surface expression of PAC-1, P-Selectin and GPIbα was significantly reduced after PCI in patients receiving bivalirudin as compared to heparin. Similarly, CD11b expression on CD14+ monocytes was diminished after bivalirudin. However, no differences were observed in cytokine levels between the bivalirudin and the heparin group, before or after PCI. In conclusion, our data suggest that bivalirudin may reduce platelet and monocyte activation in patients undergoing elective PCI. Thereby, bivalirudin might reduce periinterventional thrombotic complications.
Antithrombin Cambridge II (A384S) supports a role for antithrombin deficiency in arterial thrombosis
Authors: Roldán Vanessa , Ordoñez Adriana , Marín Francisco , Zorio Esther , Soria José M. , Miñano Antonia , España Francisco , González-Conejero Rocio , Pineda Javier , Estellés Amparo , Fontcuberta Jordi , Vicente Vicente , Corral Javier 
Published: January 2009

SummaryAlthough the control of thrombin in the microvasculature at the endothelial cell surface is crucial to prevent atherothrombosis, the role of antithrombin in arterial thrombosis is unclear. It is widely considered that antithrombin deficiency is unlikely to contribute to arterial thrombosis, but no convincing epidemiological study has been performed because of the low frequency of this deficiency. In this study we evaluated the role in myocardial infarction (MI) of a relatively common mutation affecting antithrombin gene (A384S: Antithrombin Cambridge II) that has functional features that may impair the right control of thrombogenic events caused by injury to the vascular wall. Moreover, this deficiency, which is not detected using common methods to diagnose antithrombin deficiency, also increases the risk of venous thrombosis. We included 1,224 patients with MI (691 consecutive patients and 533 survivors of a premature event), and 1,649 controls. The mutation was identified in 0.3% of controls, but 0.8% of MI patients. After adjusting for sex and other cardiovascular risk factors, the antithrombin Cambridge II significantly increased 5.66-fold the risk of MI (95% CI: 1.53–20.88; p= 0.009). Interestingly, young patients had the highest risk of MI associated with the mutation (OR: 9.98; 95%CI: 1.60–62.24; p= 0.009). This is the first epidemiological study that supports a role for anti-thrombin deficiency in arterial thrombosis. These results suggest that deficiency of antithrombin may be an independent risk factor for MI that has been underestimated, but larger studies are needed to confirm the relevance of inhibitors of thrombin in arterial thrombosis.
Stroke risk in atrial fibrillation patients on warfarin
Authors: Antonucci Emilia , Grifoni Elisa , Abbate Rosanna , Gensini Gian Franco , Prisco Domenico , Poli Daniela 
Published: January 2009

SummaryAtrial fibrillation (AF) patients are widely heterogeneous in terms of ischaemic stroke risk, and several risk stratification schemes have been developed. We performed a prospective study on 662 AF patients on long-term oral anticoagulant therapy (OAT), evaluating the agreement among the different schemes and their correlation with adverse events recorded during follow-up. Patients at low risk were similarly distributed among the different models. Instead, patients classed at moderate risk were 49.2% by CHADS2 score, 27.6% by NICE and 2.3% by ACCP. As a consequence patients classed at high risk were 46.1% by CHADS2, 69.8% by NICE and 95.3% by ACCP. CHADS2 and NICE scores were associated to the best predictive accuracy. A separate analysis was performed for patients on treatment for secondary prevention, and we observed that they were included in high risk groups by all models, except for 14 patients (6.3%) classed at moderate risk by CHADS2 even though these patients are at very high risk and the use of aspirin could be unsafe for them. During follow-up 32 major bleeding (1.35 per 100 patient/years) and 39 thrombotic events (1.64 per 100 patient/ years) were observed. Among patients on OAT for secondary prevention, both bleeding and thrombotic events mostly occurred in high-risk patients. Even if the absolute rate of adverse events is low, this finding seems to confirm the high stroke risk of this group of patients. For patients on secondary prevention there is no need for further stratification and warfarin should be the treatment of choice.
The impact of acute and chronic exercise on thrombosis in cardiovascular disease
Authors: Pelletier Roxanne , Lavoie Kim L. , Bacon Simon L. 
Published: January 2009

SummaryThere is now a large and impressive literature showing that people who engage in chronic aerobic exercise or who have better cardiovascular fitness levels, tend to live longer and have lower levels of cardiovascular disease (CVD). However, there is a paradox, as acute aerobic exercise has been associated with an increased risk of CVD events. There are now a number of review articles suggesting that the differential benefits of chronic, relative to acute, exercise might be due to thrombotic changes, though the majority of this data is derived from healthy individuals. However, acute exercise is of greater concern and chronic exercise of greater benefit to patient populations. In addition, these higher risk groups tend to present with more complex profiles, e.g. they may be taking medications that influence thrombotic pathways. As such, the current review has focused on newer information relating to exercise, physical activity and thrombosis in patient populations, and highlights some of the growing area’s in the field. For example, the impact of warm-up exercise, the interaction of medications, and issues surrounding the optimal volume and intensity of exercise.
Desmoteplase in acute massive pulmonary thromboembolism
Authors: Bramlage Peter , Graf Andreas , Lechleitner Peter , Bode Christoph , Riess Friedrich-Christian , Clemens Norbert , Al-Rawi Yasir , Konstantinides Stavros , Goldhaber Samuel Z. , Tebbe Ulrich 
Published: January 2009

SummaryAlteplase is standard therapy for patients with acute, massive pulmonary embolism. The novel plasminogen activator desmoteplase displays high fibrin specificity and selectivity for fibrin-bound plasminogen. In a preclinical model desmoteplase was twice as potent with a shorter lysis time and lower reocclusion rate. We conducted a phase II study comparing 125, 180, and 250 μg/kg bodyweight desmoteplase with 100 mg alteplase. Efficacy criteria were total pulmonary resistance (TPR), mean pulmonary artery pressure (mPAP), and Miller Index. Intention to treat analysis of 34 patients. The reduction of TPR after 24 hours was comparable between desmoteplase 180 μg/kg and alteplase (-48.0 ± 22.4 vs. –50.4 ± 16.3%; p = n.s. vs. alteplase; p = 0.0002 and p<0.0001 vs. baseline). The greatest effect was achieved with desmoteplase 250 μg/kg (-56.0 ± 29.4%; p = n.s. vs. alteplase, p = 0.0055 vs. baseline). Two hours after treatment PAP was reduced by 27.9 (p = 0.0004 vs. baseline) and 30.4% (p = 0.015 vs. baseline) with the higher doses of desmoteplase and 29.6% with alteplase (p = 0.0006 vs. baseline). Further PAP reduction after 6 hours was most pronounced in the desmoteplase 250 μg/kg group (-40.1 ± 18.0%; p = 0.0028 vs. baseline). The reduction of the Miller Index was greatest using desmoteplase 250 μg/kg (-35.0 ± 21.7%; p = 0.011 vs. baseline), and alteplase (-41.6 ± 27.2%; p = 0.0003 vs. baseline). Safety did not differ among the 4 groups. The study results suggest that desmoteplase at doses of 180 and 250 μg/kg had similar or greater efficacy compared to alteplase 100 mg. Onset of action was faster, safety was comparable.
The Choreography of Journeys of Magnificence: Arranging the Post-Nuptial Progress of Frederick, the Elector Palatine, and Princess Elizabeth of England from London to Heidelberg in 1613
Authors: Brayshay Mark 
Published: January 2009

AbstractIn examining the detailed planning and operation of an example of long-distance royal travel in the early modern period, this paper draws on contemporary documentary evidence to reconstruct the arrangements that were made for the Princess Elizabeth of England, and her new husband, Prince Frederick, the Elector Palatine, in their journey from London to Heidelberg between April and June in 1613. The progress of the royal couple is well known for its lavishness, splendour, symbolism and political significance but, in this analysis, attention is paid to the composition and character of the escort party, and the elaborate and intricate choreography that underpinned early seventeenth century European travel en fête.
Comments on “Is the Faroe Bank Channel Overflow Hydraulically Controlled?”
Authors: Enmar Linda , Borenäs Karin , Lake Iréne , Lundberg Peter 
Published: January 2009

Abstract
In a recent paper Girton et al., due to what appears to be a misunderstanding, stated that a critical-flow analysis of the deep-water transport through the Faroe Bank Channel had been undertaken by Lake et al. on the basis of rotating hydraulic theory for a channel of parabolic cross section. In fact, this quoted investigation dealt with a rectangular passage. In the present comment it is demonstrated how the use of parabolic bathymetry leads to significant improvements of the Froude number results.
Classification of Convective Areas Using Decision Trees
Authors: Gagne David John , McGovern Amy , Brotzge Jerry 
Published: January 2009

Abstract
This paper presents an automated approach for classifying storm type from weather radar reflectivity using decision trees. Recent research indicates a strong relationship between storm type (morphology) and severe weather, and such information can aid in the warning process. Furthermore, new adaptive sensing tools, such as the Center for Collaborative Adaptive Sensing of the Atmosphere’s (CASA’s) weather radar, can make use of storm-type information in real time. Given the volume of weather radar data from those tools, manual classification of storms is not possible when dealing with real-time data streams. An automated system can more quickly and efficiently sort through real-time data streams and return value-added output in a form that can be more easily manipulated and understood. The method of storm classification in this paper combines two machine learning techniques: K-means clustering and decision trees. K-means segments the reflectivity data into clusters, and decision trees classify each cluster. The K means was used to separate isolated cells from linear systems. Each cell received labels such as “isolated pulse,” “isolated strong,” or “multicellular.” Linear systems were labeled as “trailing stratiform,” “leading stratiform,” and “parallel stratiform.” The classification scheme was tested using both simulated and observed storms. The simulated training and test datasets came from the Advanced Regional Prediction System (ARPS) simulated reflectivity data, and observed data were collected from composite reflectivity mosaics from the CASA Integrative Project One (IP1) network. The observations from the CASA network showed that the classification scheme is now ready for operational use.
Variability of Surface Air Temperature over Gently Sloped Terrain
Authors: Bodine David , Klein Petra M. , Arms Sean C. , Shapiro Alan 
Published: January 2009

AbstractTemperature and wind data from a rural micronet and nearby site of the Oklahoma Mesonet are analyzed to study the frequency, strength, and formation processes of cold-pool events in a region with gentle terrain. Spatial analyses were performed for a 2-yr-long temperature record from 26 temperature/humidity surface stations, deployed across a 120 m × 320 m micronet located in a region of gently sloped terrain with maximum elevation changes of ∼25 m. Cold pools frequently formed at the base of a gentle slope in a small depression of only ∼6-m depth that is also sheltered by trees. The strength of each cold-pool event was classified according to a cold-pool index based on average nocturnal temperature perturbations within the cold-pool region. Wind data collected with sonic anemometers on a 15-m-tall tower at the micronet for a period of three months (spring 2005) suggest that flow sheltering by vegetation plays an important role in the cold-pool formation. The wind data also show signatures of katabatic flow for about 50% of the strong cold-pool events. However, a heat budget analysis for these nights suggested that the katabatic flows were associated with warm-air advection along the slope and that if katabatic jets had penetrated the cold pool, they would have produced substantial warming in the region of the cold pool. Since such warming was not observed, it is concluded that the katabatic jets did not actually penetrate the cold pool but likely flowed over it. An analysis of Richardson numbers demonstrates that cold-pool formation frequently occurs under strongly stable conditions that tend to suppress vertical turbulent mixing in the surface layer. Observations that significant temperature changes can occur even with elevation changes on the order of 6 m have important implications in agriculture as well as in data assimilation.
Wave Driving in the Tropical Lower Stratosphere as Simulated by WACCM. Part I: Annual Cycle
Authors: Taguchi Masakazu 
Published: January 2009

Abstract
This study explores the climatological annual cycle of temperature, circulation, and wave driving distributions in the tropical lower stratosphere as produced in a 50-yr simulation of the Whole Atmosphere Community Climate Model (WACCM). The simulation is forced with a climatological sea surface temperature and sea ice condition. The present diagnoses verify the primary balances of the annual cycle in this region, consistent with lower temperatures, stronger residual circulation (upwelling and local meridional outflow), and nearby stronger wave driving for Northern Hemisphere (NH) winter. An in-detail analysis on the wave driving further reveals that the stronger driving, occurring mostly in the northern tropics and subtropics, is contributed by northward and upward propagation (associated with meridional and vertical fluxes of zonal momentum, respectively) of equatorial Rossby waves forced by convective heating, and also by equatorward propagation of NH extratropical planetary and synoptic waves. The results are used to discuss implications about possible factors that may affect the different observations of the wave driving. The present framework and results will be extended to investigate ENSO-induced changes in this region during NH winter in a forthcoming paper.
The Response to Stratospheric Forcing and Its Dependence on the State of the Troposphere
Authors: Chan Cegeon J. , Plumb R. Alan 
Published: January 2009

Abstract
In simple GCMs, the time scale associated with the persistence of one particular phase of the model’s leading mode of variability can often be unrealistically large. In a particularly extreme example, the time scale in the Polvani–Kushner model is about an order of magnitude larger than the observed atmosphere. From the fluctuation–dissipation theorem, one implication of these simple models is that responses are exaggerated, since such setups are overly sensitive to any external forcing. Although the model’s equilibrium temperature is set up to represent perpetual Southern Hemisphere winter solstice, it is found that the tropospheric eddy-driven jet has a preference for two distinct regions: the subtropics and midlatitudes. Because of this bimodality, the jet persists in one region for thousands of days before “switching” to another. As a result, the time scale associated with the intrinsic variability is unrealistic. In this paper, the authors systematically vary the model’s tropospheric equilibrium temperature profile, one configuration being identical to that of Polvani and Kushner. Modest changes to the tropospheric state to either side of the parameter space removed the bimodality in the zonal-mean zonal jet’s spatial distribution and significantly reduced the time scale associated with the model’s internal mode. Consequently, the tropospheric response to the same stratospheric forcing is significantly weaker than in the Polvani and Kushner case.