bluuebunny/crossref_metadata_2025_split huggingface dataset:
CXCR4 positive and angiogenic monocytes in myocardial infarction
Authors: Wrigley Benjamin , Montoro-Garcia Silvia , Lip Gregory , Shantsila Eduard , Tapp Luke 
Published: December 2012

SummaryLimited data are available on the role of monocytes in cardiac repair. In the present study, we evaluated the dynamic alterations of monocytes with reparative and angiogenic potential in patients with myocardial infarction(MI). Reparative CXCR4+ monocytes, and CD34+ and KDR+ monocytes with angiogenic potential derived from individual monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (n=50) and stable coronary artery disease (CAD, n=40). Parameters were measured on days 1, 3, 7 and 30 post MI. Monocyte subsets were defined as CD14++CD16–CCR2+ (‘classical’, Mon1), CD14++CD16+CCR2+ (‘intermediate’, Mon2), CD14+CD16++CCR2– (‘non-classical’, Mon3). Plasma levels of inflammatory cytokines, fibrinolytic factors and microparticles (MPs) were assessed on day 1. CXCR4+ and KDR+ monocytes were increased following MI, being more prominently associated with Mon2 (median[IQR] of CXCR4+ Mon2 60[25–126] per μl in STEMI vs. 27[21–41] per μl in stable CAD). The counts of CXCR4+ Mon2 in STEMI significantly reduced by day 30 of follow-up (27[18–47], p<0.001). Expression of the pro-reparative scavenger receptor CD163 on Mon3 was reduced in acute MI (p=0.008), and on other subsets later during the follow-up with lowest levels at day 3 post-MI (p<0.001 for Mon1, p=0.02 for Mon2). CD204 expression on Mon1 correlated with tissue type plasminogen activator levels (r=0.46, p=0.001). Interleukin(IL)6 levels correlated with counts of Mon2-derived CXCR4+ and KDR+ cells. Interleukin-1β correlated with KDR+ Mon2 counts. IL10 correlated with CXCR4+ Mon2 levels. Low count of CXCR4+ Mon2 and low CD163 expression by Mon2 were associated with higher ejection fraction six-weeks after MI. In conclusion, the Mon2 subset has the most prominent role in the observed changes in reparative monocytes in MI. The association of reparative monocytes with inflammatory/fibrinolytic markers indicates a complex interplay of these cells in the post-MI state.Note: The review process for this paper was fully handled by Prof. Christian Weber, Editor in Chief.
Contribution of factor VIII light-chain residues 2007–2016 to an activated protein C-interactive site
Authors: Takeyama Masahiro , Wakabayashi Hironao , Fay Philip 
Published: December 2012

SummaryAlthough factor (F) VIIIa is inactivated by activated protein C (APC) through cleavages in the FVIII heavy chain-derived A1 (Arg336) and A2 subunits (Arg562), the FVIII light chain (LC) contributes to catalysis by binding the enzyme. ELISA-based binding assays showed that FVIII and FVIII LC bound to immobilised active site-modified APC (DEGRAPC) (apparent K d ~270 nM and 1.0 μM, respectively). Fluid-phase binding studies using fluorescence indicated an estimated K d of ~590 nM for acrylodan-labelled LC binding to DEGR-APC. Furthermore, FVIII LC effectively competed with FVIIIa in blocking APC-catalysed cleavage at Arg336 (K i = 709 nM). A binding site previously identified near the C-terminal end of the A3 domain (residues 2007–2016) of FVIII LC was subjected to Ala-scanning mutagenesis. FXa generation assays and western and dot blotting were employed to assess the contribution of these residues to FVIIIa interactions with APC. Virtually all variants tested showed reductions in the rates of APC-catalysed inactivation of the cofactor and cleavage at the primary inactivation site (Arg336), with maximal reductions in inactivation rates (~3-fold relative to WT) and cleavage rates (~3 to ~9-fold relative to WT) observed for the Met2010Ala, Ser2011Ala, and Leu2013Ala variants. Titration of FVIIIa substrate concentration monitoring cleavage by a dot blot assay indicated that these variants also showed ~3-fold increases relative to WT while a double mutant (Met2010Ala/Ser2011Ala) showed a >4-fold increase in K m. These results show a contribution of a number of residues within the 2007–2016 sequence, and in particular residues Met2010, Ser2011, and Leu2013 to an APC-interactive site.
Locally Applied Leptin Induces Regional Aortic Wall Degeneration Preceding Aneurysm Formation in Apolipoprotein E–Deficient Mice
Authors: Tao Ming , Yu Peng , Nguyen Binh T. , Mizrahi Boaz , Savion Naphtali , Kolodgie Frank D. , Virmani Renu , Hao Shuai , Ozaki C. Keith , Schneiderman Jacob 
Published: December 2012

Objective—
Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aortic aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process.

Methods and Results—

Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor, as well as mRNA for matrix metalloproteinases (MMP)-9 and MMP-12. Leptin and leptin receptor antigen were evident in all AAAs, and leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched nondilated controls. To simulate in vivo local leptin synthesis,
ApoE

–/–

mice were subjected to a paravisceral periaortic application of low-dose leptin. Leptin-treated aortas exhibited decreased transforming growth factor-β and increased MMP-9 mRNA levels 5 days after surgery, and leptin receptor mRNA was upregulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12, and periadventitial macrophage clustering. Furthermore, the combination of local periaortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size.

Conclusion—

Leptin is locally synthesized in human AAA wall. Paravisceral aortic leptin in ApoE
–/–
mice induces local medial degeneration and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation.
BIG1, a Brefeldin A–Inhibited Guanine Nucleotide-Exchange Protein Modulates ATP-Binding Cassette Transporter A-1 Trafficking and Function
Authors: Lin Sisi , Zhou Chun , Neufeld Edward , Wang Yu-Hua , Xu Suo-Wen , Lu Liang , Wang Ying , Liu Zhi-Ping , Li Dong , Li Cuixian , Chen Shaorui , Le Kang , Huang Heqing , Liu Peiqing , Moss Joel , Vaughan Martha , Shen Xiaoyan 
Published: December 2012

Objective—
Cell-surface localization and intracellular trafficking are essential for the function of ATP-binding cassette transporter A-1 (ABCA1). However, regulation of these activities is still largely unknown. Brefeldin A, an uncompetitive inhibitor of brefeldin A-inhibited guanine nucleotide-exchange proteins (BIGs), disturbs the intracellular distribution of ABCA1, and thus inhibits cholesterol efflux. This study aimed to define the possible roles of BIGs in regulating ABCA1 trafficking and cholesterol efflux, and further to explore the potential mechanism.

Methods and Results—
By vesicle immunoprecipitation, we found that BIG1 was associated with ABCA1 in vesicles preparation from rat liver. BIG1 depletion reduced surface ABCA1 on HepG2 cells, and inhibited by 60% cholesterol release. In contrast, BIG1 overexpression increased surface ABCA1 and cholesterol secretion. With partial restoration of BIG1 through overexpression in BIG1-depleted cells, surface ABCA1 was also restored. Biotinylation and glutathione cleavage revealed that BIG1 small interfering RNA dramatically decreased the internalization and recycling of ABCA1. This novel function of BIG1 was dependent on the guanine nucleotide-exchange activity and achieved through activation of ADP-ribosylation factor 1.

Conclusion—
BIG1, through its ability to activate ADP-ribosylation factor 1, regulates cell-surface levels and function of ABCA1, indicating a transcription-independent mechanism for controlling ABCA1 action.
Incidence, Locations, and Longitudinal Course of Silent Microbleeds in Moyamoya Disease
Authors: Kuroda Satoshi , Kashiwazaki Daina , Ishikawa Tatsuya , Nakayama Naoki , Houkin Kiyohiro 
Published: December 2012

Background and Purpose—
Clinical significance of silent microbleeds is unknown in moyamoya disease. This study was aimed to clarify the incidence, locations, and longitudinal course.

Methods—
This prospective cohort study included 78 nontreated patients with moyamoya disease. The incidence and locations of silent microbleeds were evaluated on T2*-weighted MRI. MR examinations were repeated every 6 or 12 months during a mean follow-up period of 43.1 months.

Results—

T2*-weighted MRI identified silent microbleeds in 17 (29.3%) of 58 adult patients with moyamoya disease, but in none of 20 pediatric patients. During follow-up periods, de novo silent microbleeds developed in 4 (6.9%) of 58 adult patients. Hemorrhagic stroke occurred in 4 patients (6.9%), all of who had silent microbleeds on initial examination. The presence of silent microbleeds was a significant predictor for subsequent hemorrhagic stroke in adult moyamoya disease (
P
<0.001).

Conclusions—
Careful and long-term follow-up of silent microbleeds would be essential to improve their outcome in adult patients with moyamoya disease.
Adherence to Hospital Discharge Medication in Patients With Ischemic Stroke
Authors: Hohmann Carina , Neumann-Haefelin Tobias , Klotz Jürgen M. , Freidank Annette , Radziwill Roland 
Published: December 2012

Background and Purpose—
Communication between hospitals and primary care physicians is essential for the continuity of care for patients being transferred from hospital to ambulatory care. Patients are often discharged from hospital on medication regimes different from those used before hospital admission. The aim of the study was to evaluate the adherence to hospital discharge medication in patients with ischemic stroke before and after implementing a systematic approach provided by a clinical pharmacist.

Methods—

Patients with transient ischemic attack/ischemic stroke taking
≥
2 drugs during hospital stay and at discharge were prospectively recruited. In the control group, the neurologist included the medication list in the discharge letter as before. In the intervention group, the clinical pharmacist listed the medication on admission and at discharge next to each other and gave detailed information for all medication changes during hospital stay.

Results—

Overall, 312 patients were enrolled in the study with 156 patients in each group. Significant differences between the control group and intervention group were ascertained with regard to adherence to both antithrombotic drugs (83.8% control group versus 91.9% intervention group [
P
=0.033]) and to statin therapy (69.8% control group versus 87.7% intervention group [
P
<0.001]).

Conclusions—
Providing detailed information on medication changes can lead to substantially improved adherence to discharge medication, probably resulting in better secondary stroke prevention.
Sensitivity of Ferry Services to the Western Isles of Scotland to Changes in Wave and Wind Climate
Authors: Coll John , Woolf David K. , Gibb Stuart W. , Challenor Peter G. 
Published: December 2012

AbstractThe roughness of the seas is rarely mentioned as a major factor in the economic or social welfare of a region. In this study, the relationship between the ocean wave climate and the economy of the Western Isles of Scotland is examined. This sparsely populated region has a high dependency on marine activities, and ferry services provide vital links between communities. The seas in the region are among the roughest in the world during autumn and winter, however, making maintenance of a reliable ferry service both difficult and expensive. A deterioration in wave and wind climate either in response to natural variability or as a regional response to anthropogenic climate change is possible. Satellite altimetry and gale-frequency data are used to analyze the contemporary response of wave and wind climate to the North Atlantic Oscillation (NAO). The sensitivity of wave climate to the NAO extends to ferry routes that are only partially sheltered and are exposed to ocean waves; thus, the reliability of ferry services is sensitive to NAO. Any deterioration of the wave climate will result in a disproportionately large increase in ferry-service disruption. The impacts associated with an unusually large storm event that affected the region in January 2005 are briefly explored to provide an insight into vulnerability to future storm events.
The Changing Energy Balance of the Polar Regions in a Warmer Climate
Authors: Bengtsson Lennart , Hodges Kevin I. , Koumoutsaris Symeon , Zahn Matthias , Berrisford Paul 
Published: December 2012

Abstract
Energy fluxes for polar regions are examined for two 30-yr periods, representing the end of the twentieth and twenty-first centuries, using data from high-resolution simulations with the ECHAM5 climate model. The net radiation to space for the present climate agrees well with data from the Clouds and the Earth’s Radiant Energy System (CERES) over the northern polar region but shows an underestimation in planetary albedo for the southern polar region. This suggests there are systematic errors in the atmospheric circulation or in the net surface energy fluxes in the southern polar region. The simulation of the future climate is based on the Intergovernmental Panel on Climate Change (IPCC) A1B scenario. The total energy transport is broadly the same for the two 30-yr periods, but there is an increase in the moist energy transport on the order of 6 W m−2 and a corresponding reduction in the dry static energy. For the southern polar region the proportion of moist energy transport is larger and the dry static energy correspondingly smaller for both periods.
The results suggest a possible mechanism for the warming of the Arctic that is discussed. Changes between the twentieth and twenty-first centuries in the northern polar region show the net ocean surface radiation flux in summer increases ~18 W m−2 (24%). For the southern polar region the response is different as there is a decrease in surface solar radiation. It is suggested that this is caused by changes in cloudiness associated with the poleward migration of the storm tracks.
Downscaling Extremes: An Intercomparison of Multiple Methods for Future Climate
Authors: Bürger G. , Sobie S. R. , Cannon A. J. , Werner A. T. , Murdock T. Q. 
Published: December 2012

Abstract
This study follows up on a previous downscaling intercomparison for present climate. Using a larger set of eight methods the authors downscale atmospheric fields representing present (1981–2000) and future (2046–65) conditions, as simulated by six global climate models following three emission scenarios. Local extremes were studied at 20 locations in British Columbia as measured by the same set of 27 indices, ClimDEX, as in the precursor study. Present and future simulations give 2 × 3 × 6 × 8 × 20 × 27 = 155 520 index climatologies whose analysis in terms of mean change and variation is the purpose of this study. The mean change generally reinforces what is to be expected in a warmer climate: that extreme cold events become less frequent and extreme warm events become more frequent, and that there are signs of more frequent precipitation extremes. There is considerable variation, however, about this tendency, caused by the influence of scenario, climate model, downscaling method, and location. This is analyzed using standard statistical techniques such as analysis of variance and multidimensional scaling, along with an assessment of the influence of each modeling component on the overall variation of the simulated change. It is found that downscaling generally has the strongest influence, followed by climate model; location and scenario have only a minor influence. The influence of downscaling could be traced back in part to various issues related to the methods, such as the quality of simulated variability or the dependence on predictors. Using only methods validated in the precursor study considerably reduced the influence of downscaling, underpinning the general need for method verification.
Simulating Clouds with Global Climate Models: A Comparison of CMIP5 Results with CMIP3 and Satellite Data
Authors: Lauer Axel , Hamilton Kevin 
Published: December 2012

AbstractClouds are a key component of the climate system affecting radiative balances and the hydrological cycle. Previous studies from the Coupled Model Intercomparison Project phase 3 (CMIP3) showed quite large biases in the simulated cloud climatology affecting all GCMs as well as a remarkable degree of variation among the models that represented the state of the art circa 2005. Here the progress that has been made in recent years is measured by comparing mean cloud properties, interannual variability, and the climatological seasonal cycle from the CMIP5 models with satellite observations and with results from comparable CMIP3 experiments. The focus is on three climate-relevant cloud parameters: cloud amount, liquid water path, and cloud radiative forcing. The comparison shows that intermodel differences are still large in the Coupled Model Intercomparison Project phase 5 (CMIP5) simulations, and reveals some small improvements of particular cloud properties in some regions in the CMIP5 ensemble over CMIP3. In CMIP5 there is an improved agreement of the modeled interannual variability of liquid water path and of the modeled longwave cloud forcing over mid- and high-latitude oceans with observations. However, the differences in the simulated cloud climatology from CMIP3 and CMIP5 are generally small, and there is very little to no improvement apparent in the tropical and subtropical regions in CMIP5.Comparisons of the results from the coupled CMIP5 models with their atmosphere-only versions run with observed SSTs show remarkably similar biases in the simulated cloud climatologies. This suggests the treatments of subgrid-scale cloud and boundary layer processes are directly implicated in the poor performance of current GCMs in simulating realistic cloud fields.
Centennial Trend and Decadal-to-Interdecadal Variability of Atmospheric Angular Momentum in CMIP3 and CMIP5 Simulations
Authors: Paek Houk , Huang Huei-Ping 
Published: December 2012

Abstract
The climatology and trend of atmospheric angular momentum from the phase 3 and the phase 5 Climate Model Intercomparison Project (CMIP3 and CMIP5, respectively) simulations are diagnosed and validated with the Twentieth Century Reanalysis (20CR). It is found that CMIP5 models produced a significantly smaller bias in the twentieth-century climatology of the relative MR and omega MΩ angular momentum compared to CMIP3. The CMIP5 models also produced a narrower ensemble spread of the climatology and trend of MR and MΩ. Both CMIP3 and CMIP5 simulations consistently produced a positive trend in MR and MΩ for the twentieth and twenty-first centuries. The trend for the twenty-first century is much greater, reflecting the role of greenhouse gas (GHG) forcing in inducing the trend. The simulated increase in MR for the twentieth century is consistent with reanalysis. Both CMIP3 and CMIP5 models produced a wide range of magnitudes of decadal and interdecadal variability of MR compared to 20CR. The ratio of the simulated standard deviation of decadal or interdecadal variability to its observed counterpart ranges from 0.5 to over 2.0 for individual models. Nevertheless, the bias is largely random and ensemble averaging brings the ratio to within 18% of the reanalysis for decadal and interdecadal variability for both CMIP3 and CMIP5. The twenty-first-century simulations from both CMIP3 and CMIP5 produced only a small trend in the amplitude of decadal or interdecadal variability, which is not statistically significant. Thus, while GHG forcing induces a significant increase in the climatological mean of angular momentum, it does not significantly affect its decadal-to-interdecadal variability in the twenty-first century.
A Satellite-Based Convective Cloud Object Tracking and Multipurpose Data Fusion Tool with Application to Developing Convection
Authors: Sieglaff Justin M. , Hartung Daniel C. , Feltz Wayne F. , Cronce Lee M. , Lakshmanan Valliappa 
Published: December 2012

Abstract
Studying deep convective clouds requires the use of available observation platforms with high temporal and spatial resolution, as well as other non–remote sensing meteorological data (i.e., numerical weather prediction model output, conventional observations, etc.). Such data are often at different temporal and spatial resolutions, and consequently, there exists the need to fuse these different meteorological datasets into a single framework. This paper introduces a methodology to identify and track convective cloud objects from convective cloud infancy [as few as three Geostationary Operational Environmental Satellite (GOES) infrared (IR) pixels] into the mature phase (hundreds of GOES IR pixels) using only geostationary imager IR window observations for the purpose of monitoring the initial growth of convective clouds.
The object tracking system described within builds upon the Warning Decision Support System-Integrated Information (WDSS-II) object tracking capabilities. The system uses an IR-window-based field as input to WDSS-II for cloud object identification and tracking and a Cooperative Institute for Meteorological Satellite Studies at the University of Wisconsin (UW-CIMSS)-developed postprocessing algorithm to combine WDSS-II cloud object output. The final output of the system is used to fuse multiple meteorological datasets into a single cloud object framework. The object tracking system performance analysis shows improved object tracking performance with both increased temporal resolution of the geostationary data and increased cloud object size. The system output is demonstrated as an effective means for fusing a variety of meteorological data including raw satellite observations, satellite algorithm output, radar observations, and derived output, numerical weather prediction model output, and lightning detection data for studying the initial growth of deep convective clouds and temporal trends of such data.
Analysis of endothelial precursor cells in chronic migraine: A case-control study
Authors: Oterino Agustin , Toriello Maria , Palacio Enrique , Quintanilla Vicente G , Ruiz-Lavilla Nuria , Montes Silvia , Vega Maria S de la , Martinez-Nieto Rosa , Castillo Jesus , Pascual Julio 
Published: December 2012

Background: Migraine has been considered a vascular risk factor especially in young women. Factors predisposing to endothelial damage in migraine are still being debated. The insufficiency of circulating endothelial precursor circulating cells (EPCs) suggested a link between migraine and cardiovascular risk. This research aimed to study a subtype of EPCs, those expressing e-selectin, to assess endothelial activation and, therefore, endothelial dysfunction in migraine. Methods: Consecutive headache patients ( n = 99) and 35 adjusted controls were recruited. Total EPCs, defined as CD34+/KDR+ cells, and EPC colony-forming units (CFUs) were assayed. We identified as “early” EPCs those CD62E– EPCs, and “late” EPCs, CD62E+, a surrogate marker for endothelial damage. Plasmatic calcitonin-gene related protein (CGRP) and vascular-endothelial growth factor (VEGF) were analyzed. Results: We did not find differences in the total number of CFUs among clinical groups. Means of total CD34+/KDR+ and “early” EPCs were not significant among clinical groups. Nevertheless, the mean of “late” EPCs was lower (log10-transformed mean = 1.715; SD = 0.393) in the control group than in the migraine patients (log10-transformed mean = 2.167; SD = 0.685), even after adjustment by VEGF plasma level and other confounding factors. Linear regression analyses disclosed significant predictors for “late” EPCs for controls vs migraine (β = 0.452 SE ± 0.13; p = 0.001). We did not observe differences between migraine with or without aura. Conclusion: We observed higher number of activated EPCs in migraine patients than in controls. CD62E+ EPCs might be considered a marker for vascular damage in migraine patients.