bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD36 Ectodomain Phosphorylation Blocks Thrombospondin-1 Binding
Authors: Chu Ling-Yun , Silverstein Roy L. 
Published: January 2012

Objective—
CD36 phosphorylation on its extracellular domain inhibits binding of thrombospondin-1. The mechanisms of cellular CD36 ectodomain phosphorylation and whether it can be regulated in cells are not known. We determined structure-function relationships of CD36 phosphorylation related to thrombospondin-1 peptide binding in vitro and explored mechanisms regulating phosphorylation by protein kinase C (PKC) in melanoma cells.

Methods and Results—
Phosphorylation of CD36 peptide on Thr92 by PKCα suppressed binding of thrombospondin-1 peptides in vitro, and the level of inhibition correlated with the level of phosphorylation. Basal phosphorylation levels of CD36 in vivo in platelets, endothelial cells, and melanoma cells were assessed by immunoprecipitation and immunoblot and were found to be very low. Treatment of CD36-transfected melanoma cells with phorbol 12-myristate 13-acetate (PMA), a PKC activator, induced substantial CD36 phosphorylation and decreased ligand-mediated recruitment of Src-family proteins to CD36. PMA treatment did not induce detectable extracellular or cell surface–associated kinase activity, and both cycloheximide and brefeldin A blocked CD36 phosphorylation.

Conclusion—
New protein synthesis and trafficking through the Golgi are required for PMA-induced CD36 phosphorylation, suggesting that phosphorylation probably occurs intracellularly. These studies suggest a novel in vivo pathway for CD36 phosphorylation that modulates cellular affinity for thrombospondin-related proteins to blunt vascular cell signaling.
EphA2 Activation Promotes the Endothelial Cell Inflammatory Response
Authors: Funk Steven Daniel , Yurdagul Arif , Albert Patrick , Traylor James G. , Jin Long , Chen Jin , Orr A. Wayne 
Published: January 2012

Objective—
Endothelial cell activation results in altered cell-cell interactions with adjacent endothelial cells and with infiltrating leukocytes. Eph receptors and their ephrin ligands regulate cell-cell interactions during tissue remodeling, and multiple proinflammatory mediators induce endothelial EphA receptor and ephrinA ligand expression. Therefore, we sought to elucidate the role of EphA receptors and ephrinA ligands in endothelial cell activation and atherosclerosis.

Methods and Results—
Quantitative reverse transcription–polymerase chain reaction screening for EphA/ephrinA expression in atherosclerosis-prone macrovascular endothelium identified EphA2, EphA4, and ephrinA1 as the dominant isoforms. Endothelial activation with oxidized low-density lipoprotein and proinflammatory cytokines induced EphA2 and ephrinA1 expression and sustained EphA2 activation, whereas EphA4 expression was unaffected. Atherosclerotic plaques from mice and humans showed enhanced EphA2 and ephrinA1 expression colocalizing in the endothelial cell layer. EphA2 activation with recombinant Fc-ephrinA1 induced proinflammatory gene expression (eg vascular cell adhesion molecule-1, E-selectin) and stimulated monocyte adhesion, whereas inhibiting EphA2 (small interfering RNA, pharmacological inhibitors) abrogated both ephrinA1-induced and oxidized low-density lipoprotein–induced vascular cell adhesion molecule-1 expression.

Conclusion—
The current data suggest that enhanced EphA2 signaling during endothelial cell activation perpetuates proinflammatory gene expression. Coupled with EphA2 expression in mouse and human atherosclerotic plaques, these data implicate EphA2 as a novel proinflammatory mediator and potential regulator of atherosclerotic plaque development.
White Matter Protection in Congenital Heart Surgery
Authors: Ishibashi Nobuyuki , Scafidi Joseph , Murata Akira , Korotcova Ludmila , Zurakowski David , Gallo Vittorio , Jonas Richard A. 
Published: January 2012

Background—
Neurodevelopmental delays in motor skills and white matter (WM) injury have been documented in congenital heart disease and after pediatric cardiac surgery. The lack of a suitable animal model has hampered our understanding of the cellular mechanisms underlying WM injury in these patients. Our aim is to identify an optimal surgical strategy for WM protection to reduce neurological injury in congenital heart disease patients.

Methods and Results—

We developed a porcine cardiopulmonary bypass model that displays area-dependent WM maturation. In this model, WM injury was identified after cardiopulmonary bypass–induced ischemia-reperfusion injury. The degree of injury was inversely correlated with the maturation stage, which indicates maturation-dependent vulnerability of WM. Within different oligodendrocyte developmental stages, we show selective vulnerability of O4
+
preoligodendrocytes, whereas oligodendrocyte progenitor cells were resistant to insults. This indicates that immature WM is vulnerable to cardiopulmonary bypass–induced injury but has an intrinsic potential for recovery mediated by endogenous oligodendrocyte progenitor cells. Oligodendrocyte progenitor cell number decreased with age, which suggests that earlier repair allows successful WM development. Oligodendrocyte progenitor cell proliferation was observed within a few days after cardiopulmonary bypass–induced ischemia-reperfusion injury; however, by 4 weeks, arrested oligodendrocyte maturation and delayed myelination were detected. Logistic model confirmed that maintenance of higher oxygenation and reduction of inflammation were effective in minimizing the risk of injury at immature stages of WM development.

Conclusions—
Primary repair in neonates and young infants potentially provides successful WM development in congenital heart disease patients. Cardiac surgery during this susceptible period should avoid ischemia-reperfusion injury and minimize inflammation to prevent long-term WM-related neurological impairment.
Factors Associated With Prehospital Delays in the Presentation of Acute Stroke in Urban China
Authors: Jin Haiqiang , Zhu Sainan , Wei Jade W. , Wang Jiguang , Liu Ming , Wu Yangfeng , Wong Lawrence K.S. , Cheng Yan , Xu En , Yang Qidong , Anderson Craig S. , Huang Yining ,   for the ChinaQUEST (Quality Evaluation of Stroke Care and Treatment) Investigators
Published: January 2012

Background and Purpose—
Low rates of thrombolysis for ischemic stroke in China have mainly been attributed to delays in presentation to the hospital. This study aimed to evaluate factors associated with these delays.

Methods—
Data were from a prospective, multicenter, hospital-based registry of patients with acute stroke (ChinaQUEST [Quality Evaluation of Stroke Care and Treatment]), which involved 62 hospitals across a variety of economic and geographic regions in China during 2006. Univariate and multivariate analyses were undertaken to determine associations between variables of interest and delays to hospital presentation.

Results—

Median time to hospital presentation was 15.0 hours for 6102 cases (interquartile range, 2.8–51.0 hours). A total of 1546 (25%) patients arrived within 3 hours and 2244 (37%) patients arrived within 6 hours after symptom onset. Factors that prolonged time to presentation were: visiting a local doctor before presenting at emergency (OR, 0.48;
P
<0.001), symptom onset at home (OR, 0.62;
P
<0.001), transfer to a large (Level III) hospital for management (OR, 0.70;
P
=0.04), and history of diabetes (OR, 0.78;
P
=0.01). In contrast, factors that accelerated presentation to the hospital were hemorrhagic stroke (OR, 2.25;
P
<0.001), history of atrial fibrillation (OR, 1.94;
P
<0.001), unconsciousness at presentation (OR, 1.91;
P
<0.001), transfer by ambulance (OR, 1.91;
P
<0.001), and history of coronary artery disease (OR, 1.20;
P
=0.04).

Conclusions—
Health promotion strategies to improve community awareness of early symptoms of stroke, establishment of an alert system to cater for patients likely to experience stroke at home, and wider availability and use of ambulance services are promising methods to help expedite presentation to hospital poststroke and thereby improve the management of stroke in China.
Transition to Collateral Flow After Arterial Occlusion Predisposes to Cerebral Venous Steal
Authors: Pranevicius Osvaldas , Pranevicius Mindaugas , Pranevicius Henrikas , Liebeskind David S. 
Published: January 2012

Background and Purpose—
Stroke-related tissue pressure increase in the core and penumbra determines regional cerebral perfusion pressure (rCPP) defined as a difference between local inflow pressure and venous or tissue pressure, whichever is higher. We previously showed that venous pressure reduction below the pressure in the core causes blood flow diversion–cerebral venous steal. Now we investigated how transition to collateral circulation after complete arterial occlusion affects rCPP distribution.

Methods—
We modified parallel Starling resistor model to simulate transition to collateral inflow after complete main stem occlusion. We decreased venous pressure from the arterial pressure to zero and investigated how arterial and venous pressure elevation augments rCPP.

Results—
When core pressure exceeded venous, rCPP=inflow pressure in the core. Venous pressure decrease from arterial pressure to pressure in the core caused smaller inflow pressure to drop augmenting rCPP. Further drop of venous pressure decreased rCPP in the core but augmented rCPP in penumbra. After transition to collateral circulation, lowering venous pressure below pressure in the penumbra further decreased rCPP and collaterals themselves became a pathway for steal. Venous pressure level at which rCPP in the core becomes zero we termed the “point of no reflow.” Transition from direct to collateral circulation resulted in decreased inflow pressure, decreased rCPP, and a shift of point of no reflow to higher venous loading values. Arterial pressure augmentation increased rCPP, but only after venous pressure exceeded point of no reflow.

Conclusions—
In the presence of tissue pressure gradients, transition to collateral flow predisposes to venous steal (collateral failure), which may be reversed by venous pressure augmentation.
Geographical Indications, Biodiversity and Traditional Knowledge: Obligations and Opportunities for the Kingdom of Saudi Arabia
Authors: Williamson Myra E.J.B. 
Published: January 2012

Abstract
This article examines the Kingdom of Saudi Arabia’s legal obligations in one area of intellectual property law, namely, geographical indications (GI). It considers the opportunities for improving the existing legal framework from both a domestic and an international perspective. After an introduction, Section 2 presents a survey of the existing domestic and international laws pertaining to the protection of GIs. Section 3 outlines the relationship between GIs, biodiversity and traditional knowledge. Section 4 summarizes some of the latest developments and points of debate regarding increased protection of GIs. Finally, Section 5 puts forward several recommendations for improving the protection of GIs in the Kingdom of Saudi Arabia.
A Large-Eddy Simulation Study of Thermal Effects on Turbulent Flow and Dispersion in and above a Street Canyon
Authors: Park Seung-Bu , Baik Jong-Jin , Raasch Siegfried , Letzel Marcus Oliver 
Published: January 2012

AbstractThermal effects on turbulent flow and dispersion in and above an idealized street canyon with a street aspect ratio of 1 are numerically investigated using the parallelized large-eddy simulation model (“PALM”). Each of upwind building wall, street bottom, and downwind building wall is heated, and passive scalars are emitted from the street bottom. When compared with the neutral (no heating) case, the heating of the upwind building wall or street bottom strengthens a primary vortex in the street canyon and the heating of the downwind building wall induces a shrunken primary vortex and a winding flow between the vortex and the downwind building wall. Heating also induces higher turbulent kinetic energy and stronger turbulent fluxes at the rooftop height. In the neutral case, turbulent eddies generated by shear instability dominate mixing at the rooftop height and appear as band-shaped perturbations in the time–space plots of turbulent momentum and scalar fluxes. In all of the heating cases, buoyancy-generated turbulent eddies as well as shear-generated turbulent eddies contribute to turbulent momentum and scalar fluxes and band-shaped or lump-shaped perturbations appear at the rooftop height. A quadrant analysis shows that at the rooftop height, in the neutral case and in the case with upwind building-wall heating, sweep events are less frequent but contribute more to turbulent momentum flux than do ejection events. By contrast, in the case with street-bottom and downwind building-wall heating, the frequency of sweep events is similar to that of ejection events and the contribution of ejection events to turbulent momentum flux is comparable to that of sweep events.
Coordinated Abrupt Weakening of the Eurasian and North African Monsoons in the 1960s and Links to Extratropical North Atlantic Cooling
Authors: Liu Y. , Chiang J. C. H. 
Published: January 2012

Abstract
Previous modeling and paleoclimate studies have suggested that cooling originating from the extratropical North Atlantic can abruptly weaken the Eurasian and North African monsoons. The climatic signature includes a widespread cooling over the Eurasian and North African continents and an associated increase to surface pressure. It is explored whether such coordinated changes are similarly exhibited in the observed twentieth-century climate, in particular with the well-documented shift of Sahel rainfall during the 1960s. Surface temperature, sea level pressure, and precipitation changes are analyzed using combined principal component analysis (CPCA). The leading mode exhibits a monotonic shift in the 1960s, and the transition is associated with a relative cooling and pressure increase over the interior Eurasia and North Africa, and rainfall reduction over the Sahel, South Asia, and East Asia. The local circulation changes suggest that the rainfall shift results from the regional response of the summer monsoons to these continental-wide changes. A similar CPCA analysis of atmospheric general circulation model (AGCM) simulations forced by twentieth-century-observed forcings shows similar results, suggesting that origins of the climate shift reside in the sea surface temperature changes, specifically over the extratropical North Atlantic. Finally, an AGCM forced with extratropical North Atlantic cooling appears to simulate these climate impacts, at least qualitatively. The result herein shows that the observed climate signature of the 1960s abrupt shift in Eurasian and North African climate is consistent with the influence of the abrupt high-latitude North Atlantic cooling that occurred in the late 1960s. A definitive causal relationship remains to be shown, and mechanisms elucidated.
Skill, Correction, and Downscaling of GCM-Simulated Precipitation
Authors: Eden Jonathan M. , Widmann Martin , Grawe David , Rast Sebastian 
Published: January 2012

The ability of general circulation models (GCMs) to correctly simulate precipitation is usually assessed by comparing simulated mean precipitation with observed climatologies. However, to what extent the skill in simulating average precipitation indicates how well the models represent temporal changes is unclear. A direct assessment of the latter is hampered by the fact that freely evolving climate simulations for past periods are not set up to reproduce the specific evolution of internal atmospheric variability. Therefore, model-to-real-world comparisons of time series of daily, monthly, or annual precipitation are not meaningful. Here, for the first time, the authors quantify GCM skill in simulating precipitation variability using simulations in which the temporal evolution of the large-scale atmospheric state closely matches that of the real world. This is achieved by nudging the atmospheric states in the ECHAM5 GCM, but crucially not the precipitation field itself, toward the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40). Global correlation maps between observed and simulated seasonal precipitation allow areas in which simulated future precipitation changes are likely to be meaningful to be identified. In many areas, correlations higher than 0.8 are found.This means also that in these regions the simulated precipitation is a very good predictor for the true precipitation, and thus a statistical correction of the simulated precipitation, which can include a downscaling component, can provide useful estimates for local-scale precipitation. The authors show that a simple scaling of the simulated precipitation performs well in a cross validation and thus appears to be a promising alternative to standard statistical downscaling approaches.
Nonlinear Trends, Long-Range Dependence, and Climate Noise Properties of Surface Temperature
Authors: Franzke Christian 
Published: January 2012

Abstract
This study investigates the significance of trends of four temperature time series—Central England Temperature (CET), Stockholm, Faraday-Vernadsky, and Alert. First the robustness and accuracy of various trend detection methods are examined: ordinary least squares, robust and generalized linear model regression, Ensemble Empirical Mode Decomposition (EEMD), and wavelets. It is found in tests with surrogate data that these trend detection methods are robust for nonlinear trends, superposed autocorrelated fluctuations, and non-Gaussian fluctuations. An analysis of the four temperature time series reveals evidence of long-range dependence (LRD) and nonlinear warming trends. The significance of these trends is tested against climate noise. Three different methods are used to generate climate noise: (i) a short-range-dependent autoregressive process of first order [AR(1)], (ii) an LRD model, and (iii) phase scrambling. It is found that the ability to distinguish the observed warming trend from stochastic trends depends on the model representing the background climate variability. Strong evidence is found of a significant warming trend at Faraday-Vernadsky that cannot be explained by any of the three null models. The authors find moderate evidence of warming trends for the Stockholm and CET time series that are significant against AR(1) and phase scrambling but not the LRD model. This suggests that the degree of significance of climate trends depends on the null model used to represent intrinsic climate variability. This study highlights that in statistical trend tests, more than just one simple null model of intrinsic climate variability should be used. This allows one to better gauge the degree of confidence to have in the significance of trends.
Effect of Atmospheric Feedbacks on the Stability of the Atlantic Meridional Overturning Circulation
Authors: Toom Matthijs den , Dijkstra Henk A. , Cimatoribus Andrea A. , Drijfhout Sybren S. 
Published: January 2012

Abstract
The impact of atmospheric feedbacks on the multiple equilibria (ME) regime of the Atlantic meridional overturning circulation (MOC) is investigated using a fully implicit hybrid coupled model (HCM). The HCM consists of a global ocean model coupled to an empirical atmosphere model that is based on linear regressions of the heat, net evaporative, and momentum fluxes generated by a fully coupled climate model onto local as well as Northern Hemisphere averaged sea surface temperatures. Using numerical continuation techniques, bifurcation diagrams are constructed for the HCM with the strength of an anomalous freshwater flux as the bifurcation parameter, which allows for an efficient first-order estimation of the effect of interactive surface fluxes on the MOC stability. The different components of the atmospheric fluxes are first considered individually and then combined. Heat feedbacks act to destabilize the present-day state of the MOC and to stabilize the collapsed state, thus leaving the size of the ME regime almost unaffected. In contrast, interactive freshwater fluxes cause a destabilization of both the present-day and collapsed states of the MOC. Wind feedbacks are found to have a minor impact. The joint effect of the three interactive fluxes is to narrow the range of ME. The shift of the saddle-node bifurcation that terminates the present-day state of the ocean is further investigated by adjoint sensitivity analysis of the overturning rate to surface fluxes. It is found that heat feedbacks primarily affect the MOC stability when they change the heat fluxes over the North Atlantic subpolar gyre, whereas interactive freshwater fluxes have an effect everywhere in the Atlantic basin.
On Estimating Wet Canopy Evaporation from Deciduous and Coniferous Forests in the Asian Monsoon Climate
Authors: Kang Minseok , Kwon Hyojung , Cheon Jung Hwa , Kim Joon 
Published: January 2012

Abstract
Continuous and direct measurement of evapotranspiration (ET) by the eddy covariance (EC) technique is still a challenge under monsoon climate because of a considerable amount of missing data during the long rainy periods and the consequential gap-filling process. Under such wet canopy conditions, especially in forests, evaporation of the intercepted precipitation (EWC) contributes significantly to the total ET. To quantify the role of EWC, leaf wetness has been measured at multiple levels in the canopy simultaneously with eddy covariance measurements at the KoFlux Gwangneung deciduous and coniferous forests for the entire year from September 2007 to August 2008. In this study, the measured EWC and the controlling mechanism during the wet canopy conditions have been scrutinized. Based on the evaluation of the four different algorithms of EWC estimation, that of the variable infiltration capacity (VIC) land surface model (LSM) has been adopted. All the missing EWC data are then recalculated by using the algorithm of VIC LSM and compared against the traditionally gap-filled EWC data based on the modified lookup table (MLT) method. The latter consistently underestimated EWC on average by 39% in deciduous forest and by 28% in coniferous forest. Major causes of such differences were due to the failure of considering aerodynamic coupling, advection of sensible heat, and heat storage in the MLT-based gap-filling method. Accordingly, a new gap-filling strategy for EWC is proposed that takes proper controlling mechanisms into account.