bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Intrinsic Xase by Protein S
Authors: Chattopadhyay Rima , Sengupta Tanusree , Majumder Rinku 
Published: August 2012

Objective—
Protein S is a vitamin K–dependent plasma protein that functions in the feedback regulation of thrombin generation. Our goal was to determine how protein S regulates the intrinsic pathway of blood coagulation.

Methods and Results—

We used plasma, including platelet-rich plasma, and in vitro methods to determine how the intrinsic pathway of blood coagulation is regulated by protein S. We obtained the following results: (1) activated partial thromboplastin time assays with protein S–supplemented plasma confirmed that protein S prolongs clotting time; (2) a modified activated partial thromboplastin time assay with factor IX (fIX)–deficient plasma confirmed that protein S affects fIX-initiated clotting; (3) a fIXa/factor VIIIa (fVIIIa)–mediated thrombin generation assay with either platelet-rich plasma or factor-deficient plasma, initiated with a limiting amount of tissue factor, was regulated by protein S; (4) in the presence of phosphatidylserine vesicles, protein S inhibited fIXa in the absence and presence of fVIIIa; and (5) protein S altered only the
K
M
for factor X activation by fIXa in the absence of fVIIIa and both
k
cat
and
K
M
in the presence of fVIIIa.

Conclusion—
From our findings, it can be concluded that protein S inhibits fIXa in the presence or absence of fVIIIa in an activated protein C–independent way.
A Disintegrin and Metalloproteinase 15 Contributes to Atherosclerosis by Mediating Endothelial Barrier Dysfunction via Src Family Kinase Activity
Authors: Sun Chongxiu , Wu Mack H. , Lee Eugene S. , Yuan Sarah Y. 
Published: August 2012

Objective—
Endothelium dysfunction is an initiating factor in atherosclerosis. A disintegrin and metalloproteinase 15 (ADAM 15) is a multidomain metalloprotease recently identified as a regulator of endothelial permeability. However, whether and how ADAM15 contributes to atherosclerosis remains unknown.

Methods and Results—
Genetic ablation of ADAM15 in apolipoprotein E–deficient mice led to a significant reduction in aortic atherosclerotic lesion size (by 52%), plaque macrophage infiltration (by 69%), and smooth muscle cell deposition (by 82%). In vitro studies implicated endothelial-derived ADAM15 in barrier dysfunction and monocyte transmigration across mouse aortic and human umbilical vein endothelial cell monolayers. This role of ADAM15 depended on intact functioning of the cytoplasmic domain, as evidenced in experiments with site-directed mutagenesis targeting the metalloprotease active site (E349A), the disintegrin domain (Arginine-Glycine-Aspartic acid→Threonine-Aspartic acid-Aspartic acid), or the cytoplasmic tail. Further investigations revealed that ADAM15-induced barrier dysfunction was concomitant with dissociation of endothelial adherens junctions (vascular endothelial [VE]-cadherin/γ-catenin), an effect that was sensitive to Src family kinase inhibition. Through small interfering RNA-mediated knockdown of distinct Src family kinase members, c-Src and c-Yes were identified as important mediators of these junctional effects of ADAM15.

Conclusion—
These results suggest that endothelial cell-derived ADAM15, signaling through c-Src and c-Yes, contributes to atherosclerotic lesion development by disrupting adherens junction integrity and promoting monocyte transmigration.
Elevated CETP Activity Improves Plasma Cholesterol Efflux Capacity From Human Macrophages in Women
Authors: Villard Elise F. , El Khoury Petra , Duchene Emilie , Bonnefont-Rousselot Dominique , Clement Karine , Bruckert Eric , Bittar Randa , Le Goff Wilfried , Guerin Maryse 
Published: August 2012

Objective—
We aim to identify the impact of endogenous cholesteryl ester transfer protein (CETP) activity on plasma capacity to mediate free cholesterol efflux from human macrophages.

Methods and Results—

Endogenous plasma CETP activity was measured in a population of 348 women. We defined a low CETP group corresponding to subjects displaying an endogenous plasma CETP activity within the first tertile and a high CETP group corresponding to subjects with an endogenous plasma CETP activity within the third tertile. Subjects from the high CETP activity group displayed a significant increase in the capacity of their plasma (+8.2%;
P
=0.001) to mediate cholesterol efflux from human acute monocytic leukemia cell line human macrophages and from ATP-binding cassette transporter A1-dependent pathway (+23.4%;
P
=0.0001) as compared with those from the low CETP activity group. Multivariate analyses revealed that the impact of CETP activity was independent of plasma lipids levels. Pre–β1-high-density lipoprotein concentrations were significantly elevated (+29.6%;
P
=0.01) in the high CETP activity group as compared with the low CETP activity group. A positive correlation between pre–β1-high-density lipoprotein levels and plasma efflux efficiency from human acute monocytic leukemia cell line human macrophages was observed (
r
=0.29,
P
=0.02).

Conclusion—
CETP leading to the improvement of plasma efflux capacity, as a result of efficient pre–β-high-density lipoprotein formation and ATP-binding cassette transporter A1 efflux, should be preserved to prevent lipid accumulation in human macrophages.
Cystatin C Identifies Patients With Stable Chronic Heart Failure at Increased Risk for Adverse Cardiovascular Events
Authors: Dupont Matthias , Wu Yuping , Hazen Stanley L. , Tang W. H. Wilson 
Published: August 2012

Background—
Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect, and cystatin C (CysC) is promoted as a better marker of glomerular filtration rate. This study compares the prognostic use of CysC and derived glomerular filtration rate estimates with other measures of renal function in patients with chronic heart failure.

Methods and Results—

We measured serum CysC levels in 823 patients with heart failure undergoing coronary angiography with follow-up of major adverse cardiovascular events (death, myocardial infarction, stroke). CysC levels strongly correlated with creatinine (
r
=0.73), blood urea nitrogen (
r
=0.70), and estimated glomerular filtration rate by the 4-variable modification of diet in renal disease equation (
r
=−0.62) (all
P
<0.001). However, the correlation was lower in estimated glomerular filtration rate ≥60 mL/min per 1.73 m
2
. CysC-based measures significantly improved areas under the receiver operating characteristic curve for the prediction of major adverse cardiovascular events, especially in estimated glomerular filtration rate ≥60 mL/min per 1.73 m
2
(
P
<0.01). Net reclassification improvement was 22.2% (
P
<0.001) in this group. CysC remained an independent predictor of major adverse cardiovascular events (
P
<0.001) after adjustment for traditional risk factors and brain natriuretic peptide.

Conclusions—
CysC is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with preserved renal function.
Current Outcomes in US Children With Cardiomyopathy Listed for Heart Transplantation
Authors: Singh Tajinder P. , Almond Christopher S. , Piercey Gary , Gauvreau Kimberlee 
Published: August 2012

Background—
Previous studies have reported worse outcomes in children with nondilated cardiomyopathy (CMP) listed for heart transplant compared with children with dilated CMP. We sought to compare wait-list and posttransplant outcomes in these groups in the current era.

Methods and Results—

We analyzed all children <18 years of age with a diagnosis of CMP listed for heart transplant in the United States between July 2004 and December 2010. Multivariable risk factors for death on the wait-list (or becoming too sick to transplant) and posttransplant graft loss (median follow-up 2 years) were assessed using Cox models. Of the 1436 children analyzed, 1197 (83%) had dilated CMP and 239 (17%) had nondilated CMP (167 restrictive CMP, 72 hypertrophic CMP). In adjusted analysis, children with nondilated CMP were at higher risk of wait-list mortality only if they were on a ventilator support at listing (hazard ratio, 2.3; CI, 1.2–4.5). The risk was similar among children not on a ventilator support (hazard ratio, 0.6; CI, 0.3–1.1). Posttransplant 30-day and 1-year survival was 98% and 94%, respectively, in children with dilated CMP versus 95% and 89%, respectively, in children with nondilated CMP (
P
=0.17, log-rank test). In adjusted analysis, the risk of posttransplant graft loss was higher in nondilated CMP (hazard ratio, 1.8; CI, 1.2–2.7) versus dilated CMP.

Conclusions—
The increased risk of wait-list mortality in children with nondilated CMP is limited to those on ventilator support at listing. Although the risk of graft loss is modestly higher in children with nondilated forms of CMP, their short-term transplant outcomes are good.
Should We Emergently Revascularize Occluded Coronaries for Cardiac Arrest?
Authors: Kagawa Eisuke , Dote Keigo , Kato Masaya , Sasaki Shota , Nakano Yoshinori , Kajikawa Masato , Higashi Akifumi , Itakura Kiho , Sera Akihiko , Inoue Ichiro , Kawagoe Takuji , Ishihara Masaharu , Shimatani Yuji , Kurisu Satoshi 
Published: August 2012

Background—
Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation.

Methods and Results—

This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%;
P
=0.01), the intra-arrest PCI was higher (88% versus 70%;
P
=0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25–51] versus 54 minutes [34–74 minutes];
P
=0.002).

Conclusions—
Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed.
Another Look at the Refractive Index Structure Function
Authors: Cherubini T. , Businger S. 
Published: August 2012

AbstractThis paper discusses the derivation of the refractive index structure function. It shows that the traditional formulation, which is based on the hydrostatic assumption, leads to increasing errors with height when compared with a formulation that is based on the potential temperature. The paper corrects a long-standing problem of extrapolating the traditional boundary layer approximation beyond its region of validity (i.e., to the upper troposphere and lower stratosphere). The new derivation may have applications in observational work to measure and seeing and in numerical modeling efforts. A preliminary analysis of the influence of the new formulation in numerical modeling of seeing suggests that impact on seeing will be small in general, because the largest contribution to seeing generally comes from the lower troposphere. However, an accurate profile is needed because other astroclimatic parameters, such as the isoplanatic angle, can suffer from the lack of accuracy at high altitude. This work may also have application in radar meteorology, since clear-air radar sensitivity depends on accurate estimation of .
Measurements of Heavy Convective Rainfall in the Presence of Hail in Flood-Prone Areas Using an X-Band Polarimetric Radar
Authors: Matrosov Sergey Y. , Cifelli Robert , Gochis David 
Published: August 2012

AbstractThe utility of X-band polarimetric radar to provide rainfall estimations with high spatial and temporal resolution in heavy convective precipitation in the presence of hail is explored. A case study involving observations of strong convective cells with a transportable polarimetric X-band radar near Boulder, Colorado, is presented. These cells produced rain–hail mixtures with a significant liquid fraction, causing local flash floods and debris flow in an environmentally sensitive burn area that had been previously affected by wildfire. It is demonstrated that the specific differential phase shift (KDP)–based rainfall estimator provided liquid accumulations that were in relatively good agreement with a network of high-density rain gauges and experimental disdrometers. This estimator was also able to capture the significant variability of accumulated rainfall in a relatively small area of interest, and the corresponding results were not significantly affected by hail. Hail presence, however, was a likely reason for significant overestimation of rainfall retrievals for X-band radar approaches that are based on radar-reflectivity Ze measurements that have been corrected for attenuation in rain. Even greater overestimations were observed with the S-band radar of the weather-service network. In part because of larger range distances, these radar data could not correctly reproduce the spatial variability of rainfall in the burn area.
Global Distribution of Hot Towers in Tropical Cyclones Based on 11-Yr TRMM Data
Authors: Tao Cheng , Jiang Haiyan 
Published: August 2012

Abstract
Global distribution of hot towers in tropical cyclones (TCs) is statistically quantified using an 11-yr Tropical Rainfall Measuring Mission (TRMM) Tropical Cyclone Precipitation Feature (TCPF) database. From 6003 individual TRMM overpasses of 869 TCs, about 1.6% of TC convective systems are found to penetrate 14 km and about 0.1% of them even reach the 380-K potential temperature level. Among six TC-prone basins, the highest population of TC convective systems and those with hot towers are found over the northwest Pacific (NWP) basin. However, the greatest percentage of TCPFs that are hot towers [overshooting TCPFs (OTCPFs)] is found over the North Indian Ocean basin. Larger overshooting distance and ice mass are also found in this basin. The monthly variation of OTCPFs resembles that of TC activities in each basin. The percentage of OTCPFs is much higher in the inner core (IC) region (10%) than that in the inner rainband (IB; 2%) and outer rainband (OB; 1%) regions. OTCPFs in the IC region have much larger overshooting distance, area, volume, and ice mass than those in the IB and OB regions. The percentage of OTCPFs in the IC region increases as both TC intensity and intensification rate increase. About 17% of IC features in rapidly intensifying storms penetrate over 14 km, while the percentage is down to 11% for slowly intensifying, 9% for neutral, and 8% for weakening storms. A very good linear relationship is found between TC intensification rate and the percentage of TCPFs that are hot towers in the IC region.
Sending the Right Bill to the Right People: Climate Change, Environmental Degradation, and Social Vulnerabilities in Central Vietnam
Authors: Bruun Ole 
Published: August 2012

Abstract
In a range of international reports Vietnam is pointed out as among the 5 to 10 most climate-vulnerable countries, which are taking center stage in global climate change assistance and thus attracting huge amounts of foreign aid for research, mitigation, adaptation, disaster management, etc. However, for various reasons relating to global and domestic politics, climate change adaptation and mitigation in Vietnam are separating from general environmental management, while at the same time failing to address social inequality. From a global justice perspective this may seem irrelevant but when the resulting technocratic approaches are applied to aid programs, addressing climate change as an autonomous field, the problems on the ground become distorted. Based on field studies in central Vietnam, the paper argues that fragmented approaches risk missing the target of helping the most vulnerable population groups, while ignoring the structural and environmental issues, which in many cases constitute more immediate threats to their livelihoods.
A Revised Factor Structure for the Post-Concussion Symptom Scale
Authors: Kontos Anthony P. , Elbin R.J. , Schatz Phillip , Covassin Tracey , Henry Luke , Pardini Jamie , Collins Michael W. 
Published: August 2012

Background: Symptom reports play a critical role in the assessment and management of concussions. Symptoms are often conceptualized as factors comprising several related symptoms (eg, somatic factor = headache, nausea, vomiting). Previous research examining the factor structure of the 22-item Post-Concussion Symptom Scale (PCSS) has been limited to small samples and has not adequately evaluated factor loadings at both baseline and postconcussion for male and female athletes at the high school and collegiate levels. Purpose: To examine the factor structure of the 22-item PCSS in independent samples of high school and collegiate athletes reported at baseline and postconcussion, and to evaluate sex and age differences in the resulting baseline and postconcussion symptom factor scores. Study Design: Case series; Level of evidence, 4. Methods: Exploratory factor analytic (EFA) methods were applied to 2 separate samples of athletes who completed the PCSS at baseline (n = 30,455) and 1 to 7 days after a sport-related concussion (n = 1438). The baseline sample (mean ± standard deviation) was 15.74 ± 1.78 years, with a range of 13 to 22 years, and the postconcussion sample was 17.14 ± 2.25 years, with a range of 13 to 24 years. Results: A 4-factor solution accounting for 49.1% of the variance at baseline included a cognitive-sensory, sleep-arousal, vestibular-somatic, and affective factor structure. A 4-factor solution that included cognitive-fatigue-migraine, affective, somatic, and sleep was revealed for the postconcussion EFA. High school athletes reported higher baseline levels of the cognitive-sensory and vestibular-somatic symptom factors and lower levels of the sleep-arousal factor than college athletes. Female participants reported higher symptoms on all postconcussion factors than male participants. Conclusion: The current findings reveal different symptom factors at baseline and postinjury and several age and sex differences on the symptom factors. At postconcussion, symptoms aggregated into a global concussion factor including cognitive, fatigue, and migraine symptoms. Symptoms reported at baseline are not the same as those reported after injury. The presence of a global postconcussion symptom comprising the fatigue factor highlights the importance of physical and cognitive rest during the first week after a concussion. Although headache was the most commonly reported symptom, it was not the greatest contributor to the global postconcussion symptom factor.
Neurogenic Pulmonary Edema and Acute Respiratory Distress Syndrome in a Healthy Child With Febrile Status Epilepticus
Authors: Nguyen Thanh T. , Hussain Elora , Grimason Michele , Goldstein Joshua , Wainwright Mark S. 
Published: August 2012

Neurogenic pulmonary edema is a clinical syndrome that manifests as an acute onset of pulmonary edema in the setting of a central nervous system injury, without cardiac dysfunction. Neurogenic pulmonary edema is rare in children, and the mechanism is still not completely understood. The clinical pathology overlaps with acute lung injury and acute respiratory distress syndrome. The authors report a case of a 14-month-old previously healthy child who presented with febrile status epilepticus, fulminant neurogenic pulmonary edema, and acute respiratory distress syndrome. Neurogenic pulmonary edema should be considered in the differential diagnosis for the rapid progression of respiratory failure following an acute neurological injury such as status epilepticus in a child. Prompt respiratory support and treatment of the acute neurological insult can prevent further cerebral hypoxemic injury.
Tyrosine phosphorylation of DEP-1/CD148 as a mechanism controlling Src kinase activation, endothelial cell permeability, invasion, and capillary formation
Authors: Spring Kathleen , Chabot Catherine , Langlois Simon , Lapointe Line , Trinh Nguyen Thu Ngan , Caron Christine , Hebda Jagoda K. , Gavard Julie , Elchebly Mounib , Royal Isabelle 
Published: August 2012

AbstractDEP-1/CD148 is a receptor-like protein tyrosine phosphatase with antiproliferative and tumor-suppressive functions. Interestingly, it also positively regulates Src family kinases in hematopoietic and endothelial cells, where we showed it promotes VE-cadherin–associated Src activation and endothelial cell survival upon VEGF stimulation. However, the molecular mechanism involved and its biologic functions in endothelial cells remain ill-defined. We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1–catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin. Accordingly, RNA interference (RNAi)–mediated knockdown of DEP-1 or expression of DEP-1 Y1311F/Y1320F impairs Src-dependent biologic responses mediated by VEGF including permeability, invasion, and branching capillary formation. In addition, our work further reveals that above a threshold expression level, DEP-1 can also dephosphorylate Src Y418 and attenuate downstream signaling and biologic responses, consistent with the quiescent behavior of confluent endothelial cells that express the highest levels of endogenous DEP-1. Collectively, our findings identify the VEGF-dependent phosphorylation of DEP-1 as a novel mechanism controlling Src activation, and show this is essential for the proper regulation of permeability and the promotion of the angiogenic response.
The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis
Authors: Bierings Ruben , Hellen Nicola , Kiskin Nikolai , Knipe Laura , Fonseca Ana-Violeta , Patel Bijal , Meli Athina , Rose Marlene , Hannah Matthew J. , Carter Tom 
Published: August 2012

AbstractWeibel-Palade body (WPB) exocytosis underlies hormone-evoked VWF secretion from endothelial cells (ECs). We identify new endogenous components of the WPB: Rab3B, Rab3D, and the Rab27A/Rab3 effector Slp4-a (granuphilin), and determine their role in WPB exocytosis. We show that Rab3B, Rab3D, and Rab27A contribute to Slp4-a localization to WPBs. siRNA knockdown of Slp4-a, MyRIP, Rab3B, Rab3D, Rab27A, or Rab3B/Rab27A, or overexpression of EGFP-Slp4-a or EGFP-MyRIP showed that Slp4-a is a positive and MyRIP a negative regulator of WPB exocytosis and that Rab27A alone mediates these effects. We found that ECs maintain a constant amount of cellular Rab27A irrespective of the WPB pool size and that Rab27A (and Rab3s) cycle between WPBs and a cytosolic pool. The dynamic redistribution of Rab proteins markedly decreased the Rab27A concentration on individual WPBs with increasing WPB number per cell. Despite this, the probability of WPB release was independent of WPB pool size showing that WPB exocytosis is not determined simply by the absolute amount of Rab27A and its effectors on WPBs. Instead, we propose that the probability of release is determined by the fractional occupancy of WPB-Rab27A by Slp4-a and MyRIP, with the balance favoring exocytosis.