bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Significance of Osteoprotegerin Expression in Human Colorectal Cancer
Authors: Tsukamoto Shunsuke , Ishikawa Toshiaki , Iida Satoru , Ishiguro Megumi , Mogushi Kaoru , Mizushima Hiroshi , Uetake Hiroyuki , Tanaka Hiroshi , Sugihara Kenichi 
Published: January 2011

Abstract
Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).
Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. The mRNA expression of candidate genes was investigated by quantitative reverse transcriptase PCR (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 274 CRC patients.
Results: Using microarray analysis, we identified 6 candidate genes related to distant metastases in CRC patients. Among these genes, osteoprotegerin (OPG) is known to be associated with aggressiveness in several cancers through inhibition of apoptosis via neutralization of the function of TNF-related apoptosis-inducing ligand. The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastases than those without metastases. Overexpression of OPG protein was associated with significantly worse overall survival and relapse-free survival. Moreover, overexpression of the OPG protein was an independent risk factor for CRC recurrence.
Conclusion: Overexpression of OPG may be a predictive biomarker of CRC recurrence and a target for treatment of this disease. Clin Cancer Res; 17(8); 2444–50. ©2011 AACR.
The Atr Protein Kinase Controls UV-Dependent Upregulation of p16INK4A Through Inhibition of Skp2-Related Polyubiquitination/Degradation
Authors: Al-Khalaf Huda H. , Hendrayani Siti-Faujiah , Aboussekhra Abdelilah 
Published: January 2011

Abstract
The tumor suppressor p16INK4A, a phosphoprotein that exists in human cells under both phosphorylated and nonphosphorylated forms, plays crucial roles during the cellular response to UV light. However, it is still unclear how this protein is activated in response to this carcinogenic agent. We have shown here that UVC upregulates p16INK4A and the phosphorylated form of the protein at the 4 serine sites; Ser-7, Ser-8, Ser-140, and Ser-152. This accumulation of p16INK4A occurred through increasing the stability of both forms of the protein. Importantly, phospho-p16INK4A showed much higher stability, and UV treatment strongly increased its level in absence of de novo protein synthesis. Furthermore, we have shown that the UV-dependent upregulation of both forms of p16INK4A is under the control of the protein kinase Atr, which suppresses their UVC-dependent proteasomal degradation. Interestingly, although this degradation is ubiquitin-related for p16INK4A through the Skp2 ubiquitin ligase protein, it is ubiquitin-independent for the phosphorylated form. In addition, we present clear evidence that Skp2 is upregulated in ATR-deficient cells, leading to the downregulation of the p27Kip1 protein in response to UVC light. Moreover, we have shown a preferential association of endogeneous phospho-p16INK4A with Cdk4. This association increased following UV-treatment mainly for p16INK4A phosphorylated at Ser-140 and Ser-152. Besides, we have shown that Atr regulates UV-related p16/Cdk4-dependent and -independent phosphorylation of pRB and G1 cell cycle delay. Together, these results indicate that p16INK4A and p27Kip1 are key targets in the Atr-dependent signaling pathway in response to UV damage. Mol Cancer Res; 9(3); 311–9. ©2011 AACR.
Long-Term Outcomes of Combined Epicardial and Endocardial Ablation of Monomorphic Ventricular Tachycardia Related to Hypertrophic Cardiomyopathy
Authors: Dukkipati Srinivas R. , d'Avila Andre , Soejima Kyoko , Bala Rupa , Inada Keiichi , Singh Sheldon , Stevenson William G. , Marchlinski Francis E. , Reddy Vivek Y. 
Published: January 2011

Background—
Monomorphic ventricular tachycardia (MMVT) is rare in patients with hypertrophic cardiomyopathy (HCM). There are limited data on the utility of catheter ablation for the treatment of MMVT in this population. This study details a series of case reports from multiple centers where combined epicardial-endocardial ablation was performed in a highly selected group of patients with HCM-related MMVT.

Methods and Results—
The cohort consisted of 10 patients with HCM-related MMVT. Pericardial access was achieved using the percutaneous subxyphoid approach. Epicardial and endocardial ventricular 3D bipolar voltage maps were generated. Ablation sites were identified using a combination of entrainment, activation, late/fractionated potential, and pace mapping. Electrophysiological-identified epicardial scar was present in 8 (80%) patients, endocardial scar in 6 (60%), and no scar in 1 (10%). In the 5 patients with inducible, stable MMVT, 3 cases were successfully terminated with ablation from the epicardium and 1 from the endocardium. The case that failed catheter ablation required surgical cryoablation to abolish the incessant VT. In the remaining 5 patients, 4 underwent epicardial and endocardial ablation of sites with good pace maps and late/fractionated potentials. No ablation was performed in the remaining patient because of noninducibility and lack of identifiable scar. After 37±17 months (limits, 2 to 62 months; median, 37 months), the freedom from recurrent implantable cardioverter-defibrillator shocks was 78% (7/9 patients) in those who underwent ablation.

Conclusions—
In highly selected patients with HCM, combined epicardial and endocardial mapping and ablation is a feasible and reasonably efficacious option for MMVT if refractory to aggressive trials of antiarrhythmic drugs and antitachycardia pacing.
Inhibition of Cardiac Ca
2+
Release Channels (RyR2) Determines Efficacy of Class I Antiarrhythmic Drugs in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Hwang Hyun Seok , Hasdemir Can , Laver Derek , Mehra Divya , Turhan Kutsal , Faggioni Michela , Yin Huiyong , Knollmann Björn C. 
Published: January 2011

Background—
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) and can be difficult to treat. The class Ic antiarrhythmic drug flecainide blocks RyR2 channels and prevents CPVT in mice and humans. It is not known whether other class I antiarrhythmic drugs also block RyR2 channels and to what extent RyR2 channel inhibition contributes to antiarrhythmic efficacy in CPVT.

Methods and Results—

We first measured the effect of all class I antiarrhythmic drugs marketed in the United States (quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, and propafenone) on single RyR2 channels incorporated into lipid bilayers. Only flecainide and propafenone inhibited RyR2 channels, with the S-enantiomer of propafenone having a significantly lower potency than R-propafenone or flecainide. In Casq2
−/−
myocytes, the propafenone enantiomers and flecainide significantly reduced arrhythmogenic Ca
2+
waves at clinically relevant concentrations, whereas Na
+
channel inhibitors without RyR2 blocking properties did not. In Casq2
−/−
mice, 5 mg/kg R-propafenone or 20 mg/kg S-propafenone prevented exercise-induced CPVT, whereas procainamide (20 mg/kg) or lidocaine (20 mg/kg) were ineffective (n=5 to 9 mice,
P
<0.05). QRS duration was not significantly different, indicating a similar degree of Na
+
channel inhibition. Clinically, propafenone (900 mg/d) prevented ICD shocks in a 22-year-old CPVT patient who had been refractory to maximal standard drug therapy and bilateral stellate ganglionectomy.

Conclusions—

RyR2 cardiac Ca
2+
release channel inhibition appears to determine efficacy of class I drugs for the prevention of CPVT in Casq2
−/−
mice. Propafenone may be an alternative to flecainide for CPVT patients symptomatic on β-blockers.
Percutaneous Transhepatic Venous Access for Catheter Ablation Procedures in Patients With Interruption of the Inferior Vena Cava
Authors: Singh Sheldon M. , Neuzil Petr , Skoka Jan , Kriz Radko , Popelova Jana , Love Barry A. , Mittnacht Alexander J.C. , Reddy Vivek Y. 
Published: January 2011

Background—
Catheter ablation of left-sided atrial arrhythmias generally is performed using a transfemoral venous approach through the inferior vena cava (IVC). In this report, we assessed the feasibility of a percutaneous transhepatic approach to ablation of left-sided atrial arrhythmias in 2 patients with interruption of the IVC.

Methods and Results—
Patient 1 had atrial flutter in the setting of complex congenital heart disease and prior Fontan for univentricular physiology and a single atrium. Patient 2 had atrial fibrillation. Percutaneous hepatic vein access was obtained with ultrasound and fluoroscopic guidance. Transseptal catheterization was performed in patient 2. After the procedure, the hepatic tract in patient 1 was cauterized using a bipolar radiofrequency catheter, and an Amplatzer vascular plug was used in patient 2 to obtain hemostasis. Percutaneous hepatic vein access was achieved without complications. After electroanatomical mapping, a linear lesion was placed between the single atrioventricular valve and the confluence of the hepatic veins in patient 1; this terminated the flutter, and bidirectional block was achieved. In patient 2, the pulmonary veins were electrically isolated using an extraostial approach, isolating the ipsilateral veins in pairs. Additionally, ablation of right-side atrial flutter was achieved by obtaining bidirectional block across a linear lesion between the tricuspid valve and confluence of the hepatic veins. Hemostasis of the transhepatic tract was attained in both patients.

Conclusions—
In patients with interrupted IVCs, a percutaneous transhepatic approach is a feasible alternative for performing catheter ablation of complex left-sided arrhythmias.
A New Parametric Model of Vortex Tangential-Wind Profiles: Development, Testing, and Verification
Authors: Wood Vincent T. , White Luther W. 
Published: January 2011

Abstract
A new parametric model of vortex tangential-wind profiles is presented that is primarily designed to depict realistic-looking tangential wind profiles such as those in intense atmospheric vortices arising in dust devils, waterspouts, tornadoes, mesocyclones, and tropical cyclones. The profile employs five key parameters: maximum tangential wind, radius of maximum tangential wind, and three power-law exponents that shape different portions of the velocity profile. In particular, a new parameter is included controlling the broadly or sharply peaked profile in the annular zone of tangential velocity maximum. Different combinations of varying the model parameters are considered to investigate and understand their effects on the physical behaviors of tangential wind and corresponding vertical vorticity profiles. Additionally, the parametric tangential velocity and vorticity profiles are favorably compared to those of an idealized Rankine model and also those of a theoretical stagnant core vortex model in which no tangential velocity exists within a core boundary and a potential flow occurs outside the core. Furthermore, the parametric profiles are evaluated against and compared to those of two other idealized vortex models (Burgers–Rott and Sullivan). The comparative profiles indicate very good agreements with low root-mean-square errors of a few tenths of a meter per second and high correlation coefficients of nearly one. Thus, the veracity of the parametric model is demonstrated.
On the Structure and Teleconnections of North Atlantic Decadal Variability
Authors: Álvarez-García Francisco J. , OrtizBevia María J. , CabosNarvaez William D. 
Published: January 2011

Abstract
Decadal variability in the North Atlantic has been associated in the literature with a tripolar pattern of sea surface temperature (SST) anomalies that show one sign in the western midlatitudinal North Atlantic and the opposite in the subpolar and tropical North Atlantic. The present analysis of observed SST from 1870 to 2009 leads to the dissection of the SST tripole into two components, each with a different time scale in the decadal band and different teleconnections in the Atlantic basin; while the subpolar and tropical poles present quasi-decadal variations with a period of about 9 years, essentially uncorrelated with other parts of the basin, the center of action in the western midlatitudes is characterized by a longer time scale of about 14 years and significant correlations with the tropical South Atlantic and the Norwegian and North Sea(s). The 9-yr period variations are associated with an atmospheric configuration resembling the east Atlantic pattern, whereas the 14-yr period fluctuations seem to be related to the North Atlantic Oscillation pattern. Each component also bears a different relationship with the decadal variability in the Pacific Ocean.
Trends in the Frequency of Intense Precipitation Events in Southern and Southeastern Brazil during 1960–2004
Authors: Teixeira Mateus da Silva , Satyamurty Prakki 
Published: January 2011

Abstract
A new approach to define heavy and extreme rainfall events based on cluster analysis and area-average rainfall series is presented. The annual frequency of the heavy and extreme rainfall events is obtained for the southeastern and southern Brazil regions. In the 1960–2004 period, 510 (98) and 466 (77) heavy (extreme) rainfall events are identified in the two regions. Monthly distributions of the events closely follow the monthly climatological rainfall in the two regions. In both regions, annual heavy and extreme rainfall event frequencies present increasing trends in the 45-yr period. However, only in southern Brazil is the trend statistically significant. Although longer time series are necessary to ensure the existence of long-term trends, the positive trends are somewhat alarming since they indicate that climate changes, in terms of rainfall regimes, are possibly under way in Brazil.
Coupled Aerosol-Chemistry–Climate Twentieth-Century Transient Model Investigation: Trends in Short-Lived Species and Climate Responses
Authors: Koch Dorothy , Bauer Susanne E. , Del Genio Anthony , Faluvegi Greg , McConnell Joseph R. , Menon Surabi , Miller Ronald L. , Rind David , Ruedy Reto , Schmidt Gavin A. , Shindell Drew 
Published: January 2011

Abstract
The authors simulate transient twentieth-century climate in the Goddard Institute for Space Studies (GISS) GCM, with aerosol and ozone chemistry fully coupled to one another and to climate including a full dynamic ocean. Aerosols include sulfate, black carbon (BC), organic carbon, nitrate, sea salt, and dust. Direct and BC-snow-albedo radiative effects are included. Model BC and sulfur trends agree fairly well with records from Greenland and European ice cores and with sulfur deposition in North America; however, the model underestimates the sulfur decline at the end of the century in Greenland. Global BC effects peak early in the century (1940s); afterward the BC effects decrease at high latitudes of the Northern Hemisphere but continue to increase at lower latitudes. The largest increase in aerosol optical depth occurs in the middle of the century (1940s–80s) when sulfate forcing peaks and causes global dimming. After this, aerosols decrease in eastern North America and northern Eurasia leading to regional positive forcing changes and brightening. These surface forcing changes have the correct trend but are too weak. Over the century, the net aerosol direct effect is −0.41 W m−2, the BC-albedo effect is −0.02 W m−2, and the net ozone forcing is +0.24 W m−2. The model polar stratospheric ozone depletion develops, beginning in the 1970s. Concurrently, the sea salt load and negative radiative flux increase over the oceans around Antarctica. Net warming over the century is modeled fairly well; however, the model fails to capture the dynamics of the observed midcentury cooling followed by the late century warming. Over the century, 20% of Arctic warming and snow–ice cover loss is attributed to the BC-albedo effect. However, the decrease in this effect at the end of the century contributes to Arctic cooling.
To test the climate responses to sulfate and BC pollution, two experiments were branched from 1970 that removed all pollution sulfate or BC. Averaged over 1970–2000, the respective radiative forcings relative to the full experiment were +0.3 and −0.3 W m−2; the average surface air temperature changes were +0.2° and −0.03°C. The small impact of BC reduction on surface temperature resulted from reduced stability and loss of low-level clouds.
Assessing Simulated Clouds and Radiative Fluxes Using Properties of Clouds Whose Tops are Exposed to Space
Authors: Cole Jason , Barker Howard W. , Loeb Norman G. , von Salzen Knut 
Published: January 2011

Abstract
Coincident top-of-atmosphere (TOA) radiative fluxes and cloud optical properties for portions of clouds whose tops are exposed to space within several pressure ranges are used to evaluate how a GCM realizes its all-sky radiative fluxes and vertical structure. In particular, observations of cloud properties and radiative fluxes from the Clouds and the Earth’s Radiant Energy System (CERES) Science Team are used to assess the Canadian Centre for Climate Modeling and Analysis atmospheric global climate model (CanAM4). Through comparison of CanAM4 with CERES observations it was found that, while the July-mean all-sky TOA shortwave and longwave fluxes simulated by CanAM4 agree well with those observed, this agreement rests on compensating biases in simulated cloud properties and radiative fluxes for low, middle, and high clouds. Namely, low and middle cloud albedos simulated by CanAM4 are larger than those observed by CERES attributable to CanAM4 simulating cloud optical depths via large liquid water paths that are too large but are partly compensated by too small cloud fractions. It was also found that CanAM4 produces 2D histograms of cloud fraction and cloud albedo for low, middle, and high clouds that are significantly different than generated using the CERES observations.
Impact of Spring Soil Moisture on Surface Energy Balance and Summer Monsoon Circulation over East Asia and Precipitation in East China
Authors: Zhang Renhe , Zuo Zhiyan 
Published: January 2011

Abstract
Numerous studies have been conducted on the impact of soil moisture on the climate, but few studies have attempted to diagnose the linkage between soil moisture and climate variability using observational data. Here, using both observed and reanalysis data, the spring (April–May) soil moisture is found to have a significant impact on the summer (June–August) monsoon circulation over East Asia and precipitation in east China by changing surface thermal conditions. In particular, the spring soil moisture over a vast region from the lower and middle reaches of the Yangtze River valley to north China (the YRNC region) is significantly correlated to the summer precipitation in east China. When the YRNC region has a wetter soil in spring, northeast China and the lower and middle reaches of the Yangtze River valley would have abnormally higher precipitation in summer, while the region south of the Yangtze River valley would have abnormally lower precipitation. An analysis of the physical processes linking the spring soil moisture to the summer precipitation indicates that the soil moisture anomaly across the YRNC region has a major impact on the surface energy balance. Abnormally wet soil would increase surface evaporation and hence decrease surface air temperature (Ta). The reduced Ta in late spring would narrow the land–sea temperature difference, resulting in the weakened East Asian monsoon in an abnormally strengthened western Pacific subtropical high that is also located farther south than its normal position. This would then enhance precipitation in the Yangtze River valley. Conversely, the abnormally weakened East Asian summer monsoon allows the western Pacific subtropical high to wander to south of the Yangtze River Valley, resulting in an abnormally reduced precipitation in the southern part of the country in east China.
Satellite and Numerical Model Investigation of Two Heavy Rain Events over the Central Mediterranean
Authors: Laviola Sante , Moscatello Agata , Miglietta Mario Marcello , Cattani Elsa , Levizzani Vincenzo 
Published: January 2011

Abstract
Two heavy rain events over the Central Mediterranean basin, which are markedly different by genesis, dimensions, duration, and intensity, are analyzed. Given the relative low frequency of this type of severe storms in the area, a synoptic analysis describing their development is included. A multispectral analysis based on geostationary multifrequency satellite images is applied to identify cloud type, hydrometeor phase, and cloud vertical extension. Precipitation intensity is retrieved from (i) surface rain gauges, (ii) satellite data, and (iii) numerical model simulations. The satellite precipitation retrieval algorithm 183-Water vapor Strong Lines (183-WSL) is used to retrieve rain rates and cloud hydrometeor type, classify stratiform and convective rainfall, and identify liquid water clouds and snow cover from the Advanced Microwave Sounding Unit-B (AMSU-B) sensor data. Rainfall intensity is also simulated with the Weather Research and Forecasting (WRF) numerical model over two nested domains with horizontal resolutions of 16 km (comparable to that of the satellite sensor AMSU-B) and 4 km. The statistical analysis of the comparison between satellite retrievals and model simulations demonstrates the skills of both methods for the identification of the main characteristics of the cloud systems with a suggested overall bias of the model toward very low rain intensities. WRF (in the version used for the experiment) seems to classify as low rain intensity regions those areas where the 183-WSL retrieves no precipitation while sensing a mixture of freshly nucleated cloud droplets and a large amount of water vapor; in these areas, especially adjacent to the rain clouds, large amounts of cloud liquid water are detected. The satellite method performs reasonably well in reproducing the wide range of gauge-detected precipitation intensities. A comparison of the 183-WSL retrievals with gauge measurements demonstrates the skills of the algorithm in discriminating between convective and stratiform precipitation using the scattering and absorption of radiation by the hydrometeors.