bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulfiredoxin Promotes Colorectal Cancer Cell Invasion and Metastasis through a Novel Mechanism of Enhancing EGFR Signaling
Authors: Jiang Hong , Wu Lisha , Chen Jing , Mishra Murli , Chawsheen Hedy A. , Zhu Haining , Wei Qiou 
Published: August 2015

Abstract
Sulfiredoxin (SRXN1/Srx) is a multifunction enzyme with a primary antioxidant role of reducing the overoxidized inactive form of peroxiredoxins (Prxs). The function and mechanisms of Srx in cancer development are not well understood. Here, Srx is preferentially expressed in human colorectal cancer cells but not in normal colon epithelial cells. Loss-of-function studies demonstrate that knockdown of Srx in poorly differentiated colorectal cancer cells not only leads to the inhibition of colony formation and cell invasion in vitro, but also reduces tumor xenograft growth and represses metastasis to distal organs in a mouse orthotopic implantation model. Notably, exactly opposite effects were observed in gain-of-function experiments when Srx was ectopically expressed in well-differentiated colorectal cancer cells. Mechanistically, expression of Srx enhances the activation of MAPK signaling through increasing the C-terminal tyrosine phosphorylation levels of EGFR. This function of Srx is mediated through its inhibition of EGFR acetylation at K1037, a novel posttranslational modification of EGFR in human colorectal cancer cells identified by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI/MS-MS) proteomic analysis. Furthermore, abolishment of K1037 acetylation in human colorectal cancer cells by site-specific mutagenesis leads to sustained activation of EGFR–MAPK signaling. Combined, these data reveal that Srx promotes colorectal cancer cell invasion and metastasis through a novel mechanism of enhancing EGFR signaling.
Implications: Sulfiredoxin is a critical oncogenic protein that can be used as a molecular target to develop therapeutics for patients with metastatic colorectal cancer. Mol Cancer Res; 13(12); 1554–66. ©2015 AACR.
Chemopreventive Effects of Dietary Eicosapentaenoic Acid Supplementation in Experimental Myeloid Leukemia
Authors: Finch Emily R. , Kudva Avinash K. , Quickel Michael D. , Goodfield Laura L. , Kennett Mary J. , Whelan Jay , Paulson Robert F. , Prabhu K. Sandeep 
Published: August 2015

Abstract
Current therapies for treatment of myeloid leukemia do not eliminate leukemia stem cells (LSC), leading to disease relapse. In this study, we supplemented mice with eicosapentaenoic acid (EPA, C20:5), a polyunsaturated omega-3 fatty acid, at pharmacologic levels, to examine whether the endogenous metabolite, cyclopentenone prostaglandin delta-12 PGJ3 (Δ12-PGJ3), was effective in targeting LSCs in experimental leukemia. EPA supplementation for 8 weeks resulted in enhanced endogenous production of Δ12-PGJ3 that was blocked by indomethacin, a cyclooxygenase (COX) inhibitor. Using a murine model of chronic myelogenous leukemia (CML) induced by bone marrow transplantation of BCR-ABL–expressing hematopoietic stem cells, mice supplemented with EPA showed a decrease in the LSC population, and reduced splenomegaly and leukocytosis, when compared with mice on an oleic acid diet. Supplementation of CML mice carrying the T315I mutation (in BCR-ABL) with EPA resulted in a similar effect. Indomethacin blocked the EPA effect and increased the severity of BCR-ABL–induced CML and decreased apoptosis. Δ12-PGJ3 rescued indomethacin-treated BCR-ABL mice and decreased LSCs. Inhibition of hematopoietic-prostaglandin D synthase (H-PGDS) by HQL-79 in EPA-supplemented CML mice also blocked the effect of EPA. In addition, EPA supplementation was effective in a murine model of acute myeloid leukemia. EPA-supplemented mice exhibited a decrease in leukemia burden and a decrease in the LSC colony-forming unit (LSC-CFU). The decrease in LSCs was confirmed through serial transplantation assays in all disease models. The results support a chemopreventive role for EPA in myeloid leukemia, which is dependent on the ability to efficiently convert EPA to endogenous COX-derived prostanoids, including Δ12-PGJ3. Cancer Prev Res; 8(10); 989–99. ©2015 AACR.
Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome
Authors: Masrani Mehta Shriti , Depta Jeremiah P. , Novak Eric , Patel Jayendrakumar S. , Patel Yogesh , Raymer David , Facey Gabrielle , Zajarias Alan , Lasala John M. , Singh Jasvindar , Bach Richard G. , Kurz Howard I. 
Published: August 2015

Background

The safety of deferring revascularization based on fractional flow reserve (
FFR
) during acute coronary syndrome (
ACS
) is unclear. We evaluated the association of
FFR
and adverse cardiac events among patients with coronary lesions deferred revascularization based on
FFR
in the setting of
ACS
versus non‐
ACS
.

Methods and Results

The study population (674 patients; 816 lesions) was divided into
ACS
(n=334) and non‐
ACS
(n=340) groups based on the diagnosis when revascularization was deferred based on
FFR
values >0.80 between October 2002 and July 2010. The association and interaction between
FFR
and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow‐up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (
DLI
), whereas the composite of
DLI
or myocardial infarction (
MI
) attributed to a deferred lesion was designated as deferred lesion failure (
DLF
). In the non‐
ACS
group, lower
FFR
values were not associated with any increase in adverse cardiac events. In the
ACS
group, every 0.01 decrease in
FFR
was associated with a significantly higher rate of cardiovascular death,
MI
, or
DLI
(hazard ratio [
HR
], 1.08; 95% confidence interval [
CI
], 1.03 to 1.12),
MI
or
DLI
(
HR
, 1.09; 95%
CI
: 1.04 to 1.14),
DLF
(
HR
, 1.12; 95%
CI
, 1.06 to 1.18),
MI
(
HR
, 1.07; 95%
CI
, 1.00 to 1.14), and
DLI
(
HR
, 1.12; 95%
CI
, 1.06 to 1.18).

Conclusion

Lower
FFR
values among
ACS
patients with coronary lesions deferred revascularization based on
FFR
are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non‐
ACS
patients.
An EF3 Multivortex Tornado over the Ionian Region: Is It Time for a Dedicated Warning System over Italy?
Authors: Miglietta Mario Marcello , Rotunno Richard 
Published: August 2015

Abstract
The possibility offered by the Internet to share pictures of tornadoes, and the storm-report archiving in the European Storm Weather Database, have made it apparent that the occurrence of tornadoes over Europe has been underestimated. Together with weak waterspouts and tornadoes, large and intense vortices are occasionally observed. Among these, an EF3 multivortex tornado with a path width of some hundreds of meters affected southeastern Italy on 28 November 2012, causing one casualty and estimated damage of &#x80;60M to the largest steel plant in Europe. A tide gauge positioned near the location of tornado landfall and a vertical atmospheric profile available a few hours later near the affected region represent unique sources of information for these events in the Mediterranean. During its transit across the port of Taranto, a waterspout, which was to become the tornado, was observed to have induced a sea level rise of about 30 cm. The supercell responsible for the tornado developed from convective cells triggered by orographic uplift over the Apennines. The 0–1-km wind shear was exceptional in comparison with other Italian tornadoes, and was remarkable in comparison with U.S. events as well. Other indices for severe convection diagnosis also showed extremely high values. The occasional occurrence of events with similar or stronger intensities over Italy emphasizes the need for the Distributed National Weather Service—which will integrate Italian meteorological institutions under one agency and is currently under development—to devise a warning system dedicated to the monitoring and prediction of severe convective events.
Bayesian Exploration of Multivariate Orographic Precipitation Sensitivity for Moist Stable and Neutral Flows
Authors: Tushaus Samantha A. , Posselt Derek J. , Miglietta M. Marcello , Rotunno Richard , Delle Monache Luca 
Published: August 2015

Abstract
Recent idealized studies examined the sensitivity of topographically forced rain and snowfall to changes in mountain geometry and upwind sounding in moist stable and neutral environments. These studies were restricted by necessity to small ensembles of carefully chosen simulations. Research presented here extends earlier studies by utilizing a Bayesian Markov chain Monte Carlo (MCMC) algorithm to create a large ensemble of simulations, all of which produce precipitation concentrated on the upwind slope of an idealized Gaussian bell-shaped mountain. MCMC-based probabilistic analysis yields information about the combinations of sounding and mountain geometry favorable for upslope rain, as well as the sensitivity of orographic precipitation to changes in mountain geometry and upwind sounding. Exploration of the multivariate sensitivity of rainfall to changes in parameters also reveals a nonunique solution: multiple combinations of flow, topography, and environment produce similar surface rainfall amount and distribution. Finally, the results also divulge that the nonunique solutions have different sensitivity profiles, and that changes in observation uncertainty also alter model sensitivity to input parameters.
Precipitation Properties Observed during Tropical Cyclone Intensity Change
Authors: Alvey III George R. , Zawislak Jonathan , Zipser Edward 
Published: August 2015

Abstract
Using a 15-yr (1998–2012) multiplatform dataset of passive microwave satellite data [tropical cyclone–passive microwave (TC-PMW)] for Atlantic and east Pacific storms, this study examines the relative importance of various precipitation properties, specifically convective intensity, symmetry, and area, to the spectrum of intensity changes observed in tropical cyclones. Analyses are presented not only spatially in shear-relative quadrants around the center, but also every 6 h during a 42-h period encompassing 18 h prior to onset of intensification to 24 h after. Compared to those with slower intensification rates, storms with higher intensification rates (including rapid intensification) have more symmetric distributions of precipitation prior to onset of intensification, as well as a greater overall areal coverage of precipitation. The rate of symmetrization prior to, and during, intensification increases with increasing intensity change as rapidly intensifying storms are more symmetric than slowly intensifying storms. While results also clearly show important contributions from strong convection, it is concluded that intensification is more closely related to the evolution of the areal, radial, and symmetric distribution of precipitation that is not necessarily intense.
Resolution Dependence of Initiation and Upscale Growth of Deep Convection in Convection-Allowing Forecasts of the 31 May–1 June 2013 Supercell and MCS
Authors: Schumacher Russ S. 
Published: August 2015

Abstract
On 31 May 2013, a supercell thunderstorm initiated in west-central Oklahoma and produced a deadly tornado. This convection then grew upscale, with a nearly stationary line developing early on 1 June that produced very heavy rainfall and caused deadly flash flooding in the Oklahoma City area. Real-time convection-allowing (Δx = 4 km) model forecasts used during the Mesoscale Predictability Experiment (MPEX) provided accurate guidance regarding the timing, location, and evolution of convection in this case. However, attempts to simulate this event at higher resolution degraded the forecast, with the primary supercell failing to initiate and the evolution of the overnight MCS not resembling the observed system. Experiments to test the dependence of forecasts of this event on model resolution show that with grid spacing smaller than 4 km, mixing along the dryline in northwest Texas was more vigorous, causing low-level dry air to move more quickly eastward into Oklahoma. This drying prevented the supercell from initiating near the triple point in the higher-resolution simulations. Then, the lack of supercellular convection and its associated cold pool altered the evolution of subsequent convection. Whereas in observations and the 4-km forecast, a nearly stationary MCS developed parallel to, but displaced from, the supercell’s cold pool, the higher-resolution simulations instead had a faster-moving squall line that produced less rainfall. Although the degradation of convective forecasts at higher resolution is probably unusual and appears sensitive to the choice of boundary layer parameterization, these findings demonstrate that how numerical models treat boundary layer processes at different grid spacings can, in some cases, have profound influences on predictions of high-impact weather.
A Dynamical–Statistical Forecasting Model of the Western Pacific Subtropical High Area Index Based on an Improved Self-Memorization Principle
Authors: Hong Mei , Zhang Ren , Wang Dong , Wang Min , Liu Kefeng , Singh Vijay P. 
Published: August 2015

Abstract
A new dynamical–statistical forecasting model of the western Pacific subtropical high (WPSH) area index (AI) was developed, based on dynamical model reconstruction and improved self-memorization, in order to address the inaccuracy of long-term WPSH forecasts. To overcome the problem of single initial prediction values, the self-memorization function was introduced to improve the traditional reconstruction model, thereby making it more effective for describing chaotic systems, such as WPSH. Processing actual data, the reconstruction equation was used as a dynamical core to overcome the problem of employing a simple core. The resulting dynamical–statistical forecasting model for AI was used to predict the strength of long-term WPSH forecasting. Based on 17 experiments with the WPSH during normal and abnormal years, forecast results for a period of 25 days were found to be good, with a correlation coefficient of ~0.80 and a mean absolute percentage error of &lt;8%, showing that the improved model produced satisfactory long-term forecasting results. Additional experiments for predicting the ridgeline index (RI) and the west ridge-point index (WI) were also performed to demonstrate that the developed model was effective for the complete prediction of the WPSH. Compared with the authors’ previous models and other established models of reasonable complexity, the current model shows better long-term WPSH forecasting ability than do other models, meaning that the aberrations of the subtropical high could be defined and forecast by the model.
Alignment of site versus adjudication committee–based diagnosis with patient outcomes: Insights from the Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 trial
Authors: Sepehrvand Nariman , Zheng Yinggan , Armstrong Paul W , Welsh Robert , Goodman Shaun G , Tymchak Wayne , Khadour Fadi , Chan Michael , Weiss Dale , Ezekowitz Justin A 
Published: August 2015

Background: Adjudication by an adjudication committee in clinical trials plays an important role in the assessment of outcomes. Controversy exists regarding the utility of adjudication committee versus site-based assessments and their relationship to subsequent clinical events. Methods: This study is a secondary analysis of the Providing Rapid Out of Hospital Acute Cardiovascular Treatment-3 trial, which randomized patients with chest pain or shortness of breath for biomarker testing in the ambulance. The emergency department physician diagnosis at the time of emergency department disposition was compared with an adjudicated diagnosis assigned by an adjudication committee. The level of agreement between emergency department and adjudication committee diagnosis was evaluated using kappa coefficient and compared to clinical outcomes (30-day re-hospitalization, 30-day and 1-year mortality). Results: Of the 477 patients, 49.3% were male with a median age of 70 years; hospital admission rate was 31.2%. The emergency department physicians and the adjudication committee disagreed in 55 cases (11.5%) with a kappa of 0.71 (95% confidence interval: 0.64, 0.78). The 30-day re-hospitalization, 30-day mortality, and 1-year mortality were 22%, 1.9%, and 9.4%, respectively. Although there were similar rates of re-hospitalization irrespective of adjudication, in cases of disagreement compared to agreement between adjudication committee and emergency department diagnosis, there was a higher 30-day (7.3% vs 1.2%, p = 0.002) and 1-year mortality (27.3% vs 7.1%, p < 0.001). Conclusion: Despite substantial agreement between the diagnosis of emergency department physicians and adjudication committee, in the subgroup of patients where there was disagreement, there was significantly worse short-term and long-term mortality.
Does the direction of tumescent solution delivery matter in endovenous laser ablation of the great saphenous vein?
Authors: Kutas Baris , Ozdemir Ferit , Tezcan Orhan , Gunes Tevfik , Erkoc Kamuran , Altin Fırat , Karahan Oguz 
Published: August 2015

Background: The aim of this study was to compare the two different directions of tumescent solution delivery (from distal to proximal knee to the saphenofemoral junction [SFJ] or proximal to distal SFJ to the knee) in terms of differences in tumescent volume, number of punctures, and pain and comfort scores of patients. Methods: A total of 100 patients were treated with endovenous laser ablation (EVLA) under local anesthesia between August 2013 and October 2013. These 100 patients were divided into two groups. In group 1, tumescent solution was delivered in a proximal to distal direction. In group 2, the tumescent solution was delivered in a distal to proximal direction. In each group, the great saphenous vein (GSV) diameter, delivered total energy, treated GSV length, delivered tumescent volume, number of punctures, and pain and comfort scores were recorded for each patient. Results: All patients were treated unilaterally. EVLA was performed with 100% technical success in all patients. There was no difference statistically between group 1 and group 2 according to GSV diameter, delivered total energy, and treated GSV length. Average tumescent volume, number of punctures, and pain scores in group 2 were lower than in group 1 ( p = 0.0001; p < 0.05). Also, the average comfort score was higher in group 2 than in group 1 ( p = 0.0001; p < 0.05). Conclusions: We believe that delivering the tumescent solution in a distal to proximal direction increases the comfort of both patient and surgeon with lower tumescent volume during the EVLA of the GSV.
Global and regional orders in the 21st century in terms of multi-layered power transition theory: The cases of US–China and China–Japan relations
Authors: Lee Sang-Hwan 
Published: August 2015

In this article I analyze double-layered power struggles from a power transition perspective. This study compares the case of global power transition between the US and China linked to a case of regional power transition between China and Japan. US–China relations in the global order have been more cooperative than China–Japan relations in the regional order since the beginning of this century. The question is about how the two cases interact with respect to each other. The first scenario shows that stability in the global order deters instability in the regional order. The US–China partnership stabilizes China–Japan conflictual relations. In this situation the US, China and Japan maintain status quo policies and regional order is stabilized. The second scenario is one in which instability in the regional order overwhelms stability in the global order. In this situation China and Japan accelerate their hegemonic struggles in Northeast Asia, and the US serves to mediate between China and Japan. The US should be making a decision as to what kind of diplomatic stance it will take to minimize the tension between China and Japan. The US must also make its own world strategy. China is more likely to be a status quo power in the global order, but a challenger in breaking down the status quo in Northeast Asia. However, the US role is critical in making this power transition stable or unstable.
Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women
Authors: Moretti Diego , Goede Jeroen S. , Zeder Christophe , Jiskra Markus , Chatzinakou Vaiya , Tjalsma Harold , Melse-Boonstra Alida , Brittenham Gary , Swinkels Dorine W. , Zimmermann Michael B. 
Published: August 2015

Key Points
Iron supplements at doses of 60 mg Fe as FeSO4 or higher increase hepcidin for up to 24 hours and are associated with lower iron absorption on the following day. The soluble transferrin receptor/ferritin ratio and hepcidin are equivalent predictors of iron absorption from supplements.
What triggers colour change? Effects of background colour and temperature on the development of an alpine grasshopper
Authors: Valverde J. Pablo , Schielzeth Holger 
Published: August 2015

AbstractBackgroundColour polymorphisms are a fascinating facet of many natural populations of plants and animals, and the selective processes that maintain such variation are as relevant as the processes which promote their development. Orthoptera, the insect group that encompasses grasshoppers and bush crickets, includes a particularly large number of species that are colour polymorphic with a marked green-brown polymorphism being particularly widespread. Colour polymorphism has been associated with the need for crypsis and background matching and background-dependent homochromy has been described in a few species. However, when and how different environmental conditions influence variation in colour remains poorly understood. Here we test for effects of background colour and ambient temperature on the occurrence of colour morph switches (green to brown or brown to green) and developmental darkening in the alpine dwelling club-legged grasshopperGomphocerus sibiricus.ResultsWe monitored individually housed nymphae across three of their four developmental stages and into the first week after final ecdysis. Our data show an absence of colour morph switches inG. sibiricus, without a single switch observed in our sample. Furthermore, we test for an effect of temperature on colouration by manipulating radiant heat, a limiting factor in alpine habitats. Radiant heat had a significant effect on developmental darkening: individuals under low radiant heat tended to darken, while individuals under high radiant heat tended to lighten within nymphal stages. Young imagoes darkened under either condition.ConclusionsOur results indicate a plastic response to a variable temperature and indicate that melanin, a multipurpose pigment responsible for dark colouration and presumed to be costly, seems to be strategically allocated according to the current environmental conditions. Unlike other orthopterans, the species is apparently unable to switch colour morphs (green/brown) during development, suggesting that colour morphs are determined genetically (or very early during development) and that other processes have to contribute to crypsis and homochromy in this species.