bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rauisuchia
Authors: Nesbitt Sterling J. , Brusatte Stephen L. , Desojo Julia B. , Liparini Alexandre , De França Marco A. G. , Weinbaum Jonathan C. , Gower David J. 
Published: January 2013

Abstract
‘Rauisuchia’ comprises Triassic pseudosuchians that ranged greatly in body size, locomotor styles and feeding ecologies. Our concept of what constitutes a rauisuchian is changing as a result of discoveries over the last 15 years. New evidence has shown that rauisuchians are probably not a natural (monophyletic) group, but instead are a number of smaller clades (e.g. Rauisuchidae, Ctenosauriscidae, Shuvosauridae) that may not be each other's closest relatives within Pseudosuchia. Here, we acknowledge that there are still large gaps in the basic understanding in the alpha-level taxonomy and relationships of these groups, but good progress is being made. As a result of renewed interest in rauisuchians, an expanding number of recent studies have focused on the growth, locomotor habits, and biomechanics of these animals, and we review these studies here. We are clearly in the midst of a renaissance in our understanding of rauisuchian evolution and the continuation of detailed descriptions, the development of explicit phylogenetic hypotheses, and explicit palaeobiological studies are essential in advancing our knowledge of these extinct animals.
The Insulin Receptor Negatively Regulates the Action of Pseudomonas Toxin-Based Immunotoxins and Native Pseudomonas Toxin
Authors: Liu Xiu Fen , FitzGerald David J. , Pastan Ira 
Published: January 2013

Abstract
SS1P is a recombinant immunotoxin composed of an antimesothelin Fv fragment fused to a truncated portion of Pseudomonas exotoxin A. SS1P targets and kills mesothelin-expressing tumors, which include mesothlioma as well as ovarian, lung, and pancreatic cancers. SS1P is currently in clinical trials in mesothelioma. Because insulin acting through the insulin receptor is a survival factor for many cancer cell lines, we explored how lowering insulin receptor level would affect the cytotoxic action of SS1P. We show here that siRNA knockdown of the insulin receptor enhanced the cytotoxic action of native Pseudomonas exotoxin and enhanced SS1P toxicity on several human cell lines, but did not affect the response to other cytotoxic agents such as TRAIL, etoposide, and cycloheximide. To determine how insulin receptor knockdown enhances SS1P action, we analyzed various steps involved in cell killing. We found that insulin receptor knockdown increases the cleavage of SS1P by furin, which allows more toxin to reach the cytosol and inactivate elongation factor 2. These findings indicate that the insulin receptor negatively regulates immunotoxin action. Cancer Res; 73(7); 2281–8. ©2013 AACR.
Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6
Authors: Van Tubergen Elizabeth A. , Banerjee Rajat , Liu Min , Broek Robert Vander , Light Emily , Kuo Shiuhyang , Feinberg Stephen E. , Willis Amanda L. , Wolf Gregory , Carey Thomas , Bradford Carol , Prince Mark , Worden Francis P. , Kirkwood Keith L. , D'Silva Nisha J. 
Published: January 2013

Abstract
Purpose: Invasion is the critical step in progression of a precancerous lesion to squamous cell carcinoma of the head and neck (HNSCC). Invasion is regulated by multiple proinflammatory mediators. Tristetraprolin (TTP) is an mRNA-degrading protein that regulates multiple proinflammatory mediators. TTP may serve as an excellent treatment target. Rap1 is a ras-like oncoprotein that induces critical signaling pathways. In this study, the role of rap1 in TTP-mediated invasion was investigated.
Experimental Design: Using complementary approaches, we modulated TTP and altered expression of interleukin (IL)-6 and matrix metalloproteinase (MMP) 2/9, which were quantified by ELISA and zymogram. Invasion was evaluated in vitro using the oral-cancer-equivalent (OCE) three-dimensional model and in vivo in the chick chorioallantoic membrane (CAM). The role of rap1 and p38 were established using knockdown strategies.
Results: Downregulation of TTP significantly increased invasion via secretion of MMP9/2 and IL-6. In the novel OCE and CAM invasion models of HNSCC, cells with downregulated TTP destroyed the basement membrane to invade the underlying connective tissue. Rap1 induces p38 mitogen-activated protein kinase (p38)-mediated inactivation of TTP. Inactive TTP enhances transcript stability via binding to the 3′-untranslated region (UTR). High IL-6 and MMP9 are prognostic for poor clinical outcomes in patients with HNSCC.
Conclusions: Targeting the rap1-p38-TTP cascade is an attractive novel treatment strategy in HNSCC to concurrently suppress multiple mediators of invasion. Clin Cancer Res; 19(5); 1169–79. ©2012 AACR.
Molecular Photoacoustic Imaging of Follicular Thyroid Carcinoma
Authors: Levi Jelena , Kothapalli Sri-Rajashekar , Bohndiek Sarah , Yoon Joon-Kee , Dragulescu-Andrasi Anca , Nielsen Carsten , Tisma Aleksandra , Bodapati Sunil , Gowrishankar Gayatri , Yan Xinrui , Chan Carmel , Starcevic Daniela , Gambhir Sanjiv Sam 
Published: January 2013

Abstract
Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma.
Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method.
Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent.
Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas. Clin Cancer Res; 19(6); 1494–502. ©2013 AACR.
Dual-Energy Computed Tomography Imaging of Atherosclerotic Plaques in a Mouse Model Using a Liposomal-Iodine Nanoparticle Contrast Agent
Authors: Bhavane Rohan , Badea Cristian , Ghaghada Ketan B. , Clark Darin , Vela Deborah , Moturu Anoosha , Annapragada Akshaya , Johnson G. Allan , Willerson James T. , Annapragada Ananth 
Published: January 2013

Background—
The accumulation of macrophages in inflamed atherosclerotic plaques has long been recognized. In an attempt to develop an imaging agent for detection of vulnerable plaques, we evaluated the feasibility of a liposomal-iodine nanoparticle contrast agent for computed tomography imaging of macrophage-rich atherosclerotic plaques in a mouse model.

Methods and Results—

Liposomal-iodine formulations varying in particle size and polyethylene glycol coating were fabricated and shown to stably encapsulate the iodine compound. In vitro uptake studies using optical and computed tomography imaging in the RAW 264.7 macrophage cell line identified the formulation that promoted maximal uptake. Dual-energy computed tomography imaging using this formulation in apolipoprotein E–deficient (ApoE
−/−
) mice (n=8) and control C57BL/6 mice (n=6) followed by spectral decomposition of the dual-energy images enabled imaging of the liposomes localized in the plaque. Imaging cytometry confirmed the presence of liposomes in the plaque and their colocalization with a small fraction (≈2%) of the macrophages in the plaque.

Conclusions—
The results demonstrate the feasibility of imaging macrophage-rich atherosclerotic plaques using a liposomal-iodine nanoparticle contrast agent and dual-energy computed tomography.
Mitigation of Murine Focal Cerebral Ischemia by the Hypocretin/Orexin System is Associated With Reduced Inflammation
Authors: Xiong Xiaoxing , White Robin E. , Xu Lijun , Yang Liya , Sun Xiaoyun , Zou Bende , Pascual Conrado , Sakurai Takeshi , Giffard Rona G. , Xie Xinmin (Simon) 
Published: January 2013

Background and Purpose—
Brain ischemia causes immediate and delayed cell death that is exacerbated by inflammation. Recent studies show that hypocretin-1/orexin-A (Hcrt-1) reduces ischemic brain injury, and Hcrt-positive neurons modulate infection-induced inflammation. Here, we tested the hypothesis that Hcrt plays a protective role against ischemia by modulating inflammation.

Methods—
Orexin/ataxin-3 (AT) mice, a transgenic strain in which Hcrt-producing neurons degenerate in early adulthood, and wild-type mice were subjected to transient middle cerebral artery occlusion (MCAO). Infarct volume, neurological score, and spontaneous home cage activity were assessed. Inflammation was measured using immunohistochemistry, ELISA, and assessment of cytokine mRNA levels.

Results—
Infarct volumes 24 and 48 hours after MCAO were significantly larger, neurological score was worse, and spontaneous activity decreased in AT compared with wild-type mice. Macrophage/microglial infiltration and myeloperoxidase-positive cells were higher in AT compared with wild-type mice. Pre-MCAO intracerebroventricular injection of Hcrt-1 significantly reduced infarct volume and macrophage/microglial infiltration in both genotypes and improved neurological score in AT mice. Post-MCAO treatment decreased infarct size in both wild-type and AT mice, but had no effect on neurological score in either genotype. Microglia express the Hcrt-1 receptor after MCAO. Tumor necrosis factor-α production by lipopolysaccharide-stimulated microglial BV2 cells was significantly reduced by Hcrt-1 pretreatment. Sham AT mice exhibit increased brain tumor necrosis factor-α and interleukin-6 mRNA, suggesting chronic inflammation.

Conclusions—
Loss of Hcrt neurons in AT mice resulted in worsened stroke outcomes, which were reversed by administration of exogenous Hcrt-1. The mechanism underlying Hcrt-mediated neuroprotection includes attenuation of inflammatory responses after ischemic insult.
From Self-Defense to an Instrument of War: Dutch Privateering Around the Malay Peninsula in the Early Seventeenth Century
Authors: Borschberg Peter 
Published: January 2013

Abstract
This article examines the transition of the Dutch East Indian Company (VOC) from a policy of self-defense into its full espousal of large-scale privateering and plundering. I argue that this shift was driven by both economic and political factors, and can be traced to the very formation of the Company as a unified trading venture. The taking of prizes became a cornerstone not only of the economic fortunes of the company, but the establishment of the Dutch colonial empire in Asia. Of particular interest is not only the instructions emanating from the company directors and the Dutch government in the metropolis, but especially the implementation and adaptation of these directives on the ground. It is this local context that adds a crucial dimension to interpretations of the eager espousal of maritime violence by the VOC and its agents in Asian waters.
Impact of TRMM Data on a Low-Latency, High-Resolution Precipitation Algorithm for Flash-Flood Forecasting
Authors: Kuligowski Robert J. , Li Yaping , Zhang Yu 
Published: January 2013

AbstractData from the Tropical Rainfall Measuring Mission (TRMM) have made great contributions to hydrometeorology from both a science and an operations standpoint. However, direct application of TRMM data to short-fuse hydrologic forecasting has been challenging because of the data refresh and latency issues inherent in an instrument in low Earth orbit (LEO). To evaluate their potential impact on low-latency satellite rainfall estimates, rain rates from both the TRMM Microwave Imager (TMI) and precipitation radar (PR) were ingested into a multisensor framework that calibrates high-refresh, low-latency IR brightness temperature data from geostationary platforms against the more accurate but low-refresh, higher-latency rainfall rates available from microwave (MW) instruments on board LEO platforms. The TRMM data were used in two ways: to bias adjust the other MW data sources to match the distribution of the TMI rain rates, and directly alongside the MW rain rates in the calibration dataset. The results showed a significant reduction in false alarms and also a significant reduction in bias for those pixels for which rainfall was correctly detected. The MW bias adjustment was found to have much greater impact than the direct use of the TMI and PR rain rates in the calibration data, but this is not surprising since the latter represented perhaps only 10% of the calibration dataset.
The Role of High-Latitude Waves in the Intraseasonal to Seasonal Variability of Tropical Upwelling in the Brewer–Dobson Circulation
Authors: Ueyama Rei , Gerber Edwin P. , Wallace John M. , Frierson Dargan M. W. 
Published: January 2013

Abstract
The forcing of tropical upwelling in the Brewer–Dobson circulation (BDC) on intraseasonal to seasonal time scales is investigated in integrations of an idealized general circulation model, ECMWF Interim Re-Analysis, and lower-stratospheric temperature measurements from the (Advanced) Microwave Sounding Unit, with a focus on the extended boreal winter season. Enhanced poleward eddy heat fluxes in the high latitudes (45°–90°N) at the 100-hPa level are associated with anomalous tropical cooling and anomalous warming on the poleward side of the polar night jet at the 70-hPa level and above. In both the model and the observations, planetary waves entering the stratosphere at high latitudes propagate equatorward to the subtropics and tropics at levels above 70 hPa over an approximately 10-day period, exerting a force at sufficiently low latitudes to modulate the tropical upwelling in the upper branch of the BDC, even on time scales longer than the radiative relaxation time scale of the lower stratosphere. To the extent that they force the BDC via downward as opposed to sideways control, planetary waves originating in high latitudes contribute to the seasonally varying climatological mean and the interannual variability of tropical upwelling at the 70-hPa level and above. Their influence upon the strength of the tropical upwelling, however, diminishes rapidly with depth below 70 hPa. In particular, tropical upwelling at the cold-point tropopause, near 100 hPa, appears to be modulated by variations in the strength of the lower branch of the BDC.
Role of the Tibetan Plateau on the Annual Variation of Mean Atmospheric Circulation and Storm-Track Activity*
Authors: Lee Sun-Seon , Lee June-Yi , Ha Kyung-Ja , Wang Bin , Kitoh Akio , Kajikawa Yoshiyuki , Abe Manabu 
Published: January 2013

Abstract
This study reexamines how the Tibetan Plateau (TP) modulates the annual variation of atmospheric circulation and storm-track activity based on the Meteorological Research Institute's atmosphere–ocean coupled model experiments with a progressive TP uplift from 0% to 100% of the present height. Three major roles of the TP on atmospheric circulation and storm-track activity are identified. First, consistent with a previous finding, the TP tends to intensify the upper-level jet and enhance baroclinicity in the North Pacific Ocean but significantly weaken storm-track activity over the TP, East Asia, and the western North Pacific during the cold season. Second, the TP amplifies stationary waves that are closely linked to transient eddies. In particular, the TP enhances the Siberian high and the Aleutian low, which together contribute to the strengthening of the East Asian winter monsoon circulation and the weakening of storm-track activity. Third, the TP significantly modulates the subseasonal variability of the Pacific storm-track (PST) activity. In particular, the TP tends to suppress PST activity during midwinter despite the fact that it strengthens baroclinicity along the Pacific jet. The midwinter suppression of PST activity, which is well reproduced in a control run with a realistic TP, gradually disappears as the TP height decreases. Major factors for the midwinter suppression of the PST associated with the TP include the 1) destructive effect of an excessively strong jet leading to an inefficiency of barotropic energy conversion, 2) reduction of baroclinicity over the northern part of the TP, and 3) subseasonally varying SST change and resulting moist static energy.
The Mean Climate of the Community Atmosphere Model (CAM4) in Forced SST and Fully Coupled Experiments
Authors: Neale Richard B. , Richter Jadwiga , Park Sungsu , Lauritzen Peter H. , Vavrus Stephen J. , Rasch Philip J. , Zhang Minghua 
Published: January 2013

Abstract
The Community Atmosphere Model, version 4 (CAM4), was released as part of the Community Climate System Model, version 4 (CCSM4). The finite volume (FV) dynamical core is now the default because of its superior transport and conservation properties. Deep convection parameterization changes include a dilute plume calculation of convective available potential energy (CAPE) and the introduction of convective momentum transport (CMT). An additional cloud fraction calculation is now performed following macrophysical state updates to provide improved thermodynamic consistency. A freeze-drying modification is further made to the cloud fraction calculation in very dry environments (e.g., the Arctic), where cloud fraction and cloud water values were often inconsistent in CAM3. In CAM4 the FV dynamical core further degrades the excessive trade-wind simulation, but reduces zonal stress errors at higher latitudes. Plume dilution alleviates much of the midtropospheric tropical dry biases and reduces the persistent monsoon precipitation biases over the Arabian Peninsula and the southern Indian Ocean. CMT reduces much of the excessive trade-wind biases in eastern ocean basins. CAM4 shows a global reduction in cloud fraction compared to CAM3, primarily as a result of the freeze-drying and improved cloud fraction equilibrium modifications. Regional climate feature improvements include the propagation of stationary waves from the Pacific into midlatitudes and the seasonal frequency of Northern Hemisphere blocking events. A 1° versus 2° horizontal resolution of the FV dynamical core exhibits superior improvements in regional climate features of precipitation and surface stress. Improvements in the fully coupled mean climate between CAM3 and CAM4 are also more substantial than in forced sea surface temperature (SST) simulations.
Western U.S. Extreme Precipitation Events and Their Relation to ENSO and PDO in CCSM4
Authors: DeFlorio Michael J. , Pierce David W. , Cayan Daniel R. , Miller Arthur J. 
Published: January 2013

Abstract
Water resources and management over the western United States are heavily impacted by both local climate variability and the teleconnected responses of precipitation to the El Niño–Southern Oscillation (ENSO) and Pacific decadal oscillation (PDO). In this work, regional precipitation patterns over the western United States and linkages to ENSO and the PDO are analyzed using output from a Community Climate System Model version 4 (CCSM4) preindustrial control run and observations, with emphasis on extreme precipitation events. CCSM4 produces realistic zonal gradients in precipitation intensity and duration over the western United States, with higher values on the windward side of the Cascade Mountains and Sierra Nevada and lower values on the leeward. Compared to its predecessor CCSM3, CCSM4 shows an improved teleconnected signal of both ENSO and the PDO to large-scale circulation patterns over the Pacific–North America region and also to the spatial pattern and other aspects of western U.S. precipitation. The so-called drizzle problem persists in CCSM4 but is significantly improved compared to CCSM3. In particular, it is found that CCSM4 has substantially less precipitation duration bias than is present in CCSM3. Both the overall and extreme intensity of wintertime precipitation over the western United States show statistically significant linkages with ENSO and PDO in CCSM4. This analysis provides a basis for future studies using greenhouse gas (GHG)-forced CCSM4 runs.
Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease
Authors: George Alex , Pushkaran Suvarnamala , Konstantinidis Diamantis G. , Koochaki Sebastian , Malik Punam , Mohandas Narla , Zheng Yi , Joiner Clinton H. , Kalfa Theodosia A. 
Published: January 2013

Key PointsSickle RBC ROS production is mediated in part by NADPH oxidase activity. Sickle RBC ROS production can be induced by plasma signaling molecules.
The silence of MUC2 mRNA induced by promoter hypermethylation associated with HBV in Hepatocellular Carcinoma
Authors: Ling Yang , Zhu Jing , Gao Lu , Liu Yongping , Zhu Changtai , Li Rong , Wei Lixin , Zhang Changsong 
Published: January 2013

Abstract

Background
To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma.

Methods
We analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC.

Results
MUC2 mRNA were lower in HCC tissues (Mean -ΔCt = −4.70) than that in Non-HCC tissues (Mean -ΔCt = −2.98). Expression of MUC2 was elevated in only 23 (31.08%) of the 74 HCC patients. MUC2 promoter was hypermethylated in 62.2% (46/74) of HCCs, and in only 18.9% (14/74) of non-tumor samples. MUC2 mRNA were lower in HCC patients with hypermethylation (Mean -ΔΔCt = −2.25) than those with demethylation (Mean -ΔΔCt = −0.22), and there is a decreased tendency for MUC2 mRNA in HCC patients with promoter hypermethylation (p = 0.011). There was a significantly correlation found between MUC2 mRNA and HBV and AFP in HCC. The loss of MUC2 mRNA and hypermethylation could be poor prognostic factors. After treated by 5-Aza-CdR and TSA, we found that MUC2 mRNA induced significantly in 7721, Huh7 and HepG2 cells.

Conclusion
The results suggested that MUC2 mRNA silenced by promoter hypermethylation is associated with high levels HBV in HCC.