bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localized granulite and eclogite facies metamorphism at Flatraket and Kråkeneset, Western Gneiss Region: U–Pb data and tectonic implications
Authors: Corfu Fernando , Austrheim Håkon , Ganzhorn Anne-Céline 
Published: December 2013

Abstract
The Flatraket Complex, in the ultra-high-pressure (UHP) domains of the Western Gneiss Region (WGR) of Norway, preserves granulite facies assemblages, which were locally overprinted by eclogite and amphibolite facies metamorphism. Zircon and monazite indicate magmatic crystallization of the rocks at 1680–1640 Ma and constrain the timing of the granulite facies overprint at 1100 Ma. This age is older than previously reported ages of 1000–950 Ma for regional metamorphism reaching anatexis and locally granulite facies in the WGR. The granulites at Flatraket may have developed as a consequence of local metasomatism, perhaps linked to metasomatism occurring at the same time in the nearby Sandvik peridotite. Granitic rocks from neighbouring Kråkeneset indicate magmatic emplacement at ≥1650 Ma, during the event that formed the Flatraket Complex and the bulk of the WGR. A gabbro body at Kråkeneset is dated at 1255±8 Ma by baddeleyite, which was not affected by the granulite event, implying that the rock remained impermeable to fluids, reacting instead to some degree during the Caledonian UHP event.
Dramatic Antitumor Effects of the Dual MET/RON Small-Molecule Inhibitor LY2801653 in Non–Small Cell Lung Cancer
Authors: Kawada Ichiro , Hasina Rifat , Arif Qudsia , Mueller Jeffrey , Smithberger Erin , Husain Aliya N. , Vokes Everett E. , Salgia Ravi 
Published: December 2013

Abstract
Lung cancer is a heterogeneous disease encompassing a wide array of genetic abnormalities. The MET receptor tyrosine kinase is altered in many lung cancers, especially non–small cell lung cancer (NSCLC), and clinical trials of MET inhibitors that are under way are documenting cases of acquired resistance. On the basis of the evidence that the RON tyrosine kinase receptor can also be overexpressed in NSCLC, we evaluated the potent MET/RON dual kinase inhibitor LY2801653 in this setting. LY2801653 was more efficacious than the MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream signaling effects. Using the PamGene platform, we found that inhibition of MET and RON was associated with decreased phosphorylation of CBL, PI3K, and STAT3. In classic and orthotopic mouse xenograft models of lung cancer, LY2801653 decreased tumor growth, dramatically inhibiting mitotic events and angiogenesis. Taken together, our results argued that specific targeting of the MET/RON kinases could provide robust inhibition of cell proliferation and tumor outgrowth in multiple in vitro and in vivo models of NSCLC. These findings offer a robust preclinical proof of concept for MET/RON targeting by LY2801653 as a promising small-molecule modality to treat NSCLC. Cancer Res; 74(3); 884–95. ©2013 AACR.
MDR1 Synonymous Polymorphisms Alter Transporter Specificity and Protein Stability in a Stable Epithelial Monolayer
Authors: Fung King Leung , Pan James , Ohnuma Shinobu , Lund Paul E. , Pixley Jessica N. , Kimchi-Sarfaty Chava , Ambudkar Suresh V. , Gottesman Michael M. 
Published: December 2013

Abstract
The drug efflux function of P-glycoprotein (P-gp) encoded by MDR1 can be influenced by genetic polymorphisms, including two synonymous changes in the coding region of MDR1. Here we report that the conformation of P-gp and its drug efflux activity can be altered by synonymous polymorphisms in stable epithelial monolayers expressing P-gp. Several cell lines with similar MDR1 DNA copy number were developed and termed LLC-MDR1-WT (expresses wild-type P-gp), LLC-MDR1-3H (expresses common haplotype P-gp), and LLC-MDR1-3HA (a mutant that carries a different valine codon in position 3435). These cell lines express similar levels of recombinant mRNA and protein. P-gp in each case is localized on the apical surface of polarized cells. However, the haplotype and its mutant P-gps fold differently from the wild-type, as determined by UIC2 antibody shift assays and limited proteolysis assays. Surface biotinylation experiments suggest that the non-wild-type P-gps have longer recycling times. Drug transport assays show that wild-type and haplotype P-gp respond differently to P-gp inhibitors that block efflux of rhodamine 123 or mitoxantrone. In addition, cytotoxicity assays show that the LLC-MDR1-3H cells are more resistant to mitoxantrone than the LLC-MDR1-WT cells after being treated with a P-gp inhibitor. Expression of polymorphic P-gp, however, does not affect the host cell's morphology, growth rate, or monolayer formation. Also, ATPase activity assays indicate that neither basal nor drug-stimulated ATPase activities are affected in the variant P-gps. Taken together, our findings indicate that “silent” polymorphisms significantly change P-gp function, which would be expected to affect interindividual drug disposition and response. Cancer Res; 74(2); 598–608. ©2013 AACR.
Protective mechanisms of adenosine 5′-monophosphate in platelet activation and thrombus formation
Authors: Fuentes Eduardo , Badimon Lina , Caballero Julio , Padró Teresa , Vilahur Gemma , Alarcón Marcelo , Pérez Pablo , Palomo Iván 
Published: December 2013

SummaryPlatelet activation is relevant to a variety of acute thrombotic events. We sought to examine adenosine 5′-monophosphate (AMP) mechanisms of action in preventing platelet activation, thrombus formation and platelet-related inflammatory response. We assessed the effect of AMP on 1) P-selectin expression and GPIIb/IIIa activation by flow cytometry; 2) Platelet aggregation and ATP secretion induced by ADP, collagen, TRAP-6, convulxin and thrombin; 3) Platelet rolling and firm adhesion, and platelet-leukocyte interactions under flow-controlled conditions; and, 4) Platelet cAMP levels, sP-selectin, sCD40L, IL-1β, TGF-β1 and CCL5 release, PDE3A activity and PKA phosphorylation. The effect of AMP on in vivo thrombus formation was also evaluated in a murine model. The AMP docking with respect to A2 adenosine receptor was determined by homology. AMP concentration-dependently (0.1 to 3 mmol/l) inhibited P-selectin expression and GPIIb/IIIa activation, platelet secretion and aggregation induced by ADP, collagen, TRAP-6 and convulxin, and diminished platelet rolling and firm adhesion. Furthermore, AMP induced a marked increase in the rolling speed of leukocytes retained on the platelet surface. At these concentrations AMP significantly decreased inflammatory mediator from platelet, increased intraplatelet cAMP levels and inhibited PDE3A activity. Interestingly, SQ22536, ZM241385 and SCH58261 attenuated the antiplatelet effect of AMP. Docking experiments revealed that AMP had the same orientation that adenosine inside the A2 adenosine receptor binding pocket. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. Considering the successful use of combined antiplatelet therapy, AMP may be further developed as a novel antiplatelet agent.
Nanoparticle-Mediated Delivery of Pitavastatin Inhibits Atherosclerotic Plaque Destabilization/Rupture in Mice by Regulating the Recruitment of Inflammatory Monocytes
Authors: Katsuki Shunsuke , Matoba Tetsuya , Nakashiro Soichi , Sato Kei , Koga Jun-ichiro , Nakano Kaku , Nakano Yasuhiro , Egusa Shizuka , Sunagawa Kenji , Egashira Kensuke 
Published: December 2013

Background—
Preventing atherosclerotic plaque destabilization and rupture is the most reasonable therapeutic strategy for acute myocardial infarction. Therefore, we tested the hypotheses that (1) inflammatory monocytes play a causative role in plaque destabilization and rupture and (2) the nanoparticle-mediated delivery of pitavastatin into circulating inflammatory monocytes inhibits plaque destabilization and rupture.

Methods and Results—

We used a model of plaque destabilization and rupture in the brachiocephalic arteries of apolipoprotein E–deficient (ApoE
−/−
) mice fed a high-fat diet and infused with angiotensin II. The adoptive transfer of CCR2
+/+
Ly-6C
high
inflammatory macrophages, but not CCR2
−/−
leukocytes, accelerated plaque destabilization associated with increased serum monocyte chemoattractant protein-1 (MCP-1), monocyte-colony stimulating factor, and matrix metalloproteinase-9. We prepared poly(lactic-co-glycolic) acid nanoparticles that were incorporated by Ly-6G
−
CD11b
+
monocytes and delivered into atherosclerotic plaques after intravenous administration. Intravenous treatment with pitavastatin-incorporated nanoparticles, but not with control nanoparticles or pitavastatin alone, inhibited plaque destabilization and rupture associated with decreased monocyte infiltration and gelatinase activity in the plaque. Pitavastatin-incorporated nanoparticles inhibited MCP-1–induced monocyte chemotaxis and the secretion of MCP-1 and matrix metalloproteinase-9 from cultured macrophages. Furthermore, the nanoparticle-mediated anti–MCP-1 gene therapy reduced the incidence of plaque destabilization and rupture.

Conclusions—
The recruitment of inflammatory monocytes is critical in the pathogenesis of plaque destabilization and rupture, and nanoparticle-mediated pitavastatin delivery is a promising therapeutic strategy to inhibit plaque destabilization and rupture by regulating MCP-1/CCR2–dependent monocyte recruitment in this model.
Seeking Prestige and Survival: Gift-exchange Practices between the Portuguese Estado da Índia and Asian Rulers
Authors: Melo João 
Published: December 2013

AbstractThe relations between the Portuguese Estado da India and other Indian powers were based on several forms of interaction from embassies to commercial exchanges. One important channel of communication was the exchange of gifts. The Estado often used gifts to consolidate its ties with local powers, to ward off the hostility of potential enemies, and to maintain allies or find new ones. This article analyses how the gifts offered and received by the Portuguese served the interests of the Portuguese Crown in India, and lead to the adoption of local ritual practices by the Estado da Índia.
The Beçin Coin Hoard and Ottoman Monetary History in the Late 16th/Early 17th Century
Authors: Pfeiffer-Taş Şule , Schindel Nikolaus 
Published: December 2013

AbstractIt is generally accepted that debasement greatly contributed to the economic and consequently also social problems of the Ottoman Empire in the late 16th/early 17th century. The numismatic data derived from the Beçin coin hoard, closing under sultan Ahmed (1603-1617) greatly challenges this view. Metal analysis has shown that only the overall weights of the coins were reduced; the fineness of silver remained unchanged at least until the 1610s.
The Poll Tax and the Decline of the Christian Presence in the Palestinian Countryside in the 17th Century
Authors: Tramontana Felicita 
Published: December 2013

AbstractBetween 13 and 23 March 1650 a number of documents related to the annual collection of thejizya(poll tax) were recorded in the Islamic (sharīʿa) court of Jerusalem. Two concern “disputes” between the appointed tax collector and some villagers who refused to pay thejizyabecause they had recently converted to Islam. It is these documents that this article analyses. Besides their intrinsic interest as records about the payment of the poll tax, they are a valuable source of information on conversion to Islam among Christian villagers in Ottoman Palestine.
Entropy Evolution Characteristics Associated with the Development of the South Asian Monsoon
Authors: Li Jiangnan , Li Tim 
Published: December 2013

AbstractThe structure and evolution characteristics of atmospheric entropy production associated with the climatologic monsoon onset and evolution were investigated using the National Centers for Environmental Prediction (NCEP) reanalysis data. The entropy balance equation contains two parts. The first part is internal entropy production that corresponds to natural dissipation. The second part is external entropy production that is associated with lower-boundary entropy supply. It is shown that the dissipation process represented by internal entropy production can be used to describe the thermal and dynamical structures of the monsoon. The thermal dissipation due to turbulent vertical diffusion and convection is highly correlated to precipitation. The dynamic dissipation due to wind stress becomes very strong over the Arabian Sea and southwestern part of India in boreal summer, and dynamic dissipation can describe the monsoon structure more clearly than variables such as wind shear. The correlation between surface entropy supply and internal entropy production is so large that the surface entropy supply can also be used to evaluate the monsoon. Over the desert region of Rajasthan, the dissipation is relatively weaker than its surroundings owing to descending large-scale eddy flow and a weak convective flux. The analysis of atmospheric entropy provides a new way to describe the monsoon development characteristics, which differs from those derived from a traditional analysis method.
The Antarctic Sea Ice Response to the Ozone Hole in Climate Models
Authors: Sigmond Michael , Fyfe John C. 
Published: December 2013

Abstract
It has been suggested that the increase of Southern Hemisphere sea ice extent since the 1970s can be explained by ozone depletion in the Southern Hemisphere stratosphere. In a previous study, the authors have shown that in a coupled atmosphere–ocean–sea ice model the ozone hole does not lead to an increase but to a decrease in sea ice extent. Here, the robustness of this result is established through the analysis of models from phases 3 and 5 of the Coupled Model Intercomparison Project (CMIP3 and CMIP5). Comparison of the mean sea ice trends in CMIP3 models with and without time-varying stratospheric ozone suggests that ozone depletion is associated with decreased sea ice extent, and ozone recovery acts to mitigate the future sea ice decrease associated with increasing greenhouse gases. All available historical simulations with CMIP5 models that were designed to isolate the effect of time-varying ozone concentrations show decreased sea ice extent in response to historical ozone trends. In most models, the historical sea ice extent trends are mainly driven by historical greenhouse gas forcing, with ozone forcing playing a secondary role.
Energetics of Semienclosed Basins with Two-Layer Flows at the Strait
Authors: Cessi Paola , Pinardi Nadia , Lyubartsev Vladislav 
Published: December 2013

Abstract
Examination of the energy budget for semienclosed seas with two-layer exchange flow at the strait shows that the energy flux at the open portion of the boundary (the strait) is proportional to the surface buoyancy flux integrated over the basin area, with the constant of proportionality given by the interface depth. When the surface buoyancy flux is positive, the energy flux is negative: these types of basins have an estuarine circulation. Antiestuarine basins have a negative surface buoyancy flux, which provides a positive energy flux, augmenting the wind work in powering the circulation. The energy budget for the semienclosed seas with vertically separated flows at the strait is examined using reanalysis products for four major semienclosed basins: the Mediterranean and Red Seas (antiestuarine) and the Black and Baltic Seas (estuarine). Important differences in the relative contribution to the energy budget of the wind work versus the surface buoyancy flux are found within basins of the same type, and these differences help explain some qualitative aspects of the basins’ flow.
On the Importance of Surface Forcing in Conceptual Models of the Deep Ocean
Authors: Stewart Andrew L. , Ferrari Raffaele , Thompson Andrew F. 
Published: December 2013

Abstract
In the major ocean basins, diapycnal mixing upwells dense Antarctic Bottom Water, which returns southward and closes the deepest cell of the meridional overturning circulation (MOC). This cell ventilates the deep ocean and regulates the partitioning of CO2 between the atmosphere and the ocean. The oceanographic community's conceptual understanding of the deep stratification and MOC has evolved from classic “abyssal recipes” arguments to a more recent appreciation of along-isopycnal upwelling in the Southern Ocean, consistent with a weakly mixed ocean interior. Both the deep stratification and the deep MOC are shown here to be sensitive to the form of the surface buoyancy forcing in a two-dimensional model that includes a circumpolar channel and northern basin. For a fixed surface buoyancy condition, the deep stratification is essentially prescribed, whereas for a fixed surface buoyancy flux, the deep stratification varies by orders of magnitude over the range of diapycnal diffusivity κ observed in the ocean. These cases also produce different scalings for the deep MOC with κ, in both weak and strong κ regimes. In addition, these scalings are shown to be sensitive not only to the type of surface boundary condition, but also to the latitudinal structure of the surface fluxes. This latter point is crucial as buoyancy budgets and dynamical features of the circulation are poorly constrained along the Antarctic margins. This study emphasizes the need for caution in the interpretation of simple conceptual models that, while useful, may not include all mechanisms that contribute to the MOC’s strength and structure.
Scanning ARM Cloud Radars. Part II: Data Quality Control and Processing
Authors: Kollias Pavlos , Jo Ieng , Borque Paloma , Tatarevic Aleksandra , Lamer Katia , Bharadwaj Nitin , Widener Kevin , Johnson Karen , Clothiaux Eugene E. 
Published: December 2013

Abstract
The scanning Atmospheric Radiation Measurement (ARM) Program cloud radars (SACRs) are the primary instruments for documenting the four-dimensional structure and evolution of clouds within a 20–30-km radius of the ARM fixed and mobile sites. Here, the postprocessing of the calibrated SACR measurements is discussed. First, a feature mask algorithm that objectively determines the presence of significant radar returns is described. The feature mask algorithm is based on the statistical properties of radar receiver noise. It accounts for atmospheric emission and is applicable even for SACR profiles with few or no signal-free range gates. Using the nearest-in-time atmospheric sounding, the SACR radar reflectivities are corrected for gaseous attenuation (water vapor and oxygen) using a line-by-line absorption model. Despite having a high pulse repetition frequency, the SACR has a narrow Nyquist velocity limit and thus Doppler velocity folding is commonly observed. An unfolding algorithm that makes use of a first guess for the true Doppler velocity using horizontal wind measurements from the nearest sounding is described. The retrieval of the horizontal wind profile from the hemispherical sky range–height indicator SACR scan observations and/or nearest sounding is described. The retrieved horizontal wind profile can be used to adaptively configure SACR scan strategies that depend on wind direction. Several remaining challenges are discussed, including the removal of insect and second-trip echoes. The described algorithms significantly enhance SACR data quality and constitute an important step toward the utilization of SACR measurements for cloud research.
Mesoscale Data Assimilation for a Local Severe Rainfall Event with the NHM–LETKF System
Authors: Kunii Masaru 
Published: December 2013

Abstract
This study seeks to improve forecasts of local severe weather events through data assimilation and ensemble forecasting approaches using the local ensemble transform Kalman filter (LETKF) implemented with the Japan Meteorological Agency’s nonhydrostatic model (NHM). The newly developed NHM–LETKF contains an adaptive inflation scheme and a spatial covariance localization scheme with physical distance, and it permits a one-way nested analysis in which a finer-resolution LETKF is conducted by using the output of an outer model. These new features enhance the potential of the LETKF for convective-scale events. The NHM–LETKF was applied to a local severe rainfall event in Japan during 2012. Comparison of the root-mean-square errors between the model first guess and analysis showed that the system assimilated observations appropriately. Analysis ensemble spreads indicated a significant increase around the time torrential rainfall occurred, implying an increase in the uncertainty of environmental fields. Forecasts initialized with LETKF analyses successfully captured intense rainfalls, suggesting that the system could work effectively for local severe weather events. Investigation of probabilistic forecasts by ensemble forecasting indicated that this could become a reliable data source for decision making in the future. A one-way nested data assimilation scheme was also tested. The results demonstrated that assimilation with a finer-resolution model improved the precipitation forecasting of local severe weather conditions.
An Evaluation of the Impact of Horizontal Resolution on Tropical Cyclone Predictions Using COAMPS-TC
Authors: Jin Hao , Peng Melinda S. , Jin Yi , Doyle James D. 
Published: December 2013

Abstract
A series of experiments have been conducted using the Coupled Ocean–Atmosphere Mesoscale Prediction System–Tropical Cyclone (COAMPS-TC) to assess the impact of horizontal resolution on hurricane intensity prediction for 10 Atlantic storms during the 2005 and 2007 hurricane seasons. The results of this study from the Hurricane Katrina (2005) simulations indicate that the hurricane intensity and structure are very sensitive to the horizontal grid spacing (9 and 3 km) and underscore the need for cloud microphysics to capture the structure, especially for strong storms with small-diameter eyes and large pressure gradients. The high resolution simulates stronger vertical motions, a more distinct upper-level warm core, stronger upper-level outflow, and greater finescale structure associated with deep convection, including spiral rainbands and the secondary circulation. A vortex Rossby wave (VRW) spectrum analysis is performed on the simulated 10-m winds and the NOAA/Hurricane Research Division (HRD) Real-Time Hurricane Wind Analysis System (H*Wind) to evaluate the impact of horizontal resolution. The degree to which the VRWs are adequately resolved near the TC inner core is addressed and the associated resolvable wave energy is explored at different grid resolutions. The fine resolution is necessary to resolve higher-wavenumber modes of VRWs to preserve more wave energy and, hence, to attain a more detailed eyewall structure. The wind–pressure relationship from the high-resolution simulations is in better agreement with the observations than are the coarse-resolution simulations for the strong storms. Two case studies are analyzed and overall the statistical analyses indicate that high resolution is beneficial for TC intensity and structure forecasts, while it has little impact on track forecasts.