bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Disease Persistence in Gastrointestinal Stromal Tumors
Authors: Ordog Tamas , Zörnig Martin , Hayashi Yujiro 
Published: May 2015

Summary

Gastrointestinal stromal tumors (GISTs) represent 20%–40% of human sarcomas. Although approximately half of GISTs are cured by surgery, prognosis of advanced disease used to be poor due to the high resistance of these tumors to conventional chemo- and radiotherapy. The introduction of molecularly targeted therapy (e.g., with imatinib mesylate) following the discovery of the role of oncogenic mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor α (PDGFRA) significantly increased patient survival. However, GIST cells persist in 95%–97% of imatinib-treated patients who eventually progress and die of the disease because of the emergence of clones with drug-resistant mutations. Because these secondary mutations are highly heterogeneous, even second- and third-line drugs that are effective against certain genotypes have only moderately increased progression-free survival. Consequently, alternative strategies such as targeting molecular mechanisms underlying disease persistence should be considered. We reviewed recently discovered cell-autonomous and microenvironmental mechanisms that could promote the survival of GIST cells in the presence of tyrosine kinase inhibitor therapy. We particularly focused on the potential role of adult precursors for interstitial cells of Cajal (ICCs), the normal counterpart of GISTs. ICC precursors share phenotypic characteristics with cells that emerge in a subset of patients treated with imatinib and in young patients with GIST characterized by loss of succinate dehydrogenase complex proteins and lack of KIT or PDGFRA mutations. Eradication of residual GIST cells and cure of GIST will likely require individualized combinations of several approaches tailored to tumor genotype and phenotype.

Significance
Gastrointestinal stromal tumors (GISTs) are one of the most common connective tissue cancers. Most GISTs that cannot be cured by surgery respond to molecularly targeted therapy (e.g., with imatinib); however, tumor cells persist in almost all patients and eventually acquire drug-resistant mutations. Several mechanisms contribute to the survival of GIST cells in the presence of imatinib, including the activation of “escape” mechanisms and the selection of stem-like cells that are not dependent on the expression of the drug targets for survival. Eradication of residual GIST cells and cure of GIST will likely require individualized combinations of several approaches tailored to the genetic makeup and other characteristics of the tumors.
Improving evaluation of predicted hydrocarbon reserve zones
Authors: Qin Weijun , Fu Zhaohui 
Published: May 2015

Abstract
Predicted hydrocarbon reserves were studied, and four evaluation methods for improving reserve estimates were proposed, including possibility evaluation, upgrading rate evaluation, economic evaluation and comprehensive evaluation. A difficulty index was used to evaluate the possibility of reserve upgrading. Reserve upgrading probability calculation and test were used to evaluate the upgrading rate. A discounted cash flow method was applied in the economic evaluation. The difficulty index, probability calculation and economic methods were jointly used in the comprehensive evaluation. The predicted hydrocarbon reserve blocks were classified into four types according to the comprehensive evaluation, including the blocks with large or medium potential for upgrading, the blocks with medium or small potential for upgrading, the blocks remaining for evaluation, and the blocks not to upgrade at present.
Reserves growth trend and potential analysis of Junggar Basin
Authors: Chen Ping , Zhang Ling , Wang Huimin 
Published: May 2015

Abstract
The Junggar Basin is one of early explored petroliferous basins in China. Since the discovery of the Karamay Oil Field in 1955, over 30 oil fields have been found. The geologic features, hydrocarbon accumulation mechanisms and distribution characteristics of the Junggar Basin were studied in this paper. The basin has under-gone rapid and effective exploration in past years, which helped potential prediction. The present estimate of recoverable oil and gas resources in the basin is 45.3% and 30.3%, respectively. Exploration is in the middle and late stages. There are (9.42~16.92)×108 t oil remaining unproved. Lithologic, igneous rocks and tight sand-stones are the main targets for future exploration in the basin.
Disaster Vulnerability of Upland and Lowland Riverine Communities in Iligan City, Philippines
Authors: BRACAMONTE NIMFA L. 
Published: May 2015

Identifying risks and vulnerabilities before and after the occurrence of disasters are important in disaster management. Using the vulnerability framework, this study examines the disaster preparedness of Iligan City communities when Tropical Storm Sendong (Washi) and Typhoon Pablo (Bopha) came. Employing a qualitative approach, this study included 129 research participants from Barangay Mandulog and Pugaan (upland) and Hinaplanon and Palao (lowland). Findings showed that communities which are lying close to Mandulog River are more vulnerable to flooding and were devastated more by Sendong than those living along Pugaan River. These Barangay were structurally ill-prepared before Sendong and even before Typhoon Pablo with respect to complete crafting and implementation of a functional DRRM Plan as mandated by RA 10121. The findings have implications to effective disaster governance of the local governmentunits. Keywords - Vulnerability, disaster preparedness, exposure, descriptive design, Philippines
Layered crustal anisotropy around the San Andreas Fault near Parkfield, California
Authors: Audet Pascal 
Published: May 2015

AbstractThe rheology of the Earth's crust controls the long‐term and short‐term strength and stability of plate boundary faults and depends on the architecture and physical properties of crustal materials. In this paper we examine the seismic structure and anisotropy of the crust around the San Andreas Fault (SAF) near Parkfield, California, using teleseismic receiver functions. These data indicate that the crust is characterized by spatially variable and strongly anisotropic upper and middle crustal layers, with a Moho at ∼35 km depth. The upper layer is ∼5–10 km thick and is characterized by strong (≥30%) anisotropy with a slow axis of hexagonal symmetry, where the plane of fast velocity has a strike parallel to that of the SAF and a dip of ∼40∘. We interpret this layer as pervasive fluid‐filled microcracks within the brittle deformation regime. The ∼10–15 km thick midcrustal layer is also characterized by a weak axis of hexagonal symmetry with ≥20% anisotropy, but the dip direction of the plane of fast velocity is reversed. The midcrustal anisotropic layer is more prominent to the northeast of the San Andreas Fault. We interpret the mid crustal anisotropic layer as fossilized fabric within fluid‐rich foliated mica schists. When combined with various other geophysical observations, our results suggest that fault creep behavior around Parkfield is favored by intrinsically weak and overpressured crustal fabric.
Interhemispheric controls on deep ocean circulation and carbon chemistry during the last two glacial cycles
Authors: Wilson David J. , Piotrowski Alexander M. , Galy Albert , Banakar Virupaxa K. 
Published: May 2015

AbstractChanges in ocean circulation structure, together with biological cycling, have been proposed for trapping carbon in the deep ocean during glacial periods of the Late Pleistocene, but uncertainty remains in the nature and timing of deep ocean circulation changes through glacial cycles. In this study, we use neodymium (Nd) and carbon isotopes from a deep Indian Ocean sediment core to reconstruct water mass mixing and carbon cycling in Circumpolar Deep Water over the past 250 thousand years, a period encompassing two full glacial cycles and including a range of orbital forcing. Building on recent studies, we use reductive sediment leaching supported by measurements on isolated phases (foraminifera and fish teeth) in order to obtain a robust seawater Nd isotope reconstruction. Neodymium isotopes record a changing North Atlantic Deep Water (NADW) component in the deep Indian Ocean that bears a striking resemblance to Northern Hemisphere climate records. In particular, we identify both an approximately in‐phase link to Northern Hemisphere summer insolation in the precession band and a longer‐term reduction of NADW contributions over the course of glacial cycles. The orbital timescale changes may record the influence of insolation forcing, for example via NADW temperature and/or Antarctic sea ice extent, on deep stratification and mixing in the Southern Ocean, leading to isolation of the global deep oceans from an NADW source during times of low Northern Hemisphere summer insolation. That evidence could support an active role for changing deep ocean circulation in carbon storage during glacial inceptions. However, mid‐depth water mass mixing and deep ocean carbon storage were largely decoupled within glacial periods, and a return to an interglacial‐like circulation state during marine isotope stage (MIS) 6.5 was accompanied by only minor changes in atmospheric CO2. Although a gradual reduction of NADW export through glacial periods may have produced slow climate feedbacks linked to the growth of Northern Hemisphere ice sheets, carbon cycling in the glacial ocean was instead more strongly linked to Southern Ocean processes.
Holocene multidecadal‐ to millennial‐scale variations in Iceland‐Scotland overflow and their relationship to climate
Authors: Mjell Tor Lien , Ninnemann Ulysses S. , Eldevik Tor , Kleiven Helga Kikki F. 
Published: May 2015

AbstractThe Nordic Seas overflows are an important part of the Atlantic thermohaline circulation. While there is growing evidence that the overflow of dense water changed on orbital time scales during the Holocene, less is known about the variability on shorter time scales beyond the instrumental record. Here we reconstruct the relative changes in flow strength of Iceland‐Scotland Overflow Water (ISOW), the eastern branch of the overflows, on multidecadal‐millennial time scales. The reconstruction is based on mean sortable silt (
) from a sediment core on the Gardar Drift (60°19′N, 23°58′W, 2081 m). Our
record reveals that the main variance in ISOW vigor occurred on millennial time scales (1–2 kyr) with particularly prominent fluctuations after 8 kyr. Superimposed on the millennial variability, there were multidecadal‐centennial flow speed fluctuations during the early Holocene (10–9 kyr) and one prominent minimum at 0.9 kyr. We find a broad agreement between reconstructed ISOW and regional North Atlantic climate, where a strong (weak) ISOW is generally associated with warm (cold) climate. We further identify the possible contribution of anomalous heat and freshwater forcing, respectively, related to reconstructed overflow variability. We infer that ocean poleward heat transport can explain the relationship between regional climate and ISOW during the middle to late Holocene, whereas freshwater input provides a possible explanation for the reduced overflow during early Holocene (8–10 kyr).
Topographic vorticity generation, submesoscale instability and vortex street formation in the Gulf Stream
Authors: Gula J. , Molemaker M. J. , McWilliams J. C. 
Published: May 2015

AbstractMeanders and eddies are routinely observed in the Gulf Stream along the South Atlantic Bight. We analyze here the instability processes that lead to the formation of submesoscale eddies on the cyclonic side of the Gulf Stream at the exit of the Florida Straits using very high resolution realistic simulations. The positive relative vorticity and potential vorticity on the cyclonic side of the Gulf Stream are strongly intensified in the Straits due to topographic drag along the continental slope. The bottom drag amplifies the cyclonic shear by generating large positive vertical vorticity values within the sloped turbulent bottom boundary layer. Downstream from the Straits the current becomes unstable to horizontal shear instability, rolls up, and forms a street of submesoscale vortices. The vortices expand as they propagate northward along the shelf, where they can generate large vertical displacements and enhance cross‐shelf exchanges.
PKP precursors: Implications for global scatterers
Authors: Waszek Lauren , Thomas Christine , Deuss Arwen 
Published: May 2015

AbstractPrecursors to the core phase PKP are generated by scattering of seismic energy from heterogeneities in the mantle. Here we examine a large global data set of PKP precursors in individual seismograms and array data, to better understand scattering locations. The precursor amplitudes from individual seismograms are analyzed with respect to the inner core phase PKIKP and mantle phase PP. We find and correct for a hemispherical asymmetry in the precursor/PKIKP amplitudes, resulting from inner core structure. Using ray tracing, we locate scatterers in our array data and use these to infer scattering locations in the individual data. The scattering strength displays regional variation; however, we find no relationship with long‐scale core‐mantle boundary velocity structure. Scattering is observed in all regions of data coverage, as are paths with no precursors. This indicates that scattering occurs from various small‐scale heterogeneities, including but not limited to ultralow velocity zones or partial melt, and slabs.
Systematic large‐scale secondary circulations in a regional climate model
Authors: Becker Nico , Ulbrich Uwe , Klein Rupert 
Published: May 2015

AbstractRegional climate models (RCMs) are used to add the effects of nonresolved scales to coarser resolved model simulations by using a finer grid within a limited domain. We identify large‐scale secondary circulations (SCs) relative to the driving global climate model (GCM) in an RCM simulation over Europe. By applying a clustering technique, we find that the SC depends on the large‐scale flow prescribed by the driving GCM data. Evidence is presented that the SC is caused by the different representations of orographic effects in the RCM and the GCM. Flow modifications in the RCM caused by the Alps lead to large‐scale vortices in the SC fields. These vortices are limited by the RCM boundaries, causing artificial boundary‐parallel flows. The SC is associated with geopotential height and temperature anomalies between RCM and GCM and has the potential to produce systematic large‐scale biases in RCMs.
Average thermodynamic and spectral properties of plasma in and around dipolarizing flux bundles
Authors: Runov A. , Angelopoulos V. , Gabrielse C. , Liu J. , Turner D. L. , Zhou X.‐Z. 
Published: May 2015

AbstractRecent observations have suggested that spatially localized flows of high‐temperature, low‐density plasma carrying a dipolarized magnetic field (dipolarizing flux bundles, DFBs) play a key role in hot plasma transport toward the inner magnetosphere. What controls plasma heating in DFBs and how do thermodynamic parameters (such as density, temperature, pressure, and specific entropy) and spectral properties of the DFB population depend on ambient plasma sheet properties and geocentric distance R remains unknown. By statistical analysis of 271 DFB events detected by the Time History of Events and Macroscale Interactions during Substorms mission during the 2008–2009 tail seasons, we find that on average, plasma inside DFBs is a factor of 0.6 less dense and a factor of 1.5 to 2 hotter than ambient tail plasma. The radial profiles of average thermodynamic parameters inside and outside DFBs are similar; when fitted by the κ‐function, their energy spectra have similar κ‐exponents, but a factor of 2 larger peak energies inside DFBs. Our analysis suggests that average DFB plasma properties are closely linked to those of the ambient plasma sheet population. Estimations show that on average, adiabatic heating of the ambient plasma in the increased magnetic field is the major factor in DFB plasma heating.
Carbon export efficiency and phytoplankton community composition in the Atlantic sector of the Arctic Ocean
Authors: Le Moigne Frédéric A. C. , Poulton Alex J. , Henson Stephanie A. , Daniels Chris J. , Fragoso Glaucia M. , Mitchell Elaine , Richier Sophie , Russell Benjamin C. , Smith Helen E. K. , Tarling Geraint A. , Young Jeremy R. , Zubkov Mike 
Published: May 2015

AbstractArctic primary production is sensitive to reductions in sea ice cover, and will likely increase into the future. Whether this increased primary production (PP) will translate into increased export of particulate organic carbon (POC) is currently unclear. Here we report on the POC export efficiency during summer 2012 in the Atlantic sector of the Arctic Ocean. We coupled 234‐thorium based estimates of the export flux of POC to onboard incubation‐based estimates of PP. Export efficiency (defined as the fraction of PP that is exported below 100 m depth: ThE‐ratio) showed large variability (0.09 ± 0.19–1.3 ± 0.3). The highest ThE‐ratio (1.3 ± 0.3) was recorded in a mono‐specific bloom of Phaeocystis pouchetii located in the ice edge. Blooming diatom dominated areas also had high ThE‐ratios (0.1 ± 0.1–0.5 ± 0.2), while mixed and/or prebloom communities showed lower ThE‐ratios (0.10 ± 0.03–0.19 ± 0.05). Furthermore, using oxygen saturation, bacterial abundance, bacterial production, and zooplankton oxygen demand, we also investigated spatial variability in the degree to which this sinking material may be remineralized in the upper mesopelagic (<300 m). Our results suggest that blooming diatoms and P. pouchetii can export a significant fraction of their biomass below the surface layer (100 m) in the open Arctic Ocean. Also, we show evidence that the material sinking from a P. pouchetii bloom may be remineralized (>100 m) at a similar rate as the material sinking from diatom blooms in the upper mesopelagic, contrary to previous findings.
Identification of a neurovascular signaling pathway regulating seizures in mice
Authors: Fredriksson Linda , Stevenson Tamara K. , Su Enming J. , Ragsdale Margaret , Moore Shannon , Craciun Stefan , Schielke Gerald P. , Murphy Geoffrey G. , Lawrence Daniel A. 
Published: May 2015

AbstractObjectiveA growing body of evidence suggests that increased blood–brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures.MethodsAn experimental model of kainate‐induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA−/−), its inhibitor neuroserpin (Nsp−/−), or both (Nsp:tPA−/−), and in mice conditionally deficient in the platelet‐derived growth factor receptor alpha (PDGFRα).ResultsCompared to wild‐type (WT) mice, Nsp−/− mice have significantly reduced latency to seizure onset and generalization; whereas tPA−/− mice have the opposite phenotype, as do Nsp:tPA−/− mice. Furthermore, interventions that maintain BBB integrity delay seizure propagation, whereas osmotic disruption of the BBB in seizure‐resistant tPA−/− mice dramatically reduces the time to seizure onset and accelerates seizure progression. The phenotypic differences in seizure progression between WT, tPA−/−, and Nsp−/− mice are also observed in electroencephalogram recordings in vivo, but absent in ex vivo electrophysiological recordings where regulation of the BBB is no longer necessary to maintain the extracellular environment. Finally, we demonstrate that these effects on seizure progression are mediated through signaling by PDGFRα on perivascular astrocytes.InterpretationTogether, these data identify a specific molecular pathway involving tPA‐mediated PDGFRα signaling in perivascular astrocytes that regulates seizure progression through control of the BBB. Inhibition of PDGFRα signaling and maintenance of BBB integrity might therefore offer a novel clinical approach for managing seizures.
Analysis of Interactions between the Epidermal Growth Factor Receptor and Soluble Ligands on the Basis of Single‐Molecule Diffusivity in the Membrane of Living Cells
Authors: Kim Do‐Hyeon , Zhou Kai , Kim Dong‐Kyun , Park Soyeon , Noh Jungeun , Kwon Yonghoon , Kim Dayea , Song Nam Woong , Lee Jong‐Bong , Suh Pann‐Ghill , Lee Nam Ki , Ryu Sung Ho 
Published: May 2015

AbstractWe present a single‐molecule diffusional‐mobility‐shift assay (smDIMSA) for analyzing the interactions between membrane and water‐soluble proteins in the crowded membrane of living cells. We found that ligand–receptor interactions decreased the diffusional mobility of ErbB receptors and β‐adrenergic receptors, as determined by single‐particle tracking with super‐resolution microscopy. The shift in diffusional mobility was sensitive to the size of the water‐soluble binders that ranged from a few tens of kilodaltons to several hundred kilodaltons. This technique was used to quantitatively analyze the dissociation constant and the cooperativity of antibody interactions with the epidermal growth factor receptor and its mutants. smDIMSA enables the quantitative investigation of previously undetected ligand–receptor interactions in the intact membrane of living cells on the basis of the diffusivity of single‐molecule membrane proteins without ligand labeling.
Single Benzene Green Fluorophore: Solid‐State Emissive, Water‐Soluble, and Solvent‐ and pH‐Independent Fluorescence with Large Stokes Shifts
Authors: Beppu Teruo , Tomiguchi Kosuke , Masuhara Akito , Pu Yong‐Jin , Katagiri Hiroshi 
Published: May 2015

AbstractBenzene is the simplest aromatic hydrocarbon with a six‐membered ring. It is one of the most basic structural units for the construction of π conjugated systems, which are widely used as fluorescent dyes and other luminescent materials for imaging applications and displays because of their enhanced spectroscopic signal. Presented herein is 2,5‐bis(methylsulfonyl)‐1,4‐diaminobenzene as a novel architecture for green fluorophores, established based on an effective push–pull system supported by intramolecular hydrogen bonding. This compound demonstrates high fluorescence emission and photostability and is solid‐state emissive, water‐soluble, and solvent‐ and pH‐independent with quantum yields of Φ=0.67 and Stokes shift of 140 nm (in water). This architecture is a significant departure from conventional extended π‐conjugated systems based on a flat and rigid molecular design and provides a minimum requirement for green fluorophores comprising a single benzene ring.