bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoglin (CD105) Contributes to Platinum Resistance and Is A Target for Tumor-Specific Therapy in Epithelial Ovarian Cancer
Authors: Ziebarth Angela J. , Nowsheen Somaira , Steg Adam D. , Shah Monjri M. , Katre Ashwini A. , Dobbin Zachary C. , Han Hee-Dong , Lopez-Berestein Gabriel , Sood Anil K. , Conner Michael , Yang Eddy S. , Landen Charles N. 
Published: November 2012

Abstract
Purpose: Endoglin (CD105) is a membranous protein overexpressed in tumor-associated endothelial cells, chemoresistant populations of ovarian cancer cells, and potentially stem cells. Our objective was to evaluate the effects and mechanisms of targeting endoglin in ovarian cancer.
Experimental Design: Global and membranous endoglin expression was evaluated in multiple ovarian cancer lines. In vitro, the effects of siRNA-mediated endoglin knockdown with and without chemotherapy were evaluated by MTT assay, cell-cycle analysis, alkaline comet assay, γ-H2AX foci formation, and quantitative PCR. In an orthotopic mouse model, endoglin was targeted with chitosan-encapsulated siRNA with and without carboplatin.
Results: Endoglin expression was surprisingly predominantly cytoplasmic, with a small population of surface-positive cells. Endoglin inhibition decreased cell viability, increased apoptosis, induced double-stranded DNA damage, and increased cisplatin sensitivity. Targeting endoglin downregulates expression of numerous DNA repair genes, including BARD1, H2AFX, NBN, NTHL1, and SIRT1. BARD1 was also associated with platinum resistance, and was induced by platinum exposure. In vivo, antiendoglin treatment decreased tumor weight in both ES2 and HeyA8MDR models when compared with control (35%–41% reduction, P &lt; 0.05). Endoglin inhibition with carboplatin was associated with even greater inhibitory effect when compared with control (58%–62% reduction, P &lt; 0.001).
Conclusions: Endoglin downregulation promotes apoptosis, induces significant DNA damage through modulation of numerous DNA repair genes, and improves platinum sensitivity both in vivo and in vitro. Antiendoglin therapy would allow dual treatment of both tumor angiogenesis and a subset of aggressive tumor cells expressing endoglin and is being actively pursued as therapy in ovarian cancer. Clin Cancer Res; 19(1); 170–82. ©2012 AACR.
The Severity of Neural Invasion Is Associated with Shortened Survival in Colon Cancer
Authors: Liebl Florian , Demir Ihsan Ekin , Rosenberg Robert , Boldis Alexandra , Yildiz Esra , Kujundzic Kristina , Kehl Timo , Dischl Dominic , Schuster Tibor , Maak Matthias , Becker Karen , Langer Rupert , Laschinger Melanie , Friess Helmut , Ceyhan Güralp O. 
Published: November 2012

Abstract
Purpose: Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer.
Experimental Design: NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)–neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined.
Results: NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neurite-targeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer.
Conclusion: NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer. Clin Cancer Res; 19(1); 50–61. ©2012 AACR.
Word Segmentation, Unknown-word Resolution, and Morphological Agreement in a Hebrew Parsing System
Authors: Goldberg Yoav , Elhadad Michael 
Published: November 2012

We present a constituency parsing system for Modern Hebrew. The system is based on the PCFG-LA parsing method of Petrov et al. 2006 , which is extended in various ways in order to accommodate the specificities of Hebrew as a morphologically rich language with a small treebank. We show that parsing performance can be enhanced by utilizing a language resource external to the treebank, specifically, a lexicon-based morphological analyzer. We present a computational model of interfacing the external lexicon and a treebank-based parser, also in the common case where the lexicon and the treebank follow different annotation schemes. We show that Hebrew word-segmentation and constituency-parsing can be performed jointly using CKY lattice parsing. Performing the tasks jointly is effective, and substantially outperforms a pipeline-based model. We suggest modeling grammatical agreement in a constituency-based parser as a filter mechanism that is orthogonal to the grammar, and present a concrete implementation of the method. Although the constituency parser does not make many agreement mistakes to begin with, the filter mechanism is effective in fixing the agreement mistakes that the parser does make. These contributions extend outside of the scope of Hebrew processing, and are of general applicability to the NLP community. Hebrew is a specific case of a morphologically rich language, and ideas presented in this work are useful also for processing other languages, including English. The lattice-based parsing methodology is useful in any case where the input is uncertain. Extending the lexical coverage of a treebank-derived parser using an external lexicon is relevant for any language with a small treebank.
The Layered Structure of the Winter Atmospheric Boundary Layer in the Interior of Alaska
Authors: Mayfield John A. , Fochesatto Gilberto J. 
Published: November 2012

AbstractThe high-latitude winter atmospheric boundary layer of interior Alaska continually exhibits a complex layered structure as a result of extreme meteorological conditions. In this paper the occurrence of elevated inversions (EI), surface-based inversions (SBI), and stratified layers in the sub-Arctic from January 2000 to December 2009 is reported. This statistical analysis is based on radiosonde observation data from the Fairbanks National Weather Service station complemented by Winter Boundary Layer Experiment observations in the period 2010–11. This study found that SBIs occurred 64% of the time. An SBI occurred in combination with one, two, three, or four simultaneous EIs 84.86%, 48.49%, 21.23%, and 7.99% of the time, respectively, in 2326 total cases. The calculated mean SBI height was 377 m; EIs occurred at 1231, 2125, 2720, and 3125 m, respectively. This analysis was able to discriminate between locally controlled inversion layers and synoptic-dependent inversions and to identify their formation mechanisms. It was found that, in the presence of an SBI layer, the first EI layer formed 35.8% of the time under anticyclonic conditions at a mean height of 1249 m and 22% of the time in warm-air-advection situations at a mean height of 1049 m. The remaining 23.4% resulted from combined synoptic situations, and 18.8% were unclassified.
The Generation of Turbulence below Midlevel Cloud Bases: The Effect of Cooling due to Sublimation of Snow
Authors: Kudo Atsushi 
Published: November 2012

AbstractIn the author’s experience as a forecaster, commercial aircraft sometimes report turbulence beneath midlevel clouds that extend above upper frontal zones. Turbulence caused by Kelvin–Helmholtz instability occurs in upper frontal zones with strong vertical shear of horizontal winds. However, the turbulence seems to occur not only in the cloud bases (where upper frontal zones are) but also below the cloud bases where the vertical shear is not strong. Because those clouds are usually accompanied by precipitation that does not reach the ground, cooling by evaporation or sublimation seems to contribute to the generation of turbulence. In this paper, the mechanisms generating turbulence below midlevel cloud bases are examined by using observations and high-resolution three-dimensional numerical simulations with idealized initial conditions. The numerical simulations showed that the following sequence of events led to turbulence. Falling snow sublimated below cloud bases and cooled the air, which created absolute instability. This generated Rayleigh–Bénard convection cells. The vertical motion caused turbulence. The horizontal scale of the convection was about 800–1000 m, and the variations of vertical wind velocity were up to about 7 m s−1. The cloud base was accompanied by a virga-like distribution of snow. Sensitivity experiments showed the appropriate conditions to cause the turbulence: 1) the cloud-base temperature was between about 0° and −15°C, 2) the relative humidity in subcloud layers was sufficiently low, and 3) the stability in subcloud layers was weak. The results of the numerical simulations agreed well with the observations.
Observational Analysis of Tropical Cyclone Formation Associated with Monsoon Gyres
Authors: Wu Liguang , Zong Huijun , Liang Jia 
Published: November 2012

Abstract
Large-scale monsoon gyres and the involved tropical cyclone formation over the western North Pacific have been documented in previous studies. The aim of this study is to understand how monsoon gyres affect tropical cyclone formation. An observational study is conducted on monsoon gyres during the period 2000–10, with a focus on their structures and the associated tropical cyclone formation.
A total of 37 monsoon gyres are identified in May–October during 2000–10, among which 31 monsoon gyres are accompanied with the formation of 42 tropical cyclones, accounting for 19.8% of the total tropical cyclone formation. Monsoon gyres are generally located on the poleward side of the composited monsoon trough with a peak occurrence in August–October. Extending about 1000 km outward from the center at lower levels, the cyclonic circulation of the composited monsoon gyre shrinks with height and is replaced with negative relative vorticity above 200 hPa. The maximum winds of the composited monsoon gyre appear 500–800 km away from the gyre center with a magnitude of 6–10 m s−1 at 850 hPa. In agreement with previous studies, the composited monsoon gyre shows enhanced southwesterly flow and convection on the south-southeastern side. Most of the tropical cyclones associated with monsoon gyres are found to form near the centers of monsoon gyres and the northeastern end of the enhanced southwesterly flows, accompanying relatively weak vertical wind shear.
The Effects of Explicit versus Parameterized Convection on the MJO in a Large-Domain High-Resolution Tropical Case Study. Part I: Characterization of Large-Scale Organization and Propagation*
Authors: Holloway Christopher E. , Woolnough Steven J. , Lister Grenville M. S. 
Published: November 2012

Abstract
High-resolution simulations over a large tropical domain (~20°S–20°N, 42°E–180°) using both explicit and parameterized convection are analyzed and compared to observations during a 10-day case study of an active Madden–Julian oscillation (MJO) event. The parameterized convection model simulations at both 40- and 12-km grid spacing have a very weak MJO signal and little eastward propagation. A 4-km explicit convection simulation using Smagorinsky subgrid mixing in the vertical and horizontal dimensions exhibits the best MJO strength and propagation speed. Explicit convection simulations at 12 km also perform much better than the 12-km parameterized convection run, suggesting that the convection scheme, rather than horizontal resolution, is key for these MJO simulations. Interestingly, a 4-km explicit convection simulation using the conventional boundary layer scheme for vertical subgrid mixing (but still using Smagorinsky horizontal mixing) completely loses the large-scale MJO organization, showing that relatively high resolution with explicit convection does not guarantee a good MJO simulation. Models with a good MJO representation have a more realistic relationship between lower-free-tropospheric moisture and precipitation, supporting the idea that the moisture–convection feedback is a key process for MJO propagation. There is also increased generation of available potential energy and conversion of that energy into kinetic energy in models with a more realistic MJO, which is related to larger zonal variance in convective heating and vertical velocity, larger zonal temperature variance around 200 hPa, and larger correlations between temperature and ascent (and between temperature and diabatic heating) between 500 and 400 hPa.
Upper Oceanic Energy Response to Tropical Cyclone Passage
Authors: Knaff John A. , DeMaria Mark , Sampson Charles R. , Peak James E. , Cummings James , Schubert Wayne H. 
Published: November 2012

Abstract
The upper oceanic temporal response to tropical cyclone (TC) passage is investigated using a 6-yr daily record of data-driven analyses of two measures of upper ocean energy content based on the U.S. Navy’s Coupled Ocean Data Assimilation System and TC best-track records. Composite analyses of these data at points along the TC track are used to investigate the type, magnitude, and persistence of upper ocean response to TC passage, and to infer relationships between routinely available TC information and the upper ocean response. Upper oceanic energy decreases in these metrics are shown to persist for at least 30 days—long enough to possibly affect future TCs. Results also indicate that TC kinetic energy (KE) should be considered when assessing TC impacts on the upper ocean, and that existing TC best-track structure information, which is used here to estimate KE, is sufficient for such endeavors. Analyses also lead to recommendations concerning metrics of upper ocean energy. Finally, parameterizations for the lagged, along-track, upper ocean response to TC passage are developed. These show that the sea surface temperature (SST) is best related to the KE and the latitude whereas the upper ocean energy is a function of KE, initial upper ocean energy conditions, and translation speed. These parameterizations imply that the 10-day lagged SST cooling is approximately 0.7°C for a “typical” TC at 30° latitude, whereas the same storm results in 10-day (30-day) lagged decreases of upper oceanic energy by about 12 (7) kJ cm−2 and a 0.5°C (0.3°C) cooling of the top 100 m of ocean.
The Impact of Oceanic Near-Inertial Waves on Climate
Authors: Jochum Markus , Briegleb Bruce P. , Danabasoglu Gokhan , Large William G. , Norton Nancy J. , Jayne Steven R. , Alford Matthew H. , Bryan Frank O. 
Published: November 2012

Abstract
The Community Climate System Model, version 4 (CCSM4) is used to assess the climate impact of wind-generated near-inertial waves (NIWs). Even with high-frequency coupling, CCSM4 underestimates the strength of NIWs, so that a parameterization for NIWs is developed and included into CCSM4. Numerous assumptions enter this parameterization, the core of which is that the NIW velocity signal is detected during the model integration, and amplified in the shear computation of the ocean surface boundary layer module. It is found that NIWs deepen the ocean mixed layer by up to 30%, but they contribute little to the ventilation and mixing of the ocean below the thermocline. However, the deepening of the tropical mixed layer by NIWs leads to a change in tropical sea surface temperature and precipitation. Atmospheric teleconnections then change the global sea level pressure fields so that the midlatitude westerlies become weaker. Unfortunately, the magnitude of the real air-sea flux of NIW energy is poorly constrained by observations; this makes the quantitative assessment of their climate impact rather uncertain. Thus, a major result of the present study is that because of its importance for global climate the uncertainty in the observed tropical NIW energy has to be reduced.
A Comparison of Methods for Filling Gaps in Hourly Near-Surface Air Temperature Data
Authors: Henn Brian , Raleigh Mark S. , Fisher Alex , Lundquist Jessica D. 
Published: November 2012

AbstractNear-surface air temperature observations often have periods of missing data, and many applications using these datasets require filling in all missing periods. Multiple methods are available to fill missing data, but the comparative accuracy of these approaches has not been assessed. In this comparative study, five techniques were used to fill in missing temperature data: spatiotemporal correlations in the form of empirical orthogonal functions (EOFs), time series diurnal interpolation, and three variations of lapse rate–based filling. The method validation used sets of hourly surface temperature observations in complex terrain from five regions. The most accurate method for filling missing data depended on the number of available stations and the number of hours of missing data. Spatiotemporal correlations using EOF reconstruction were most accurate provided that at least 16 stations were available. Temporal interpolation was the most accurate method when only one or two stations were available or for 1-h gaps. Lapse rate–based filling was most accurate for intermediate numbers of stations. The accuracy of the lapse rate and EOF methods was found to be sensitive to the vertical separation of stations and the degree of correlation between them, which also explained some of the regional differences in performance. Horizontal distance was less significantly correlated with method performance. From these findings, guidelines are presented for choosing a filling method based on the duration of the missing data and the number of stations.
A Surface-Aware Projection Basis for Quasigeostrophic Flow
Authors: Smith K. Shafer , Vanneste Jacques 
Published: November 2012

Abstract
Recent studies indicate that altimetric observations of the ocean’s mesoscale eddy field reflect the combined influence of surface buoyancy and interior potential vorticity anomalies. The former have a surface-trapped structure, while the latter are often well represented by the barotropic and first baroclinic modes. To assess the relative importance of each contribution to the signal, it is useful to project the observed field onto a set of modes that separates their influence in a natural way. However, the surface-trapped dynamics are not well represented by standard baroclinic modes; moreover, they are dependent on horizontal scale.
Here the authors derive a modal decomposition that results from the simultaneous diagonalization of the energy and a generalization of potential enstrophy that includes contributions from the surface buoyancy fields. This approach yields a family of orthonormal bases that depend on two parameters; the standard baroclinic modes are recovered in a limiting case, while other choices provide modes that represent surface and interior dynamics in an efficient way.
For constant stratification, these modes consist of symmetric and antisymmetric exponential modes that capture the surface dynamics and a series of oscillating modes that represent the interior dynamics. Motivated by the ocean, where shears are concentrated near the upper surface, the authors consider the special case of a quiescent lower surface. In this case, the interior modes are independent of wavenumber, and there is a single exponential surface mode that replaces the barotropic mode. The use and effectiveness of these modes is demonstrated by projecting the energy in a set of simulations of baroclinic turbulence.
Eddy Saturation of Equilibrated Circumpolar Currents
Authors: Munday David R. , Johnson Helen L. , Marshall David P. 
Published: November 2012

Abstract
This study uses a sector configuration of an ocean general circulation model to examine the sensitivity of circumpolar transport and meridional overturning to changes in Southern Ocean wind stress and global diapycnal mixing. At eddy-permitting, and finer, resolution, the sensitivity of circumpolar transport to forcing magnitude is drastically reduced. At sufficiently high resolution, there is little or no sensitivity of circumpolar transport to wind stress, even in the limit of no wind. In contrast, the meridional overturning circulation continues to vary with Southern Ocean wind stress, but with reduced sensitivity in the limit of high wind stress. Both the circumpolar transport and meridional overturning continue to vary with diapycnal diffusivity at all model resolutions. The circumpolar transport becomes less sensitive to changes in diapycnal diffusivity at higher resolution, although sensitivity always remains. In contrast, the overturning circulation is more sensitive to change in diapycnal diffusivity when the resolution is high enough to permit mesoscale eddies.
Ophthalmoplegic migraine: Migraine or oculomotor neuropathy?
Authors: Margari Lucia , Legrottaglie Anna R , Craig Francesco , Petruzzelli Maria G , Procoli Ugo , Dicuonzo Franca 
Published: November 2012

Background Ophthalmoplegic migraine (OM) is a rare condition characterized by the association of headaches and an oculomotor nerve palsy. The third cranial nerve is commonly involved in recurrent attacks, whereas involvement of the sixth and fourth nerves is uncommon. It is still debated whether an uncontrolled migraine or an oculomotor neuropathy may be the primary cause of ophthalmoplegic migraine. Cases We report two patients affected by OM with normal magnetic resonance imaging findings and a history of uncontrolled migraine before an attack of OM. Conclusion The cases reported allow us to hypothesize that OM may be considered a form of migraine rather than a cranial neuralgia. It is possible that different factors such as inflammatory or structural factors, may represent a vulnerability of the nerve during a severe migraine attack causing ophthalmoplegia.
Migraine is not associated with enhanced atherosclerosis
Authors: Stam Anine H , Weller Claudia M , Janssens A Cecile JW , Aulchenko Yurii S , Oostra Ben A , Frants Rune R , van den Maagdenberg Arn MJM , Ferrari Michel D , van Duijn Cornelia M , Terwindt Gisela M 
Published: November 2012

Aim Migraine, in particular with aura, has been associated with an increased risk for ischemic stroke and coronary heart disease. The underlying mechanism is unknown. In a cross-sectional case control study we investigated whether an enhanced risk of atherosclerosis in migraineurs explains this increased cardiovascular risk. Methods Subjects were participants from the population-based Erasmus Rucphen Family study. Atherosclerosis was assessed in 360 migraineurs (209 without aura and 151 with aura) and 617 subjects without migraine or severe headache. Atherosclerosis was quantified by intima media thickness, pulse wave velocity and ankle-brachial index. Results Migraineurs, especially with aura, were found more likely to smoke, have diabetes or a modestly decreased HDL-cholesterol. No differences were found for the atherosclerosis parameters. Conclusion In this large population-based study, migraineurs have no increased risk of atherosclerosis. Therefore, enhanced atherosclerosis is an unlikely explanation for the increased cardiovascular risk seen in migraineurs.