bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF-03732010: A Fully Human Monoclonal Antibody against P-Cadherin with Antitumor and Antimetastatic Activity
Authors: Zhang Cathy C. , Yan Zhengming , Zhang Qin , Kuszpit Kyle , Zasadny Kenneth , Qiu Ming , Painter Cory L. , Wong Anthony , Kraynov Eugenia , Arango Maria E. , Mehta Pramod P. , Popoff Ian , Casperson Gerald F. , Los Gerrit , Bender Steve , Anderes Kenna , Christensen James G. , VanArsdale Todd 
Published: September 2010

Abstract
Purpose: P-cadherin is a membrane glycoprotein that functionally mediates tumor cell adhesion, proliferation, and invasiveness. We characterized the biological properties of PF-03732010, a human monoclonal antibody against P-cadherin, in cell-based assays and tumor models.
Experimental Design: The affinity, selectivity, and cellular inhibitory activity of PF-03732010 were tested in vitro. Multiple orthotopic and metastatic tumor models were used for assessing the antitumor and antimetastatic activities of PF-03732010. Treatment-associated pharmacodynamic changes were also investigated.
Results: PF-03732010 selectively inhibits P-cadherin–mediated cell adhesion and aggregation in vitro. In the P-cadherin–overexpressing tumor models, including MDA-MB-231-CDH3, 4T1-CDH3, MDA-MB-435HAL-CDH3, HCT116, H1650, PC3M-CDH3, and DU145, PF-03732010 inhibited the growth of primary tumors and metastatic progression, as determined by bioluminescence imaging. Computed tomography imaging, H&E stain, and quantitative PCR analysis confirmed the antimetastatic activity of PF-03732010. In contrast, PF-03732010 did not show antitumor and antimetastatic efficacy in the counterpart tumor models exhibiting low P-cadherin expression. Mechanistic studies via immunofluorescence, immunohistochemical analyses, and 3′-[18F]fluoro-3′-deoxythymidine–positron emission tomography imaging revealed that PF-03732010 suppressed P-cadherin levels, caused degradation of membrane β-catenin, and concurrently suppressed cytoplasmic vimentin, resulting in diminished metastatic capacity. Changes in the levels of Ki67, caspase-3, and 3′-[18F]fluoro-3′-deoxythymidine tracer uptake also indicated antiproliferative activity and increased apoptosis in the tested xenografts.
Conclusions: These findings suggest that interrupting the P-cadherin signaling pathway may be a novel therapeutic approach for cancer therapy. PF-03732010 is presently undergoing evaluation in Phase 1 clinical trials. Clin Cancer Res; 16(21); 5177–88. ©2010 AACR.
Heterogeneous Blood–Tumor Barrier Permeability Determines Drug Efficacy in Experimental Brain Metastases of Breast Cancer
Authors: Lockman Paul R. , Mittapalli Rajendar K. , Taskar Kunal S. , Rudraraju Vinay , Gril Brunilde , Bohn Kaci A. , Adkins Chris E. , Roberts Amanda , Thorsheim Helen R. , Gaasch Julie A. , Huang Suyun , Palmieri Diane , Steeg Patricia S. , Smith Quentin R. 
Published: September 2010

AbstractPurpose: Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood–tumor barrier (BTB) is compromised in many brain metastases; however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain.Experimental Design:Experimental brain metastasis drug uptake and BTB permeability were simultaneously measured using novel fluorescent and phosphorescent imaging techniques in immune-compromised mice. Drug-induced apoptosis and vascular characteristics were assessed using immunofluorescent microscopy.Results: Analysis of over 2,000 brain metastases from two models (human 231-BR-Her2 and murine 4T1-BR5) showed partial BTB permeability compromise in greater than 89% of lesions, varying in magnitude within and between metastases. Brain metastasis uptake of 14C-paclitaxel and 14C-doxorubicin was generally greater than normal brain but less than 15% of that of other tissues or peripheral metastases, and only reached cytotoxic concentrations in a small subset (∼10%) of the most permeable metastases. Neither drug significantly decreased the experimental brain metastatic ability of 231-BR-Her2 tumor cells. BTB permeability was associated with vascular remodeling and correlated with overexpression of the pericyte protein desmin.Conclusions: This work shows that the BTB remains a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will be needed. Evidence is presented for vascular remodeling in BTB permeability alterations. Clin Cancer Res; 16(23); 5664–78. ©2010 AACR.
A MicroRNA Screen to Identify Modulators of Sensitivity to BCL2 Inhibitor ABT-263 (Navitoclax)
Authors: Lam Lloyd T. , Lu Xin , Zhang Haichao , Lesniewski Rick , Rosenberg Saul , Semizarov Dimitri 
Published: September 2010

AbstractEvasion of apoptosis is a known feature of cancer cells. One mechanism of deregulating the apoptotic pathway is through overexpression of antiapoptotic BCL2 family members. ABT-263 (navitoclax) is a first-in-class BCL2 family inhibitor that restores the ability of cancer cells to undergo apoptosis. However, many cancer cells are resistant to ABT-263 due to high levels of a BCL2 family member, MCL1, which is not targeted by the drug. MCL1 expression is regulated transcriptionally, translationally, and through proteasome-mediated degradation. Recently, MCL1 expression was shown to be affected by microRNAs (miRNA). To identify miRNAs that modulate the sensitivity of cancer cells to ABT-263, we screened a library of 810 human miRNA mimics in HCT-116 cells in the presence of ABT-263. The screen revealed 19 miRNAs that sensitize HCT-116 cells to ABT-263. Fifteen of these miRNAs were also shown to sensitize CHL1 melanoma cells to the same agent. We further evaluated 12 of the strongest sensitizers in these cell lines. We found that these sensitizers induced apoptosis only in the presence of ABT-263. In addition, whereas all 12 of these miRNAs reduced MCL1 protein expression, only 10 of them targeted MCL1 through direct binding to the 3′-untranslated region of the gene, raising the possibility that other resistance regulators of MCL1 expression may be identified using our method. Finally, because sensitizing miRNA expression is lower in tumors compared with normal tissues, our data can facilitate the design of miRNA replacement therapies to increase sensitivity to BCL2 antagonists. Mol Cancer Ther; 9(11); 2943–50. ©2010 AACR.
Increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and colorectal adenocarcinoma determined by a newly developed ELISA using a specific monoclonal antibody
Authors: Ordóñez Adriana , Yélamos Jose , Pedersen Shona , Miñano Antonia , Conesa-Zamora Pablo , Kristensen Soren R. , Stender Mogens T. , Thorlacius-Ussing Ole , Martínez-Martínez Irene , Vicente Vicente , Corral Javier 
Published: September 2010

SummaryCitrullination is a post-translational modification that plays essential roles in both physiological processes and disease. Recent studies have found increased levels of citrullinated antithrombin in patients with rheumatoid arthritis and in different malignant tumours. Antithrombin, the main haemostatic serpin, loses its anticoagulant function via citrullination, which might contribute to the pathogenesis or thrombotic side effects of these disorders. We have developed a specific monoclonal antibody against citrullinated antithrombin. We determined the levels of citrullinated antithrombin and anti-FXa activity in plasma from 66 donors, 17 patients with rheumatoid arthritis and 77 patients with colorectal adenocarcinoma (42 suffering from venous thrombosis). Healthy subjects had negligible amounts of citrullinated antithrombin in plasma (7.9 ± 22.1 ng/ml), while it significantly increased in patients with rheumatoid arthritis or adenocarcinoma (159.7 ± 237.6 ng/ml and 36.8 ± 66.1 ng/ml), levels that, however, did not modify the plasma anticoagulant activity. Moreover, we did not find association between citrullinated antithrombin and the thrombotic risk in patients with adenocarcinoma. In conclusion, we have developed an antibody specific for citrullinated antithrombin that allows its quantification in biological samples, offering a new tool for the analysis of citrullination in different diseases. We confirm increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and adenocarcinoma. This modification, probably local, could have pathological consequences in both disorders, but only affects a minor fraction of plasma antithrombin, resulting in no significant reduction of global anticoagulant activity. This result explains the absence of association of this marker with an increased risk of thrombosis in patients with colorectal adenocarcinoma.
The Decline of African American Theology? A Critical Response to Thabiti Anyabwile
Authors: Yong Amos , Brogdon Lewis 
Published: September 2010

AbstractThabiti Anyabwile’s recent book, The Decline of African American Theology: From Biblical Faith to Cultural Captivity, presents a historical and theological critique of developments in the African American theological tradition. Yet Anyabwile’s polemic is questionable as it is based on Reformed theology’s reading of the Bible. This essay raises questions about the methodological underpinnings of Anyabwile’s thesis, particularly its problematic and uncritical application to the African American Christian experience, and suggests in turn that the author should have written another kind of book to further the conversation about African American theology.
Numerical Investigations of Seasonal and Interannual Variability of North Pacific Subtropical Mode Water and Its Implications for Pacific Climate Variability
Authors: Davis Xujing Jia , Rothstein Lewis M. , Dewar William K. , Menemenlis Dimitris 
Published: September 2010

Abstract
North Pacific Subtropical Mode Water (NPSTMW) is an essential feature of the North Pacific subtropical gyre imparting significant influence on regional SST evolution on seasonal and longer time scales and, as such, is an important component of basin-scale North Pacific climate variability. This study examines the seasonal-to-interannual variability of NPSTMW, the physical processes responsible for this variability, and the connections between NPSTMW and basin-scale climate signals using an eddy-permitting 1979–2006 ocean simulation made available by the Estimating the Circulation and Climate of the Ocean, Phase II (ECCO2). The monthly mean seasonal cycle of NPSTMW in the simulation exhibits three distinct phases: (i) formation during November–March, (ii) isolation during March–June, and (iii) dissipation during June–November—each corresponding to significant changes in upper-ocean structure. An interannual signal is also evident in NPSTMW volume and other characteristic properties with volume minima occurring in 1979, 1988, and 1999. This volume variability is correlated with the Pacific decadal oscillation (PDO) with zero time lag. Further analyses demonstrate the connection of NPSTMW to the basin-scale ocean circulation. With this, modulations of upper-ocean structure driven by the varying strength and position of the westerlies as well as the regional air–sea heat flux pattern are seen to contribute to the variability of NPSTMW volume on interannual time scales.
Mechanisms Associated with Large Daily Rainfall Events in Northeast Brazil
Authors: Liebmann Brant , Kiladis George N. , Allured Dave , Vera Carolina S. , Jones Charles , Carvalho Leila M. V. , Bladé Ileana , Gonzáles Paula L. M. 
Published: September 2010

Abstract
The mechanisms resulting in large daily rainfall events in Northeast Brazil are analyzed using data filtering to exclude periods longer than 30 days. Composites of circulation fields that include all independent events do not reveal any obvious forcing mechanisms as multiple patterns contribute to Northeast Brazil precipitation variability. To isolate coherent patterns, subsets of events are selected based on anomalies that precede the Northeast Brazil precipitation events at different locations. The results indicate that at 10°S, 40°W, the area of lowest annual rainfall in Brazil, precipitation occurs mainly in association with trailing midlatitude synoptic wave trains originating in either hemisphere. Closer to the equator at 5°S, 37.5°W, an additional convection precursor is found to the west, with a spatial structure consistent with that of a Kelvin wave. Although these two sites are located within only several hundred kilometers of each other and the midlatitude patterns that induce precipitation appear to be quite similar, the dates on which large precipitation anomalies occur at each location are almost entirely independent, pointing to separate forcing mechanisms.
Relationship between the Arctic Oscillation and Cold Surges over East Asia
Authors: Park Tae-Won , Ho Chang-Hoi , Yang Song 
Published: September 2010

Abstract
The present study reveals the changes in the characteristics of cold surges over East Asia associated with the Arctic Oscillation (AO). Based on circulation features, cold surges are grouped into two general types: wave train and blocking types. The blocking type of cold surge tends to occur during negative AO periods, that is, the AO-related polarity of the blocking type. However, the wave train type is observed during both positive and negative AO periods, although the wave train features associated with negative AO are relatively weaker. The cold surges during negative AO are stronger than those during positive AO in terms of both amplitude and duration. The cold surges during positive AO in which the extent of effect is confined to inland China passes through East Asia quickly because of weaker Siberian high and Aleutian low, leading to short duration of these cold surges. In contrast, the cold surge during negative AO, characterized by a well-organized anticyclone–cyclone couplet with high pressure over continental East Asia and low pressure over Japan, brings continuous cold air into the entire East Asian region for more than one week with long-lasting cold advection. It is also found that the tracks of the cold surges during negative AO tend to occur more frequently over Korea and Japan and less frequently over China, compared with those during positive AO. The tracks are related to a west–east dipole structure of the ratio of rain conversion to snow according to AO phase, resulting in freezing precipitation or snowfall events over inland China (Korea and Japan) are likely to occur more frequently during the positive (negative) AO periods.
Bayesian Forecasting of Seasonal Typhoon Activity: A Track-Pattern-Oriented Categorization Approach
Authors: Chu Pao-Shin , Zhao Xin , Ho Chang-Hoi , Kim Hyeong-Seog , Lu Mong-Ming , Kim Joo-Hong 
Published: September 2010

AbstractA new approach to forecasting regional and seasonal tropical cyclone (TC) frequency in the western North Pacific using the antecedent large-scale environmental conditions is proposed. This approach, based on TC track types, yields probabilistic forecasts and its utility to a smaller region in the western Pacific is demonstrated. Environmental variables used include the monthly mean of sea surface temperatures, sea level pressures, low-level relative vorticity, vertical wind shear, and precipitable water of the preceding May. The region considered is the vicinity of Taiwan, and typhoon season runs from June through October. Specifically, historical TC tracks are categorized through a fuzzy clustering method into seven distinct types. For each cluster, a Poisson or probit regression model cast in the Bayesian framework is applied individually to forecast the seasonal TC activity. With a noninformative prior assumption for the model parameters, and following Chu and Zhao for the Poisson regression model, a Bayesian inference for the probit regression model is derived. A Gibbs sampler based on the Markov chain Monte Carlo method is designed to integrate the posterior predictive distribution. Because cluster 5 is the most dominant type affecting Taiwan, a leave-one-out cross-validation procedure is applied to predict seasonal TC frequency for this type for the period of 1979–2006, and the correlation skill is found to be 0.76.
Advection of the Salt Wedge and Evolution of the Internal Flow Structure in the Rotterdam Waterway
Authors: de Nijs Michel A. J. , Pietrzak Julie D. , Winterwerp Johan C. 
Published: September 2010

Abstract
An analysis of field measurements recorded over a tidal cycle in the Rotterdam Waterway is presented. These measurements are the first to elucidate the processes influencing the along-channel current structure and the excursion of the salt wedge in this estuary. The salt wedge structure remained stable throughout the measuring period. The velocity measurements indicate decoupling effects between the layers and that bed-generated turbulence is confined below the pycnocline. The barotropic M4 overtide structure is imposed at the mouth of the estuary, and the generation of M4 overtides within the estuary is found to be relatively small. Internal tidal asymmetry does not make a significant contribution to the M4 velocity frequency band. Instead, the combination of barotropic and baroclinic forcing, in conjunction with the suppression of turbulence at the interface, provides the main explanation for the time dependence and mean structure of the flow in the Rotterdam Waterway. This gives rise to the observed differences in the length of the flood and ebb, in the magnitudes of the flood and ebb velocities, in the length of the slack water periods, and in the timing of the onset of slack water at the surface and near the bed. It results in the formation of distinct exchange flow profiles at the head of the salt wedge around slack water and the creation of maximal velocities at the pycnocline during flood. Advection governs the displacement and structure of the salt wedge since turbulent mixing is suppressed. The tidal displacement of the salt wedge controls the height of the pycnocline above the bed at a particular site. Hence, it controls the height to which bed-generated turbulence can protrude into the water column. Consequently, the authors find asymmetries in the structure of the internal flow, turbulent mixing, and bed stresses that are not related to classical internal tidal asymmetry.
Typhoon Kai-Tak: An Ocean’s Perfect Storm
Authors: Chiang Tzu-Ling , Wu Chau-Ron , Oey Lie-Yauw 
Published: September 2010

Abstract
An unusually intense sea surface temperature drop (ΔSST) of about 10.8°C induced by the Typhoon Kai-Tak is observed in the northern South China Sea (SCS) in July 2000. Observational and high-resolution SCS model analyses were carried out to study the favorable conditions and relevant physical processes that cause the intense surface cooling by Kai-Tak. Upwelling and entrainment induced by Kai-Tak account for 62% and 31% of the ΔSST, respectively, so that upwelling dominates vertical entrainment in producing the surface cooling for a subcritical storm such as Kai-Tak. However, wind intensity and propagation speed alone cannot account for the large ΔSST. Prior to Kai-Tak, the sea surface was anomalously warm and the main thermocline was anomalously shallow. The cause was a delayed transition of winter to summer monsoon in the northern SCS in May 2000. This produced an anomalously strong wind stress curl and a cold eddy capped by a thin layer of very warm surface water west of Luzon. Kai-Tak was the ocean’s perfect storm in passing over the eddy at the “right time,” producing the record SST drop and high chlorophyll-a concentration.
Examining the Probability of Identification for Gifted Programs for Students in Georgia Elementary Schools: A Multilevel Path Analysis Study
Authors: McBee Matthew 
Published: September 2010

This study focused on the analysis of a large-scale data set ( N = 326,352) collected by the Georgia Department of Education using multilevel path analysis to model the probability that a student would be identified for participation in a gifted program. The model examined individual- and school-level factors that influence the probability that an individual would be identified. The probability of being identified as gifted depended strongly on student race and socioeconomic status and varied strongly across schools. Putting the Research to Use This study provides a comprehensive examination of racial and socioeconomic disparities in gifted program participation in one state mandating gifted education and an identification scheme designed to increase participation among traditionally underrepresented groups of students. In spite of these policies, identification rates still varied widely across race and socioeconomic status. The study found that race still exerted strong effects on the probability of identification even after socioeconomic status was controlled. Furthermore, the study found that schools varied widely in the gifted identification rate even when some student characteristics were controlled. This study suggests that much work remains to be done in terms of ensuring that all students, regardless of background, have access to advanced educational programs.