bluuebunny/crossref_metadata_2025 huggingface dataset:
CX-4945, an Orally Bioavailable Selective Inhibitor of Protein Kinase CK2, Inhibits Prosurvival and Angiogenic Signaling and Exhibits Antitumor Efficacy
Authors: Siddiqui-Jain Adam , Drygin Denis , Streiner Nicole , Chua Peter , Pierre Fabrice , O'Brien Sean E. , Bliesath Josh , Omori Mayuko , Huser Nanni , Ho Caroline , Proffitt Chris , Schwaebe Michael K. , Ryckman David M. , Rice William G. , Anderes Kenna
Published: December 2010

Malignant transformation and maintenance of the malignant phenotype depends on oncogenic and non-oncogenic proteins that are essential to mediate oncogene signaling and to support the altered physiologic demands induced by transformation. Protein kinase CK2 supports key prosurvival signaling pathways and represents a prototypical non-oncogene. In this study, we describe CX-4945, a potent and selective orally bioavailable small molecule inhibitor of CK2. The antiproliferative activity of CX-4945 against cancer cells correlated with expression levels of the CK2α catalytic subunit. Attenuation of PI3K/Akt signaling by CX-4945 was evidenced by dephosphorylation of Akt on the CK2-specific S129 site and the canonical S473 and T308 regulatory sites. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. In models of angiogenesis, CX-4945 inhibited human umbilical vein endothelial cell migration, tube formation, and blocked CK2-dependent hypoxia-induced factor 1 alpha (HIF-1α) transcription in cancer cells. When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145). The observed antiproliferative and anti-angiogenic responses to CX-4945 in tumor cells and endothelial cells collectively illustrate that this compound exerts its antitumor effects through inhibition of CK2-dependent signaling in multiple pathways. Finally, CX-4945 is the first orally bioavailable small molecule inhibitor of CK2 to advance into human clinical trials, thereby paving the way for an entirely new class of targeted treatment for cancer. Cancer Res; 70(24); 10288–98. ©2010 AACR.
Dual Functional Monoclonal Antibody PF-04605412 Targets Integrin α5β1 and Elicits Potent Antibody-Dependent Cellular Cytotoxicity
Authors: Li Gang , Zhang Lianglin , Chen Enhong , Wang Jianying , Jiang Xin , Chen Jeffrey H. , Wickman Grant , Amundson Karin , Bergqvist Simon , Zobel James , Buckman Dana , Baxi Sangita M. , Bender Steven L. , Casperson Gerald F. , Hu-Lowe Dana D.
Published: December 2010

Integrin α5β1 is overexpressed in tumor-associated stroma and cancer cells, and has been implicated in angiogenesis, tumor survival, and metastasis. Antibody-dependent cellular cytotoxicity (ADCC) by immune effector cells has been shown to contribute to clinical efficacy for several IgG1 monoclonal antibody (mAb) therapeutics. Taking advantage of these two mechanisms, we generated a fully human, fragment crystalizable (Fc)-engineered IgG1 mAb, PF-04605412 (PF-5412), which specifically neutralizes α5 and binds the Fcγ receptors (FcγR) with enhanced affinity. In vitro, PF-5412 potently inhibited α5β1-mediated intracellular signaling, cell adhesion, migration, and endothelial cell (EC) tubulogenesis. PF-5412 induced significantly greater ADCC in α5-expressing tumor cells and ECs compared with a wild-type IgG1 (IgG1/wt) or IgG2 of identical antigen specificity. The degree of ADCC correlated with the abundance of natural killer (NK) cells in the peripheral blood mononuclear cells but was independent of donor FcγRIIIa polymorphism. In animal studies, PF-5412 displayed robust and dose-dependent antitumor efficacy superior to that observed with IgG1/wt, IgG2, or IgG4 of identical antigen specificity. The degree of efficacy correlated with α5 expression, macrophage and NK cell infiltration, and NK activity in the tumor. Depletion of host macrophages abrogated antitumor activity, suggesting a critical contribution of macrophage-mediated antitumor activity of PF-5412. Combination of PF-5412 with sunitinib significantly improved antitumor efficacy compared with either agent alone. The dual mechanism of action and robust antitumor efficacy of PF-5412 support its clinical development for the treatment of a broad spectrum of human malignancies. Cancer Res; 70(24); 10243–54. ©2010 AACR.
Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase
Authors: Colombo Riccardo , Caldarelli Marina , Mennecozzi Milena , Giorgini Maria Laura , Sola Francesco , Cappella Paolo , Perrera Claudia , Depaolini Stefania Re , Rusconi Luisa , Cucchi Ulisse , Avanzi Nilla , Bertrand Jay Aaron , Bossi Roberto Tiberio , Pesenti Enrico , Galvani Arturo , Isacchi Antonella , Colotta Francesco , Donati Daniele , Moll Jürgen
Published: December 2010

MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. Here we report the identification and characterization of NMS-P715, a selective and orally bioavailable MPS1 small-molecule inhibitor, which selectively reduces cancer cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical cancer models. Inhibiting the SAC could represent a promising new approach to selectively target cancer cells. Cancer Res; 70(24); 10255–64. ©2010 AACR.
Prognostic Value and Function of KLF4 in Prostate Cancer: RNAa and Vector-Mediated Overexpression Identify KLF4 as an Inhibitor of Tumor Cell Growth and Migration
Authors: Wang Ji , Place Robert F. , Huang Vera , Wang Xiaoling , Noonan Emily J. , Magyar Clara E. , Huang Jiaoti , Li Long-Cheng
Published: December 2010

KLF4/GLKF4 is a transcription factor that can have divergent functions in different malignancies. The role of KLF4 in prostate cancer etiology remains unclear. We have recently reported that small double-stranded RNA can induce gene expression by targeting promoter sequence in a phenomenon referred to as RNA activation (RNAa). In this study, we examine KLF4 levels in prostate cancer tissue and utilize RNAa as a tool for gene overexpression to investigate its function. Expression analysis indicated that KLF4 is significantly downregulated in prostate cancer cell lines compared with nontumorigenic prostate cells. Meta-analysis of existing cDNA microarray data also revealed that KLF4 is frequently depleted in prostate cancer tissue with more pronounced reduction in metastases. In support, tissue microarray analysis of tumors and patient-matched controls indicated downregulation of KLF4 in metastatic tumor samples. Logistic regression analysis found that tumors with a KLF4 staining score less than 5 had a 15-fold higher risk for developing metastatic prostate cancer (P = 0.001; 95% confidence interval, 3.0–79.0). In vitro analysis indicated that RNAa-mediated overexpression of KLF4 inhibited prostate cancer cell proliferation and survival and altered the expression of several downstream cell-cycle–related genes. Ectopic expression of KLF4 via viral transduction recapitulated the RNAa results, validating its inhibitory effects on cancer growth. Reactivation of KLF4 also suppressed migration and invasion of prostate cancer cells. These results suggest that KLF4 functions as an inhibitor of tumor cell growth and migration in prostate cancer and decreased expression has prognostic value for predicting prostate cancer metastasis. Cancer Res; 70(24); 10182–91. ©2010 AACR.
Free Tubulin Modulates Mitochondrial Membrane Potential in Cancer Cells
Authors: Maldonado Eduardo N. , Patnaik Jyoti , Mullins Matthew R. , Lemasters John J.
Published: December 2010

Formation of the mitochondrial membrane potential (ΔΨ) depends on flux of respiratory substrates, ATP, ADP, and Pi through voltage-dependent anion channels (VDAC). As tubulin promotes single-channel closure of VDAC, we hypothesized that tubulin is a dynamic regulator of ΔΨ, which in cultured cancer cells was assessed by confocal microscopy of the potential-indicating fluorophore tetramethylrhodamine methylester (TMRM). Microtubule destabilizers, rotenone, colchicine, and nocodazole, and the microtubule stabilizer paclitaxel increased and decreased cellular free tubulin, respectively, and in parallel decreased and increased ΔΨ. Protein kinase A (PKA) activation by cAMP analogues and glycogen synthase kinase 3β (GSK-3β) inhibition decreased ΔΨ, whereas PKA inhibition hyperpolarized, consistent with reports that PKA and GSK-3β decrease and increase VDAC conductance, respectively. Plasma membrane potential assessed by DiBAC4(3) was not altered by any of the treatments. We propose that inhibition of VDAC by free tubulin limits mitochondrial metabolism in cancer cells. Cancer Res; 70(24); 10192–201. ©2010 AACR.
Imaging Cycling Tumor Hypoxia
Authors: Matsumoto Shingo , Yasui Hironobu , Mitchell James B. , Krishna Murali C.
Published: December 2010

Cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. Cycling hypoxia can exist more than 100-μm distances from a microvessel, and some of these regions have been shown to exist adjacent to normal tissue. Fluctuations in pO2 of approximately 20 mm Hg can occur with periodicities of minutes to hours and even days. These fluctuations have been attributed to changes in erythrocyte flux, perfusion, and also development of newer vascular networks. Cycling hypoxia has been shown to induce the expression of hypoxia-inducible transcription factor-1α (HIF-1α) and also confer tumor cells and tumor vascular endothelial cells with enhanced prosurvival pathways, making tumors less responsive to radiation and chemotherapy. Imaging of cycling hypoxia in tumors can provide capabilities to help plan appropriate treatment, by taking into account the magnitude and frequency of fluctuations and also their locations adjacent to normal tissue. Electron paramagnetic resonance imaging (EPRI) provides the ability to distinguish chronic and cycling hypoxic regions and has the required spatial and temporal resolutions to provide quantitative maps of tumor pO2. EPRI can serve as a valuable tool in examining tumor pO2 longitudinally in response to treatment and in an experimentally chosen time window to spatially map fluctuations in pO2 noninvasively in animal models of implanted or orthotopic tumors, with a potential for human applications. Cancer Res; 70(24); 10019–23. ©2010 AACR.
Monensin Is a Potent Inducer of Oxidative Stress and Inhibitor of Androgen Signaling Leading to Apoptosis in Prostate Cancer Cells
Authors: Ketola Kirsi , Vainio Paula , Fey Vidal , Kallioniemi Olli , Iljin Kristiina
Published: December 2010

Current treatment options for advanced and hormone refractory prostate cancer are limited and responses to commonly used androgen pathway inhibitors are often unsatisfactory. Our recent results indicated that sodium ionophore monensin is one of the most potent and cancer-specific inhibitors in a systematic sensitivity testing of most known drugs and drug-like molecules in a panel of prostate cancer cell models. Because monensin has been extensively used in veterinary applications to build muscle mass in cattle, the link to prostate cancer and androgen signaling was particularly interesting. Here, we showed that monensin effects at nanomolar concentrations are linked to induction of apoptosis and potent reduction of androgen receptor mRNA and protein in prostate cancer cells. Monensin also elevated intracellular oxidative stress in prostate cancer cells as evidenced by increased generation of intracellular reactive oxygen species and by induction of a transcriptional profile characteristic of an oxidative stress response. Importantly, the antiproliferative effects of monensin were potentiated by combinatorial treatment with the antiandrogens and antagonized by antioxidant vitamin C. Taken together, our results suggest monensin as a potential well-tolerated, in vivo compatible drug with strong proapoptotic effects in prostate cancer cells, and synergistic effects with antiandrogens. Moreover, our data suggest a general strategy by which the effects of antiandrogens could be enhanced by combinatorial administration with agents that increase oxidative stress in prostate cancer cells. Mol Cancer Ther; 9(12); 3175–85. ©2010 AACR.
Combined Inhibition of Notch Signaling and Bcl-2/Bcl-xL Results in Synergistic Antimyeloma Effect
Authors: Li Ming , Chen Feng , Clifton Nicholas , Sullivan Daniel M. , Dalton William S. , Gabrilovich Dmitry I. , Nefedova Yulia
Published: December 2010

Signaling through the receptor/transcriptional regulator Notch plays an important role in tumor cell survival. Recent studies have demonstrated that pharmacological inhibition of the Notch pathway with γ-secretase inhibitor (GSI) induces apoptosis of multiple myeloma (MM) cells via upregulation of the proapoptotic protein Noxa. ABT-737, a novel BH3 mimetic, was shown to block Bcl-2 and Bcl-xL and induce MM cell apoptosis. Here, we investigated whether the inhibition of Notch signaling could enhance the proapoptotic effect of ABT-737. The antimyeloma effect of ABT-737 on MM cell lines or primary cells was substantially increased by the addition of Notch inhibitor. The synergistic effect of the GSI+ABT-737 combination was mediated by activation of Bak and Bax and release of cytochrome c. While toxic for MM cells, the combination of GSI and ABT-737 did not affect survival of peripheral blood mononuclear cells isolated from healthy donors. In vivo experiments using xenograft and SCID-hu models of MM demonstrated a significant antitumor effect of the GSI/ABT-737 combination as compared to the effect of Notch or Bcl-2/Bcl-xL inhibitors alone. Thus, this drug combination may be therapeutically beneficial for patients with MM. Mol Cancer Ther; 9(12); 3200–9. ©2010 AACR.
Combination of Vorinostat and Flavopiridol Is Selectively Cytotoxic to Multidrug-Resistant Neuroblastoma Cell Lines with Mutant TP53
Authors: Huang Jen-Ming , Sheard Michael A. , Ji Lingyun , Sposto Richard , Keshelava Nino
Published: December 2010

As p53 loss of function (LOF) confers high-level drug resistance in neuroblastoma, p53-independent therapies might have superior activity in recurrent neuroblastoma. We tested the activity of vorinostat, a histone deacetylase inhibitor, and flavopiridol, a pan-Cdk inhibitor, in a panel of multidrug-resistant neuroblastoma cell lines that included lines with wild-type (wt) and transcriptionally active TP53 (n = 3), mutated (mt), and LOF TP53 (n = 4) or p14ARF deletion (n = 1). The combination of vorinostat and flavopiridol was synergistic and significantly more cytotoxic (P < 0.001) in cell lines with p53-LOF and in the clones stably transfected with dominant-negative p53 plasmids. Cell cycle analysis by flow cytometry showed prominent cell-cycle arrest in G2/M (37%) for a cell line with wt TP53 (SK-N-RA) at 16 to 20 hours, while cells with mt TP53 (CHLA-90) slipped into sub-G1 at 6 to 24 hours (25%–40% specific cell death). The morphological hallmarks of mitotic cell death, including defective spindle formation and abnormal cytokinesis, were detected by confocal microscopy after the treatment with vorinostat + flavopiridol combination in CHLA-90. The combination caused reduction in the expression of G2/M proteins (cyclin B1, Mad2, MPM2) in 2 cell lines with mt TP53 but not in those with wt TP53. Plk1 expression was reduced in all treated lines. Small interfering RNA knockdown of Mad2 and cyclin B1 or Plk1 synergistically reduced the clonogenicity of CHLA-90 cells. The combination of HDAC inhibitor and flavopiridol may be a unique approach to treating neuroblastomas with p53 LOF, one that evokes induction of mitotic failure. Mol Cancer Ther; 9(12); 3289–301. ©2010 AACR.
The Histone Deacetylase Inhibitor, Vorinostat, Reduces Tumor Growth at the Metastatic Bone Site and Associated Osteolysis, but Promotes Normal Bone Loss
Authors: Pratap Jitesh , Akech Jacqueline , Wixted John J. , Szabo Gabriela , Hussain Sadiq , McGee-Lawrence Meghan E. , Li Xiaodong , Bedard Krystin , Dhillon Robinder J. , van Wijnen Andre J. , Stein Janet L. , Stein Gary S. , Westendorf Jennifer J. , Lian Jane B.
Published: December 2010

Vorinostat, an oral histone deacetylase inhibitor with antitumor activity, is in clinical trials for hematologic and solid tumors that metastasize and compromise bone structure. Consequently, there is a requirement to establish the effects of vorinostat on tumor growth within bone. Breast (MDA-231) and prostate (PC3) cancer cells were injected into tibias of SCID/NCr mice and the effects of vorinostat on tumor growth and osteolytic disease were assessed by radiography, micro-computed tomography, and histologic and molecular analyses. Vorinostat-treated and control mice without tumors were also examined. Tumor growth in bone was reduced ∼33% by vorinostat with inhibited osteolysis in the first few weeks of the experiment. However, osteolysis became more severe in both the vehicle and vorinostat-treated groups. Vorinostat increased the expression of tumor-derived factors promoting bone resorption, including PTHrP, IL-8, and osteopontin. After 4 weeks of vorinostat therapy, the non–tumor-bearing contralateral femurs and limbs from vorinostat-treated tumor-free SCID mice showed significant bone loss (50% volume density of controls). Thus, our studies indicate that vorinostat effectively inhibits tumor growth in bone, but has a negative systemic effect reducing normal trabecular bone mass. Vorinostat treatment reduces tumor growth in bone and accompanying osteolytic disease as a result of decreased tumor burden in bone. However, vorinostat can promote osteopenia throughout the skeleton independent of tumor cell activity. Mol Cancer Ther; 9(12); 3210–20. ©2010 AACR.
GT-094, a NO-NSAID, Inhibits Colon Cancer Cell Growth by Activation of a Reactive Oxygen Species-MicroRNA-27a: ZBTB10-Specificity Protein Pathway
Authors: Pathi Satya S. , Jutooru Indira , Chadalapaka Gayathri , Sreevalsan Sandeep , Anand S , Thatcher Gregory RJ , Safe Stephen
Published: December 2010

Ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094) is a novel nitric oxide (NO) chimera containing an nonsteroidal anti-inflammatory drug (NSAID) and NO moieties and also a disulfide pharmacophore that in itself exhibits cancer chemopreventive activity. In this study, the effects and mechanism of action of GT-094 were investigated in RKO and SW480 colon cancer cells. GT-094 inhibited cell proliferation and induced apoptosis in both cell lines and this was accompanied by decreased mitochondrial membrane potential (MMP) and induction of reactive oxygen species (ROS), and these responses were reversed after cotreatment with the antioxidant glutathione. GT-094 also downregulated genes associated with cell growth [cyclin D1, hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR)], survival (bcl-2, survivin), and angiogenesis [VEGF and its receptors (VEGFR1 and VEGFR2)]. Results of previous RNA interference studies in this laboratory has shown that these genes are regulated, in part, by specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 that are overexpressed in colon and other cancer cell lines and not surprisingly, GT-094 also decreased Sp1, Sp3, and Sp4 in colon cancer cells. GT-094–mediated repression of Sp and Sp-regulated gene products was due to downregulation of microRNA-27a (miR-27a) and induction of ZBTB10, an Sp repressor that is regulated by miR-27a in colon cancer cells. Moreover, the effects of GT-094 on Sp1, Sp3, Sp4, miR-27a, and ZBTB10 were also inhibited by glutathione suggesting that the anticancer activity of GT-094 in colon cancer cells is due, in part, to activation of an ROS-miR-27a:ZBTB10-Sp transcription factor pathway. Mol Cancer Res; 9(2); 195–205. ©2010 AACR.
A Modified Technique to Reduce Spillage and Operative Time: Laparoscopic Ovarian Dermoid Cyst Enucleation ‘in a Bag’
Authors: Campo Sebastiano , Campo Vincenzo
Published: December 2010

Background: To describe the outcomes of a modified technique for conservative laparoscopic enucleation of ovarian dermoid cyst, placing the ovary in an endobag during enucleation to prevent intraperitoneal spillage. Methods: Laparoscopic dermoid cyst enucleation was performed in 35 cases of premenopausal patients placing the ovary in an endobag at the beginning of the procedure and removing the cyst from the abdominal cavity by the same endobag. Results: Dermoid cysts with a mean diameter of 6.3 ± 2.7 cm were enucleated and removed laparoscopically ‘in a bag’ without intra- or postoperative complications. Cyst rupture occurred in 10 cases (28.5%), but evident peritoneal contamination occurred in only 2 (5.7%; 95% confidence interval: 0.7–19.2%), because in 8 patients spillage was contained by the surrounding bag. The mean operative time was 64.6 ± 27 min. No signs or symptoms of peritonitis were observed. The mean postoperative hospitalization was 1.6 ± 1.4 days. Among the 12 infertile patients, 7 spontaneous pregnancies (58%) occurred. Conclusions: Laparoscopic conservative excision of dermoid cysts placing the ovary in an endobag at the beginning of surgery and removing the cyst by the same bag is a safe and effective approach to reduce intraperitoneal spillage and operative time.
Effects of a Highly Selective Acetylcholine-Activated K+Channel Blocker on Experimental Atrial Fibrillation
Authors: Machida Taiichi , Hashimoto Norio , Kuwahara Ippei , Ogino Yasuhiro , Matsuura Junji , Yamamoto Wataru , Itano Yasuhiro , Zamma Akira , Matsumoto Ryo , Kamon Junji , Kobayashi Tsunefumi , Ishiwata Norihisa , Yamashita Toru , Ogura Takehiko , Nakaya Haruaki
Published: December 2010

Background—

The acetylcholine-activated K+current (IK,ACh) is a novel candidate for atrial-specific antiarrhythmic therapy. The present study investigates the involvement ofIK,AChin atrial fibrillation (AF) using NTC-801, a novel potent and selectiveIK,AChblocker.

Methods and Results—

The effects of NTC-801, substituted 4-(aralkylamino)-2,2-dimethyl-3,4-dihydro-2H-benzopyran-3-ol, onIK,AChand other cardiac ionic currents (INa,ICaL,Ito,IKur,IKr,IKs,IKl,IKATP, andIf) and on atrial and ventricular action potentials were examined in vitro. NTC-801 potently inhibited carbachol-inducedIK,AChin guinea pig atrial cells and the GIRK1/4 current inXenopusoocytes with IC50values of 5.7 and 0.70 nmol/L, respectively. NTC-801 selectively inhibitedIK,ACh>1000-fold over other cardiac ionic currents. NTC-801 (10 to 100 nmol/L) reversed the action potential duration (APD90) shortened by carbachol or adenosine in atrial cells, whereas it did not affect APD90at 100 nmol/L in ventricular cells. Antiarrhythmic effects of NTC-801 were evaluated in 3 AF models in vivo. NTC-801 significantly prolonged atrial effective refractory period without affecting ventricular effective refractory period under vagal nerve stimulation. NTC-801 dose-dependently converted AF to normal sinus rhythm in both vagal nerve stimulation–induced (0.3 to 3 μg · kg−1· min−1IV) and aconitine-induced (0.01 to 0.1 mg/kg IV) models. In a rapid atrial pacing model, NTC-801 (3 μg · kg−1· min−1IV) significantly decreased AF inducibility with a prolonged atrial effective refractory period that was frequency-independent.

Conclusions—

A selectiveIK,AChblockade induced by NTC-801 exerted anti-AF effects mediated by atrial-selective effective refractory period prolongation. These findings suggest thatIK,AChmay be important in the development and maintenance of AF.
Willingness To Pay To Eliminate the Risk of Restenosis Following Percutaneous Coronary Intervention
Authors: Guertin Jason R. , Liu Aihua , Abrahamowicz Michal , Cohen David J. , Ismail Salma , LeLorier Jacques , Brophy James M. , Rinfret Stéphane
Published: December 2010

Background—

Percutaneous coronary intervention (PCI) remains limited by the risk of restenosis. Patients' perceptions of the health benefits and value of avoiding restenosis are incompletely known.

Methods and Results—

We used a contingent valuation approach to assess the willingness to pay (WTP) for a hypothetical treatment that eliminates the risk of restenosis among 270 PCI patients. Patients were provided with a scenario describing a baseline 10% or 20% probability of restenosis in the year following the procedure, which could lead to repeat PCI or, more rarely, bypass surgery, without any increase in mortality. Six different “take it or leave it” bids ($500, $1000, $1500, $2000, $2500, and $3000) and both risk levels were randomly assigned. Multiple logistic regression was used to identify independent predictors of a positive response to the WTP question. Using nonparametric methods, the median WTP to eliminate the risk of restenosis was estimated at $2802. As expected, higher income was independently associated with a higher probability of a positive response to the WTP question (odds ratio, 2.81; 95% CI, 1.32 to 5.97). Bids also were independently associated with the probability of being willing to pay, and this association followed a quadratic effect. Below $1500, bid had little impact on patient answers. However, as prices increased, the probability of being willing to pay started to decrease sharply.

Conclusion—

The potential to eliminate the risk of restenosis, a benign complication, would have substantial value for patients undergoing PCI.
An Analysis of Near-Surface Winds, Air Temperature, and Cyclone Activity in Terra Nova Bay, Antarctica, from 1993 to 2009
Authors: Knuth Shelley L. , Cassano John J.
Published: December 2010

In September 2009, the first unmanned aerial vehicles were flown over Terra Nova Bay, Antarctica, to collect information regarding air–sea interactions. Prior to the field season, wind and temperature data from a local automatic weather station (AWS) were collected from 1993 to 2007 and compared with an August–October 2006–08 satellite cyclone analysis to place the September 2009 observations into a broader context. AWS wind data revealed a strong tendency toward downslope flow in the region regardless of season, as the majority (55%) of winds were from the west to northwesterly directions. Most winds observed at the site were less than 20 m s−1, but 83% of the stronger winds were associated with downslope flow. Of 15 strong wind events (greater than 20 m s−1 for more than 10 h) evaluated during the cyclone analysis period, 100% occurred in the presence of a cyclone in the adjacent Ross Sea. Winter experienced the greatest number of strong wind events (68%), and summer had the least (4%). Most temperatures were between −15° and −25°C, with temperatures influenced by wind fluctuations. The cyclone analysis revealed that 64% of systems were comma shaped, and most cyclones (84%) within the Ross Sea were mesocyclones. A comparison of AWS data for Septembers 1993–2007 and September 2009 showed more strong wind events during 2009, while the cyclone analysis revealed a shift in cyclonic activity eastward. Reanalysis data comparing September 1993–2007 and September 2009 show an eastward shift in a deeper upper-level trough, indicating that September 2009 was an anomalous year.
On the Dynamics of Concentric Eyewall Genesis: Space–Time Empirical Normal Modes Diagnosis
Authors: Martinez Y. , Brunet G. , Yau M. K. , Wang X.
Published: December 2010

A novel statistical technique called space–time empirical normal mode (ST-ENM) is applied in a diagnostic study of the genesis of a secondary eyewall in a simulated hurricane using the nonhydrostatic, high-resolution fifth-generation Pennsylvania State University (PSU)–National Center for Atmospheric Research (NCAR) Mesoscale Model (MM5). The bases obtained from the ST-ENM technique are nonstationary, dynamically relevant, and orthogonal in the sense of wave activity.

The wave activity spectra of the wavenumber-1 anomalies show that the leading modes (1–6) exhibit mainly characteristics of vortex Rossby waves (VRWs). These modes together explain about 75% of the total wavenumber-1 variance in a period of 24 h.

Analysis of the Eliassen–Palm (EP) flux and its time-mean divergence corresponding to the total contribution from these modes indicated that in the lower troposphere VRWs not only propagate inward (outward) in the primary eyewall region where the radial gradient of the basic-state potential vorticity is large and positive (large and negative), but there is also wave activity propagating outside the primary eyewall. Consequently, maximum cyclonic eddy angular momentum is transported not only inside the radius of maximum wind (RMW) by VRWs in the primary eyewall region, but also close to the location where the secondary eyewall forms by VRWs propagating outside the inner eyewall.

The fact that the critical radius for some of the ST-ENMs is contained inside the region where the secondary eyewall forms and the existence of a signal of maximum eddy cyclonic angular momentum flux propagating outward up to the critical radius suggests that a wave–mean flow interaction mechanism and redistribution of angular momentum may be suitable to explain important dynamical aspects of concentric eyewall genesis.
The Variability of the Atlantic Storm Track and the North Atlantic Oscillation: A Link between Intraseasonal and Interannual Variability
Authors: Luo Dehai , Diao Yina , Feldstein Steven B.
Published: December 2010

The winter-mean North Atlantic Oscillation (NAO) index has been mostly positive since the 1980s, with a linear upward trend during the period from 1978 to 1990 (P1) and a linear downward trend during the period from 1991 to 2009 (P2). Further calculations show that the Atlantic storm-track eddy activity is more intense during P2 than during P1, which is statistically significant at the 90% confidence level for a t test. This study proposes a hypothesis that the change in the trend of the positive NAO index from P1 to P2 may be associated with the marked intensification of the Atlantic storm track during P2.

A generalized nonlinear NAO model is used to explain the observed trend of the positive NAO index within P2. It is found that even when the Atlantic storm-track eddies are less intense, a positive-phase NAO event can form under the eddy forcing if the planetary-scale wave has an initial value with a low-over-high dipole structure during P1 and P2. A blocking flow can occur in the downstream side (over Europe) of the Atlantic basin as a result of the energy dispersion of Rossby waves during the decay of the positive-phase NAO event. This blocking flow does not strictly correspond to a negative-phase NAO event because the blocking stays mainly over the European continent. However, when the Atlantic storm-track eddies are rather strong, the blocking flow occurring over the European continent is enhanced and can retrograde into the Atlantic region and finally become a long-lived negative-phase NAO event. In this case, the NAO event can transit from the positive phase to the negative phase. Thus, the winter-mean NAO index during P2 will inevitably decline because of the increase in days of negative-phase NAO events in winter because the Atlantic storm track exhibits a marked intensification in the time interval. The transition of the NAO event from the positive phase to the negative phase can also be observed only when the downstream development of the Atlantic storm-track eddy activity is rather prominent.

Thus, it appears that there is a physical link between intraseasonal and interannual time scales of the NAO when the Atlantic storm track exhibits an interannual variability.
Indirect Impact of Atmospheric Aerosols in Idealized Simulations of Convective–Radiative Quasi Equilibrium. Part II: Double-Moment Microphysics
Authors: Grabowski Wojciech W. , Morrison Hugh
Published: December 2010

This paper extends the previous cloud-resolving modeling study concerning the impact of cloud microphysics on convective–radiative quasi equilibrium (CRQE) over a surface with fixed characteristics and prescribed solar input, both mimicking the mean conditions on earth. The current study applies sophisticated double-moment warm-rain and ice microphysics schemes, which allow for a significantly more realistic representation of the impact of aerosols on precipitation processes and on the coupling between clouds and radiative transfer. Two contrasting cloud condensation nuclei (CCN) characteristics are assumed, representing pristine and polluted conditions, as well as contrasting representations of the effects of entrainment and mixing on the mean cloud droplet size. In addition, four sets of sensitivity simulations are also performed with changes that provide a reference for the main simulation set.

As in the previous study, the CRQE mimics the estimates of globally and annually averaged water and energy fluxes across the earth’s atmosphere. There are some differences from the previous study, however, consistent with the slightly lower water vapor content in the troposphere and significantly reduced lower-tropospheric cloud fraction in current simulations. There is also a significant reduction of the difference between the pristine and polluted cases, from ∼20 to ∼4 W m−2 at the surface from ∼20 to ∼9 W m−2 at the top of the atmosphere (TOA). The difference between the homogeneous and extremely inhomogeneous mixing scenarios, ∼20 W m−2 in the previous study, is reduced to a mere 2 (1) W m−2 at the surface (TOA). An unexpected difference between the previous and current simulations is the lower Bowen ratio of the surface heat flux, the partitioning of the total flux into sensible and latent components. It is shown that most of the change comes from the difference in the representation of rain evaporation in the subcloud layer in the single- and double-moment microphysics schemes. The difference affects the mean air temperature and humidity near the surface, and thus the Bowen ratio. The differences between the various simulations are discussed, contrasting the process-level approach with the impact of cloud microphysics on the quasi-equilibrium state with a more appropriate system dynamics approach. The key distinction is that the latter includes the interactions among all the processes in the modeled system.
Precipitation Water Stable Isotopes in the South Tibetan Plateau: Observations and Modeling*
Authors: Gao Jing , Masson-Delmotte V. , Yao T. , Tian L. , Risi C. , Hoffmann G.
Published: December 2010

Measurements of precipitation isotopic composition have been conducted on a daily basis for 1 yr at Bomi, in the southeast Tibetan Plateau, an area affected by the interaction of the southwest monsoon, the westerlies, and Tibetan high pressure systems, as well as at Lhasa, situated west of Bomi. The measured isotope signals are analyzed both on an event basis and on a seasonal scale using available meteorological information and airmass trajectories. The processes driving daily and seasonal isotopic variability are investigated using multidecadal climate simulations forced by twentieth-century boundary conditions and conducted with two different isotopic atmospheric general circulation models [the isotopic version of the Laboratoire de Météorologie Dynamique GCM (LMDZiso) and the ECHAM4iso model]. Both models use specific nudging techniques to mimic observed atmospheric circulation fields. The models simulate a wet and cold bias on the Tibetan Plateau together with a dry bias in its southern part. A zoomed LMDZ simulation conducted with ~50-km local spatial resolution dramatically improves the simulation of isotopic compositions of precipitation on the Tibetan Plateau. Simulated water isotope fields are compared with new data and with previous observations, and regional differences in moisture origins are analyzed using back-trajectories. Here, the focus is on relationships between the water isotopes and climate variables on an event and seasonal scale and in terms of spatial and altitudinal isotopic gradients. Enhancing the spatial resolution is crucial for improving the simulation of the precipitation isotopic composition.
Equatorial Asymmetry of the East Pacific ITCZ: Observational Constraints on the Underlying Processes
Authors: Masunaga Hirohiko , L’Ecuyer Tristan S.
Published: December 2010

The equatorial asymmetry of the east Pacific intertropical convergence zone (ITCZ) is explored on the basis of an ocean surface heat budget analysis carried out with a variety of satellite data products. The annual mean climatology of absorbed shortwave flux exhibits a pronounced meridional asymmetry due to a reduction of insolation by high clouds in the north ITCZ. Ocean mixed layer advection has the largest, if not exclusive, effect of counteracting this shortwave-exerted asymmetry. Other heat fluxes, in particular latent heat flux, predominate over the advective heat flux in magnitude but are secondary with respect to equatorial asymmetry. The asymmetry in advective heat flux stems from a warm pool off the Central American coast and, to a lesser extent, the North Equatorial Counter Current, neither of which exist in the Southern Hemisphere. The irregular continental geography presumably comes into play by generating a warm pool north of the equator and bringing cold waters to the south in the far eastern Pacific.

In addition to the annual climatology, the north–south contrast in the seasonal cycle of surface heat flux is instrumental in sustaining the north ITCZ throughout the year. The northeast Pacific is exposed to a seasonal cycle that is considerably weaker than that in the southeast Pacific, arising from multiple causes including the finite eccentricity of the earth’s orbit and meridional gradient in mixed layer absorptivity. Simple experiments generating synthetic sea surface temperature (SST) illustrate that the muted seasonal cycle of heat flux forcing moderates the SST seasonal variability in the northeast Pacific and thus allows the north ITCZ to persist year round. Existing theories on the ITCZ asymmetry are briefly examined in light of the present findings.
WRF Model Experiments on the Antarctic Atmosphere in Winter
Authors: Tastula Esa-Matti , Vihma Timo
Published: December 2010

The standard and polar versions 3.1.1 of the Weather Research and Forecasting (WRF) model, both initialized by the 40-yr ECMWF Re-Analysis (ERA-40), were run in Antarctica for July 1998. Four different boundary layer–surface layer–radiation scheme combinations were used in the standard WRF. The model results were validated against observations of the 2-m temperature, surface pressure, and 10-m wind speed at 9 coastal and 2 inland stations. The best choice for boundary layer and radiation parameterizations of the standard WRF turned out to be the Yonsei University boundary layer scheme in conjunction with the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) surface layer scheme and the Rapid Radiative Transfer Model for longwave radiation. The respective temperature bias was on the order of 3°C less than the biases obtained with the other combinations. Increasing the minimum value for eddy diffusivity did, however, improve the performance of the asymmetric convective scheme by 0.8°C. Averaged over the 11 stations, the error growths in 24-h forecasts were almost identical for the standard and Polar WRF, but in 9-day forecasts Polar WRF gave a smaller 2-m temperature bias. For the Vostok station, however, the standard WRF gave a less positively biased 24-h temperature forecast. On average, the polar version gave the least biased surface pressure simulation. The wind speed simulation was characterized by low correlation values, especially under weak winds and for stations surrounded by complex topography.
Defensive Projection, Superimposed On Simplistic Object Relations, Erodes Patient-Provider Relationships in High-Risk Pregnancy: an Empirical Investigation
Authors: Shahar Golan , Porcerelli John H. , Kamoo Ray , Epperson C. Neill , Czarkowski Kathryn A. , Magriples Urania , Mayes Linda C.
Published: December 2010

In an attempt to illustrate the relevance of psychoanalytic theory and research to behavior medicine, an empirical investigation was conducted of females treated at a high-risk pregnancy specialty clinic (N = 58). Drawing from psychoanalytic object relations theory, it was hypothesized and confirmed that use of projection as a defense mechanism during pregnancy, superimposed on simplistic object relations, predicted an erosion of patient-provider relationships during the pregnancy/postdelivery period. Findings are interpreted through the perspective of mentalization, pertaining to individuals’ ability to understand the mental states of self and others, specifically under significant stress. Implications for psychoanalytically oriented assessment and treatment, and for the rift between psychoanalysis and research, are discussed.
The Racial Wealth Gap and the Borrower’s Dilemma
Authors: Chiteji N.S.
Published: December 2010

This article examines the relationship between the Black-White wealth gap and household borrowing. Financial markets have been applauded for making credit available to all U.S. households since the 1990s—for democratizing credit. This study finds that the rates charged to borrowers can differ substantially by race, however. Because a household’s wealth status is affected by both the value of its assets and its outstanding debt, the author argues that the natural operation of credit markets inevitably depresses African Americans’ ability to accumulate wealth. The implications for the position of African Americans within U.S. society are also discussed.
An Application of the Socioegocentric Model to Information-Sharing Discussions: In Search of Group-Level Communication Influences
Authors: Bonito Joseph A. , Ruppel Erin K.
Published: December 2010

Hewes’s socioegocentric model is applied to discussion data from an information-sharing task. The primary question is whether discussion data display psychological (individual-level) or interactional (group-level) associations among contributions. Two studies are described. The first used a card sort task to group the 42 items from the choose-the-best-candidate task. The second study used the groupings from the first task to code information-based contributions to discussion. Results indicated that participants reliably group the items into valence-based categories and that there were valence-based associations between items contributed to discussion. However, the associations were at the individual level of analysis—there were no group-level effects for information sharing. However, other features of the discussions did have group-level effects, and we argue for a better understanding of information sharing in terms of the comments that frame information-based contributions to interaction.
Science on Television in the 21st Century
Authors: Dudo Anthony , Brossard Dominique , Shanahan James , Scheufele Dietram A. , Morgan Michael , Signorielli Nancy
Published: December 2010

Twenty-five years after George Gerbner and colleagues’ seminal report on television and science attitudes, there is a need to update the data on television’s portrayals of science and to revisit the cultivation question. We address this need by analyzing 21st-century television depictions of science and examining the relationships between exposure to television and attitudes toward science with an analysis of 2006 General Social Survey data. Content results show that scientists appear infrequently in prime-time dramatic programs, are typically White males, and are frequently cast in good or mixed roles rather than as evil scientists. Regarding the cultivation effect, we do not find a significant direct relationship between television viewing and negative attitudes toward science after relevant controls are taken into account. Additional results, however, indicate a displacement effect of television viewing on science attitudes and show significant interaction effects consistent with mainstreaming.
Florestan Fernandes, Oracy Nogueira, and the UNESCO Project on Race Relations in São Paulo
Authors: Chor Maio Marcos
Published: December 2010

Analysis of the work of Florestan Fernandes (1920—1995) and Oracy Nogueira (1917—1996) on race relations in São Paulo in the context of the UNESCO project in which both participated sheds light on the link between the institutionalization of the social sciences in Brazil and the sociologists’ social engagement with subaltern sectors represented in the research on blacks. It also reveals that the two men held different views on the relationship between race and class. While in Fernandes’s work race was subsumed under class, in Nogueira’s it was an independent variable. Thus the UNESCO research called attention to differing interpretations of Brazilian racism.
Cross-validation of the Emotion Awareness Questionnaire for Children in Three Populations
Authors: Lahaye Magali , Mikolajczak Moïra , Rieffe Carolien , Villanueva Lidón , Van Broeck Nady , Bodart Eddy , Luminet Olivier
Published: December 2010

The main aim of the present study was to examine the cross-cultural equivalence of a newly developed questionnaire, the Emotion Awareness Questionnaire (EAQ30) that assesses emotional awareness of children through self-report. Participants were recruited in three countries: the Netherlands ( N = 665), Spain ( N = 464), and Belgium ( N = 707), reflecting three languages: Dutch, Spanish, and French respectively. The results of multigroup confirmatory factor analysis showed that the 6-factor structure of the EAQ30 is similar in all three samples. These results were confirmed by the high coefficients of congruence that indicated factorial invariance across samples. Comparison between the three samples showed minor cultural differences. These findings support the factorial and construct validity of the EAQ30 and suggest that the EAQ30 accurately captures the structure of children’s emotional dispositions, regardless of cultural differences.
A Summary and Analysis of Warrantless Arrest Statutes for Domestic Violence in the United States
Authors: Zeoli April M. , Norris Alexis , Brenner Hannah
Published: December 2010

In the United States, all 50 states and the District of Columbia have enacted statutes that allow police officers to make warrantless arrests for domestic violence given probable cause; however, state laws differ from one another in multiple, important ways. Research on domestic violence warrantless arrest laws rarely describe them as anything more than discretionary, preferred, or mandatory, either within their analyses or within the texts of their publications; researchers, and their audiences, may not be aware of the vast and potentially important differences among these laws. In this article, we list the domestic violence warrantless arrest laws for each state, and discuss them in terms of five common elements: the phrasing of the arrest authority; whether additional factors to domestic violence are required to trigger the arrest authority; qualifications to the arrest authority; time limits for warrantless arrest to occur; and whether police officers are required to report why they made a dual or no arrest. We then analyze the common elements of the laws, paying particular attention to how they may encourage or discourage the arrest of alleged domestic violence perpetrators. It is critical that researchers, advocates, and policymakers are aware of these variations in state statutes when conducting or interpreting research or making policy recommendations.