bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Efficacy of Therapeutic Cancer Vaccines Produced by Co-Treatment withMycobacterium tuberculosisHeparin-Binding Hemagglutinin, a Novel TLR4 Agonist
Authors: Jung In Duk , Jeong Soo Kyung , Lee Chang-Min , Noh Kyung Tae , Heo Deok Rim , Shin Yong Kyoo , Yun Cheol-Heui , Koh Won-Jung , Akira Shizuo , Whang Jake , Kim Hwa-Jung , Park Won Sun , Shin Sung Jae , Park Yeong-Min 
Published: March 2011

AbstractEffective activation of dendritic cells (DCs) toward T helper (Th)-1 cell polarization would improve DC-based antitumor immunotherapy, helping promote the development of immunotherapeutic vaccines based on T-cell immunity. To achieve this goal, it is essential to develop effective immune adjuvants that can induce powerful Th1 cell immune responses. The pathogenic organism Mycobacterium tuberculosis includes certain constitutes, such as heparin-binding hemagglutinin (HBHA), that possess a strong immunostimulatory potential. In this study, we report the first clarification of the functions and precise mechanism of HBHA in immune stimulation settings relevant to cancer. HBHA induced DC maturation in a TLR4-dependent manner, elevating expression of the surface molecules CD40, CD80, and CD86, MHC classes I and II and the proinflammatory cytokines IL-6, IL-12, IL-1β, TNF-α, and CCR7, as well as stimulating the migratory capacity of DCs in vitro and in vivo. Mechanistic investigations established that MyD88 and TRIF signaling pathways downstream of TLR4 mediated secretion of HBHA-induced proinflammatory cytokines. HBHA-treated DCs activated naïve T cells, polarized CD4+ and CD8+ T cells to secrete IFN-γ, and induced T-cell–mediated cytotoxicity. Notably, systemic administration of DCs that were HBHA-treated and OVA251–264-pulsed ex vivo greatly strengthened immune priming in vivo, inducing a dramatic regression of tumor growth associated with long-term survival in a murine E.G7 thymoma model. Together, our findings highlight HBHA as an immune adjuvant that favors Th1 polarization and DC function for potential applications in DC-based antitumor immunotherapy. Cancer Res; 71(8); 2858–70. ©2011 AACR.
Chromosomal Instability Confers Intrinsic Multidrug Resistance
Authors: Lee Alvin J.X. , Endesfelder David , Rowan Andrew J. , Walther Axel , Birkbak Nicolai J. , Futreal P. Andrew , Downward Julian , Szallasi Zoltan , Tomlinson Ian P.M. , Howell Michael , Kschischo Maik , Swanton Charles 
Published: March 2011

Abstract
Aneuploidy is associated with poor prognosis in solid tumors. Spontaneous chromosome missegregation events in aneuploid cells promote chromosomal instability (CIN) that may contribute to the acquisition of multidrug resistance in vitro and heighten risk for tumor relapse in animal models. Identification of distinct therapeutic agents that target tumor karyotypic complexity has important clinical implications. To identify distinct therapeutic approaches to specifically limit the growth of CIN tumors, we focused on a panel of colorectal cancer (CRC) cell lines, previously classified as either chromosomally unstable (CIN+) or diploid/near-diploid (CIN−), and treated them individually with a library of kinase inhibitors targeting components of signal transduction, cell cycle, and transmembrane receptor signaling pathways. CIN+ cell lines displayed significant intrinsic multidrug resistance compared with CIN− cancer cell lines, and this seemed to be independent of somatic mutation status and proliferation rate. Confirming the association of CIN rather than ploidy status with multidrug resistance, tetraploid isogenic cells that had arisen from diploid cell lines displayed lower drug sensitivity than their diploid parental cells only with increasing chromosomal heterogeneity and isogenic cell line models of CIN+ displayed multidrug resistance relative to their CIN− parental cancer cell line derivatives. In a meta-analysis of CRC outcome following cytotoxic treatment, CIN+ predicted worse progression-free or disease-free survival relative to patients with CIN− disease. Our results suggest that stratifying tumor responses according to CIN status should be considered within the context of clinical trials to minimize the confounding effects of tumor CIN status on drug sensitivity. Cancer Res; 71(5); 1858–70. ©2011 AACR.
Aberrations of EZH2 in Cancer
Authors: Chase Andrew , Cross Nicholas C.P. 
Published: March 2011

Abstract
Control of gene expression is exerted at a number of different levels, one of which is the accessibility of genes and their controlling elements to the transcriptional machinery. Accessibility is dictated broadly by the degree of chromatin compaction, which is influenced in part by polycomb group proteins. EZH2, together with SUZ12 and EED, forms the polycomb repressive complex 2 (PRC2), which catalyzes trimethylation of histone H3 lysine 27 (H3K27me3). PRC2 may recruit other polycomb complexes, DNA methyltransferases, and histone deacetylases, resulting in additional transcriptional repressive marks and chromatin compaction at key developmental loci. Overexpression of EZH2 is a marker of advanced and metastatic disease in many solid tumors, including prostate and breast cancer. Mutation of EZH2 Y641 is described in lymphoma and results in enhanced activity, whereas inactivating mutations are seen in poor prognosis myeloid neoplasms. No histone demethylating agents are currently available for treatment of patients, but 3-deazaneplanocin (DZNep) reduces EZH2 levels and H3K27 trimethylation, resulting in reduced cell proliferation in breast and prostate cancer cells in vitro. Furthermore, synergistic effects are seen for combined treatment with DNA demethylating agents and histone deacetylation inhibitors, opening up the possibility of refined epigenetic treatments in the future. Clin Cancer Res; 17(9); 2613–8. ©2011 AACR.
Prevention of Radiation-Induced Salivary Hypofunction Following hKGF Gene Delivery to Murine Submandibular Glands
Authors: Zheng Changyu , Cotrim Ana P. , Rowzee Anne , Swaim William , Sowers Anastasia , Mitchell James B. , Baum Bruce J. 
Published: March 2011

Abstract
Purpose: Salivary glands are significantly affected when head and neck cancer patients are treated by radiation. We evaluated the effect of human keratinocyte growth factor (hKGF) gene transfer to murine salivary glands on the prevention of radiation-induced salivary hypofunction.
Experimental Design: A hybrid serotype 5 adenoviral vector encoding hKGF (AdLTR2EF1α-hKGF) was constructed. Female C3H mice, 8 weeks old, were irradiated by single (15 Gy) or fractionated (6 Gy for 5 days) doses to induce salivary hypofunction. AdLTR2EF1α-hKGF or AdControl was administered (108 – 1010 particles per gland) to both submandibular glands (SG) by retrograde ductal instillation before irradiation (IR). Salivary flow was measured following pilocarpine stimulation. Human KGF levels were measured by ELISA. SG cell proliferation was measured with bromodeoxyuridine labeling. Endothelial and progenitor or stem cells in SGs were measured by flow cytometry. The effect of SG hKGF production on squamous cell carcinoma (SCC VII) tumor growth was assessed.
Results: In 3 separate single-dose IR experiments, salivary flow rates of mice administered the AdLTR2EF1α-hKGF vector were not significantly different from nonirradiated control mice (P &gt; 0.05). Similarly, in 3 separate fractionated IR experiments, the hKGF-expressing vector prevented salivary hypofunction dramatically. Transgenic hKGF protein was found at high levels in serum and SG extracts. AdLTR2EF1α-hKGF–treated mice showed increased cell proliferation and numbers of endothelial cells, compared with mice treated with AdControl. hKGF gene transfer had no effect on SCC VII tumor growth ± radiation.
Conclusions: hKGF gene transfer prevents salivary hypofunction caused by either single or fractionated radiation dosing in mice. The findings suggest a potential clinical application. Clin Cancer Res; 17(9); 2842–51. ©2011 AACR.
Melanoma Prevention Using Topical PBISe
Authors: Chung Chin-Ying , Madhunapantula SubbaRao V. , Desai Dhimant , Amin Shantu , Robertson Gavin P. 
Published: March 2011

Abstract
Malignant melanoma is the deadliest form of skin cancer, known for its drug resistance and high metastatic potential. Deregulated PI3 and mitogen activated protein (MAP) kinase pathways promote early melanocytic lesion development and confer drug resistance. No agent exists to target these deregulated pathways to prevent cutaneous noninvasive melanocytic cells or invasive melanomas from developing into more aggressive widely disseminated metastatic disease. In this study, a selenium containing isosteric analogue of PBIT [S, S′-1,4-phenylenebis(1,2-ethanediyl)bis-isothiourea] called PBISe [Se, Se′-1,4-phenylenebis(1,2-ethanediyl)bis-isoselenourea] is shown to moderate these 2 major signaling pathways to prevent cutaneous melanocytic lesion or melanoma development. Topical application of PBISe retarded melanocytic lesion development in laboratory-generated skin by 70% to 80% and in animal skin by approximately 50%. Mechanistically, prevention of lesion development occurred due to decreased Akt3 signaling, which increased MAP kinase pathway activity to inhibitory levels. The combined effect of targeting these pathways led to decreased cell proliferation and increased apoptotic cell death thereby preventing melanoma development. Thus, topically applied PBISe treatment has potential to prevent noninvasive melanocytic lesion and invasive metastatic melanoma development in skin. Cancer Prev Res; 4(6); 935–48. ©2011 AACR.
Effect of Suppressive Oligodeoxynucleotides on the Development of Inflammation-Induced Papillomas
Authors: Ikeuchi Hidekazu , Kinjo Takeshi , Klinman Dennis M. 
Published: March 2011

Abstract
Inflammation contributes to the development of papillomas and squamous cell carcinomas in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-l3-acetate (TPA) model of skin carcinogenesis. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs have been shown to block deleterious inflammatory reactions in murine models of autoimmunity, pneumonitis, and shock. This article examines whether treatment with suppressive (Sup) ODN can interfere with DMBA/TPA-induced inflammation, thereby reducing papilloma formation. Results indicate that Sup ODN block TPA-dependent skin hyperplasia, edema, and leukocytic infiltration. Sup ODN also inhibit the upregulation of genes encoding pro-oncogenic chemokines and other markers of inflammation including CXCL2, CCL2, COX-2, and ODC (ornithine decarboxylase). Of greatest import, Sup ODN reduce papilloma formation in a dose- and sequence-dependent manner. These findings suggest that Sup ODN may provide a novel means of preventing inflammation and associated oncogenesis. Cancer Prev Res; 4(5); 752–7. ©2011 AACR.
Zerumbone Induces Heme Oxygenase-1 Expression in Mouse Skin and Cultured Murine Epidermal Cells through Activation of Nrf2
Authors: Shin Jun-Wan , Ohnishi Kohta , Murakami Akira , Lee Jeong-Sang , Kundu Joydeb Kumar , Na Hye-Kyung , Ohigashi Hajime , Surh Young-Joon 
Published: March 2011

Abstract
Zerumbone, a sesquiterpene derived from tropical ginger, contains an electrophilic α,β-unsaturated carbonyl moiety and was found to suppress chemically induced papilloma formation in mouse skin. Here, we report that topical application of zerumbone onto dorsal skin of hairless mice induces activation of NF-E2–related factor 2 (Nrf2) and expression of heme oxygenase-1 (HO-1). We compared the levels of HO-1 protein in the skin of zerumbone-treated Nrf2 wild-type and Nrf2 knockout mice, and nrf2-deficient mice expressed HO-1 protein to a much lesser extent than the wild-type animals following topical application of zerumbone. Treatment of mouse epidermal JB6 cells with zerumbone caused a marked increase of Nrf2 nuclear translocation followed by the promoter activity of HO-1, and also enhanced direct binding of Nrf2 to the antioxidant response element. Moreover, knockdown of Nrf2 in JB6 cells diminished the zerumbone-induced upregulation of HO-1. Notably, α-humulene and 8-hydroxy-α-humulene, the structural analogues of zerumbone that lack the α,β-unsaturated carbonyl group, failed to activate Nrf2 and were unable to increase HO-1 expression. Unlike zerumbone, these nonelectrophilic analogues could not suppress the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 cell transformation and the intracellular accumulation of reactive oxygen species (ROS). Interestingly, when JB6 cells were treated with carbon monoxide–releasing molecule that mimics the HO-1 activity, the TPA-induced ROS production was markedly reduced. Taken together, these findings suggest that upregulation of HO-1 expression by zerumbone is mediated through activation of Nrf2 signaling, which provides a mechanistic basis for the chemopreventive effects of this sesquiterpene on mouse skin carcinogenesis. Cancer Prev Res; 4(6); 860–70. ©2011 AACR.
Estimating Spatial Velocity Statistics with Coherent Doppler Lidar
Authors: Frehlich Rod , Cornman Larry 
Published: March 2011

Abstract
The spatial statistics of a simulated turbulent velocity field are estimated using radial velocity estimates from simulated coherent Doppler lidar data. The structure functions from the radial velocity estimates are processed to estimate the energy dissipation rate ε and the integral length scale Li, assuming a theoretical model for isotropic wind fields. The performance of the estimates are described by their bias, standard deviation, and percentiles. The estimates of ε2/3 are generally unbiased and robust. The distribution of the estimates of Li are highly skewed; however, the median of the distribution is generally unbiased. The effects of the spatial averaging by the atmospheric movement transverse to the lidar beam during the dwell time of each radial velocity estimate are determined, as well as the error scaling as a function of the dimensions of the total measurement region. Accurate estimates of Li require very large measurement domains in order to observe a large number of independent samples of the spatial scales that define Li.
Assessment of Acoustic Coherent Doppler and Cross-Correlation Techniques for Measuring Near-Bed Velocity and Suspended Sediment Profiles in the Marine Environment
Authors: Betteridge Kyle F. E. , Thorne Peter D. , Bell Paul S. 
Published: March 2011

Abstract
The simultaneous measurement of current flow and suspended sediment concentration in the marine environment is central to the study of sediment transport processes. In view of this, two acoustic approaches for measuring flow were tested in a tidal estuary to assess their capabilities in this environment. A coherent Doppler velocity profiler and a cross-correlation velocity profiler were assessed using conventional current meters and a commercially available acoustic Doppler velocimeter. Mean velocity profiles were obtained up to a range of 1.47 m in 0.046-m range bins over a number of flood tides. The measurements compared well with the reference instruments and regression analysis produced gradients close to unity. Turbulent velocities measured with the coherent Doppler profiler were comparable with turbulent fluctuations measured with the acoustic Doppler velocimeter. The cross-correlation velocity profiler was shown to be unable to measure turbulent velocities. The backscattered signals received on the cross-correlation transducers were also used to compute the sediment concentration profiles using an explicit solution to the acoustic backscatter equation. Combining the concentration and flow measurements enabled sediment flux profiles to be obtained, the results of which compared favorably with flux measurements obtained from the conventional current meters and pumped sampling.
A Wavelet-Based Technique for Identifying, Labeling, and Tracking of Ocean Eddies
Authors: Luo Jingjia , Jameson Leland 
Published: March 2011

AbstractWavelet analysis offers a new approach for viewing and analyzing various large datasets by dividing information according to scale and location. Here a new method is presented that is designed to characterize time-evolving structures in large datasets from computer simulations and from observational data. An example of the use of this method to identify, classify, label, and track eddylike structures in a time-evolving dataset is presented. The initial target application is satellite data from the TOPEX/Poseiden satellite. But, the technique can certainly be used in any large dataset that might contain time-evolving or stationary structures.
XBT Fall Rate in Waters of Extreme Temperature: A Case Study in the Antarctic Ocean
Authors: Thadathil Pankajakshan , Saran A. K. , Gopalakrishna V. V. , Vethamony P. , Araligidad Nilesh , Bailey Rick 
Published: March 2011

AbstractXBT fall-rate variation in waters of extreme temperature and the resulting depth error has been addressed using controlled XBT–CTD datasets collected from two cruises in the Southern Ocean. Mean depth errors deduced from both the datasets are significantly different from those reported earlier for tropical and subtropical regions. The comprehensive study of Hanawa et al. (making use of controlled XBT–CTD data, mostly from tropical and subtropical waters) showed that the manufacturer's equation underestimates the probe's fall rate. This is manifested by the mean negative depth error reported from this region. However, results from the present study show that the manufacturer's equation slightly overestimates the fall rate in this region, as indicated by the small positive error (5–10 m).In order to provide theoretical support to the observed depth error, an analytical approach is adopted based on the viscosity effect on the probe's fall rate. Observed as well as analytical results suggest that the probe has a decelerating tendency due to the viscosity effect in high-latitude waters, and the existing correction scheme is not appropriate for XBT data from regions of such extreme low temperature.The existing correction scheme is valid for tropical and subtropical waters of negative depth error zones. However, for XBT data from high-latitude waters it is reasonable not to correct XBT data based on the existing scheme until the exact nature of depth error from this region is known. Though the mean depth errors from both the datasets show nearly identical values, it is necessary to conduct more controlled XBT–CTD experiments in this region in order to substantiate the exact nature of error for this region and then develop an appropriate depth-correction scheme.
An Examination of the Uncertainty in Interpolated Winds and Its Effect on the Validation and Intercomparison of Forecast Models
Authors: Greene J. Scott , Cook W. Ethan , Knapp David , Haines Patrick 
Published: March 2011

Abstract
Meteorological models need to be compared to long-term, routinely collected meteorological data. Whenever numerical forecast models are validated and compared, verification winds are normally interpolated to individual model grid points. To be statistically significant, differences between model and verification data must exceed the uncertainty of verification winds due to instrument error, sampling, and interpolation. This paper will describe an approach to examine the uncertainty of interpolated boundary layer winds and illustrate its practical effects on model validation and intercomparison efforts. This effort is part of a joint model validation project undertaken by the Environmental Verification and Analysis Center at the University of Oklahoma (http://www.evac.ou.edu) and the Battlefield Environment Directorate of the Army Research Laboratory. The main result of this study is to illustrate that it is crucial to recognize the errors inherent in gridding verification winds when conducting model validation and intercomparison work. Defendable model intercomparison results may rely on proper scheduling of model tests with regard to seasonal wind climatology and choosing instrument networks and variogram functions capable of providing adequately small errors due to sampling and imperfect modeling. Thus, it is important to quantify verification wind uncertainty when stating forecast errors or differences in the accuracy of forecast models.
Winter Precipitation Microphysics Characterized by Polarimetric Radar and Video Disdrometer Observations in Central Oklahoma
Authors: Zhang Guifu , Luchs Sean , Ryzhkov Alexander , Xue Ming , Ryzhkova Lily , Cao Qing 
Published: March 2011

AbstractThe study of precipitation in different phases is important to understanding the physical processes that occur in storms, as well as to improving their representation in numerical weather prediction models. A 2D video disdrometer was deployed about 30 km from a polarimetric weather radar in Norman, Oklahoma, (KOUN) to observe winter precipitation events during the 2006/07 winter season. These events contained periods of rain, snow, and mixed-phase precipitation. Five-minute particle size distributions were generated from the disdrometer data and fitted to a gamma distribution; polarimetric radar variables were also calculated for comparison with KOUN data. It is found that snow density adjustment improves the comparison substantially, indicating the importance of accounting for the density variability in representing model microphysics.
A Square Prism Urban Canopy Scheme for the NHM and Its Evaluation on Summer Conditions in the Tokyo Metropolitan Area, Japan
Authors: Aoyagi Toshinori , Seino Naoko 
Published: March 2011

AbstractA single-layered square prism urban canopy (SPUC) scheme for the Japan Meteorological Agency nonhydrostatic model (NHM) was developed. This scheme considers the urban canopy layer with square prism–shaped buildings. The basic concept of this scheme is similar to those of the conventional energy balance models for an urban canyon structure. The scheme presented here differs slightly from them in its representation of the bulk resistance circuit and some treatments of radiation processes, however, as well as by considering the water reservoir on building surfaces. A comparison between the SPUC scheme and the existing slab scheme of the NHM was made on summer days in the Tokyo metropolitan area. The SPUC run more accurately reproduced the expected behavior of the urban canopy effect than did the slab run. The effective albedo was smaller in the SPUC run than in the slab run (the upward shortwave radiation of the SPUC run was smaller than that of the slab run). The forecast heat fluxes in the SPUC run, however, showed worse performances. Adequate parameter settings (especially concerning latent heat fluxes) are needed in the SPUC run. The mean bias errors of the surface air temperature during nighttime were less negative and slightly improved in the SPUC run than in the slab run.