bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Vascular Endothelial Growth Factor Receptor-2 Inhibitor Enhances Antitumor Immunity through an Immune-Based Mechanism
Authors: Manning Elizabeth A. , Ullman John G.M. , Leatherman James M. , Asquith Justin M. , Hansen Timothy R. , Armstrong Todd D. , Hicklin Daniel J. , Jaffee Elizabeth M. , Emens Leisha A. 
Published: July 2007

AbstractPurpose: Given the complex tumor microenvironment, targeting multiple cellular components may be the most effective cancer treatment strategy. Therefore, we tested whether antiangiogenic and immune-based therapy might synergize by characterizing the activity of DC101, an antiangiogenic monoclonal antibody specific for vascular endothelial growth factor receptor-2 (VEGF-R2), alone and with HER-2/neu (neu)–targeted vaccination.Experimental Design: Neu-expressing breast tumors were measured in treated nontolerant FVB mice and immune-tolerant neu transgenic (neu-N) mice. Neu-specific and tumor cell–specific immune responses were assessed by intracellular cytokine staining, ELISPOT, and CTL assays.Results: DC101 decreased angiogenesis and increased tumor cell apoptosis. Although DC101 increased serum levels of the immunosuppressive cytokine VEGF, no evidence of systemic immune inhibition was detected. Moreover, DC101 did not impede the influx of tumor-infiltrating lymphocytes. In FVB mice, DC101 inhibited tumor growth in part through a T cell–dependent mechanism, resulting in both increased tumor-specific CD8+ T cells and tumor regression. Combining DC101 with neu-specific vaccination accelerated tumor regression, augmenting the lytic activity of CD8+ cytotoxic T cells. In tolerant neu-N mice, DC101 only delayed tumor growth without inducing frank tumor regression or antigen-specific T-cell activation. Notably, mitigating immune tolerance by inhibiting regulatory T cell activity with cyclophosphamide revealed DC101-mediated augmentation of antitumor responses in vaccinated neu-N mice.Conclusions: This is the first report of DC101-induced antitumor immune responses. It establishes the induction of tumor-specific T-cell responses as one consequence of VEGF-R2 targeting with DC101. These data support the development of multitargeted cancer therapy combining immune-based and antiangiogenic agents for clinical translation.
Mechanism of Action and Preclinical Antitumor Activity of the Novel Hypoxia-Activated DNA Cross-Linking Agent PR-104
Authors: Patterson Adam V. , Ferry Dianne M. , Edmunds Shelley J. , Gu Yongchuan , Singleton Rachelle S. , Patel Kashyap , Pullen Susan M. , Hicks Kevin O. , Syddall Sophie P. , Atwell Graham J. , Yang Shangjin , Denny William A. , Wilson William R. 
Published: July 2007

Abstract
Purpose: Hypoxia is a characteristic of solid tumors and a potentially important therapeutic target. Here, we characterize the mechanism of action and preclinical antitumor activity of a novel hypoxia-activated prodrug, the 3,5-dinitrobenzamide nitrogen mustard PR-104, which has recently entered clinical trials.
Experimental Design: Cytotoxicity in vitro was evaluated using 10 human tumor cell lines. SiHa cells were used to characterize metabolism under hypoxia, by liquid chromatography-mass spectrometry, and DNA damage by comet assay and γH2AX formation. Antitumor activity was evaluated in multiple xenograft models (PR-104 ± radiation or chemotherapy) by clonogenic assay 18 h after treatment or by tumor growth delay.
Results: The phosphate ester “pre-prodrug” PR-104 was well tolerated in mice and converted rapidly to the corresponding prodrug PR-104A. The cytotoxicity of PR-104A was increased 10- to 100-fold by hypoxia in vitro. Reduction to the major intracellular metabolite, hydroxylamine PR-104H, resulted in DNA cross-linking selectively under hypoxia. Reaction of PR-104H with chloride ion gave lipophilic cytotoxic metabolites potentially able to provide bystander effects. In tumor excision assays, PR-104 provided greater killing of hypoxic (radioresistant) and aerobic cells in xenografts (HT29, SiHa, and H460) than tirapazamine or conventional mustards at equivalent host toxicity. PR-104 showed single-agent activity in six of eight xenograft models and greater than additive antitumor activity in combination with drugs likely to spare hypoxic cells (gemcitabine with Panc-01 pancreatic tumors and docetaxel with 22RV1 prostate tumors).
Conclusions: PR-104 is a novel hypoxia-activated DNA cross-linking agent with marked activity against human tumor xenografts, both as monotherapy and combined with radiotherapy and chemotherapy.
Description and Evaluation of the Characteristics of the NCAR High-Resolution Land Data Assimilation System
Authors: Chen Fei , Manning Kevin W. , LeMone Margaret A. , Trier Stanley B. , Alfieri Joseph G. , Roberts Rita , Tewari Mukul , Niyogi Dev , Horst Thomas W. , Oncley Steven P. , Basara Jeffrey B. , Blanken Peter D. 
Published: July 2007

AbstractThis paper describes important characteristics of an uncoupled high-resolution land data assimilation system (HRLDAS) and presents a systematic evaluation of 18-month-long HRLDAS numerical experiments, conducted in two nested domains (with 12- and 4-km grid spacing) for the period from 1 January 2001 to 30 June 2002, in the context of the International H2O Project (IHOP_2002). HRLDAS was developed at the National Center for Atmospheric Research (NCAR) to initialize land-state variables of the coupled Weather Research and Forecasting (WRF)–land surface model (LSM) for high-resolution applications. Both uncoupled HRDLAS and coupled WRF are executed on the same grid, sharing the same LSM, land use, soil texture, terrain height, time-varying vegetation fields, and LSM parameters to ensure the same soil moisture climatological description between the two modeling systems so that HRLDAS soil state variables can be used to initialize WRF–LSM without conversion and interpolation. If HRLDAS is initialized with soil conditions previously spun up from other models, it requires roughly 8–10 months for HRLDAS to reach quasi equilibrium and is highly dependent on soil texture. However, the HRLDAS surface heat fluxes can reach quasi-equilibrium state within 3 months for most soil texture categories. Atmospheric forcing conditions used to drive HRLDAS were evaluated against Oklahoma Mesonet data, and the response of HRLDAS to typical errors in each atmospheric forcing variable was examined. HRLDAS-simulated finescale (4 km) soil moisture, temperature, and surface heat fluxes agreed well with the Oklahoma Mesonet and IHOP_2002 field data. One case study shows high correlation between HRLDAS evaporation and the low-level water vapor field derived from radar analysis.
Single-Scattering Properties of Aggregates of Bullet Rosettes in Cirrus
Authors: Um Junshik , McFarquhar Greg M. 
Published: July 2007

Abstract
During the March 2000 Cloud Intensive Operational Period, the University of North Dakota Citation executed spiral descents through midlatitude cirrus of a nonconvective origin over the Atmospheric Radiation Measurement Program’s Southern Great Plains site. Aggregates of bullet rosettes (ABRs) observed during the descents using a cloud particle imager are used to derive a relationship between the length L and width W of bullets that are the fundamental components of the ABRs, which is given by W = 7.14L0.455, where 100 μm ≤ L ≤ 600 μm. To derive a representation of an aggregate of bullet rosettes, six bullet rosettes, each of which is composed of six bullets of the same size but each of which has different-sized bullets from the other bullet rosettes, are attached together randomly without overlap. Using a geometric ray-tracing method, the phase function, asymmetry parameter g, and single-scattering albedo of the representation of ABR (rABR) and the component bullets and bullet rosettes are calculated at wavelengths λ of 0.55, 0.64, 1.38, 1.62, 2.11, and 3.78 μm. As the aspect ratio of the component bullets increases, the forward scattering increases by up to 1.3% and the lateral and backward scattering decrease by up to 8.9% and 10.2%, respectively, for a bullet rosette at a nonabsorbing λ (0.55 μm). For longer λ, light absorption decreases the rate at which these scatterings change with aspect ratio. The shape of the aggregates also affects the scattering properties. The rABR constructed here scatters up to 4.4% (7.0%; 20.4%) and 34.2% (11.1%; 32.7%) more light in the lateral and backward directions, respectively, and 1.2% (1.3%; 2.4%) less in the forward direction in comparison with the component bullets (component bullet rosettes; equivalent projected area bullet rosette), resulting in up to 2.5% (1.6%; 3.8%) decrease in g at 0.55 μm. In addition, as the aspect ratio and number of attached bullets in ABRs increase, g increases by up to 1.8% and decreases by up to 2.0% at 0.55 μm, increases by 2.0% and decreases by 0.3% at 2.11 μm, and increases by 1.1% and decreases by 0.5% at 3.78 μm, respectively. As an implication for remote sensing studies, the difference in the bidirectional reflectance distribution function calculated using the rABR and a bullet rosette is shown to vary by up to 107% at moderately absorbing (2.11 μm) wavelengths and by up to 35% and 28% at nonabsorbing (0.55 μm) and strongly absorbing (3.78 μm) wavelengths.
Estimation of Daylight Downward Longwave Atmospheric Irradiance under Clear-Sky and All-Sky Conditions
Authors: Bilbao Julia , de Miguel Argimiro H. 
Published: July 2007

Abstract
Daylight downward longwave irradiance data recorded over a flat place for the period between April 2001 and December 2004 in Valladolid, Spain, have been compared with estimates generated using four different schemes. The parameterization schemes of Brutsaert, Swinbank, Idso, and Brunt have been considered and calibrated for the comparison. Root-mean-square errors (rmse), mean bias errors, and linear regression correlations have been used to compare measured and estimated values. The results of this comparison show that, for clear-sky conditions, rmse values range between 19.57 and 8.85 W m−2 for calibrated schemes and between 39.78 and 11.13 W m−2 for original ones. The Idso and Brunt schemes give the best results with calibrated coefficients, and the Brunt scheme performs the best with original coefficients. A new scheme for estimating daylight downward longwave irradiance under “all-sky” conditions has been developed based on clear-sky schemes and solar global shortwave irradiance, and, after comparing measured and estimated values by calibrated schemes, it has been found that the Idso and Brunt schemes give the best results.
Penalized Maximal t Test for Detecting Undocumented Mean Change in Climate Data Series
Authors: Wang Xiaolan L. , Wen Qiuzi H. , Wu Yuehua 
Published: July 2007

Abstract
In this paper, a penalized maximal t test (PMT) is proposed for detecting undocumented mean shifts in climate data series. PMT takes the relative position of each candidate changepoint into account, to diminish the effect of unequal sample sizes on the power of detection. Monte Carlo simulation studies are conducted to evaluate the performance of PMT, in comparison with the most popularly used method, the standard normal homogeneity test (SNHT). An application of the two methods to atmospheric pressure series recorded at a Canadian site is also presented. It is shown that the false-alarm rate of PMT is very close to the specified level of significance and is evenly distributed across all candidate changepoints, whereas that of SNHT can be up to 10 times the specified level for points near the ends of series and much lower for the middle points. In comparison with SNHT, therefore, PMT has higher power for detecting all changepoints that are not too close to the ends of series and lower power for detecting changepoints that are near the ends of series. On average, however, PMT has significantly higher power of detection. The smaller the shift magnitude Δ is relative to the noise standard deviation σ, the greater is the improvement of PMT over SNHT. The improvement in hit rate can be as much as 14%–25% for detecting small shifts (Δ &lt; σ) regardless of time series length and up to 5% for detecting medium shifts (Δ = σ–1.5σ) in time series of length N &lt; 100. For all detectable shift sizes, the largest improvement is always obtained when N &lt; 100, which is of great practical importance, because most annual climate data series are of length N &lt; 100.
Error Propagation of Radar Rainfall Nowcasting Fields through a Fully Distributed Flood Forecasting Model
Authors: Vivoni Enrique R. , Entekhabi Dara , Hoffman Ross N. 
Published: July 2007

Abstract
This study presents a first attempt to address the propagation of radar rainfall nowcasting errors to flood forecasts in the context of distributed hydrological simulations over a range of catchment sizes or scales. Rainfall forecasts with high spatiotemporal resolution generated from observed radar fields are used as forcing to a fully distributed hydrologic model to issue flood forecasts in a set of nested subbasins. Radar nowcasting introduces errors into the rainfall field evolution that result from spatial and temporal changes of storm features that are not captured in the forecast algorithm. The accuracy of radar rainfall and flood forecasts relative to observed radar precipitation fields and calibrated flood simulations is assessed. The study quantifies how increases in nowcasting errors with lead time result in higher flood forecast errors at the basin outlet. For small, interior basins, rainfall forecast errors can be simultaneously amplified or dampened in different flood forecast locations depending on the forecast lead time and storm characteristics. Interior differences in error propagation are shown to be effectively averaged out for larger catchment scales.
Cellulose-binding Heptapeptides Identified by Phage Display Methods
Authors: Serizawa Takeshi , Iida Kyoko , Matsuno Hisao , Kurita Kimio 
Published: July 2007

Abstract
Phage libraries displaying random and linear heptapeptides were applied to crystalline cellulose. Binding affinities of obtained phage clones were quantitatively analyzed by enzyme-linked immunosorbent assays (ELISAs). Clones were obtained with greater apparent affinity constants (Kapps) than those of the library, suggesting the isolation of cellulose-binding peptides with characteristic sequences.
Palladium–Copper/Hydrophobic Active Carbon as a Highly Active and Selective Catalyst for Hydrogenation of Nitrate in Water
Authors: Wang Yi , Kasuga Tomohiro , Mikami Ikkou , Kamiya Yuichi , Okuhara Toshio 
Published: July 2007

Abstract
Cu–Pd supported on active carbon (AC), in which Cu/Pd ratio is strictly controlled, is an excellent catalyst for selective hydrogenation of NO3− to harmless products in the presence of H2 at low partial pressure. 3.6 wt % Cu; 2.0 wt % Pd/AC, coupled with another Pd/AC catalyst, showed high selectivity to N2 (98% at 298 K), while suppressing NH3 production (2% selectivity, 0.5 from 100 ppm of NO3−). Modification of the Cu–Pd/AC catalyst with PTFE results in further enhancement; the activity more than tripled, while suppression of NH3 production was retained.
Laboratory rearing of woodpigeons (Columba palumbus)
Authors: Haque A. K. M. Fazlul , Broom D. M. , Gaitens J. F. 
Published: July 2007

18 woodpigeons were reared. Weight gain was similar to that of wild-reared birds if they were collected from the nest at 5-11 days of age, but slower if they were collected later. The woodpigeon ( Columba palumbus) is an agricultural pest in Britain. As part of a field and laboratory study of pigeon-scaring methods, we have reared woodpigeons in captivity. There are very few reports on hand-rearing of woodpigeons in laboratory conditions. Colquhoun (1951) recorded the bodyweight of squabs (young pigeons) during laboratory rearing. These weights were much lower than those recorded by Murton, Isaacson & Westwood (1963) for birds of comparable age in field studies. Kenward & Sibly (1978) also reported the hand-rearing of woodpigeons. The present paper deals with the methods of rearing and with weight gain in the laboratory.
Alendronate Has an Anabolic Effect on Bone Through the Differentiation of Mesenchymal Stem Cells
Authors: Duque Gustavo , Rivas Daniel 
Published: July 2007

Abstract
We committed MSCs to differentiate into either osteoblasts or adipocytes and examined the effect of ALN on both adipogenesis and osteoblastogenesis. ALN inhibited adipogenesis while promoting osteoblast differentiation and activity. Our results reveal a new anabolic effect of ALN in differentiating bone marrow cells.
Introduction: Alendronate (ALN) prevents bone loss in postmenopausal patients through the regulation of osteoclastic activity. However, it has also proven to be effective in older adults where the pathophysiological mechanism is the predominance of adipogenesis over osteoblastogenesis. The aim of this study is to determine the in vitro effect of ALN on both osteoblastogenesis and adipogenesis.
Materials and Methods: Human mesenchymal stem cells (MSCs) were plated at a density of 5 × 105 cells/well in 100-cm 2 dishes containing MSC growth media. After confluence, cells were committed to differentiate adding either adipogenic or osteogenic media with and without 1,25(OH)2D3 (10−8 M) and supplemented with ALN at increasing concentrations (10−9 to 10−7 M). Untreated differentiating MSCs were used as control. Alkaline phosphatase (ALP), oil red O, and Alizarin red staining were performed at timed intervals (weeks 1 and 2). Additionally, levels of expression of both osteogenesis and adipogenesis transcription factors were measured in protein extracts. Finally, the effect of ALN on PPARγ2 nuclear activation complex was assessed.
Results: We found that ALN has a significant and dose-dependent effect on osteoblastogenesis. This effect was not modified by the presence of 1,25(OH)2D3 in the medium. Furthermore, adipogenic differentiation of MSCs was affected by addition of both ALN and 1,25(OH)2D3 to the media as confirmed by phenotype changes and lower number of lipid droplets. Finally, expression of adipogenic transcription factors and PPARγ2 activation were reduced in adipose differentiating MSCs treated with either ALN or ALN + 1,25(OH)2D3.
Conclusions: This study shows a potential anabolic effect of ALN in vitro through the stimulation of osteogenic differentiation of MSCs. Additionally, a previously unknown inhibitory effect of ALN on bone marrow adipogenesis was also found.
Osteogenic Potential of Postnatal Skeletal Muscle–Derived Stem Cells Is Influenced by Donor Sex
Authors: Corsi Karin A , Pollett Jonathan B , Phillippi Julie A , Usas Arvydas , Li Guangheng , Huard Johnny 
Published: July 2007

Abstract
This study compared the osteogenic differentiation of F-MDSCs and M-MDSCs. Interestingly, M-MDSCs expressed osteogenic markers and underwent mineralization more readily than F-MDSCs; a characteristic likely caused by more osteoprogenitor cells within the M-MDSCs than the F-MDSCs and/or an accelerated osteogenic differentiation of M-MDSCs.
Introduction: Although therapies involving stem cells will require both female and male cells, few studies have investigated whether sex-related differences exist in their osteogenic potential. Here, we compared the osteogenic differentiation of female and male mouse skeletal muscle–derived stem cells (F- and M-MDSCs, respectively), a potential cell source for orthopedic tissue engineering.
Materials and Methods: F- and M-MDSCs were stimulated with bone morphogenetic protein (BMP)4, followed by quantification of alkaline phosphatase (ALP) activity and expression of osteogenic genes. F- and M-MDSCs were also cultured as pellets in osteogenic medium to evaluate mineralization. Single cell–derived colonies of F- and M-MDSCs were stimulated with BMP4, stained for ALP, and scored as either Low ALP+ or High ALP+ to detect the presence of osteoprogenitor cells. F- and M-MDSCs were transduced with a BMP4 retrovirus (MDSC-BMP 4 cells) and used for the pellet culture and single cell–derived colony formation assays. As well, F- and M-MDSC -BMP 4 cells were implanted in the intramuscular pocket of sex-matched and sex-mismatched hosts, and bone formation was monitored radiographically.
Results and Conclusions: When stimulated with BMP4, both F- and M-MDSCs underwent osteogenic differentiation, although M-MDSCs had a significantly greater ALP activity and a larger increase in the expression of osteogenic genes than F-MDSCs. In the pellet culture assay, M-MDSCs showed greater mineralization than F-MDSCs. BMP4 stimulation of single cell–derived colonies from M-MDSCs showed higher levels of ALP than those from F-MDSCs. Similar results were obtained with the MDSC-BMP 4 cells. In vivo, F-MDSC -BMP 4 cells displayed variability in bone area and density, whereas M-MDSC -BMP 4 cells showed a more consistent and denser ectopic bone formation. More bone formation was also seen in male hosts compared with female hosts, regardless of the sex of the implanted cells. These results suggest that M-MDSCs may contain more osteoprogenitor cells than F-MDSCs, which may have implications in the development of cellular therapies for bone healing.
Evidence that the Localization of the Elongation Factor Spt16 Across Transcribed Genes Is Dependent Upon Histone H3 Integrity in Saccharomyces cerevisiae
Authors: Duina Andrea A , Rufiange Anne , Bracey John , Hall Jeffrey , Nourani Amine , Winston Fred 
Published: July 2007

Abstract
A previous study of histone H3 in Saccharomyces cerevisiae identified a mutant with a single amino acid change, leucine 61 to tryptophan, that confers several transcriptional defects. We now present several lines of evidence that this H3 mutant, H3-L61W, is impaired at the level of transcription elongation, likely by altered interactions with the conserved factor Spt16, a subunit of the transcription elongation complex yFACT. First, a selection for suppressors of the H3-L61W cold-sensitive phenotype has identified novel mutations in the gene encoding Spt16. These genetic interactions are allele specific, suggesting a direct interaction between H3 and Spt16. Second, similar to several other elongation and chromatin mutants, including spt16 mutants, an H3-L61W mutant allows transcription from a cryptic promoter within the FLO8 coding region. Finally, chromatin-immunoprecipitation experiments show that in an H3-L61W mutant there is a dramatically altered profile of Spt16 association over transcribed regions, with reduced levels over 5′-coding regions and elevated levels over the 3′ regions. Taken together, these and other results provide strong evidence that the integrity of histone H3 is crucial for ensuring proper distribution of Spt16 across transcribed genes and suggest a model for the mechanism by which Spt16 normally dissociates from DNA following transcription.
Inferring Somatic Mutation Rates Using the Stop-Enhanced Green Fluorescent Protein Mouse
Authors: Ro Simon , Rannala Bruce 
Published: July 2007

AbstractA new method is developed for estimating rates of somatic mutation in vivo. The stop-enhanced green fluorescent protein (EGFP) transgenic mouse carries multiple copies of an EGFP gene with a premature stop codon. The gene can revert to a functional form via point mutations. Mice treated with a potent mutagen, N-ethyl-N-nitrosourea (ENU), and mice treated with a vehicle alone are assayed for mutations in liver cells. A stochastic model is developed to model the mutation and gene expression processes and maximum-likelihood estimators of the model parameters are derived. A likelihood-ratio test (LRT) is developed for detecting mutagenicity. Parametric bootstrap simulations are used to obtain confidence intervals of the parameter estimates and to estimate the significance of the LRT. The LRT is highly significant (α &lt; 0.01) and the 95% confidence interval for the relative effect of the mutagen (the ratio of the rate of mutation during the interval of mutagen exposure to the rate of background mutation) ranges from a minimum 200-fold effect of the mutagen to a maximum 2000-fold effect.