bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Tumor Cell–Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth
Authors: Bennewith Kevin L. , Huang Xin , Ham Christine M. , Graves Edward E. , Erler Janine T. , Kambham Neeraja , Feazell Jonathan , Yang George P. , Koong Albert , Giaccia Amato J. 
Published: January 2009

Abstract
Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA–expressing clones showed dramatically reduced growth in soft agar and when implanted s.c. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by positron emission tomography imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed colocalization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell–derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer. [Cancer Res 2009;69(3):775–84]
From Stabat Pater to Prophetic Virgin: Harriet Beecher Stowe's Recovery of the Madonna-Figure
Authors: Adams Kimberly VanEsveld 
Published: January 2009

AbstractThis study of Harriet Beecher Stowe's Madonna-figures questions some influential arguments about the novelist's treatment of motherhood and domesticity. Critics such as Jane Tompkins, Elizabeth Ammons, and Gillian Brown have claimed that the novels privilege an alternative maternal culture and may even present the Christian Savior in feminized terms. But the early novels in fact reveal the gender restrictions of nineteenth-century Protestantism, which allowed no sanctified female roles. Uncle Tom's Cabin and Dred, for example, have Christ-figures but no Madonnas. Stowe's travels overseas, which exposed her to European religious art, and her gradual movement from the Congregational to the Episcopal church (documented by John Gatta), had a profound impact on two subsequent novels, The Minister's Wooing and Agnes of Sorrento. Here, for the first time, female characters are made Madonna-figures. But the novelist presents them as contemplative saints and prophetic virgins, rather than as mothers. Only in her late religious writings does Stowe portray the biblical Mary as not only prophet and poet but also mother—and then in an inimitable way. In The Minister's Wooing and Agnes as well as her religious writings, Stowe examines the New Testament sisters Martha and Mary of Bethany, who in church tradition represent, respectively, the active and the contemplative life. These discussions reveal the conflict the author experienced between her domestic responsibilities and artistic vocation, and her misgivings about many of the maternal characters found throughout her fiction. Stowe's contemplative and creative Mary-figures include Mary Scudder, Agnes, and the Virgin Mary herself. The contrasting Martha-figures are domestic geniuses but have “worldly” values, which sometimes threaten their daughters' happiness. These Marthas, who are increasingly subjected to authorial criticism, suggest some needed qualifications of arguments for the consistently positive valence of motherhood and domesticity in Stowe.
How Similar Are the Values of the People of China and Taiwan?
Authors: Marsh Robert 
Published: January 2009

AbstractThe reunification of Taiwan with China is one possible future development. Value differences can make the merging of two previously divided societies more difficult. How similar are the values – conceptions of the desirable – of the people now living in China and Taiwan? Representative national sample data from the World Values Surveys for both countries enable us to compare values in eleven domains. There are statistically significant differences on most values between respondents in the two societies, but the degree of difference varies among domains. The largest differences are found in religious values; lesser differences exist in trust and confidence, economic values, and values concerning the environment and science. Value similarities are greatest in the domains of family values, personal satisfaction, social stratification, and gender. The bearing of social structural conditions in China and Taiwan on these value differences and similarities is shown.
Ensemble Forecasts of Drought Indices Using a Conditional Residual Resampling Technique
Authors: Hwang Yeonsang , Carbone Gregory J. 
Published: January 2009

AbstractThe historical climate record and seasonal temperature and precipitation records provide useful datasets for making short-term drought predictions. A variety of methods have exploited these resources, but few have quantitatively measured uncertainties associated with predictions of drought index values commonly used in management plans. In this paper, stochastic approaches for estimating uncertainty are applied to drought index predictions. National Oceanic and Atmospheric Administration (NOAA) Climate Prediction Center (CPC) seasonal forecasts and resampling of nearest-neighbor residuals are incorporated to measure uncertainty in monthly forecasts of Palmer drought severity index (PDSI) and standardized precipitation index (SPI) in central South Carolina. Kuiper skill scores of PDSI indicate good forecast performance with up to 3-month lead time and improvements for 1-month-lead SPI forecasts. NOAA CPC climate outlook improved the forecast skill by as much as 40%, and the degree of improvement varies by season and forecast lead time.
The Path Density of Interhemispheric Surface-to-Surface Transport. Part II: Transport through the Troposphere and Stratosphere Diagnosed from NCEP Data
Authors: Holzer Mark 
Published: January 2009

Abstract
Interhemispheric transport from the earth’s surface north of 32.4°N (region ΩN) to the surface south of 32.4°S (region ΩS) is quantified using the path-density diagnostic developed in Part I of this study. The path density is computed using the Model of Atmospheric Transport and Chemistry (MATCH) driven by NCEP reanalyses. The structure of both the ΩN → ΩS and ΩN → ΩN zonally averaged path densities is examined in detail for air that had last ΩN contact (“ΩN air”) during January and July. The path density provides the joint probability that ΩN air will make its next surface contact with either ΩN or ΩS, that it will have surface-to-surface transit time τ ∈ (τ, τ + dτ), and that it can be found in volume element d 3r during its surface-to-surface journey. The distribution of surface-to-surface transit times, the probability of ΩN air making next contact with ΩS, and the probability of finding ΩN air destined for ΩS in the stratosphere are computed from suitable integrations of the path density. Approximately one-third of the ΩN air undergoes interhemispheric transport to ΩS, with a ∼20% probability of being found in the stratosphere during its surface-to-surface journey. The stratospheric fraction has about equal contributions from the part of the stratosphere that is isentropically isolated from the troposphere and from the part that is isentropically connected to the troposphere (i.e., from the overworld and the stratospheric middleworld in the terminology of Hoskins). The flow rate through the stratospheric middleworld is about twice as large as the flow rate through the overworld.
An Application of Reflectivity Climatology in Constructing Radar Hybrid Scans over Complex Terrain
Authors: Chang Pao-Liang , Lin Pin-Fang , Jong-Dao Jou Ben , Zhang Jian 
Published: January 2009

Abstract
Three years’ worth of radar reflectivity data from four radars in an area of complex terrain (Taiwan) from 2005 to 2007 were analyzed and a reflectivity climatology was developed. The climatology was applied in the construction of new hybrid scans to minimize the impacts of ground clutter and beam blockages. The reflectivity climatology showed significant seasonal variations and captured distributions of ground/sea clutters, beam blockages, and anomalous propagations in addition to precipitation systems in the radar domains.
By comparing the reflectivity climatology with gauge observations, it was found that 15 (20) dBZ was a good approximation for rain/no-rain segregation during cool (warm) seasons. Comparisons between the standard (i.e., based on terrain and scan strategies only with the assumption of standard propagations) and nonstandard (i.e., standard plus the clutter and blockage mitigation using the reflectivity climatology) hybrid scans showed that the former did not accurately reflect the clutter and blockage distributions in the real atmosphere. The application of the reflectivity climatology was shown to significantly reduce the impacts of clutter and blockages and provided improved radar quantitative precipitation estimates (QPEs) in the complex terrain.
Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia
Authors: Wu Qing-Li , Zierold Claudia , Ranheim Erik A. 
Published: January 2009

AbstractWnt/Fzd signaling is known to play a key role in development, tissue-specific stem-cell maintenance, and tumorigenesis, particularly through the canonical pathway involving stabilization of β-catenin. We have previously shown that Fzd9−/− mice have a deficiency in pre-B cells at a stage when self-renewing division is occurring in preference to further differentiation, before light chain immunoglobulin recombination. To determine whether pathologic usurpation of this pathway plays a role in B-cell leukemogenesis, we examined the expression of Wnt/Fzd pathway genes in the Eμ-TCL1 mouse model of chronic lymphocytic leukemia. We find that, in the course of leukemogenesis, the expression of Wnt16, Wnt10α, Fzd1, and most dramatically, Fzd6, is progressively up-regulated in the transformed CD5+ B cells of these mice, as are β-catenin protein levels. Elimination of Fzd6 expression by crossing into Fzd6−/− mice significantly delays development of chronic lymphocytic leukemia in this model. Our findings suggest that the self-renewal signals mediated by Wnt/Fzd that are enlisted during B-cell development may be pathologically reactivated in the neoplastic transformation of mature B cells.
Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell–depleted allogeneic hematopoietic cell transplantation
Authors: Yu Junli , Venstrom Jeffrey M. , Liu Xiao-Rong , Pring James , Hasan Reenat S. , O'Reilly Richard J. , Hsu Katharine C. 
Published: January 2009

Abstract
Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient (“missing self”). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR (“missing ligand”), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell–depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-γ and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell–derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.
Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine
Authors: Höglund Andreas , Nilsson Lisa M. , Forshell Linus Plym , Maclean Kirsteen H. , Nilsson Jonas A. 
Published: January 2009

Abstract
Decitabine (also referred to as 5-aza-2′-deoxycytidine) is a drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed to be the blocking of DNA methylation and thereby reactivating silenced genes involved in harnessing MDS. When analyzing reactivation of genes involved in Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells by inducing DNA damage. This sensitization is grossly augmented by the MYC oncogene, which is overexpressed in BL, and occurs in cells lacking a functional p53 tumor suppressor pathway. In p53-deficient BL cells and p53−/− mouse embryo fibroblasts, Myc overrides a transient G2-block exerted by decitabine via activation of Chk1. This triggers aneuploidy and cell death that correlates with, but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase activation, and/or expression of the BH3-only protein Puma. In vivo modeling of Myc-induced lymphoma suggests that decitabine constitutes a potential new drug against lymphoma that would selectively sensitize tumor cells but spare normal tissue.
Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation
Authors: Bachanova Veronika , Verneris Michael R. , DeFor Todd , Brunstein Claudio G. , Weisdorf Daniel J. 
Published: January 2009

Abstract
Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced-intensity conditioning followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m2 × 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n = 4) or umbilical cord (n = 18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n = 14) led to significantly less TRM (8%, P < .04) and improved overall survival (81%, P < .01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719.
Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance
Authors: Vachon Celine M. , Kyle Robert A. , Therneau Terry M. , Foreman Barbara J. , Larson Dirk R. , Colby Colin L. , Phelps Tara K. , Dispenzieri Angela , Kumar Shaji K. , Katzmann Jerry A. , Rajkumar S. Vincent 
Published: January 2009

Abstract
We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, ≥ 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.
Impact of genotyping errors on the type I error rate and the power of haplotype-based association methods
Authors: Marquard Vivien , Beckmann Lars , Heid Iris M , Lamina Claudia , Chang-Claude Jenny 
Published: January 2009

Abstract

Background
We investigated the influence of genotyping errors on the type I error rate and empirical power of two haplotype based association methods applied to candidate regions. We compared the performance of the Mantel Statistic Using Haplotype Sharing and the haplotype frequency based score test with that of the Armitage trend test.
Our study is based on 1000 replication of simulated case-control data settings with 500 cases and 500 controls, respectively. One of the examined markers was set to be the disease locus with a simulated odds ratio of 3. Differential and non-differential genotyping errors were introduced following a misclassification model with varying mean error rates per locus in the range of 0.2% to 15.6%.

Results
We found that the type I error rate of all three test statistics hold the nominal significance level in the presence of nondifferential genotyping errors and low error rates. For high and differential error rates, the type I error rate of all three test statistics was inflated, even when genetic markers not in Hardy-Weinberg Equilibrium were removed. The empirical power of all three association test statistics remained high at around 89% to 94% when genotyping error rates were low, but decreased to 48% to 80% for high and nondifferential genotyping error rates.

Conclusion
Currently realistic genotyping error rates for candidate gene analysis (mean error rate per locus of 0.2%) pose no significant problem for the type I error rate as well as the power of all three investigated test statistics.
The UDP-glucosyltransferase multigene family in Bombyx mori
Authors: Huang Fei-Fei , Chai Chun-Li , Zhang Ze , Liu Zeng-Hu , Dai Fang-Yin , Lu Cheng , Xiang Zhong-Huai 
Published: January 2009

Abstract

Background
Glucosidation plays a major role in the inactivation and excretion of a great variety of both endogenous and exogenous compounds. A class of UDP-glycosyltransferases (UGTs) is involved in this process. Insect UGTs play important roles in several processes, including detoxication of substrates such as plant allelochemicals, cuticle formation, pigmentation, and olfaction. Identification and characterization of Bombyx mori UGT genes could provide valuable basic information for this important family and explain the detoxication mechanism and other processes in insects.

Results
Taking advantage of the newly assembled genome sequence, we performed a genome-wide analysis of the candidate UGT family in the silkworm, B. mori. Based on UGT signature and their similarity to UGT homologs from other organisms, we identified 42 putative silkworm UGT genes. Most of them are clustered on the silkworm chromosomes, with two major clusters on chromosomes 7 and 28, respectively. The phylogenetic analysis of these identified 42 UGT protein sequences revealed five major groups. A comparison of the silkworm UGTs with homologs from other sequenced insect genomes indicated that some UGTs are silkworm-specific genes. The expression patterns of these candidate genes were investigated with known expressed sequence tags (ESTs), microarray data, and RT-PCR method. In total, 36 genes were expressed in tissues examined and showed different patterns of expression profile, indicating that these UGT genes might have different functions.

Conclusion

B. mori possesses a largest insect UGT gene family characterized to date, including 42 genes. Phylogenetic analysis, genomic organization and expression profiles provide an overview for the silkworm UGTs and facilitate their functional studies in future.
Comparative transcriptomic analysis of Porphyromonas gingivalisbiofilm and planktonic cells
Authors: Lo Alvin W , Seers Christine A , Boyce John D , Dashper Stuart G , Slakeski Nada , Lissel J Patricia , Reynolds Eric C 
Published: January 2009

Abstract

Background

Porphyromonas gingivalis in subgingival dental plaque, as part of a mature biofilm, has been strongly implicated in the onset and progression of chronic periodontitis. In this study using DNA microarray we compared the global gene expression of a P. gingivalis biofilm with that of its planktonic counterpart grown in the same continuous culture.

Results
Approximately 18% (377 genes, at 1.5 fold or more, P-value < 0.01) of the P. gingivalis genome was differentially expressed when the bacterium was grown as a biofilm. Genes that were down-regulated in biofilm cells, relative to planktonic cells, included those involved in cell envelope biogenesis, DNA replication, energy production and biosynthesis of cofactors, prosthetic groups and carriers. A number of genes encoding transport and binding proteins were up-regulated in P. gingivalis biofilm cells. Several genes predicted to encode proteins involved in signal transduction and transcriptional regulation were differentially regulated and may be important in the regulation of biofilm growth.

Conclusion
This study analyzing global gene expression provides insight into the adaptive response of P. gingivalis to biofilm growth, in particular showing a down regulation of genes involved in growth and metabolic activity.