bluuebunny/crossref_metadata_2025_split huggingface dataset:
Political Challenges of Innovation in the Developing World1
Authors: Doner Richard F. , Hicken Allen , Ritchie Bryan K. 
Published: March 2009

AbstractIn this article, we seek to rectify the absence of political analysis characterizing most literature on innovation and development. Although existing research is careful to note the lack of any single recipe or model of innovation, most scholars identify a range of institutions and policies influencing innovative performance. But such explanations beg the question of where institutions, so critical to policy implementation, actually come from. We argue that the answer lies in (1) the desire of political leaders to promote innovation and related institutions, and (2) the structure of political arrangements—especially the number of actors with the power and interest to block or promote reform—through which leaders must operate. We argue that both of these variables are strongly influenced by the threats facing leaders and the resources available to address such threats.
Are overweight adolescents at higher risk of engaging in unhealthy weight‐control behaviours?
Authors: Fonseca Helena , Matos Margarida G , Guerra António , Pedro J Gomes 
Published: March 2009

AbstractAim: To examine correlates of unhealthy weight‐control behaviours (UNWCB), and to explore possible associated variables.Methods: Sample included 3762, 8th and 10th grade public school Portuguese students who participated in the 2002 Health Behaviour in School‐Aged Children (HBSC)/World Health Organization (WHO) survey of adolescent health. Factor analysis was used, and two scales were identified as ‘healthy weight‐control behaviours’ (HWCB) and ‘UNWCB’ through Kaiser criteria analysis. Frequency scores were developed and used in analysis of variance (ANOVAs) test as dependent variables, according to gender and age. Pearson correlations and post‐hoc analysis were performed to identify potential associations.Results: UNWCB were significantly higher among those who were dieting or not dieting, but considering they should, and were significantly and progressively increasing from those perceiving themselves as thin, to those perceiving themselves as being the right size and those perceiving themselves as fat. Overweight reported more frequently than non‐overweight, both HWCB and UNWCB. Finally, there were significant differences concerning alcohol use, with UNWCB increasing progressively from reporting ‘drinking rarely or never’ to ‘drinking every week’ and ‘everyday’. Conclusion: Because UNWCB are associated with both medical and psychological health risks, routine screening is warranted. Special attention needs to be directed towards youth at greatest risk for disordered eating, including overweight youth.
DRYING EFFECTS OF TWO AIR‐DRYING SHELTERS IN A PILOT TEST ON SULTANA GRAPES
Authors: LI LINGLING , WANG ZHENGFU , HU XIAOSONG , WU JIHONG , LIAO XIAOJUN , CHEN FANG , ZHAO GUANGHUA 
Published: March 2009

ABSTRACT The drying effects of sultana grapes in two different air‐drying shelters were tested and analyzed. Ten different thin‐layer drying mathematical models were compared according to their coefficients of determination andχ2test. The Wang and Singh model was found to be the most suitable for describing the air‐drying curves of sultana grapes. As compared with the local traditional shelter, the reformed shelter with a greenhouse can reduce about 12–18% of air‐drying time, increase about 23% in green‐grade rate of raisins and increase 33% in the effective moisture diffusivity of sultana grapes.PRACTICAL APPLICATIONSGrapes are one of the most popular and palatable fruits in the world. The preservation of grapes by drying is a major industry in many parts of the world where grapes are grown. Drying grapes, either by open sun drying, shade drying or mechanical drying, produces raisins. Air‐drying of solar energy has been demonstrated to be cost‐effective and could be an effective alternative to traditional and mechanical drying systems, especially in locations with good sunshine during the harvest season. The traditional air‐drying shelter of grapes has been used for thousands of years in Asia and other places around the world. However, less investigation was done about the drying characteristics and the optimization of the shelter. The work of this manuscript provides interesting information that is useful for design of the drying shelter of raisins and for the improvement of raisin quality, especially using air‐drying of solar energy.
ADP-Ribosylation Factor 6 Regulates Tumorigenic and Invasive Properties In vivo
Authors: Muralidharan-Chari Vandhana , Hoover Holly , Clancy James , Schweitzer Jill , Suckow Mark A. , Schroeder Valerie , Castellino Francis J. , Schorey Jeffrey S. , D'Souza-Schorey Crislyn 
Published: March 2009

Abstract
This study shows that the small GTP-binding protein ADP-ribosylation factor 6 (ARF6) is an important regulator of tumor growth and metastasis. Using spontaneous melanoma tumor growth assays and experimental metastasis assays in nude mice, we show that sustained activation of ARF6 reduces tumor mass growth but significantly enhances the invasive capacity of tumor cells. In contrast, mice injected with tumor cells expressing a dominantly inhibitory ARF6 mutant exhibited a lower incidence and degree of invasion and lung metastasis compared with control animals. Effects on tumor growth correlate with reduced cell proliferation capacity and are linked at least in part to alterations in mitotic progression induced by defective ARF6 cycling. Furthermore, phospho-ERK levels in subcultured cells from ARF6(GTP) and ARF6(GDP) tumor explants correlate with invasive capacity. ARF6-induced extracellular signal-regulated kinase (ERK) signaling leads to Rac1 activation to promote invadopodia formation and cell invasion. These findings document an intricate role for ARF6 and the regulation of ERK activation in orchestrating mechanisms underlying melanoma growth, invasion, and metastases. [Cancer Res 2009;69(6):2201–9]
Common Polymorphisms in the Prostaglandin Pathway Genes and Their Association with Breast Cancer Susceptibility and Survival
Authors: Abraham Jean E. , Harrington Patricia , Driver Kristy E. , Tyrer Jonathan , Easton Douglas F. , Dunning Alison M. , Pharoah Paul D.P. 
Published: March 2009

Abstract
Purpose: There is evidence that genetic variation in the prostaglandin pathway affects cancer susceptibility and progression. Conflicting data from several studies exist for the association of PTGS2 (cyclooxygenase 2) polymorphisms with breast cancer risk. We investigated associations between common germ-line variations in seven genes in the prostaglandin pathway and breast cancer susceptibility and survival among women with invasive breast cancer in the SEARCH study.
Experimental Design: DNA samples from 9,030 cases and controls were genotyped for 64 single nucleotide polymorphisms tagging known common variants (minor allele frequency &gt; 0.05) in PTGS1, PTGS2, TBXAS1, PTGIS, PTGES, PTGDS, and PGDS with a two-stage case-control study design.
Results: Four tagging single nucleotide polymorphisms showed modest association with breast cancer susceptibility. All four fit a recessive genetic model. Minor allele homozygotes for PTGISrs5602 [odds ratio (OR), 1.15; 95% confidence interval (95% CI), 1.04-1.27; P = 0.005], PTGISrs8183919 (OR, 1.22; 95% CI, 1.06-1.41; P = 0.006), and TBXASrs41727 (OR, 1.83; 95% CI, 1.22-2.73; P = 0.003) are associated with an increased risk compared with common allele carriers. For PTGISrs44627 minor allele homozygotes (OR, 0.66; 95% CI, 0.5-0.86; P = 0.002), a protective effect was observed.
Conclusion: Specific PTGIS and TBXAS1 variants may affect breast cancer susceptibility, but common variants in PTGS1, PTGS2, PTGES, PTGDS, and PGDS have no major role in breast cancer susceptibility. None of the variants in the seven genes studied appear to affect survival. Further larger studies correlating clinical and genotypic data are required to establish if the clinical utility of prostaglandin-targeted therapies, as chemoprevention agents, is influenced by an individual's profile of genetic variants in key prostaglandin pathway genes.
Sperm-Derived SPANX-B Is a Clinically Relevant Tumor Antigen That Is Expressed in Human Tumors and Readily Recognized by Human CD4+ and CD8+ T Cells
Authors: Almanzar Giovanni , Olkhanud Purevdorj B. , Bodogai Monica , Dell'Agnola Chiara , Baatar Dolgor , Hewitt Stephen M. , Ghimenton Claudio , Tummala Mohan K. , Weeraratna Ashani T. , Hoek Keith Sean , Kouprina Natalay , Larionov Vladimir , Biragyn Arya 
Published: March 2009

Abstract
Purpose: The sperm-derived SPANX family proteins can be found expressed in human tumors. Here, we aimed to perform a comprehensive study to evaluate immunotherapeutic relevance of one of its members, SPANX-B. We wanted to test its expression pattern in human tumors and to evaluate CD4+ and CD8+ T-cell responses in healthy humans after in vitro immunizations.
Experimental Design: Expression of SPANX-B in human malignancies, including a multitumor tissue array of 145 primary tumors, was assessed using reverse transcription-PCR, Western blotting, and immunohistochemical analysis. T-cell immunogenicity and immunodominant epitopes of SPANX-B were studied using in vitro immunizations of healthy human donor-derived leukocytes.
Results: SPANX-B was abundantly expressed in melanoma and carcinomas of lung, ovary, colon, and breast. In melanoma, tissue array data indicated that it was expressed in advanced and metastatic disease. Unlike most tumor-associated antigens, SPANX-B was an immunogenic antigen that was recognized by circulating T-cell precursors in healthy humans. Importantly, these T cells were readily expanded to generate SPANX-B-specific helper CD4+ and cytolytic CD8+ T cells that recognized unique immunodominant epitopes: at least one HLA-DR-restricted Pep-9 epitope (SPANX-B12-23) and two HLA-A2-restricted Pep-2 and Pep-4 epitopes (SPANX-B23-31 and SPANX-B57-65, respectively). CD8+ T cells were fully functional to recognize and lyse HLA-A2-expressing tumors, including primary human melanomas.
Conclusions: SPANX-B is an immunogenic sperm-derived antigen that is expressed in several human tumors. SPANX-B is also efficiently recognized by the human T-cell immune arm, indicating its significant value for the development of protective and therapeutic cancer vaccines.
Sunitinib Mediates Reversal of Myeloid-Derived Suppressor Cell Accumulation in Renal Cell Carcinoma Patients
Authors: Ko Jennifer S. , Zea Arnold H. , Rini Brian I. , Ireland Joanna L. , Elson Paul , Cohen Peter , Golshayan Ali , Rayman Patricia A. , Wood Laura , Garcia Jorge , Dreicer Robert , Bukowski Ronald , Finke James H. 
Published: March 2009

AbstractPurpose: Immune dysfunction reported in renal cell carcinoma (RCC) patients may contribute to tumor progression. Myeloid-derived suppressor cells (MDSC) represent one mechanism by which tumors induce T-cell suppression. Several factors pivotal to the accumulation of MDSC are targeted by the tyrosine kinase inhibitor, sunitinib. The effect of sunitinib on MDSC-mediated immunosuppression in RCC patients has been investigated.Experimental Design: Patient peripheral blood levels of MDSC and regulatory T-cell (Treg) and T-cell production of IFN-γ were evaluated before and after sunitinib treatment. Correlations between MDSC and Treg normalization as well as T-cell production of IFN-γ were examined. The in vitro effect of sunitinib on patient MDSC was evaluated.Results: Metastatic RCC patients had elevated levels of CD33+HLA-DR− and CD15+CD14− MDSC, and these were partially overlapping populations. Treatment with sunitinib resulted in significant reduction in MDSC measured by several criteria. Sunitinib-mediated reduction in MDSC was correlated with reversal of type 1 T-cell suppression, an effect that could be reproduced by the depletion of MDSC in vitro. MDSC reduction in response to sunitinib correlated with a reversal of CD3+CD4+CD25hiFoxp3+ Treg cell elevation. No correlation existed between a change in tumor burden and a change in MDSC, Treg, or T-cell production of IFN-γ. In vitro addition of sunitinib reduced MDSC viability and suppressive effect when used at ≥1.0 μg/mL. Sunitinib did not induce MDSC maturation in vitro.Conclusions: Sunitinib-based therapy has the potential to modulate antitumor immunity by reversing MDSC-mediated tumor-induced immunosuppression.
Constitutive NF-κB Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor Growth
Authors: Sakamoto Kei , Maeda Shin , Hikiba Yohko , Nakagawa Hayato , Hayakawa Yoku , Shibata Wataru , Yanai Ayako , Ogura Keiji , Omata Masao 
Published: March 2009

Abstract
Purpose: Nuclear factor κB (NF-κB) is an important transcription factor in various biological processes. Constitutive NF-κB activation has been noted in many tumors, including colorectal cancers. However, the precise role of this activation in colorectal cancer is unclear.
Experimental Design: Constitutive NF-κB activation was evaluated in colorectal cancer tissues and cell lines. To inhibit NF-κB activation, we established cancer cells with stable knockdown of IκB kinase γ (NF-κB essential modulator), which is the regulatory subunit of the IκB kinase complex, by RNA interference. Cell growth and apoptosis were evaluated in wild-type cells (WT) and knocked-down cells (KD). Microarray and protein array analysis were also done. To determine involvement of angiogenesis, human umbilical vein endothelial cells were used. By s.c. transplantation of the cells into nude mice, tumor sizes, vascularity, and chemodrug sensitivity were analyzed.
Results: Constitutive NF-κB activation was observed in 40% of colorectal cancer tissues and 67% of cell lines. Cell proliferation was not different between WT and KD in vitro, whereas apoptosis mediated by tumor necrosis factor-α and 5-fluorouracil were increased in KD. Several angiogenic chemokines were decreased in KD. Human umbilical vein endothelial cells incubated in WT supernatant showed more branch points than in KD, suggesting that constitutive NF-κB activation was involved in angiogenesis. Subcutaneous tumor expansion was suppressed to 23% in KD, and vessels were also decreased. By 5-fluoruracil treatment, tumor expansion was suppressed to a greater extent in KD (to 6%) than in WT (to 50%).
Conclusion: NF-κB inhibition may represent a potent treatment modality in colorectal cancer, especially in cases with constitutive NF-κB activation.
Medulloblastoma Variants: Age-Dependent Occurrence and Relation to Gorlin Syndrome—A New Clinical Perspective
Authors: Garrè Maria Luisa , Cama Armando , Bagnasco Francesca , Morana Giovanni , Giangaspero Felice , Brisigotti Massimo , Gambini Claudio , Forni Marco , Rossi Andrea , Haupt Riccardo , Nozza Paolo , Barra Salvina , Piatelli Gianluca , Viglizzo GianMaria , Capra Valeria , Bruno William , Pastorino Lorenza , Massimino Maura , Tumolo Miriam , Fidani Paola , Dallorso Sandro , Schumacher Riccardo Fabian , Milanaccio Claudia , Pietsch Torsten 
Published: March 2009

Abstract
Purpose: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS).
Experimental Design: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages &lt;14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004.
Results: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages ≤3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P &lt; 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages ≤3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001).
Conclusions: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages ≤3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.
Randomized Phase II Designs
Authors: Rubinstein Larry , Crowley John , Ivy Percy , LeBlanc Michael , Sargent Dan 
Published: March 2009

Abstract
As the use of molecularly targeted agents, which are anticipated to increase overall survival (OS)and progression-free survival (PFS) but not necessarily tumor response, has increased in oncology, there has been a corresponding increase in the recommendation and use of randomized phase II designs. Such designs reduce the potential for bias, existent in comparisons with historical controls, but also substantially increase the sample size requirements. We review the principal statistical designs for historically controlled and randomized phase II trials, along with their advantages, disadvantages, and statistical design considerations. We review the arguments for and against the use of randomization in phase II studies, the situations in which the use of historical controls is preferred, and the situations in which the use of randomized designs is preferred. We review methods used to calculate predicted OS or PFS values from historical controls, adjusted so as to be appropriate for an experimental sample with particular prognostic characteristics. We show how adjustment of the type I and type II error bounds for randomized studies can facilitate the detection of appropriate target increases in median PFS or OS with sample sizes appropriate for phase II studies. Although there continue to be differences among investigators concerning the use of randomization versus historical controls in phase II trials, there is agreement that each approach will continue to be appropriate, and the optimal approach will depend upon the circumstances of the individual trial.
LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer
Authors: Xie Han , Valera Vladimir A. , Merino Maria J. , Amato Angela M. , Signoretti Sabina , Linehan William M. , Sukhatme Vikas P. , Seth Pankaj 
Published: March 2009

Abstract
The genetic basis for the hereditary leiomyomatosis and renal cell cancer syndrome is germ-line inactivating mutation in the gene for the Krebs/tricarboxylic acid cycle enzyme, fumarate hydratase (FH), the enzyme that converts fumarate to malate. These individuals are predisposed to development of leiomyomas of the skin and uterus as well as highly aggressive kidney cancers. Inhibition of FH should result in significant decrease in oxidative phosphorylation necessitating that glycolysis followed by fermentation of pyruvate to lactate will be required to provide adequate ATP as well as to regenerate NAD+. Moreover, FH deficiency is known to up-regulate expression of hypoxia-inducible factor (HIF)-1α by enhancing the stability of HIF transcript. This leads to activation of various HIF-regulated genes including vascular endothelial growth factor and glucose transporter GLUT1 and increased expression of several glycolytic enzymes. Because lactate dehydrogenase-A (LDH-A), also a HIF-1α target, promotes fermentative glycolysis (conversion of pyruvate to lactate), a step essential for regenerating NAD+, we asked whether FH-deficient cells would be exquisitely sensitive to LDH-A blockade. Here, we report that hereditary leiomyomatosis and renal cell cancer tumors indeed overexpress LDH-A, that LDH-A inhibition results in increased apoptosis in a cell with FH deficiency and that this effect is reactive oxygen species mediated, and that LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model. [Mol Cancer Ther 2009;8(3):626–35]
Activation of p38 Mitogen-Activated Protein Kinase Is Required for Death Receptor–Independent Caspase-8 Activation and Cell Death in Response to Sphingosine
Authors: Yoon Chang-Hwan , Kim Min-Jung , Park Moon-Taek , Byun Joo-Yun , Choi Young-Hyun , Yoo Hwan-Soo , Lee Yong-Moon , Hyun Jin-Won , Lee Su-Jae 
Published: March 2009

Abstract
Sphingosine induces activation of multiple signaling pathways that play critical roles in controlling cell death. However, the precise molecular mechanism of cell death induced by sphingosine remains to be clarified. In this study, we show that sphingosine induces death receptor–independent caspase-8 activation and apoptotic cell death via p38 mitogen-activated protein kinase (MAPK) activation and that suppression of the MAPK/extracellular signal–regulated kinase (ERK) kinase/ERK pathway by protein phosphatase 2A (PP2A) is required for p38 MAPK activation. Treatment of cells with sphingosine induced suppression of ERK and activation of p38 MAPK. Inhibition of p38 MAPK led to the marked suppression of death receptor–independent caspase-8 activation and subsequent cell death induced by sphingosine. Interestingly, pretreatment with phorbol 12-myristate 13-acetate or transfection of MAPK/ERK kinase/ERK resulting in ERK activation completely attenuated sphingosine-induced p38 MAPK activation. PP2A activity was additionally elevated on sphingosine treatment. Small interfering RNA targeting of PP2A effectively attenuated sphingosine-induced p38 MAPK activation through restoration of ERK activity, suggesting PP2A-mediated opposing regulation of ERK and p38 MAPK. Our findings clearly imply that activation of p38 MAPK promotes death receptor–independent activation of caspase-8 and apoptotic cell death pathways, thus providing a novel cellular mechanism for the anticancer activity of sphingolipid metabolites. (Mol Cancer Res 2009;7(3):361–70)
Analysis of Atlantic SST Variability Factoring Interbasin Links and the Secular Trend: Clarified Structure of the Atlantic Multidecadal Oscillation
Authors: Guan Bin , Nigam Sumant 
Published: March 2009

Abstract
Atlantic SST variability in the twentieth century is analyzed factoring the influence of natural SST variability in the Pacific basin and the secular change in global SSTs. The tropical and northern extratropical basins are analyzed together using the extended EOF technique, which permits extraction of the interannual and multidecadal modes in the pan-Atlantic basin in a single step.
The leading mode of Pacific-uninfluenced SST variability is a multidecadal oscillation focused in the extratropical basin, with a period of ∼70 yr. The mode differs from the conventional Atlantic multidecadal oscillation (AMO) in the near quiescence of the tropical–subtropical basin, highlighting the significant influence of the Pacific basin on this region in conventional analysis; as much as 45% of the regional variance resulting from the conventional AMO is due to this influence.
The second and third modes capture the growth (east-to-west development) and decay (near-simultaneous loss of amplitudes) of interannual SST variability in the eastern tropical Atlantic. A nominal 4-yr evolution cycle is identified, but phase transitions are irregular.
The fourth mode describes a north–south tripole with the mature-phase structure resembling the North Atlantic Oscillation’s (NAO’s) SST footprint in winter. The mode lags the NAO by two seasons. Modal evolution involves eastward extension of the main lobe (centered near the separation of the Gulf Stream) along with shrinkage of the oppositely signed two side lobes.