bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cyclic and declining food supply on great grey owls in boreal Sweden
Authors: Hipkiss T. , Stefansson O. , Hörnfeldt B. 
Published: December 2008

In this study of 35 years of data, we examine the short-term (cyclic) and long-term relationship between breeding success of great grey owls ( Strix nebulosa Forster, 1772) and their food supply (bank voles ( Clethrionomys glareolus (Schreber, 1780)), grey-sided voles ( Clethrionomys rufocanus (Sundevall, 1846)), and field voles ( Microtus agrestis (L., 1761))) in northern Sweden. Annual number of owl nests showed a 3 year cyclicity, which as predicted, corresponded to the length of the vole cycle in the region. Mean annual brood size also fluctuated and was positively dependent on the vole supply during the same spring. In this region, there has also been a decline in vole numbers in recent decades, from high-amplitude cycles in the 1970s to subsequent low-amplitude cycles. Correspondingly, and as predicted, mean annual brood size of the owls also declined, although only during the third years of the vole cycle when vole supply in spring and brood size of the owls is at its highest level in high-amplitude cycles. We predict that in the long run the vole decline, associated with increasingly milder winters, and the reduction of the brood size of the owls, especially in years of high owl breeding success, will have serious implications for the population of great grey owls in Scandinavia.
The future of geological modelling in hydrocarbon development: introduction
Authors: Robinson Adam 
Published: December 2008

Abstract
The 3D geological model is still regarded as one of the newest and most innovative tools for reservoir management purposes. The computer modelling of structures, rock properties and fluid flow in hydrocarbon reservoirs has evolved from a specialist activity to part of the standard desktop toolkit and the application of these techniques has allowed all disciplines of the subsurface team to collaborate in a common workspace. The papers in this volume result from a two-day conference at the Geological Society that brought together modelling software practitioners from the geoscience community. The papers presented here provide an excellent illustration from across the industry and academia of where we are and give some interesting pointers to where we are heading. The authors and their parent companies and institutes are thanked for sharing this information.
Assessing structural controls on reservoir performance in different stratigraphic settings
Authors: Tveranger J. , Howell J. , Aanonsen S. I. , Kolbjørnsen O. , Semshaug S. L. , Skorstad A. , Ottesen S. 
Published: December 2008

Abstract
The present study attempts to qualify the impact of tectonic parameters on hydrocarbon production in reservoir models representing four clastic depositional environments. Eleven sectors from existing 3D reservoir models, representing fluvial, tidal, shallow marine and deep marine depositional settings, were re-sampled into a fixed-volume, unfaulted model grid. Each sample was permutated into 73 different faulted model configurations by using predefined combinations of fault patterns, maximum fault-throw, shale gouge ratio and shale smear factor. The resulting 803 models were run in a fluid flow simulator and results statistically analysed to identify changes in fluid flow response caused by changing model input parameters. Finally, outcomes for each of the four depositional environments were compared. Although an inadequate database and technical limitations with the input models restrict our ability to draw quantitative conclusions, a number of qualitative interpretations can be made. The four investigated stratigraphies respond differently to identical fault parameter settings. Thus, there is a clear link between the depositional model input and the impact that faults have on production parameters. This suggests that sedimentological factors have a significant influence on which and to what extent fault parameters affect petroleum production. Varying degrees of impact can be identified for each fault parameter in each of the four depositional model types. Within the limitation of this study, a qualitative assessment of these is formulated.
Reservoir-scale 3D sedimentary modelling: approaches to integrate sedimentology into a reservoir characterization workflow
Authors: Labourdette Richard , Hegre Joann , Imbert Patrice , Insalaco Enzo 
Published: December 2008

Abstract
Reservoir production is highly dependent on reservoir models. A key problem faced in the development of a hydrocarbon reservoir is that of constructing a reservoir model that can generate reliable production forecasts under various development scenarios. Therefore, geological models have to be built in three dimensions (3D). Unfortunately, manual construction of 3D geological models (deterministically) is almost impossible, which explains why geologists often limit their interpretation to two dimensional (2D) correlation panels, fence-diagrams or maps. Consequently, geological conceptual models are rarely included or considerably simplified in reservoir models used for flow simulations and replaced by stochastic or geostatistic approaches. In spite of this admission of failure, sedimentological cross-sections and maps contain most of the knowledge and concepts of sedimentologists. They represent the outcome of sedimentological studies, including available well data, seismic interpretation and especially sedimentological and environmental concepts, incorporating all facies transitions and successions in a high-resolution stratigraphic framework. They allow fine temporal- and spatial-scale sedimentological heterogeneities to be identified. The integration of these fine-scale sedimentological heterogeneities is an essential step in improving the precision and accuracy of static reservoir models and volumetric calculations. This paper demonstrates the quantitative influence of introducing sedimentological information into the reservoir characterization workflow using a simple deterministic workflow. The described incorporation of sedimentological knowledge through facies 3D proportions cubes allows a direct assessment to facies distribution multi-realization scheme and associated uncertainties by applying stochastic simulations.
IL-6–Induced Stimulation of c-Myc Translation in Multiple Myeloma Cells Is Mediated by Myc Internal Ribosome Entry Site Function and the RNA-Binding Protein, hnRNP A1
Authors: Shi Yijiang , Frost Patrick J. , Hoang Bao Q. , Benavides Angelica , Sharma Sanjai , Gera Joseph F. , Lichtenstein Alan K. 
Published: December 2008

Abstract
Prior work indicates that c-myc translation is up-regulated in multiple myeloma cells. To test a role for interleukin (IL)-6 in myc translation, we studied the IL-6–responsive ANBL-6 and IL-6–autocrine U266 cell lines as well as primary patient samples. IL-6 increased c-myc translation, which was resistant to rapamycin, indicating a mechanism independent of mammalian target of rapamycin (mTOR) and cap-dependent translation. In contrast, the cytokine enhanced cap-independent translation via a stimulatory effect on the myc internal ribosome entry site (IRES). As known IRES-trans–activating factors (ITAF) were unaffected by IL-6, we used a yeast-three-hybrid screen to identify novel ITAFs and identified hnRNP A1 (A1) as a mediator of the IL-6 effect. A1 specifically interacted with the myc IRES in filter binding assays as well as EMSAs. Treatment of myeloma cells with IL-6 induced serine phosphorylation of A1 and increased its binding to the myc IRES in vivo in myeloma cells. Primary patient samples also showed binding between A1 and the IRES. RNA interference to knock down hnRNP A1 prevented an IL-6 increase in myc protein expression, myc IRES activity, and cell growth. These data point to hnRNP A1 as a critical regulator of c-myc translation and a potential therapeutic target in multiple myeloma. [Cancer Res 2008;68(24):10215–22]
Phospholipase Cγ1 Is Required for Metastasis Development and Progression
Authors: Sala Gianluca , Dituri Francesco , Raimondi Claudio , Previdi Sara , Maffucci Tania , Mazzoletti Marco , Rossi Cosmo , Iezzi Manuela , Lattanzio Rossano , Piantelli Mauro , Iacobelli Stefano , Broggini Massimo , Falasca Marco 
Published: December 2008

Abstract
Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase Cγ1 (PLCγ1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLCγ1 expression severely impairs activation of the small GTP-binding protein Rac and cell invasion in breast cancer cell lines and U87 in vitro. Experimental metastasis assays in nude mice show that inducible knockdown of PLCγ1 strongly inhibits development of MDA-MB-231–derived lung metastasis and reverts metastasis formation. In addition, analysis of 60 breast cancer patients' tissues revealed an increase of PLCγ1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data show a critical role of PLCγ1 in the metastatic potential of cancer cells, and they further indicate that PLCγ1 inhibition has a therapeutic potential in the treatment of metastasis dissemination. [Cancer Res 2008;68(24):10187–96]
p53-Responsive MicroRNAs 192 and 215 Are Capable of Inducing Cell Cycle Arrest
Authors: Braun Christian J. , Zhang Xin , Savelyeva Irina , Wolff Sonja , Moll Ute M. , Schepeler Troels , Ørntoft Torben F. , Andersen Claus L. , Dobbelstein Matthias 
Published: December 2008

Abstract
microRNAs provide a novel layer of regulation for gene expression by interfering with the stability and/or translation of specific target mRNAs. Overall levels of microRNAs are frequently down-regulated in cancer cells, and reducing general microRNA processing increases cancerogenesis in transgenic models, suggesting that at least some microRNAs might act as effectors in tumor suppression. Accordingly, the tumor suppressor p53 up-regulates miR-34a, a microRNA that contributes to apoptosis and acute senescence. Here, we used array hybridization to find that p53 induces two additional, mutually related clusters of microRNAs, leading to the up-regulation of miR-192, miR-194, and miR-215. The same microRNAs were detected at high levels in normal colon tissue but were severely reduced in many colon cancer samples. On the other hand, miR-192 and its cousin miR-215 can each contribute to enhanced CDKN1A/p21 levels, colony suppression, cell cycle arrest, and cell detachment from a solid support. These effects were partially dependent on the presence of wild-type p53. Antagonizing endogenous miR-192 attenuated 5-fluorouracil–induced accumulation of p21. Hence, miR-192 and miR-215 can act as effectors as well as regulators of p53; they seem to suppress cancerogenesis through p21 accumulation and cell cycle arrest. [Cancer Res 2008;68(24):10094–104]
p53 Small-Molecule Inhibitor Enhances Temozolomide Cytotoxic Activity against Intracranial Glioblastoma Xenografts
Authors: Dinca Eduard B. , Lu Kan V. , Sarkaria Jann N. , Pieper Russell O. , Prados Michael D. , Haas-Kogan Daphne A. , VandenBerg Scott R. , Berger Mitchel S. , James C. David 
Published: December 2008

Abstract
In this study, we investigated the precursor and active forms of a p53 small-molecule inhibitor for their effects on temozolomide (TMZ) antitumor activity against glioblastoma (GBM), using both in vitro and in vivo experimental approaches. Results from in vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased when p53 wild-type (p53wt) GBMs were cotreated with the active form of p53 inhibitor, and this heightened cytotoxic response was accompanied by increased poly(ADP-ribose) polymerase cleavage as well as elevated cellular phospho-H2AX. Analysis of the same series of GBMs, as intracranial xenografts in athymic mice, and administering corresponding p53 inhibitor precursor, which is converted to the active compound in vivo, yielded results consistent with the in vitro analyses: TMZ + p53 inhibitor precursor cotreatment of three distinct p53wt GBM xenografts resulted in significant enhancement of TMZ antitumor effect relative to treatment with TMZ alone, as indicated by serial bioluminescence monitoring as well as survival analysis (P &lt; 0.001 for cotreatment survival benefit in each case). Mice receiving intracranial injection with p53null GBM showed similar survival benefit from TMZ treatment regardless of the presence or absence of p53 inhibitor precursor. In total, our results indicate that the p53 active and precursor inhibitor pair enhances TMZ cytotoxicity in vitro and in vivo, respectively, and do so in a p53-dependent manner. [Cancer Res 2008;68(24):10034–8]
Interaction between Single Nucleotide Polymorphisms in Selenoprotein P and Mitochondrial Superoxide Dismutase Determines Prostate Cancer Risk
Authors: Cooper Matthew L. , Adami Hans-Olov , Grönberg Henrik , Wiklund Fredrik , Green Fiona R. , Rayman Margaret P. 
Published: December 2008

Abstract
Selenium may affect prostate cancer risk via its plasma carrier selenoprotein P which shows dramatically reduced expression in prostate cancer tumors and cell lines. The selenoprotein P (SEPP1) Ala234 single nucleotide polymorphism (SNP) allele is associated with lower plasma selenoprotein P in men, reducing the concentration/activity of other antioxidant selenoproteins. Selenium status also modifies the effect of the mitochondrial superoxide dismutase (SOD2) SNP Ala16Val on prostate cancer risk. We investigated the relationship of these SNPs with prostate cancer risk. DNA from 2,975 cases and 1,896 age-matched controls from the population-based Prostate Cancer in Sweden study were genotyped using TaqMan assays. Cases were designated aggressive or nonaggressive prostate cancers at diagnosis by clinical criteria. Association with prostate cancer was investigated by logistic regression; gene-gene interaction using a general linear model. The mean plasma selenium concentration measured in 169 controls was relatively low (76.0 ± 17.2 μg/L). SNP genotype distributions were in Hardy-Weinberg equilibrium. SOD2-Ala16+ men were at a greater risk of prostate cancer [odds ratios (OR), 1.19; 95% confidence intervals (CI), 1.03–1.37] compared with SOD2-Val16 homozygotes. Men homozygous for SEPP1-Ala234 who were also SOD2-Ala16+ had a higher risk of prostate cancer (OR, 1.43; 95% CI, 1.17–1.76) and aggressive prostate cancer (OR, 1.60; 95% CI, 1.22–2.09) than those who were SOD2-Val16 homozygotes (interaction, prostate cancer P = 0.05; aggressive prostate cancer P = 0.01). This interaction was stronger in ever-smokers: SOD2-Ala16+ men homozygous for SEPP1-Ala234 had an almost doubled risk of prostate cancer (OR, 1.97; 95% CI, 1.33–2.91; interaction P = 0.001). In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H2O2 that they cannot remove, thereby promoting prostate tumor cell proliferation and migration. [Cancer Res 2008;68(24):10171–7]
MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic Target in Human Epithelial Ovarian Cancer
Authors: Yang Nuo , Kaur Sippy , Volinia Stefano , Greshock Joel , Lassus Heini , Hasegawa Kosei , Liang Shun , Leminen Arto , Deng Shan , Smith Lori , Johnstone Cameron N. , Chen Xian-Ming , Liu Chang-Gong , Huang Qihong , Katsaros Dionyssios , Calin George Adrian , Weber Barbara L. , Bützow Ralf , Croce Carlo M. , Coukos George , Zhang Lin 
Published: December 2008

Abstract
MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that negatively regulate protein-coding gene expression in a sequence-specific manner via translational inhibition or mRNA degradation. Our recent studies showed that miRNAs exhibit genomic alterations at a high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. In the present study, we performed miRNA microarray to identify the miRNAs associated with chemotherapy response in ovarian cancer and found that let-7i expression was significantly reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This result was further validated by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor) and gain-of-function (by retroviral overexpression of let-7i) studies showed that reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum. Finally, using miRNA microarray, we found that decreased let-7i expression was significantly associated with the shorter progression-free survival of patients with late-stage ovarian cancer (n = 72, P = 0.042). This finding was further validated in the same sample set by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.001) and in an independent sample set by in situ hybridization (n = 53, P = 0.049). Taken together, our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer. [Cancer Res 2008;68(24):10307–14]
Tissue Factor Regulation by Epidermal Growth Factor Receptor and Epithelial-to-Mesenchymal Transitions: Effect on Tumor Initiation and Angiogenesis
Authors: Milsom Chloe C. , Yu Joanne L. , Mackman Nigel , Micallef Johann , Anderson G. Mark , Guha Abhijit , Rak Janusz W. 
Published: December 2008

Abstract
ErbB oncogenes drive the progression of several human cancers. Our study shows that in human carcinoma (A431) and glioma (U373) cells, the oncogenic forms of epidermal growth factor receptor (EGFR; including EGFRvIII) trigger the up-regulation of tissue factor (TF), the transmembrane protein responsible for initiating blood coagulation and signaling through interaction with coagulation factor VIIa. We show that A431 cancer cells in culture exhibit a uniform TF expression profile; however, these same cells in vivo exhibit a heterogeneous TF expression and show signs of E-cadherin inactivation, which is coupled with multilineage (epithelial and mesenchymal) differentiation. Blockade of E-cadherin in vitro, leads to the acquisition of spindle morphology and de novo expression of vimentin, features consistent with epithelial-to-mesenchymal transition. These changes were associated with an increase in EGFR-dependent TF expression, and with enhanced stimulation of vascular endothelial growth factor production, particularly following cancer cell treatment with coagulation factor VIIa. In vivo, cells undergoing epithelial-to-mesenchymal transition exhibited an increased metastatic potential. Furthermore, injections of the TF-blocking antibody (CNTO 859) delayed the initiation of A431 tumors in immunodeficient mice, and reduced tumor growth, vascularization, and vascular endothelial growth factor expression. Collectively, our data suggest that TF is regulated by both oncogenic and differentiation pathways, and that it functions in tumor initiation, tumor growth, angiogenesis, and metastasis. Thus, TF could serve as a therapeutic target in EGFR-dependent malignancies. [Cancer Res 2008;68(24):10068–76]
Chromosomal Rearrangements Leading to MLL Gene Fusions: Clinical and Biological Aspects
Authors: Harper David P. , Aplan Peter D. 
Published: December 2008

Abstract
Rearrangements of the MLL gene located at 11q23 are common chromosomal abnormalities associated with acute leukemia, especially infant and therapy-related leukemias. A variety of chimeric oncoproteins resulting from these rearrangements has been described; all of these include the NH2-terminal region of MLL implicated in protein-protein interactions and transcriptional repression. Although the molecular basis for the oncogenic activity of MLL chimeric proteins is incompletely understood, it seems to be derived, at least in part, through activation of clustered homeobox (HOX) genes. Here, we survey MLL gene rearrangements that are associated with acute leukemia and discuss molecular pathways leading to these rearrangements. [Cancer Res 2008;68(24):10024–7]
Drug Resistance Caused by Reversion Mutation
Authors: Ashworth Alan 
Published: December 2008

Abstract
Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel “synthetic lethal” approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer. [Cancer Res 2008;68(24):10021–3]
Premature Cell Cycle Entry Induced by Hepatitis B Virus Regulatory HBx Protein during Compensatory Liver Regeneration
Authors: Hodgson Amanda J. , Keasler Victor V. , Slagle Betty L. 
Published: December 2008

Abstract
The cycles of cell death and compensatory regeneration that occur during chronic hepatitis B virus (HBV) infection are central to viral pathogenesis and are a risk factor for the development of liver cancer. The HBV genome encodes one regulatory protein, HBx, which is required for virus replication, although its precise role in replication and pathogenesis is unclear. Because HBx can induce the G0-G1 transition in cultured cells, the purpose of this study was to examine the effect of HBx during liver regeneration. Transgenic mice expressing HBx (ATX) and their wild-type (WT) littermates were used in the partial hepatectomy (PH) model for compensatory regeneration. Liver tissues collected from ATX and WT mice at varying sacrifice time points after PH were examined for markers of cell cycle progression. When compared with WT liver tissues, ATX livers had evidence of premature cell cycle entry as assessed by several variables (BrdUrd incorporation, proliferating cell nuclear antigen and mitotic indices, and reduced steady-state p21 protein levels). However, HBx did not affect apoptosis, glycogen storage, or PH-induced steatosis. Together, these results show that HBx expression can induce cell cycle progression within the regenerating liver. Our data are consistent with a model in which HBx expression contributes to liver disease and cancer formation by affecting early steps in liver regeneration. [Cancer Res 2008;68(24):10341–8]