bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syn-extensional granitoids in the Menderes core complex and the late Cenozoic extensional tectonics of the Aegean province
Authors: Dilek Yildirim , Altunkaynak Şafak , Öner Zeynep 
Published: October 2009

Abstract
The Miocene granitoid plutons exposed in the footwalls of major detachment faults in the Menderes core complex in western Anatolia represent syn-extensional intrusions, providing important geochronological and geochemical constraints on the nature of the late Cenozoic magmatism associated with crustal extension in the Aegean province. Ranging in composition from granite, granodiorite to monzonite, these plutons crosscut the extensional deformation fabrics in their metamorphic host rocks but are foliated, mylonitized and cataclastically deformed in shear zones along the detachment faults structurally upward near the surface. Crystallization and cooling ages of the granitoid rocks are nearly coeval with the documented ages of metamorphism and deformation dating back to the latest Oligocene–early Miocene that record tectonic extension and exhumation in the Menderes massif. The Menderes granitoids (MEG) are represented by mainly metaluminous-slightly peraluminous, high-K calc-alkaline and partly shoshonitic rocks with their silica contents ranging from 62.5 to 78.2 wt%. They display similar major and trace element characteristics and overlapping inter-element ratios (Zr/Nb, La/Nb, Rb/Nb, Ce/Y) suggesting common melt sources. Their enrichment in LILE, strong negative anomalies in Ba, Ta, Nb, Sr and Ti and high incompatible element abundances are consistent with derivation of their magmas from a subduction-metasomatized, heterogeneous sub-continental lithospheric mantle source. Fractional crystalization processes and lower to middle crustal contamination also affected the evolution of the MEG magmas. These geochemical characteristics of the MEG are similar to those of the granitoids in the Cyclades to the west and the Rhodope massif to the north. Partial melting of the subduction-metasomatized lithospheric mantle and the overlying lower-middle crust produced the MEG magmas starting in the late Oligocene–early Miocene. The heat and the basaltic material to induce this partial melting were provided by asthenospheric upwelling caused by lithospheric delamination. Rapid slab rollback of the post-Eocene Hellenic subduction zone may have peeled off the base of the subcontinental lithosphere, triggering the inferred lithospheric delamination. Both slab retreat-generated upper plate deformation and magmatically induced crustal weakening led to the onset of the Aegean extension, which has migrated southward through time.
The frictional strength of granular fault gouge: application of theory to the mechanics of low-angle normal faults
Authors: Boulton Carolyn , Davies Tim , McSaveney Mauri 
Published: October 2009

AbstractThere is a persistent body of literature that suggests low-angle normal faults (LANF) form and slip seismically; if true, the effective friction coefficient is much lower (<0.3) than that found in laboratory tests of rock friction (c.0.8) and in low-displacement faults that lack well-developed fault cores. This paper summarizes and discusses the mechanisms proposed to explain the low apparent friction of crustal-scale faults with low resolved shear stresses. Emphasis is placed on differentiating static weakening mechanisms, operating at strain ratesc.10−12s−1–10−15s−1, from dynamic weakening mechanisms, operating at strain rates >10−1s−1. Previous published explanations for low fault friction do not appear to meet the key requirements of (i) reducing both static and dynamic frictional strength of LANF and (ii) operating only along crustal-scale faults. Fault rock assemblages in quartzo-feldspathic continental crust reveal that grain size reduction, or comminution, plays a fundamental role in fault zone development. As a fault accrues displacement, a fault core forms that contains granular material. We postulate that dynamic rock fragmentation occurs during the shearing of confined granular material; dynamic fragmentation is a volume-dependent mechanism responsible for reducing the static and dynamic frictional strengths of faults.
Reconciling short- and long-term measures of extension in continental back arcs: heat flux, crustal structure and rotations within central North Island, New Zealand
Authors: Stern T. A. 
Published: October 2009

Abstract

Geodetic, palaeomagnetic and andesite-age data all point to a fan-like opening of central North Island, New Zealand, in the past 5 Ma. Palaeomagnetic rotation rates for the eastern North Island are
c.
6° Ma
−1
and this is accompanied by back-arc extension of up to 19 mm a
−1
at the Bay of Plenty coast and lesser values further south. Although the geodetic observations only span a decade, they show a remarkable consistency with the palaeomagnetic and volcanic arc migration data that span 5 Ma. A fan-like pattern of extension in central North Island is implied, similar to that seen in other continental back-arcs. When rapid fan-like openings do occur, they are likely to be accompanied by extreme thermal events. Heat flux from the central North Island occurs at one of the highest continental rates recorded:
c.
26 MW per km of strike of volcanic zone, or 4.3 GW in total. Prior to the Pliocene extension and rotation, central North Island had a
c.
20 Ma history of compression and overthrusting. It is proposed that thickening, then subsequent detachment of mantle lithosphere during this phase had a role to play in the Pliocene back-arc opening and the consequent extreme heat flux.
Timing and nature of formation of the Ios metamorphic core complex, southern Cyclades, Greece
Authors: Thomson Stuart N. , Ring Uwe , Brichau Stephanie , Glodny Johannes , Will Thomas M. 
Published: October 2009

Abstract

We apply low-temperature thermochronology, Rb/Sr geochronology, petrological data, and structural mapping to constrain the timing and kinematics of the Ios metamorphic core complex. Top-to-north extension in the lower plate Headland Shear Zone was active at 18–19 Ma under metamorphic conditions of 475–610 °C and 0.65–1.1 GPa. The South Cyclades Shear Zone/Ios Detachment Fault (SCSZ/IDF) system shows top-to-south extensional shear active at
c.
19 Ma at 380–550 °C, with local top-to-north bands. Extensional shear above the SCSZ/IDF is dominantly top-to-south to top-to-SW.
PT
estimates from an eclogite boudin constrain Eocene high-pressure metamorphism to 430–560 °C and 1.21±0.42 GPa to 0.66±0.37 GPa. Similar low-temperature thermochronometric ages across Ios demonstrate that ductile extensional movement ceased by
c.
15 Ma. Exhumation to shallow crustal levels took place between
c.
15 and 9 Ma at cooling rates of up to 120 °C Ma
−1
with a slow down to <20 °C Ma
−1
between 12 and 9 Ma, most likely accommodated by extensional slip at rates of
c.
3 km Ma
−1
along the top-to-SW Coastal Fault System. We propose a model of bivergent extension for exhumation of the Ios core complex between 19 and 9 Ma, with Ios forming a secondary antithetic top-to-south to top-to-SW extensional fault system to a more dominant top-to-north Naxos/Paros detachment system.
Cenozoic tectonic evolution of Naxos Island through a multi-faceted approach of fission-track analysis
Authors: Seward Diane , Vanderhaeghe Olivier , Siebenaller Luc , Thomson Stuart , Hibsch Christian , Zingg Anatol , Holzner Patrick , Ring Uwe , Duchêne Stephanie 
Published: October 2009

Abstract

New zircon and apatite fission-track ages obtained on samples from all lithotectonic units exposed on Naxos Island are presented. Zircon ages of the exhumed metamorphic rocks range from 25.2 to 9.3 Ma and from 13.0 to 6.4 Ma for apatite. Zircon track-length analysis distinguishes partial overprinting of an earlier event (M
1
) in the south. Northwards no overprint is seen and the ages there represent rapid exhumation since
c.
12 Ma. Both zircon and apatite ages are slightly older toward the north of the island probably due to variation of the geotherm in the proximity of the fault.

Zircon fission-track ages of the granodiorite range from 13.7 to 12.2 Ma are statistically identical to previously determined U–Pb ages. Apatite fission-track ages however, yield a younging trend from south to north from 12.9 to 9.0 Ma. This could be due to differential depth of emplacement and/or to differential exhumation during tectonic unroofing by a top-to-the north detachment.
Fission-track ages on detrital grains in Lower Miocene sediments indicate a source not identified within the present outcropping rocks of Naxos. Ages on boulders and grains in the Middle to Upper Miocene sediments point to rapid erosion until about 8.5–7 Ma.
Novel Lipogenic Enzyme ELOVL7 Is Involved in Prostate Cancer Growth through Saturated Long-Chain Fatty Acid Metabolism
Authors: Tamura Kenji , Makino Asami , Hullin-Matsuda Françoise , Kobayashi Toshihide , Furihata Mutsuo , Chung Suyoun , Ashida Shingo , Miki Tsuneharu , Fujioka Tomoaki , Shuin Taro , Nakamura Yusuke , Nakagawa Hidewaki 
Published: October 2009

Abstract
A number of epidemiologic studies have indicated a strong association between dietary fat intake and prostate cancer development, suggesting that lipid metabolism plays some important roles in prostate carcinogenesis and its progression. In this study, through our genome-wide gene expression analysis of clinical prostate cancer cells, we identified a novel lipogenic gene, ELOVL7, coding a possible long-chain fatty acid elongase, as overexpressed in prostate cancer cells. ELOVL7 expression is regulated by the androgen pathway through SREBP1, as well as other lipogenic enzymes. Knockdown of ELOVL7 resulted in drastic attenuation of prostate cancer cell growth, and it is notable that high-fat diet promoted the growth of in vivo tumors of ELOVL7-expressed prostate cancer. In vitro fatty acid elongation assay and fatty acid composition analysis indicated that ELOVL7 was preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids (SVLFA, C20:0∼). Lipid profiles showed that knockdown of ELOVL7 in prostate cancer cells affected SVLFAs in the phospholipids and the neutral lipids, such as cholesterol ester. Focusing on cholesterol ester as a source of de novo steroid synthesis, we show that ELOVL7 affected de novo androgen synthesis in prostate cancer cells. These findings suggest that EVOLV7 could be involved in prostate cancer growth and survival through the metabolism of SVLFAs and their derivatives, could be a key molecule to elucidate the association between fat dietary intake and prostate carcinogenesis, and could also be a promising molecular target for development of new therapeutic or preventive strategies for prostate cancers. [Cancer Res 2009;69(20):8133–40]
Immunoselection of Breast and Ovarian Cancer Cells with Trastuzumab and Natural Killer Cells: Selective Escape of CD44high/CD24low/HER2low Breast Cancer Stem Cells
Authors: Reim Florian , Dombrowski Yvonne , Ritter Cathrin , Buttmann Mathias , Häusler Sebastian , Ossadnik Monika , Krockenberger Mathias , Beier Dagmar , Beier Christoph P. , Dietl Johannes , Becker Jürgen C. , Hönig Arnd , Wischhusen Jörg 
Published: October 2009

Abstract
Although trastuzumab (Herceptin) has substantially improved the overall survival of patients with mammary carcinomas, even initially well-responding tumors often become resistant. Because natural killer (NK) cell–mediated antibody-dependent cell-mediated cytotoxicity (ADCC) is thought to contribute to the therapeutic effects of trastuzumab, we have established a cell culture system to select for ADCC-resistant SK-OV-3 ovarian cancer and MCF7 mammary carcinoma cells. Ovarian cancer cells down-regulated HER2 expression, resulting in a more resistant phenotype. MCF7 breast cancer cells, however, failed to develop resistance in vitro. Instead, treatment with trastuzumab and polyclonal NK cells resulted in the preferential survival of individual sphere-forming cells that displayed a CD44highCD24low “cancer stem cell–like” phenotype and expressed significantly less HER2 compared with non–stem cells. Likewise, the CD44highCD24low population was also found to be more immunoresistant in SK-BR3, MDA-MB231, and BT474 breast cancer cell lines. When immunoselected MCF7 cells were then re-expanded, they mostly lost the observed phenotype to regenerate a tumor cell culture that displayed the initial HER2 surface expression and ADCC-susceptibility, but was enriched in CD44highCD24low cancer stem cells. This translated into increased clonogenicity in vitro and tumorigenicity in vivo. Thus, we provide evidence that the induction of ADCC by trastuzumab and NK cells may spare the actual tumor-initiating cells, which could explain clinical relapse and progress. Moreover, our observation that the “relapsed” in vitro cultures show practically identical HER2 surface expression and susceptibility toward ADCC suggests that the administration of trastuzumab beyond relapse might be considered, especially when combined with an immune-stimulatory treatment that targets the escape variants. [Cancer Res 2009;69(20):8058–66]
Altered Runx1 Subnuclear Targeting Enhances Myeloid Cell Proliferation and Blocks Differentiation by Activating a miR-24/MKP-7/MAPK Network
Authors: Zaidi Sayyed K. , Dowdy Christopher R. , van Wijnen Andre J. , Lian Jane B. , Raza Azra , Stein Janet L. , Croce Carlo M. , Stein Gary S. 
Published: October 2009

Abstract
Disruption of Runx1/AML1 subnuclear localization, either by a single amino acid substitution or by a chromosomal translocation [e.g., t(8;21)], is linked to the etiology of acute myeloid leukemia (AML). Here, we show that this defect induces a select set of micro-RNAs (miR) in myeloid progenitor cells and AML patients with t(8;21). Both Runx1 and the t(8;21)-encoded AML1-ETO occupy the miR-24-23-27 locus and reciprocally control miR-24 transcription. miR-24 directly downregulates mitogen-activated protein kinase (MAPK) phosphatase-7 and enhances phosphorylation of both c-jun-NH2-kinase and p38 kinases. Expression of miR-24 stimulates myeloid cell growth, renders proliferation independent of interleukin-3, and blocks granulocytic differentiation. Thus, compromised Runx1 function induces a miR-dependent mechanism that, through MAPK signaling, enhances myeloid proliferation but blocks differentiation—key steps that contribute to leukemia. [Cancer Res 2009;69(21):8249–55]
microRNA-21 Negatively Regulates Cdc25A and Cell Cycle Progression in Colon Cancer Cells
Authors: Wang Peng , Zou Fangdong , Zhang Xiaodong , Li Hua , Dulak Austin , Tomko Robert J. , Lazo John S. , Wang Zhenghe , Zhang Lin , Yu Jian 
Published: October 2009

Abstract
microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting. Unbiased microarray analysis combined with bioinformatics identified cell cycle regulator Cdc25A as a miR-21 target. miR-21 suppressed Cdc25A expression through a defined sequence in its 3′-untranslated region. We found that miR-21 is induced by serum starvation and DNA damage, negatively regulates G1-S transition, and participates in DNA damage–induced G2-M checkpoint through down-regulation of Cdc25A. In contrast, miR-21 deficiency did not affect apoptosis induced by a variety of commonly used anticancer agents or cell proliferation under normal cell culture conditions. Furthermore, miR-21 was found to be underexpressed in a subset of Cdc25A-overexpressing colon cancers. Our data show a role of miR-21 in modulating cell cycle progression following stress, providing a novel mechanism of Cdc25A regulation and a potential explanation of miR-21 in tumorigenesis. [Cancer Res 2009;69(20):8157–65]
Glioblastoma Cells Require Glutamate Dehydrogenase to Survive Impairments of Glucose Metabolism or Akt Signaling
Authors: Yang Chendong , Sudderth Jessica , Dang Tuyen , Bachoo Robert G. , McDonald Jeffrey G. , DeBerardinis Ralph J. 
Published: October 2009

Abstract
Oncogenes influence nutrient metabolism and nutrient dependence. The oncogene c-Myc stimulates glutamine metabolism and renders cells dependent on glutamine to sustain viability (“glutamine addiction”), suggesting that treatments targeting glutamine metabolism might selectively kill c-Myc–transformed tumor cells. However, many current or proposed cancer therapies interfere with the metabolism of glucose, not glutamine. Here, we studied how c-Myc–transformed cells maintained viability when glucose metabolism was impaired. In SF188 glioblastoma cells, glucose deprivation did not affect net glutamine utilization but elicited a switch in the pathways used to deliver glutamine carbon to the tricarboxylic acid cycle, with a large increase in the activity of glutamate dehydrogenase (GDH). The effect on GDH resulted from the loss of glycolysis because it could be mimicked with the glycolytic inhibitor 2-deoxyglucose and reversed with a pyruvate analogue. Furthermore, inhibition of Akt signaling, which facilitates glycolysis, increased GDH activity whereas overexpression of Akt suppressed it, suggesting that Akt indirectly regulates GDH through its effects on glucose metabolism. Suppression of GDH activity with RNA interference or an inhibitor showed that the enzyme is dispensable in cells able to metabolize glucose but is required for cells to survive impairments of glycolysis brought about by glucose deprivation, 2-deoxyglucose, or Akt inhibition. Thus, inhibition of GDH converted these glutamine-addicted cells to glucose-addicted cells. The findings emphasize the integration of glucose metabolism, glutamine metabolism, and oncogenic signaling in glioblastoma cells and suggest that exploiting compensatory pathways of glutamine metabolism can improve the efficacy of cancer treatments that impair glucose utilization. [Cancer Res 2009;69(20):7986–93]
Lung Adenocarcinoma with EGFR Amplification Has Distinct Clinicopathologic and Molecular Features in Never-Smokers
Authors: Sholl Lynette M. , Yeap Beow Y. , Iafrate A. John , Holmes-Tisch Alison J. , Chou Yi-Ping , Wu Ming-Tsang , Goan Yih-Gang , Su Li , Benedettini Elisa , Yu Jian , Loda Massimo , Jänne Pasi A. , Christiani David C. , Chirieac Lucian R. 
Published: October 2009

Abstract
In a subset of lung adenocarcinomas, the epidermal growth factor receptor (EGFR) is activated by kinase domain mutations and/or gene amplification, but the interaction between the two types of abnormalities is complex and unclear. For this study, we selected 99 consecutive never-smoking women of East Asian origin with lung adenocarcinomas that were characterized by histologic subtype. We analyzed EGFR mutations by PCR-capillary sequencing, EGFR copy number abnormalities by fluorescence and chromogenic in situ hybridization and quantitative PCR, and EGFR expression by immunohistochemistry with both specific antibodies against exon 19 deletion–mutated EGFR and total EGFR. We compared molecular and clinicopathologic features with disease-free survival. Lung adenocarcinomas with EGFR amplification had significantly more EGFR exon 19 deletion mutations than adenocarcinomas with disomy, and low and high polysomy (100% versus 54%, P = 0.009). EGFR amplification occurred invariably on the mutated and not the wild-type allele (median mutated/wild-type ratios 14.0 versus 0.33, P = 0.003), was associated with solid histology (P = 0.008), and advanced clinical stage (P = 0.009). EGFR amplification was focally distributed in lung cancer specimens, mostly in regions with solid histology. Patients with EGFR amplification had a significantly worse outcome in univariate analysis (median disease-free survival, 16 versus 31 months, P = 0.01) and when adjusted for stage (P = 0.027). Lung adenocarcinomas with EGFR amplification have a unique association with exon 19 deletion mutations and show distinct clinicopathologic features associated with a significantly worsened prognosis. In these cases, EGFR amplification is heterogeneously distributed, mostly in areas with a solid histology. [Cancer Res 2009;69(21):8341–8]
Phase I Biodistribution and Pharmacokinetic Study of Lewis Y–Targeting Immunoconjugate CMD-193 in Patients with Advanced Epithelial Cancers
Authors: Herbertson Rebecca A. , Tebbutt Niall C. , Lee Fook-Thean , MacFarlane David J. , Chappell Bridget , Micallef Noel , Lee Sze-Ting , Saunder Timothy , Hopkins Wendie , Smyth Fiona E. , Wyld David K. , Bellen John , Sonnichsen Daryl S. , Brechbiel Martin W. , Murone Carmel , Scott Andrew M. 
Published: October 2009

AbstractPurpose: This phase I study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 [a humanized anti–Lewis Y (Ley) antibody conjugated with calicheamicin in patients with advanced cancers expressing the Ley antigen.Experimental Design: The primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. Secondary objectives included response rates and change in tumor metabolism. Patients with progressive, measurable, and Ley positive malignancies were eligible for enrollment in one of two dose cohorts, 1.0 and 2.6 mg/m2. The first cycle was trace labeled with 111In for biodistribution assessment using γ camera imaging. Subsequent cycles were administered every 3 weeks up to a maximum of six cycles, depending on toxicity and response. Pharmacokinetic analysis was based on radioassay and ELISA.Results: Nine patients were enrolled in the study. Biodistribution images showed initial blood pool activity, followed by markedly increased hepatic uptake by day 2, and fast blood clearance in all patients. There was low uptake in tumor in all patients. The overall T½β of 111In-CMD-193 was 102.88 ± 35.67 hours, with no statistically significant difference between the two dose levels. One patient had a partial metabolic response on 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET) after four cycles, but no radiological responses were observed. Myelosuppression and effects on liver function were the most significant adverse effects.Conclusions: CMD-193 shows rapid blood clearance and increased hepatic uptake compared with prior studies of the parental antibody hu3S193. These results highlight the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics to assist in clinical development. (Clin Cancer Res 2009;15(21):6709–15)