bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structure, fabrics and AMS of the Slieve Gullion ring-complex, Northern Ireland: testing the ring-dyke emplacement model
Authors: Stevenson Carl T. E. , O'Driscoll Brian , Holohan Eoghan P. , Couchman Rebecca , Reavy R. John , Andrews Graham D. M. 
Published: July 2008

Abstract
A structural investigation of the Slieve Gullion ring-complex, part of the approximately 56 Ma Slieve Gullion Igneous Centre, County Armagh, Northern Ireland was carried out with a view to testing the ring-dyke emplacement mechanism. This investigation involved the detailed examination and mapping of critical field relationships and the measurement of visible and magnetic fabrics, within the porphyritic rhyolite (felsite) and the porphyritic granite (granophyre) parts of the ring-complex. Set against existing theories for the emplacement of this complex, our investigation failed to find steep outward-dipping fabrics and lineations that would support the emplacement of this ring-complex as a ring-dyke. Instead, we propose that the ring-complex was emplaced as a series of extrusive and intrusive subhorizontal sheets, controlled by a circular zone of deformation, and subsequently domed by the emplacement of the younger central complex. From its gently dipping bulk geometries and a disharmonically folded eutaxitic internal fabric (supported by AMS – anisotropy of magnetic susceptibilty), the earlier rhyolite is reinterpreted as a pyroclastic deposit. The rhyolite was probably deposited against the wall of a subsiding caldera and is now preserved in the SW quadrant of the complex. From primary intrusive contact geometries with pre-Palaeogene country rocks, magnetic fabrics and subtle visible foliations – all of which are gently dipping – the younger and more extensive granitic ring is suggested to have initially been a subhorizontal sheet that is now domed. Only its gently outward-dipping floor is exposed around the ring-complex, and this is for much of its circumference bounded by a circular zone of deformation – a ring-fault. This study highlights the importance of detailed structural investigation in assessing the emplacement of igneous ring-complexes, emphasizing the need to look further than a simple ring-dyke emplacement model.
Textural analysis of a Late Palaeozoic coherent-pyroclastic rhyolitic dyke system near Burkersdorf (Erzgebirge, Saxony, Germany)
Authors: Winter Cornelia , Breitkreuz Christoph , Lapp Manuel 
Published: July 2008

Abstract
Located between two large Late Palaeozoic rhyolitic Caldera systems (the Tharandter Wald Caldera (TWC) and the Altenberg–Teplice Caldera (ATC)) in the eastern Erzgebirge region, the extended NE–SW-trending rhyolitic Sayda–Berggießhübel dyke swarm (SBDS) was emplaced into Variscan gneisses. The dykes expose massive coherent rhyolite (CR), and four pyroclastic bodies reveal welded rhyolitic tuffs (WRT).
Overlying the CR dykes, the WRT form subcircular topographic elevations of up to 1 km in diameter. These have been interpreted by previous authors as erosional remnants of the ATC ignimbrite sheet. Another hill located on a dyke is built up of a columnar jointed rhyolitic lava dome or laccolith. An abandoned quarry near Mulda exposes sills propagating from a dyke into weathered gneiss. The WRT display a fluidal moderately to mostly vertically dipping welded texture with fiamme-like fragments up to 90 cm long. Strike orientation of the fiamme varies greatly. Gneiss lithic fragments make up to 2 vol.% of the analysed area of rock samples. The WRT are columnar jointed. The columns have a predominantly horizontal–subhorizontal orientation.
In outcrop, rock slab and thin section maximum particle size and the relative proportions of fiamme, phenocrysts in fiamme, lithic fragments and of crystal clasts (QZ, KF, PL, BT) in tuff have been measured. The correlation of the data with the regional geology shows that the welded rhyolitic tuff bodies resemble individual vent systems. Compared to the fiamme, the tuff matrix has a higher crystal clast content, indicating that pyroclastic fractionation has taken place.
Comparison of granulometric and geochemical SBDS data with ignimbrite samples from TWC and ATC confirms a close relationship between the SBDS and ATC. The SBDS is a possible vent area for the ATC. The textural data, the orientation of both fiamme and cooling columns, and other field relations suggest that the WRT of the SBDS represent welded fall-back tuffs. They formed in vents positioned on an active magmatic dyke system.
Volcanic craters, pit craters and high-level magma-feeding systems of a mafic island-arc volcano: Ambrym, Vanuatu, South Pacific
Authors: Németh Károly , Cronin Shane J. 
Published: July 2008

Abstract
Ambrym is one of the largest volcanic islands of the Vanuatu arc. It has been the focus of exclusively mafic volcanism and has a structure dominated by a central 13 km-diameter caldera. Contained within the caldera are two major cone complexes, Marum and Benbow, which have been the locus of most historic eruptions. Vents within these are constantly in a state of strong degassing, with visible lava lakes periodically being observed in several subcraters. Vulcanian and strombolian explosive eruptions occur at least yearly, along with larger subplinian events every 20–30 years. The active vent systems are enclosed by several 100 m-deep vertical-walled pit craters that expose cross-sectional views through the transition zone between the conduit and the crater. Units include coherent magma bodies with interbedded pyroclastic successions. One of the Marum craters, Niri Taten, exposes portions of solidified lava lakes, magma pods that fed spatter cones, small shallow-level intrusions and larger sills that connect through a complex network of dykes to the surface and/or into the pyroclastic edifice. These features show that shallow-level infiltration of degassed and low-viscosity melts into pyroclastic-deposit-dominated volcanic sequences of Marum plays an important role in the growth of scoria and spatter cones. Once solidified, the large intrusive bodies apparently provide important buttressing of pyroclastic cones, but during emplacement they may also cause cone collapse and lateral escape of magma to form lava flows.
Constraining melt concentration and strain distribution around basalt dykes in partially molten olivines
Authors: Vinciguerra S. , Xiao X. , Evans B. 
Published: July 2008

Abstract

Experiments were performed to determine melt concentration and strain distributions around basalt dykes in a San Carlos olivine matrix containing 10 wt% MORB (mid-ocean ridge basalt). Undrained triaxial compression tests were conducted at 1473 K and a confining pressure of 300 MPa, at constant stresses (80–160 MPa) and constant strain rates ranging from 5×10
−5
to 3×10
−4
s
−1
. Melt distribution in the dyke–matrix interface was determined by image analysis and chemical profiles. Melt migration appears to be enhanced by porosity of the microstructure and by the loading conditions. The presence of the dyke does not influence the bulk strength of the sample. Highest melt concentrations, and, presumably, the highest stress concentrations, are found at the tip of the dyke. The matrix deformation appears to be controlled by granular flow, but dilatancy occurs near the tip of the dyke, indicating coupled MORB transport and granular flow.
Evolution and morphology of saucer-shaped sills in analogue experiments
Authors: Bunger Andrew P. , Jeffrey Robert G. , Detournay Emmanuel 
Published: July 2008

Abstract

The growth of shallow sills is studied in analogue experiments performed in polymethyl methacrylate (PMMA) and glass. The experimental fractures curve towards the surface to become saucer-shaped, which is consistent with many field observations of dolerite sills. The curvature of the saucer is shown to decrease as the
in situ
stress acting parallel to the surface increases relative to an estimate of the strength of the fracture-induced stress field. The initially circular fractures also elongate in plan view to become egg-shaped, a tendency that decreases with increasing importance of viscous dissipation in the growth process. Sill emplacement is further examined mathematically by considering a shallow, circular, fluid-driven fracture propagating in a homogeneous brittle elastic material. The fractures are shown to undergo three transitions related to the mechanics of sill growth. Each transition is associated with a characteristic time that is derived from analysis of the governing equations using scaling methods. These characteristic times provide an estimate of how long viscous flow is the dominant energy dissipation mechanism, how long significant lag between the fluid and fracture fronts is expected to persist, and how long the sill will take to attain an extent that is of the same order as its depth.
Therapeutic targeting of human hepatocyte growth factor with a single neutralizing monoclonal antibody reduces lung tumorigenesis
Authors: Stabile Laura P. , Rothstein Mary E. , Keohavong Phouthone , Jin Jide , Yin Jinling , Land Stephanie R. , Dacic Sanja , Luong The Minh , Kim K. Jin , Dulak Austin M. , Siegfried Jill M. 
Published: July 2008

Abstract
The hepatocyte growth factor (HGF)/c-Met signaling pathway is involved in lung tumor growth and progression, and agents that target this pathway have clinical potential for lung cancer treatment. L2G7, a single potent anti-human HGF neutralizing monoclonal antibody, showed profound inhibition of human HGF-induced phosphorylated mitogen-activated protein kinase induction, wound healing, and invasion in lung tumor cells in vitro. Transgenic mice that overexpress human HGF in the airways were used to study the therapeutic efficacy of L2G7 for lung cancer prevention. Mice were treated with the tobacco carcinogen, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, over 4 weeks. Beginning at week 3, i.p. treatment with 100 μg L2G7 or isotype-matched antibody control, 5G8, was initiated and continued through week 15. The mean number of tumors per mouse in the L2G7-treated group was significantly lower than in the control group (1.58 versus 3.19; P = 0.0005). Proliferative index was decreased by 48% (P = 0.013) in tumors from L2G7-treated mice versus 5G8-treated mice, whereas extent of apoptosis was increased in these same tumors by 5-fold (P = 0.0013). Phosphorylated mitogen-activated protein kinase expression was also significantly decreased by 84% in tumors from L2G7-treated mice versus 5G8-treated mice (P = 0.0003). Tumors that arose in HGF transgenic animals despite L2G7 treatment were more likely to contain mutant K-ras, suggesting that targeting the HGF/c-Met pathway may not be as effective if downstream signaling is activated by a K-ras mutation. These preclinical results show that blocking the HGF/c-Met interaction with a single monoclonal antibody delivered systemically can have profound inhibitory effects on development of lung tumors. [Mol Cancer Ther 2008;7(7):1913–22]
Single-chain antibody/activated BID chimeric protein effectively suppresses HER2-positive tumor growth
Authors: Qiu Xiu-Chun , Xu Yan-Ming , Wang Fang , Fan Qing-Yu , Wang Li-Feng , Ma Bao-An , Jia Lin-Tao , Zhao Jing , Meng Yan-Ling , Yao Li-Bo , Chen Si-Yi , Yang An-Gang 
Published: July 2008

Abstract
BH3-interacting domain death agonist (BID) is a crucial element in death signaling pathways and is recognized as an intracellular link connecting the intrinsic mitochondrial apoptotic and extrinsic death receptor–mediated apoptotic pathways. Herein, we describe experiments conducted with a fusion protein, which was generated by fusing a human epidermal growth factor receptor-2 (HER2)–specific single-chain antibody with domain II of Pseudomonas exotoxin A and the truncated active BID (tBID). These experiments extend our previous work on several other immuno-proapoptotic proteins. Specifically, by excluding cells with undetectable HER2, we showed that the secreted immuno-tBID molecule selectively recognized and killed HER2-overexpressing tumor cells in vitro by attacking their mitochondria and inducing their apoptotic death. This apoptosis could only be inhibited partially by caspase pan-inhibitor zVAD and mitochondrial protector TAT-BH4. Subsequently, we transferred the immuno-tbid gene into BALB/c athymic mice bearing HER2-positive tumors together with other immuno-proapoptotic proteins using i.m. injections of liposome-encapsulated vectors. The expression of the immuno-tbid gene suppressed tumor growth and prolonged animal survival significantly. We also shortened the translocation domain of Pseudomonas exotoxin A II to only 10–amino acid sequence, which were crucial for furin cleavage. The new recombinant molecule retained the translocation efficiency and the ability of specific killing HER2-positive tumor cells. Our data showed that, compared with the toxins employed before, the chimeric immuno-tBID molecule can not only specifically recognize HER2-positive tumor cells but also certainly induce apoptosis even in the presence of zVAD and TAT-BH4, thereby suggesting an alternative approach to treating HER2/neu-positive tumors. [Mol Cancer Ther 2008;7(7):1890–9]
Cyclooxygenase inhibitors block uterine tumorigenesis in HMGA1a transgenic mice and human xenografts
Authors: Di Cello Francescopaolo , Hillion Joelle , Kowalski Jeanne , Ronnett Brigitte M. , Aderinto Abimbola , Huso David L. , Resar Linda M.S. 
Published: July 2008

Abstract
Uterine cancer is a common cause for cancer death in women and there is no effective therapy for metastatic disease. Thus, research is urgently needed to identify new therapeutic agents. We showed previously that all female HMGA1a transgenic mice develop malignant uterine tumors, indicating that HMGA1a causes uterine cancer in vivo. We also demonstrated that HMGA1a up-regulates cyclooxygenase-2 (COX-2) during tumorigenesis in this model. Similarly, we found that HMGA1a and COX-2 are overexpressed in human leiomyosarcomas, a highly malignant uterine cancer. Although epidemiologic studies indicate that individuals who take COX inhibitors have a lower incidence of some tumors, these inhibitors have not been evaluated in uterine cancer. Here, we show that HMGA1a mice on sulindac (a COX-1/COX-2 inhibitor) have significantly smaller uterine tumors than controls. To determine if COX inhibitors are active in human uterine cancers that overexpress HMGA1a, we treated cultured cells with sulindac sulfide or celecoxib (a specific COX-2 inhibitor). Both drugs block anchorage-independent growth in high-grade human uterine cancer cells that overexpress HMGA1a (MES-SA cells). In contrast, neither inhibitor blocked transformation in cells that do not overexpress HMGA1a. Moreover, xenograft tumors from MES-SA cells were significantly inhibited in mice on sulindac. More strikingly, no tumors formed in mice on celecoxib. These preclinical studies suggest that COX inhibitors could play a role in preventing tumor onset or progression in uterine cancers with dysregulation of the HMGA1a-COX-2 pathway. Importantly, these drugs have lower toxicity than chemotherapeutic agents used to treat advanced-stage uterine cancers. [Mol Cancer Ther 2008;7(7):2090–5]
5,5′-Dibromo-bis(3′-indolyl)methane induces Krüppel-like factor 4 and p21 in colon cancer cells
Authors: Cho Sung Dae , Chintharlapalli Sudhakar , Abdelrahim Maen , Papineni Sabitha , Liu Shengxi , Guo Jingjing , Lei Ping , Abudayyeh Ala , Safe Stephen 
Published: July 2008

AbstractBis(3′-indolyl)methane (DIM) is a metabolite of the phytochemical indole-3-carbinol, and both compounds exhibit a broad spectrum of anticancer activities. We have developed a series of synthetic symmetrical ring-substituted DIM analogues, including 5,5′-dibromoDIM, which are more potent than DIM as inhibitors of cancer cell and tumor growth. In colon cancer cells, 5,5′-dibromoDIM decreased cell proliferation and inhibited G0-G1- to S-phase progression, and this was accompanied by induction of the cyclin-dependent kinase inhibitor p21 in HT-29 and RKO colon cancer cells. Mechanistic studies showed that induction of p21 in both RKO (p53 wild-type) and HT-29 (p53 mutant) cells by 5,5′-dibromoDIM was Krüppel-like factor 4 (KLF4) dependent, and induction of p53 in RKO cells was also KLF4 dependent. Analysis of the p21 promoter in p53-dependent RKO cells showed that 5,5′-dibromoDIM activated p21 gene expression through the proximal GC-rich sites 1 and 2, and chromatin immunoprecipitation assays showed that KLF4 and p53 bound to this region of the promoter, whereas in HT-29 cells unidentified upstream cis-elements were required for induction of p21. 5,5′-DibromoDIM (30 mg/kg/d) also inhibited tumor growth and induced p21 in athymic nude mice bearing RKO cells as xenografts, showing that ring-substituted DIM such as 5,5′-dibromoDIM represent a novel class of mechanism-based drugs for clinical treatment of colon cancer. [Mol Cancer Ther 2008;7(7):2109–20]
Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-α-dependent and estrogen receptor-α-independent mechanisms
Authors: Long Xinghua , Fan Meiyun , Bigsby Robert M. , Nephew Kenneth P. 
Published: July 2008

Abstract
Breast cancer resistance to the antiestrogens tamoxifen (OHT) and fulvestrant is accompanied by alterations in both estrogen-dependent and estrogen-independent signaling pathways. Consequently, effective inhibition of both pathways may be necessary to block proliferation of antiestrogen-resistant breast cancer cells. In this study, we examined the effects of apigenin, a dietary plant flavonoid with potential anticancer properties, on estrogen-responsive, antiestrogen-sensitive MCF7 breast cancer cells and two MCF7 sublines with acquired resistance to either OHT or fulvestrant. We found that apigenin can function as both an estrogen and an antiestrogen in a dose-dependent manner. At low concentrations (1 μmol/L), apigenin stimulated MCF7 cell growth but had no effect on the antiestrogen-resistant MCF7 sublines. In contrast, at high concentrations (&gt;10 μmol/L), the drug inhibited growth of MCF7 cells and the antiestrogen-resistant sublines, and the combination of apigenin with either OHT or fulvestrant showed synergistic, growth-inhibitory effects on both antiestrogen-sensitive and antiestrogen-resistant breast cancer cells. To further elucidate the molecular mechanism of apigenin as either an estrogen or an antiestrogen, effects of the drug on estrogen receptor-α (ERα); transactivation activity, mobility, stability, and ERα-coactivator interactions were investigated. Low-dose apigenin enhanced receptor transcriptional activity by promoting interaction between ERα and its coactivator amplified in breast cancer-1. However, higher doses (&gt;10 μmol/L) of apigenin inhibited ERα mobility (as determined by fluorescence recovery after photobleaching assays), down-regulated ERα and amplified in breast cancer-1 expression levels, and inhibited multiple protein kinases, including p38, protein kinase A, mitogen-activated protein kinase, and AKT. Collectively, these results show that apigenin can function as both an antiestrogen and a protein kinase inhibitor with activity against breast cancer cells with acquired resistance to OHT or fulvestrant. We conclude that apigenin, through its ability to target both ERα-dependent and ERα-independent pathways, holds promise as a new therapeutic agent against antiestrogen-resistant breast cancer. [Mol Cancer Ther 2008;7(7):2096–108]
Array-based analysis of the effects of trichostatin A and CG-1521 on cell cycle and cell death in LNCaP prostate cancer cells
Authors: Roy Somdutta , Jeffrey Randy , Tenniswood Martin 
Published: July 2008

Abstract
Previous studies comparing the effects of two histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) and CG-1521, have shown that these compounds selectively inhibit HDAC and induce differentially acetylated p53 isoforms and assembly of mutually exclusive transcriptional complexes on the p21 promoter. To determine whether the differential transcriptional regulation seen in p21 gene is unique or whether it is representative of the genome-wide effects of these two HDAC inhibitors, we have used microarray and Ingenuity pathway analysis to compare the effects of TSA and CG-1521 on gene expression on LNCaP cells. Gene array analysis confirmed by quantitative real-time PCR shows that CG-1521 modulates the expression of a highly circumscribed group of genes involved in cell cycle progression and cell death. In contrast, TSA appears to induce widespread transrepression of many genes and does not modulate the expression of the same cohort as CG-1521. These data show that the selective effects of CG-1521 and TSA on the assembly of transcription complexes are not unique to the p21 gene and suggest that selective inhibition of HDAC can lead to significant changes in gene expression through the acetylation of transcription factors including but not limited to p53. [Mol Cancer Ther 2008;7(7):1931–9]
Proteomic characterization of cytoskeletal and mitochondrial class III β-tubulin
Authors: Cicchillitti Lucia , Penci Roberta , Di Michele Michela , Filippetti Flavia , Rotilio Domenico , Donati Maria Benedetta , Scambia Giovanni , Ferlini Cristiano 
Published: July 2008

AbstractClass III β-tubulin (TUBB3) has been discovered as a marker of drug resistance in human cancer. To get insights into the mechanisms by which this protein is involved in drug resistance, we analyzed TUBB3 in a panel of drug-sensitive and drug-resistant cell lines. We identified two main different isoforms of TUBB3 having a specific electrophoretic profile. We showed that the apparently higher molecular weight isoform is glycosylated and phosphorylated and it is localized in the cytoskeleton. The apparently lower molecular weight isoform is instead found exclusively in mitochondria. We observed that levels of phosphorylation and glycosylation of TUBB3 are associated with the resistant phenotype and compartmentalization into cytoskeleton. By two-dimensional nonreduced/reduced SDS-PAGE analysis, we also found that TUBB3 protein in vivo forms protein complexes through intermolecular disulfide bridges. Through TUBB3 immunoprecipitation, we isolated protein species able to interact with TUBB3. Following trypsin digestion, these proteins were characterized by mass spectrometry analysis. Functional analysis revealed that these proteins are involved in adaptation to oxidative stress and glucose deprivation, thereby suggesting that TUBB3 is a survival factor able to directly contribute to drug resistance. Moreover, glycosylation of TUBB3 could represent an attractive pathway whose inhibition could hamper cytoskeletal compartmentalization and TUBB3 function. [Mol Cancer Ther 2008;7(7):2070–9]