bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress deflections around salt diapirs in the Gulf of Mexico
Authors: King Rosalind , Backé Guillaume , Tingay Mark , Hillis Richard , Mildren Scott 
Published: August 2012

Abstract
Delta–deepwater fold–thrust belts are linked systems of extension and compression. Margin-parallel maximum horizontal stresses (extension) on the delta top are generated by gravitational collapse of accumulating sediment, and drive downdip margin-normal maximum horizontal stresses (compression) in the deepwater fold–thrust belt (or delta toe). This maximum horizontal stress rotation has been observed in a number of delta systems. Maximum horizontal stress orientations, determined from 32 petroleum wells in the Gulf of Mexico, are broadly margin-parallel on the delta top with a mean orientation of 060 and a standard deviation of 49°. However, several orientations show up to 60° deflection from the regional margin-parallel orientation. Three-dimensional (3D) seismic data from the Gulf of Mexico delta top demonstrate the presence of salt diapirs piercing the overlying deltaic sediments. These salt diapirs are adjacent to wells (within 500 m) that demonstrate deflected stress orientations. The maximum horizontal stresses are deflected to become parallel to the interface between the salt and sediment. Two cases are presented that account for the alignment of maximum horizontal stresses parallel to this interface: (1) the contrast between geomechanical properties of the deltaic sediments and adjacent salt diapirs; and (2) gravitational collapse of deltaic sediments down the flanks of salt diapirs.
Modelling of sediment wedge movement along low-angle detachments using ABAQUS™
Authors: Tuitt A. , King R. , Hergert T. , Tingay M. , Hillis R. 
Published: August 2012

Abstract
Delta–deepwater fold–thrust belts (DDWFTBs) develop over low-angle detachment faults which link extension to downslope contraction. Detachment faults have been examined in previous studies for the Amazon Fan, Niger, Nile, Angola, Baram and Bight Basin DDWFTBs. The driving mechanisms for the movement along the detachment remain uncertain, however. Previous authors have attributed the movement along detachment faults to high pore-fluid pressure, which reduces the effective normal stress acting on a fault surface thereby encouraging sliding along the fault. However, high pore-fluid pressure has not been directly confirmed in many of these faults due to a lack of well data in detachment surfaces. In this study, finite element modelling was used to test the effects of pore-fluid pressure, coefficient of friction, sediment rigidity and sediment wedge angle on sliding along the detachment. The modelling suggests that increased pore-fluid pressures and decreased coefficients of friction increase slip along a detachment. At hydrostatic pore-fluid pressures, sediment rigidity and sediment wedge angle have relatively little effect on the movement of the sediment wedge along the detachment. Modelling of these conditions using ABAQUS™ improves our understanding of the nature and mechanics of DDWFTBs and their underlying detachments.
On the nucleation of non-Andersonian faults along phyllosilicate-rich mylonite belts
Authors: Bistacchi Andrea , Massironi Matteo , Menegon Luca , Bolognesi Francesca , Donghi Valeriano 
Published: August 2012

Abstract
The weakness of fault zones is generally explained by invoking an elevated fluid pressure or the presence of extremely weak minerals in a continuous fault gouge horizon. This allows for faults to slip under an unfavourable normal to shear stress ratio, in contrast to E. M. Anderson's theory of faulting. However, these mechanisms do not explain why faults should nucleate in such an orientation as to make them misoriented and non-Andersonian. Here we present a weakening mechanism, involving the mechanical anisotropy of phyllosilicate-bearing mylonite belts, which is likely to influence the nucleation of faults in addition to their subsequent activity. Considering three natural examples from the Alps (the Simplon, Brenner and Sprechenstein-Mules fault zones) and a review of laboratory tests on anisotropic rocks, we apply anisotropic slip tendency analysis and show that misoriented weak faults can nucleate along a sub-planar phyllosilicate-rich mylonitic foliation, constituting a large-scale mechanical anisotropy belt and preventing the development of Andersonian optimally oriented faults.
Anisotropic poroelasticity and the response of faulted rock to changes in pore-fluid pressure
Authors: Healy David 
Published: August 2012

Abstract
The Law of Effective Stress has found wide application in structural geology, rock mechanics and petroleum geology. The commonly used form of this law relies on an assumption of isotropic porosity. The porosity in and around fluid-saturated fault zones is likely to be dominated by tectonically induced cracks of various shapes and sizes. Previously published field and laboratory data show that these cracks occur in distinct patterns of preferred orientation, and that these patterns vary around the fault zone. This paper uses the more general form of the Law of Effective Stress which incorporates anisotropic poroelasticity to model the geomechanical response of fault zones surrounded by patterns of oriented cracks. Predictions of fault stability in response to fluid pressure changes are shown to depend on both the nature (or symmetry) of the crack pattern and the orientation of the crack patterns with respect to the in situ stress. More complete data on the porosity of natural fault zones will enable more accurate predictions of fault stability in the subsurface.
Andersonian wrench faulting in a regional stress field during the 2010–2011 Canterbury, New Zealand, earthquake sequence
Authors: Sibson R. H. , Ghisetti F. C. , Crookbain R. A. 
Published: August 2012

Abstract

The initial
M
w
7.1 Darfield earthquake sequence was centred west of Christchurch City in the South Island of New Zealand but aftershocks, including a highly destructive
M
w
6.3 event, eventually extended eastwards across the city to the coast. The mainshock gave rise to right-lateral strike-slip of up to 5 m along the segmented rupture trace of a subvertical fault trending 085±5° across the Canterbury Plains for
c
. 30 km, in agreement with teleseismic focal mechanisms. Near-field data however suggest that the mainshock was composite, initiating with reverse-slip north of the surface rupture. Stress determinations for the central South Island show maximum compressive stress σ
1
to be horizontal and oriented 115±5°. The principal dextral rupture therefore lies at
c
. 30° to regional σ
1
, the classic ‘Andersonian’ orientation for a low-displacement wrench fault. An aftershock lineament trending
c
. 145° possibly represents a conjugate left-lateral strike-slip structure. This stress field is also consistent with predominantly reverse-slip reactivation of NNE–NE faults along the Southern Alps range front. The main strike-slip fault appears to have a low cumulative displacement and may represent either a fairly newly formed fault in the regional stress field, or an existing subvertical fault that happens to be optimally oriented for frictional reactivation.
NFAT1 Supports Tumor-induced Anergy of CD4+ T Cells
Authors: Abe Brian T. , Shin Daniel S. , Mocholi Enric , Macian Fernando 
Published: August 2012

AbstractCancer cells express antigens that elicit T cell-mediated responses, but these responses are limited during malignant progression by the development of immunosuppressive mechanisms in the tumor microenvironment that drive immune escape. T-cell hyporesponsiveness can be caused by clonal anergy or adaptive tolerance, but the pathophysiological roles of these processes in specific tumor contexts has yet to be understood. In CD4+ T cells, clonal anergy occurs when the T-cell receptor is activated in the absence of a costimulatory signal. Here we report that the key T-cell transcription factor NFAT mediates expression of anergy-associated genes in the context of cancer. Specifically, in a murine model of melanoma, we found that cancer cells induced anergy in antigen-specific CD4+ T-cell populations, resulting in defective production of several key effector cytokines. NFAT1 deficiency blunted the induction of anergy in tumor antigen-specific CD4+ T cells, enhancing antitumor responses. These investigations identified tumor-induced T-cell hyporesponsiveness as a form of clonal anergy, and they supported an important role for CD4+ T-cell anergy in driving immune escape. By illustrating the dependence of tumor-induced CD4+ T-cell anergy on NFAT1, our findings open the possibility of targeting this transcription factor to improve the efficacy of cancer immunotherapy or immunochemotherapy. Cancer Res; 72(18); 4642–51. ©2012 AACR.
CD133+ Melanoma Subpopulations Contribute to Perivascular Niche Morphogenesis and Tumorigenicity through Vasculogenic Mimicry
Authors: Lai Chiou-Yan , Schwartz Brian E. , Hsu Mei-Yu 
Published: August 2012

Abstract
Tumor cell subpopulations that express cancer stem cell markers such as CD133 (prominin1) or ABCB5 are thought to be crucial for tumor initiation and heterogeneity, but their biological significance in melanoma has been controversial. Here, we report that CD133+ and ABCB5+ subpopulations are colocalized in melanomas in perivascular niches that contain CD144 (VE-cadherin)+ melanoma cells forming vessel-like channels, a phenomenon termed vasculogenic mimicry (VM). RNAi-mediated attenuation of CD133 established its critical function in morphogenesis of these perivascular niches as well as in melanoma tumorigenicity. Niche-associated genes CD144 and ABCB5 were downregulated in tumors derived from CD133 knockdown (KD) melanoma cells compared with controls. CD133KD cells also lacked the ability to form CD144+ VM-like channels in a manner that was associated with a depletion of the ABCB5+ cell subpopulation. Finally, CD133 KD cells exhibited poorer tumor growth in vivo. Taken together, our findings corroborate models in which CD133+/ABCB5+ melanoma cells reside in a complex anastomosing microvascular niche that encompasses CD144+ VM channels as well as authentic endothelial cell-lined blood vessels. Further, they indicate that CD133+ cells act as stem-like cells, which drive tumor growth by promoting VM and the morphogenesis of a specialized perivascular niche in melanoma. Cancer Res; 72(19); 5111–8. ©2012 AACR.
Alternative Cleavage and Polyadenylation during Colorectal Cancer Development
Authors: Morris Adam R. , Bos Arnold , Diosdado Begoña , Rooijers Koos , Elkon Ran , Bolijn Anne S. , Carvalho Beatriz , Meijer Gerrit A. , Agami Reuven 
Published: August 2012

Abstract
Purpose: Alternative cleavage and polyadenylation (APA) of mRNAs is a phenomenon that alters 3′-untranslated region length leading to altered posttranscriptional regulation of gene expression. Changing APA patterns have been shown to result in misregulation of genes involved in carcinogenesis; therefore, we hypothesized that altered APA contributes to progression of colorectal cancer, and that measurement of APA may lead to discovery of novel biomarkers.
Experimental Design: We used next-generation sequencing to directly measure global patterns of APA changes during colorectal carcinoma progression in 15 human patient samples. Results were validated in a larger cohort of 50 patients, including 5 normal/carcinoma pairs from individuals.
Results: We discovered numerous genes presenting progressive changes in APA. Genes undergoing untranslated region (3′UTR) shortening were enriched for functional groups such as cell-cycle and nucleic acid–binding and processing factors, and those undergoing 3′UTR lengthening or alternative 3′UTR usage were enriched for categories such as cell–cell adhesion and extracellular matrix. We found indications that APA changes result from differential processing of transcripts because of increased expression of cleavage and polyadenylation factors. Quantitative PCR analysis in a larger series of human patient samples, including matched pairs, confirmed APA changes in DMKN, PDXK, and PPIE genes.
Conclusions: Our results suggest that genes undergoing altered APA during human cancer progression may be useful novel biomarkers and potentially targeted for disease prevention and treatment. We propose that the strategy presented here may be broadly useful in discovery of novel biomarkers for other types of cancer and human disease. Clin Cancer Res; 18(19); 5256–66. ©2012 AACR.
A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets
Authors: Weisbart Richard H. , Gera Joseph F. , Chan Grace , Hansen James E. , Li Erica , Cloninger Cheri , Levine Arnold J. , Nishimura Robert N. 
Published: August 2012

AbstractThe therapeutic use of antibodies is restricted by the limited access of antibodies to intracellular compartments. To overcome this limitation, we developed a cell-penetrating monoclonal antibody, mAb 3E10, as an intracellular delivery vehicle for the intracellular and intranuclear delivery of antibodies constructed as bispecific single-chain Fv fragments. Because MDM2 is an important target in cancer therapy, we selected monoclonal antibody (mAb) 3G5 for intracellular transport. mAb 3G5 binds MDM2 and blocks binding of MDM2 to p53. Here, we show that the resulting 3E10-3G5 bispecific antibody retains cell-penetrating and MDM2-binding activity, increases tumor p53 levels, and inhibits growth of MDM2-addicted tumors. The use of cell-penetrating bispecific antibodies in targeted molecular therapy will significantly broaden the spectrum of accessible intracellular targets and may have a profound impact in cancer therapy. Mol Cancer Ther; 11(10); 2169–73. ©2012 AACR.
Abstract 100: Somatic mutations in Pyk2 in melanoma alter protein activity, interactions and localization
Authors: Willard Melinda D. , Wulur Isabella H. , Samuels Yardena , Barber Thomas D. , Gartner Jared , Parker Stephen C.J. 
Published: August 2012

Abstract
Data indicates that focal adhesion kinases (FAKs) play a critical role in cancer. Specifically, accumulating evidence suggests that overexpression and altered activity of FAKs promotes tumorigenesis, metastasis, and correlates with reduced survival. Proline-rich tyrosine kinase 2 (PYK2, FAK2) and its role in physiological processes in bone and inflammatory cellular responses have been well-documented. Recently, the role of PYK2 in the induction of endothelial to mesenchymal transition and cancer progression has emerged. Somatic mutations altering the coding region of PTK2B have been detected in melanoma and lung cancer, but the functional significance of these mutations is unknown. Here we demonstrate that cancer-associated mutations of PYK2 found in malignant melanoma lead to altered protein localization, interactions, and activity, and consequently, abnormal cellular behavior. These findings suggest that somatic mutations in PTK2B may promote tumor progression through deregulated protein activity, and highlight the importance of evaluating PYK2 inhibitors to block both the normal and mutant forms of the kinase.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 100. doi:1538-7445.AM2012-100
Abstract 1001: Reductive tricarboxylic acid metabolism of glutamine mediates lipogenesis under hypoxia
Authors: Metallo Christian , Gameiro Paulo , Heiden Matthew Vander , Ilioupoulos Othon , Stephanopoulos Greg 
Published: August 2012

Abstract
Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and adenosine triphosphate citrate lyase (ACL) in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle (TCA) and fatty acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and utilization of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells employ reductive metabolism of alpha-ketoglutarate (aKG) to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase 1 (IDH1) dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived aKG for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau (VHL) tumor suppressor protein preferentially utilize reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon utilization in order to produce AcCoA and support lipid synthesis in mammalian cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1001. doi:1538-7445.AM2012-1001
Abstract 1006: Soluble epoxide hydrolase gene deficiency attenuates colitis-induced carcinogenesis in IL-10 knockout mice
Authors: Zhang Wanying , Liao Jie , Li Haonan , Dong Hua , Bai Han , Yang Allison Liao , Hammack Bruce D. , Yang Guang-Yu 
Published: August 2012

Abstract
Soluble epoxide hydrolase (sEH) can quickly inactivate epoxyeicosatrienoic acids (EETs) anti-inflammatory function via converting it to dihydroxyeicosatrienoic acid (DHETs). Inhibition of sEH has shown effects against inflammation. But little is studied about the effect of sEH on colitis-induced carcinogenesis. In this study, we determined the role of sEH gene deficiency in suppressing the development of colitis-induced tumor using chronic colitis mouse model in IL-10 knockout mice combined with sEH gene deficiency. Tumor formation in the bowel was examined at age of 25 weeks for male mice and 35 weeks for female mice. Our results showed that sEH (-/-)/IL-10 (-/-) mice exhibited a significant decrease of tumor multiplicity (2 tumor/mouse vs. 1 tumor/mouse) and tumor size (344.55±71.73 vs. 126.94±23.18 mm3, p=0.028) as compared to IL-10(-/-) mice. But no difference was observed for tumor incidence. Colitis-induced dysplasia was further identified by Ki67-labeled luminal surface epithelial cell proliferation combined with morphologic features and revealed that the number of dysplasia was significantly decreased in sEH (-/-)/IL-10 (-/-) mice. Histopathological analysis of inflammatory activity in the bowel showed the significantly lower inflammation scores, including inflammation-involved area (1.4±0.18 vs. 0.70±0.16, P=0.007), ulcer (2.15±0.18 vs. 1.55±0.35, P=0.032), and myeloperoxidase-labeled inflammatory cell infiltrates in sEH (-/-)/ IL-10(-/-) mice compared to IL-10(-/-) mice. qPCR and western blotting assays showed a downregulation of inflammatory cytokines and NF-kB signals. Analysis of eicsanoid acid metabolic profile confirmed sEH functional deficiency and showed a significant increase in the ratios of EETs/DHET and EpOME/DiOME in sEH (-/-)/IL-10 (-/-) mice compared to IL-10(-/-) mice. The results indicate that sEH gene plays an important role in the development of chronic colitis-induced carcinoma and could serve as a crucial target of cancer chemoprevention. (Supported by NIH R01 grant CA137467)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1006. doi:1538-7445.AM2012-1006
Abstract 1008: Retinoids and TRAIL target early stage intestinal polyps in ApcMin/+ mice
Authors: Davis Jennifer S. , Huang Shaoyi , Ren Xiaoyang , Wu Xiangwei 
Published: August 2012

Abstract
The purpose of this study is to determine the optimal timing of treatment for a novel chemoprevention approach in a mouse model of Familial Adenomatous Polyposis (FAP). FAP is an autosomal dominantly inherited disorder caused by mutations in the tumor suppressor Apc (adenomatous polyposis coli) gene, which results in the formation of hundreds to thousands of polyps, predominantly in the colon and rectum. Left untreated, these polyps will form colorectal adenocarcinomas. Although surgical removal of the colon eliminates the colon cancer risk, these individuals are also at increased risk for other primary cancers, including tumors of the small intestine and stomach. Systemic chemopreventive interventions to specifically remove the pre-cancerous cells in these individuals could greatly improve their outcomes and quality of life. Recently, we have developed a new method based on the ability of combined retinoid and TRAIL (tumor necrosis factor related apoptosis inducing ligand) treatment to induce apoptosis and regression of intestinal polyps in ApcMin/+ mice, a mouse model of FAP. Treatment of these mice with retinoid causes an increase in TRAIL death receptors DR4 and DR5 as well as a concomitant decrease in the decoy receptors. APC deficiency leads to a decreased level of the anti-apoptotic protein FLIP (flice-like inhibitory protein). Thus, the combination of TRAIL and retinoid specifically targets APC deficient cells for apoptosis. Following up on these findings, we have tested the hypothesis that early stage adenomas of the intestine will respond more readily to TRAIL and retinoid treatment than those at a later stage. We used ApcMin/+ mice at either two months of age or five-six months of age. Each group of mice was given three treatments of retinyl acetate and TRAIL within one week. Following the last treatment, the intestine was harvested from each mouse and the polyps were counted. The number of polyps in each group of mice was compared with the polyp number in age matched non-treated mice. Results: When treated at two months of age, ApcMin/+ exhibit a nearly 50% decrease in polyp number following only one week of therapy. Conversely, ApcMin/+ treated at five-six months of age did not show any significant difference in polyp number compared to non-treated mice. Conclusion: Earlier stage adenomas respond more readily to the combined treatment of retinoid and TRAIL. This is likely due to additional mutations acquired by the later stage polyps. The cause of this resistance is a current area of study.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1008. doi:1538-7445.AM2012-1008