bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chapter 46 Scientific deep-sea drilling in high northern latitudes
Authors: Thiede Jörn , Eldholm Olav , Myhre Annik M. 
Published: August 2011

Abstract

Some 30 years ago the regional aspects of the plate tectonic history of the Norwegian–Greenland Sea and the eastern Arctic Ocean were unravelled and showed that these ocean basins had opened in early Eocene, 55–56 Ma ago. Drilling by
Glomar Challenger
in the Norwegian–Greenland Sea during Leg 38 of the Deep Sea Drilling Project confirmed the plate tectonic model and established a marine biostratigraphy framework for the region. The leg set the stage for three subsequent Ocean Drilling Program legs of thematically oriented drilling by the
Joides Resolution
. Leg 104 drilled a deep acoustic basement hole on the Vøring Plateau, which has become a legacy hole for volcanic margin studies, and provided new key information on the Northern Hemisphere Glaciation and the history of the Norwegian Current. Legs 151 and 162 addressed North Atlantic–Arctic gateways problems. During Leg 151 the
Joides Resolution
succeeded, with icebreaker support, in reaching the ice-free waters north of Svalbard, thus for the first time bringing a scientific drill ship into the Arctic Ocean. In 2004, the Integrated Ocean Drilling Program organized the mission-specific Expedition 302 to the Lomonosov Ridge in the permanently ice-covered central Arctic Ocean. Comprising a flotilla of three icebreakers, it was a major logistical venture, and resulted in a huge scientific success. The same year the deep site on the Vøring Plateau was revisited and a thermal borehole observatory installed. During these legs a large quantity of core samples has allowed the scientific community to address fundamental questions in terms of continental margin development; plate tectonics; nature of basement; marine biostratigraphy; and the temporal and spatial evolution of the high-latitude northern climate and environments. However, major challenges remain, in particular related to the deep basins, ridges and margins of the Arctic Ocean proper. The next advance in knowledge is contingent on new technology and research infrastructure both for drilling and site surveying. Presently, plans for a new research icebreaker with drilling capability are being developed, the
Aurora Borealis
project. It will allow systematic drilling in most of the permanently ice-covered basins in the high north. The northern high latitudes have been predicted to contain vast hydrocarbon resources and cooperative ventures between industry and academia may be advantageous.
Chapter 47 Extending coastal state boundaries into the central Arctic Ocean: outer continental shelves beyond 200 nautical miles and the quest for hydrocarbons
Authors: Marcussen Christian , Macnab Ron 
Published: August 2011

Abstract
Five Arctic coastal states – Canada, Denmark (on behalf of Greenland), Norway, Russia and the United States – are qualified to define Outer Continental Shelves beyond 200 nautical miles in the central Arctic Ocean, in accordance with the provisions of Article 76 of the UN Convention on the Law of the Sea. This paper provides an overview of recent and ongoing initiatives by those states, describing operational difficulties and offering a regional preview of possible outcomes. For the most part, the process is driven by a desire to expand national control over resources of the seabed, but recent appraisals suggest that the areas of interest are unlikely to contain significant and commercially exploitable quantities of hydrocarbons.
Chapter 8 US Geological Survey Circum-Arctic Resource Appraisal (CARA): introduction and summary of organization and methods
Authors: Charpentier Ronald R. , Gautier Donald L. 
Published: August 2011

Abstract
The USGS has assessed undiscovered petroleum resources in the Arctic through geological mapping, basin analysis and quantitative assessment. The new map compilation provided the base from which geologists subdivided the Arctic for burial history modelling and quantitative assessment. The CARA was a probabilistic, geologically based study that used existing USGS methodology, modified somewhat for the circumstances of the Arctic. The assessment relied heavily on analogue modelling, with numerical input as lognormal distributions of sizes and numbers of undiscovered accumulations. Probabilistic results for individual assessment units were statistically aggregated taking geological dependencies into account. Fourteen papers in this Geological Society volume present summaries of various aspects of the CARA.
Chapter 9 Oil and gas resource potential north of the Arctic Circle
Authors: Gautier Donald L. , Bird Kenneth J. , Charpentier Ronald R. , Grantz Arthur , Houseknecht David W. , Klett Timothy R. , Moore Thomas E. , Pitman Janet K. , Schenk Christopher J. , Schuenemeyer John H. , Sørensen Kai , Tennyson Marilyn E. , Valin Zenon C. , Wandrey Craig J. 
Published: August 2011

Abstract
The US Geological Survey recently assessed the potential for undiscovered conventional petroleum in the Arctic. Using a new map compilation of sedimentary elements, the area north of the Arctic Circle was subdivided into 70 assessment units, 48 of which were quantitatively assessed. The Circum-Arctic Resource Appraisal (CARA) was a geologically based, probabilistic study that relied mainly on burial history analysis and analogue modelling to estimate sizes and numbers of undiscovered oil and gas accumulations. The results of the CARA suggest the Arctic is gas-prone with an estimated 770–2990 trillion cubic feet of undiscovered conventional natural gas, most of which is in Russian territory. On an energy-equivalent basis, the quantity of natural gas is more than three times the quantity of oil and the largest undiscovered gas field is expected to be about 10 times the size of the largest undiscovered oil field. In addition to gas, the gas accumulations may contain an estimated 39 billion barrels of liquids. The South Kara Sea is the most prospective gas assessment unit, but giant gas fields containing more than 6 trillion cubic feet of recoverable gas are possible at a 50% chance in 10 assessment units. Sixty per cent of the estimated undiscovered oil resource is in just six assessment units, of which the Alaska Platform, with 31% of the resource, is the most prospective. Overall, the Arctic is estimated to contain between 44 and 157 billion barrels of recoverable oil. Billion barrel oil fields are possible at a 50% chance in seven assessment units. Undiscovered oil resources could be significant to the Arctic nations, but are probably not sufficient to shift the world oil balance away from the Middle East.
Proto-oncogene PBF/PTTG1IP Regulates Thyroid Cell Growth and Represses Radioiodide Treatment
Authors: Read Martin L. , Lewy Greg D. , Fong Jim C.W. , Sharma Neil , Seed Robert I. , Smith Vicki E. , Gentilin Erica , Warfield Adrian , Eggo Margaret C. , Knauf Jeffrey A. , Leadbeater Wendy E. , Watkinson John C. , Franklyn Jayne A. , Boelaert Kristien , McCabe Christopher J. 
Published: August 2011

Abstract
Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized proto-oncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created a murine transgenic model to target PBF expression to the thyroid gland (PBF-Tg mice) and found that these mice exhibited normal thyroid function, but a striking enlargement of the thyroid gland associated with hyperplastic and macrofollicular lesions. Expression of the sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators of thyrocyte proliferation, along with upregulation of the downstream proliferative marker cyclin D1. We extended and confirmed findings from the mouse model by examining PBF expression in human multinodular goiters (MNG), a hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in human primary thyrocytes was sufficient to increase radioiodine uptake. Together, our findings indicate that overexpression of PBF causes thyroid cell proliferation, macrofollicular lesions, and hyperplasia, as well as repression of the critical therapeutic route for radioiodide uptake. Cancer Res; 71(19); 6153–64. ©2011 AACR.
Wnt5a Suppresses Epithelial Ovarian Cancer by Promoting Cellular Senescence
Authors: Bitler Benjamin G. , Nicodemus Jasmine P. , Li Hua , Cai Qi , Wu Hong , Hua Xiang , Li Tianyu , Birrer Michael J. , Godwin Andrew K. , Cairns Paul , Zhang Rugang 
Published: August 2011

AbstractEpithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in the United States. Thus, there is an urgent need to develop novel therapeutics for this disease. Cellular senescence is an important tumor suppression mechanism that has recently been suggested as a novel mechanism to target for developing cancer therapeutics. Wnt5a is a noncanonical Wnt ligand that plays a context-dependent role in human cancers. Here, we investigate the role of Wnt5a in regulating senescence of EOC cells. We show that Wnt5a is expressed at significantly lower levels in human EOC cell lines and in primary human EOCs (n = 130) compared with either normal ovarian surface epithelium (n = 31; P = 0.039) or fallopian tube epithelium (n = 28; P &lt; 0.001). Notably, a lower level of Wnt5a expression correlates with tumor stage (P = 0.003) and predicts shorter overall survival in EOC patients (P = 0.003). Significantly, restoration of Wnt5a expression inhibits the proliferation of human EOC cells both in vitro and in vivo in an orthotopic EOC mouse model. Mechanistically, Wnt5a antagonizes canonical Wnt/β-catenin signaling and induces cellular senescence by activating the histone repressor A/promyelocytic leukemia senescence pathway. In summary, we show that loss of Wnt5a predicts poor outcome in EOC patients and Wnt5a suppresses the growth of EOC cells by triggering cellular senescence. We suggest that strategies to drive senescence in EOC cells by reconstituting Wnt5a signaling may offer an effective new strategy for EOC therapy. Cancer Res; 71(19); 6184–94. ©2011 AACR.
ABT-898 Induces Tumor Regression and Prolongs Survival in a Mouse Model of Epithelial Ovarian Cancer
Authors: Campbell Nicole , Greenaway James , Henkin Jack , Petrik Jim 
Published: August 2011

Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and is often not diagnosed until late stages due to its asymptomatic nature. Women diagnosed with EOC typically undergo surgical debulking followed by chemotherapy; however, disease recurrence often occurs. In this study, we evaluated the ability of the thrombospondin-1 mimetic peptide, ABT-898, to regress established, late-stage tumors in a mouse model of human EOC. Ovarian tumors were induced and ABT-898 treatment was initiated at time points that were representative of late stages of the disease to study tumor regression. ABT-898 induced tumor regression and reduced the morbidity of treated animals compared with controls. Analysis of tumors from ABT-898–treated animals showed reduced abnormal tumor vasculature, decreased expression of the proangiogenic compound VEGF, and reduced tumor tissue hypoxia. ABT-898 treatment initiated at late-stage disease also significantly prolonged disease-free survival compared with control animals. Results from this study show that ABT-898 is capable of regressing established ovarian tumors in an animal model of the disease. As most women are detected at advanced stage EOC, ABT-898 may improve our treatment of ovarian cancer. Mol Cancer Ther; 10(10); 1876–85. ©2011 AACR.
p57Kip2 and Cancer: Time for a Critical Appraisal
Authors: Borriello Adriana , Caldarelli Ilaria , Bencivenga Debora , Criscuolo Maria , Cucciolla Valeria , Tramontano Annunziata , Oliva Adriana , Perrotta Silverio , Della Ragione Fulvio 
Published: August 2011

Abstractp57Kip2 is a cyclin-dependent kinase inhibitor belonging to the Cip/Kip family, which also includes p21Cip1 and p27Kip1. So far, p57Kip2 is the least-studied Cip/Kip protein, and for a long time its relevance has been related mainly to its unique role in embryogenesis. Moreover, genetic and molecular studies on animal models and patients with Beckwith-Wiedemann syndrome have shown that alterations in CDKN1C (the p57Kip2 encoding gene) have functional relevance in the pathogenesis of this disease. Recently, a number of investigations have identified and characterized heretofore unexpected roles for p57Kip2. The protein appears to be critically involved in initial steps of cell and tissue differentiation, and particularly in neuronal development and erythropoiesis. Intriguingly, p27Kip1, the Cip/Kip member that is most homologous to p57Kip2, is primarily involved in the process of cell cycle exit. p57Kip2 also plays a critical role in controlling cytoskeletal organization and cell migration through its interaction with LIMK-1. Furthermore, p57Kip2 appears to modulate genome expression. Finally, accumulating evidence indicates that p57Kip2 protein is frequently downregulated in different types of human epithelial and nonepithelial cancers as a consequence of genetic and epigenetic events. In summary, the emerging picture is that several aspects of p57Kip2's functions are only poorly clarified. This review represents an appraisal of the data available on the p57Kip2 gene and protein structure, and its role in human physiology and pathology. We particularly focus our attention on p57Kip2 changes in cancers and pharmacological approaches for modulating p57Kip2 levels. Mol Cancer Res; 9(10); 1269–84. ©2011 AACR.
MicroRNA-21 Regulates Vascular Smooth Muscle Cell Function via Targeting Tropomyosin 1 in Arteriosclerosis Obliterans of Lower Extremities
Authors: Wang Mian , Li Wen , Chang Guang-Qi , Ye Cai-Sheng , Ou Jing-Song , Li Xiao-Xi , Liu Yong , Cheang Tuck-Yun , Huang Xue-Ling , Wang Shen-Ming 
Published: August 2011

Objective
—The goal of this study was to determine the expression signature and the potential role of microRNAs in human arteries with arteriosclerosis obliterans (ASO).

Methods and Results
—The expression profiles of microRNAs in human arteries with ASO and in normal control arteries were determined by quantitative reverse transcription–polymerase chain reaction array. Among the 617 detected microRNAs, multiple microRNAs were aberrantly expressed in arteries with ASO. Some of these dysregulated microRNAs were further verified by quantitative reverse transcription–polymerase chain reaction. Among them, microRNA-21 (miR-21) was mainly located in arterial smooth muscle cells (ASMCs) and was increased by more than 7-fold in ASO that was related to hypoxia inducible factor 1-α. In cultured human ASMCs, cell proliferation and migration were significantly decreased by inhibition of miR-21. 3′-Untranslated region luciferase assay confirmed that tropomyosin 1 was a target of miR-21 that was involved in miR-21-mediated cellular effects, such as cell shape modulation.

Conclusion
—The results suggest that miR-21 is able to regulate ASMC function by targeting tropomyosin 1. The hypoxia inducible factor-1 α/miR-21/tropomyosin 1 pathway may play a critical role in the pathogenesis of ASO. These findings might provide a new therapeutic target for human ASO.
Smooth Muscle Calponin
Authors: Long Xiaochun , Slivano Orazio J. , Cowan Sarah L. , Georger Mary A. , Lee Ting-Hein , Miano Joseph M. 
Published: August 2011

Objective—

Smooth muscle calponin (
CNN1
) contains multiple conserved intronic CArG elements that bind serum response factor and display enhancer activity in vitro. The objectives here were to evaluate these CArG elements for activity in transgenic mice and determine the effect of human CNN1 on injury-induced vascular remodeling.

Methods and Results—

Mice carrying a lacZ reporter under control of intronic CArG elements in the human
CNN1
gene failed to show smooth muscle cell (SMC)-restricted activity. However, deletion of the orthologous sequences in mice abolished endogenous
Cnn1
promoter activity, suggesting their necessity for in vivo
Cnn1
expression. Mice carrying a 38-kb bacterial artificial chromosome (BAC) harboring the human
CNN1
gene displayed SMC- restricted expression of the corresponding CNN1 protein, as measured by immunohistochemistry and Western blotting. Extensive BAC recombineering studies revealed the absolute necessity of a single intronic CArG element for correct SMC-restricted expression of human CNN1. Overexpressing human CNN1 suppressed neointimal formation following arterial injury. Mice with an identical BAC carrying mutations in CArG elements that inhibit human CNN1 expression showed outward remodeling and neointimal formation.

Conclusion—
A single intronic CArG element is necessary but insufficient for proper CNN1 expression in vivo. CNN1 overexpression antagonizes arterial injury-induced neointimal formation.
Cathepsin K Deficiency Reduces Elastase Perfusion–Induced Abdominal Aortic Aneurysms in Mice
Authors: Sun Jiusong , Sukhova Galina K. , Zhang Jie , Chen Han , Sjöberg Sara , Libby Peter , Xia Mingcan , Xiong Na , Gelb Bruce D. , Shi Guo-Ping 
Published: August 2011

Objective—
Cathepsin K (CatK) is one of the most potent mammalian elastases. We have previously shown increased expression of CatK in human abdominal aortic aneurysm (AAA) lesions. Whether this protease participates directly in AAA formation, however, remains unknown.

Methods and Results—

Mouse experimental AAA was induced with aortic perfusion of a porcine pancreatic elastase. Using this experimental model, we demonstrated that absence of CatK prevented AAA formation in mice 14 days postperfusion. CatK deficiency significantly reduced lesion CD4
+
T-cell content, total lesion and medial cell proliferation and apoptosis, medial smooth muscle cell (SMC) loss, elastinolytic CatL and CatS expression, and elastin fragmentation, but it did not affect AAA lesion Mac-3
+
macrophage accumulation or CD31
+
microvessel numbers. In vitro studies revealed that CatK contributed importantly to CD4
+
T-cell proliferation, SMC apoptosis, and other cysteinyl cathepsin and matrix metalloproteinase expression and activities in SMCs and endothelial cells but played negligible roles in microvessel growth and monocyte migration. AAA lesions from CatK-deficient mice showed reduced elastinolytic cathepsin activities compared with those from wild-type control mice.

Conclusion—
This study demonstrates that CatK plays an essential role in AAA formation by promoting T-cell proliferation, vascular SMC apoptosis, and elastin degradation and by affecting vascular cell protease expression and activities.
Role of Perivascular Adipose Tissue–Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension
Authors: Lee Yuan-Chieh , Chang Hsi-Hsien , Chiang Chih-Lung , Liu Chin-Hung , Yeh Jih-I , Chen Mei-Fang , Chen Po-Yi , Kuo Jon-Son , Lee Tony J.F. 
Published: August 2011

Background—
Perivascular adipose tissue (PVAT)–derived relaxing factor (PVATRF) significantly regulates vascular tone. Its chemical nature remains unknown. We determined whether palmitic acid methyl ester (PAME) was the PVATRF and whether its release and/or vasorelaxing activity decreased in hypertension.

Methods and Results—
Using superfusion bioassay cascade technique, tissue bath myography, and gas chromatography/mass spectrometry, we determined PVATRF and PAME release from aortic PVAT preparations of Wistar Kyoto rats and spontaneously hypertensive rats. The PVAT of Wistar Kyoto rats spontaneously and calcium dependently released PVATRF and PAME. Both induced aortic vasorelaxations, which were inhibited by 4-aminopyridine (2 mmol/L) and tetraethylammonium 5 and 10 mmol/L but were not affected by tetraethylammonium 1 or 3 mmol/L, glibenclamide (3 μmol/L), or iberiotoxin (100 nmol/L). Aortic vasorelaxations induced by PVATRF- and PAME-containing Krebs solutions were not affected after heating at 70°C but were equally attenuated after hexane extractions. Culture mediums of differentiated adipocytes, but not those of fibroblasts, contained significant PAME and caused aortic vasorelaxation. The PVAT of spontaneously hypertensive rats released significantly less PVATRF and PAME with an increased release of angiotensin II. In addition, PAME-induced relaxation of spontaneously hypertensive rats aortic smooth muscle diminished drastically, which was ameliorated significantly by losartan.

Conclusions—

We found that PAME is the PVATRF, causing vasorelaxation by opening voltage-dependent K
+
channels on smooth muscle cells. Diminished PAME release and its vasorelaxing activity and increased release of angiotensin II in the PVAT suggest a noble role of PVAT in pathogenesis of hypertension. The antihypertensive effect of losartan is attributed partly to its reversing diminished PAME-induced vasorelaxation.
Patent Foramen Ovale May Be Causal for the First Stroke but Unrelated to Subsequent Ischemic Events
Authors: Mono Marie-Luise , Geister Laura , Galimanis Aekaterini , Jung Simon , Praz Fabien , Arnold Marcel , Fischer Urs , Wolff Stefan , Findling Oliver , Windecker Stephan , Wahl Andreas , Meier Bernhard , Mattle Heinrich P. , Nedeltchev Krassen 
Published: August 2011

Background and Purpose—
Studies with very long follow-up are scarce in patients with cryptogenic stroke and patent foramen ovale (PFO). Little is known about the etiology of recurrent cerebrovascular events (CVE) in PFO patients.

Methods—
We collected information on recurrent CVE in 308 patients with cryptogenic stroke and PFO and sought to determine concurrent stroke causes that had emerged or been newly detected since the index event. One hundred fifty-eight patients received aspirin (48%), clopidogrel (2%), or oral anticoagulants (50%; medical group). One hundred fifty patients underwent percutaneous PFO closure (closure group).

Results—

Mean age at index event was 50 years (SD 13). In 33% of patients, the index stroke or transient ischemic attack was preceded by at least 1 CVE. Mean follow-up was 8.7±4.0 years. During follow-up, 32 recurrent CVE (13 strokes and 19 transient ischemic attacks) occurred in the medical and 16 recurrent CVE (8 strokes and 8 transient ischemic attacks) in the closure group. Concurrent etiologies were identified for 12 recurrent CVE in the medical group (38%): large artery disease (9%), small artery disease (6%), cardioembolism (13%), cerebral vasculitis (3%), and antiphospholipid-antibody-syndrome (6%). In the closure group, 7 recurrent CVE had a concurrent etiology (44%): large artery disease (6%), small artery disease (19%), cardioembolism (13%), and thrombophilic disorder (6%). The frequency of concurrent etiologies did not differ between patients with recurrent CVE under medical treatment and those undergoing PFO closure (
P
=0.68).

Conclusions—
Concurrent etiologies are identified for more than one third of recurrent ischemic events in patients with cryptogenic stroke, casting doubt on the sole causal role of PFO.