bluuebunny/crossref_metadata_2025 huggingface dataset:
Chapter 36 Petroleum prospectivity of the Triassic–Jurassic succession of Sverdrup Basin, Canadian Arctic Archipelago
Authors: Embry Ashton
Published: August 2011

The Sverdrup Basin of the Canadian Arctic Archipelago is an established petroliferous, rift/sag basin with 17 discovered oil and gas fields. Almost all the hydrocarbons occur in Triassic–Jurassic shallow marine sandstones and were sourced from Middle to Upper Triassic bituminous shales. The discovered fields occur on the culminations of Palaeogene structures. Three prospective areas for future discoveries in the Triassic–Jurassic succession include western Sverdrup, southeastern Sverdrup and the Fosheim Peninsula area. Most of the large structures in these prospective areas were mapped and tested in the initial round of hydrocarbon exploration. The largest potential play which has not been tested involves a stratigraphic component as part of the hydrocarbon trapping mechanism. Potential reservoir units are developed on the third-order sequence scale and 22 such sequences have been delineated in the Triassic–Jurassic succession. Most of them contain a progradational, shallow marine sandstone unit which is in part porous within the prospective areas. These units are often truncated by unconformities on the basin margins and change facies to nonporous strata basinward. The pinchouts of these porous units in proper structural orientations provide good petroleum prospects because they were already present during the maturation and migration of the Triassic-sourced hydrocarbons.
Chapter 38 Thermal maturity of the Sverdrup Basin, Arctic Canada and its bearing on hydrocarbon potential
Authors: Dewing Keith , Obermajer Mark
Published: August 2011

Analysis of a large thermal maturity dataset indicates that the Carboniferous to Eocene Sverdrup Basin in the Canadian Arctic had a uniform response to thermal stress with depth for Mesozoic strata. Thermal maturity was established at the level of the widespread Upper Triassic Gore Point Member; a good seismic reflector, occurring in close vertical proximity to the two main oil-prone source rocks in the basin. The Gore Point Member is in the gas window (
R
o
>1.35%) in the northeastern part of the Sverdrup Basin, whereas in the western Sverdrup Basin its maturity does not exceed 1.2%
R
o
. This would support the hypothesis that large quantities of gas found at the Drake, Hecla and Whitefish fields have derived from a deeper source, probably in Permian or lower Palaeozoic strata. A normal burial curve is established using boreholes drilled in areas with no structural complexity at time of maximum burial. Low-amplitude structures, including the Drake, Hecla and Whitefish fields, show little or no uplift following maximum burial in the Paleocene, indicating that these structures formed prior to the Eocene folding related to the Eurekan Orogeny. Because they were present at the time of maximum burial, they were available to be charged during hydrocarbon migration. In contrast, high-amplitude structures show evidence of large uplifts following maximum burial. They formed in the Eocene and hence post-date most hydrocarbon migration.
Chapter 4 Regional magnetic domains of the Circum-Arctic: a framework for geodynamic interpretation
Authors: Saltus R. W. , Miller E. L. , Gaina C. , Brown P. J.
Published: August 2011

We identify and discuss 57 magnetic anomaly pattern domains spanning the Circum-Arctic. The domains are based on analysis of a new Circum-Arctic data compilation. The magnetic anomaly patterns can be broadly related to general geodynamic classification of the crust into stable, deformed (magnetic and nonmagnetic), deep magnetic high, oceanic and large igneous province domains. We compare the magnetic domains with topography/bathymetry, regional geology, regional free air gravity anomalies and estimates of the relative magnetic ‘thickness’ of the crust. Most of the domains and their geodynamic classification assignments are consistent with their topographic/bathymetric and geological expression. A few of the domains are potentially controversial. For example, the extent of the Iceland Faroe large igneous province as identified by magnetic anomalies may disagree with other definitions for this feature. Also the lack of definitive magnetic expression of oceanic crust in Baffin Bay, the Norwegian–Greenland Sea and the Amerasian Basin is at odds with some previous interpretations. The magnetic domains and their boundaries provide clues for tectonic models and boundaries within this poorly understood portion of the globe.
Chapter 40 Baffin Fan and its inverted rift system of Arctic eastern Canada: stratigraphy, tectonics and petroleum resource potential
Authors: Harrison J. C. , Brent T. A. , Oakey G. N.
Published: August 2011

Baffin Fan is a 12 km-thick sedimentary wedge of Eocene to Pleistocene age in northwestern Baffin Bay, with size and resource potential comparable to Beaufort–Mackenzie Basin. A widespread Moho detachment originating in Mesoproterozoic strata may have influenced development of Cretaceous–Palaeogene horst blocks and half-grabens throughout the region, and their transformation by later phases of inversion. Reflection profiles indicate 12 depositional sequences in lower Palaeozoic and Cretaceous to Pleistocene strata. Notable is syntectonic sedimentation with possible volcanism and rifting in the Cretaceous–Danian. Sequences associated with inversion in the later Paleocene and Eocene display out-of-graben thrust anticlines formed over horst blocks in Lady Ann and Lancaster Sound basins. The Oligocene to mid-Miocene is associated with fluvial–deltaic systems, replaced since then by glacial–interglacial sequences including submarine canyons and deepwater fans. Exploration targets are located in Lancaster Sound, and a Baffin Bay fairway that runs 220 km northwestward to east of Coburg Island. Sixty-five per cent of prospects are located under Neogene cover. Fourteen are each greater than 70 km
2
, and five are between 334 and 592 km
2
. Based on drilling success rates elsewhere and the existence of a petroleum system, 12 of the 40 mapped structures may contain hydrocarbons in significant quantity.
Chapter 42 Greenland petroleum exploration: history, breakthroughs in understanding and future challenges
Authors: Christiansen F. G.
Published: August 2011

In recent years there has been a growing interest from the industry for exploration in the Arctic and other high-latitude areas, including possible future petroleum provinces in Greenland. Exploration focus in Greenland has mainly been on central west Greenland with several licensing rounds and, as a promising result, the highest number of licences ever seen in Greenland. Activities in the coming years are likely to be directed more towards Baffin Bay and to the NE Greenland shelf. Both of these regions offer very promising exploration targets but also major technical challenges due to many months of ice coverage every year. Preparations for new exploration, data acquisition and geological and geophysical work are in progress in these two regions. Both of the regions benefit from excellent outcrops in the neighbouring onshore areas and a rapidly increasing geophysical database offshore. The history behind data acquisition and the most important results and models for exploration in some of the possible future petroleum provinces are described with particular focus on positive indications for structures and petroleum systems together with uncertainties in interpretation and the most critical risks for exploration.

Supplementary material:

Supplementary Table 1 is available at
http://www.geolsoc.org.uk/SUP18477
.
Chapter 43 Assessment of NE Greenland: prototype for development of Circum-Arctic Resource Appraisal methodology
Authors: Gautier Donald L. , Stemmerik Lars , Christiansen Flemming G. , Sørensen Kai , Bidstrup Torben , Bojesen-Koefoed Jørgen A. , Bird Kenneth J. , Charpentier Ronald R. , Houseknecht David W. , Klett T. R. , Schenk Christopher J. , Tennyson Marilyn E.
Published: August 2011

Geological features of NE Greenland suggest large petroleum potential, as well as high uncertainty and risk. The area was the prototype for development of methodology used in the US Geological Survey (USGS) Circum-Arctic Resource Appraisal (CARA), and was the first area evaluated. In collaboration with the Geological Survey of Denmark and Greenland (GEUS), eight ‘assessment units’ (AU) were defined, six of which were probabilistically assessed. The most prospective areas are offshore in the Danmarkshavn Basin. This study supersedes a previous USGS assessment, from which it differs in several important respects: oil estimates are reduced and natural gas estimates are increased to reflect revised understanding of offshore geology. Despite the reduced estimates, the CARA indicates that NE Greenland may be an important future petroleum province.
Chapter 45 Geophysical exploration of the Arctic Ocean: the physical environment, survey techniques and brief summary of knowledge
Authors: Kristoffersen Yngve
Published: August 2011

The areal extent of the ice covered Arctic Ocean is about four times the size of the Mediterranean Sea. More than 50 years after identification of the main bathymetric features in the deep polar basin, our coverage of modern multichannel seismic data is still limited to what a single ship would complete under open-ocean conditions in about two and a half months. In addition, an estimated one-fifth of the deepwater area is inaccessible to icebreaker surveys with surface-towed equipment. Signal-to-noise levels achieved in multichannel seismic data acquisition from icebreakers are sufficient to identify acoustic basement below more than 3 s (two-way travel time) of sediments in spite of reduced source and receiver arrays. Our current reconnaissance stage in deep basin exploration will at least include the coming decade as surveys by diesel-driven icebreakers are largely restricted by contemporary patterns of open leads in the sea ice cover.
Chapter 49 A first look at the petroleum geology of the Lomonosov Ridge microcontinent, Arctic Ocean
Authors: Moore Thomas E. , Grantz Arthur , Pitman Janet K. , Brown Philip J.
Published: August 2011

The Lomonosov microcontinent is an elongated continental fragment that transects the Arctic Ocean between North America and Siberia via the North Pole. Although it lies beneath polar pack ice, the geological framework of the microcontinent is inferred from sparse seismic reflection data, a few cores, potential field data and the geology of its conjugate margin in the Barents–Kara Shelf. Petroleum systems inferred to be potentially active are comparable to those sourced by condensed Triassic and Jurassic marine shale of the Barents Platform and by condensed Jurassic and (or) Cretaceous shale probably present in the adjacent Amerasia Basin. Cenozoic deposits are known to contain rich petroleum source rocks but are too thermally immature to have generated petroleum. For the 2008 USGS Circum Arctic Resource Appraisal (CARA), the microcontinent was divided into shelf and slope assessment units (AUs) at the tectonic hinge line along the Amerasia Basin margin. A low to moderate probability of accumulation in the slope AU yielded fully risked mean estimates of 123 MMBO oil and 740 BCF gas. For the shelf AU, no quantitative assessment was made because the probability of petroleum accumulations of the 50 MMBOE minimum size was estimated to be less than 10% owing to rift-related uplift, erosion and faulting.
Chapter 50 Geology and tectonic development of the Amerasia and Canada Basins, Arctic Ocean
Authors: Grantz Arthur , Hart Patrick E. , Childers Vicki A.
Published: August 2011

Amerasia Basin is the product of two phases of counterclockwise rotational opening about a pole in the lower Mackenzie Valley of NW Canada. Phase 1 opening brought ocean–continent transition crust (serpentinized peridotite?) to near the seafloor of the proto-Amerasia Basin, created detachment on the Eskimo Lakes Fault Zone of the Canadian Arctic margin and thinned the continental crust between the fault zone and the proto-Amerasia Basin to the west, beginning about 195 Ma and ending prior to perhaps about 160 Ma. The symmetry of the proto-Amerasia Basin was disrupted by clockwise rotation of the Chukchi Microcontinent into the basin from an original position along the Eurasia margin about a pole near 72°N, 165 W about 145.5–140 Ma. Phase 2 opening enlarged the proto-Amerasia Basin by intrusion of mid-ocean ridge basalt along its axis between about 131 and 127.5 Ma. Following intrusion of the Phase 2 crust an oceanic volcanic plateau, the Alpha–Mendeleev Ridge LIP (large igneous province), was extruded over the northern Amerasia Basin from about 127 to 89–75 Ma. Emplacement of the LIP halved the area of the Amerasia Basin, and the area lying south of the LIP became the Canada Basin.
Gut-derived factors promote neurogenesis of CNS-neural stem cells and nudge their differentiation to an enteric-like neuronal phenotype
Authors: Kulkarni Subhash , Zou Bende , Hanson Jesse , Micci Maria-Adelaide , Tiwari Gunjan , Becker Laren , Kaiser Martin , Xie Xinmin (Simon) , Pasricha Pankaj Jay
Published: August 2011

Recent studies have explored the potential of central nervous system-derived neural stem cells (CNS-NSC) to repopulate the enteric nervous system. However, the exact phenotypic fate of gut-transplanted CNS-NSC has not been characterized. The aim of this study was to investigate the effect of the gut microenvironment on phenotypic fate of CNS-NSC in vitro. With the use of Transwell culture, differentiation of mouse embryonic CNS-NSC was studied when cocultured without direct contact with mouse intestinal longitudinal muscle-myenteric plexus preparations (LM-MP) compared with control noncocultured cells, in a differentiating medium. Differentiated cells were analyzed by immunocytochemistry and quantitative RT-PCR to assess the expression of specific markers and by whole cell patch-clamp studies for functional characterization of their phenotype. We found that LM-MP cocultured cells had a significant increase in the numbers of cells that were immune reactive against the panneuronal marker β-tubulin, neurotransmitters neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and neuropeptide vasoactive intestinal peptide (VIP) and showed an increase in expression of these genes, compared with control cells. Whole cell patch-clamp analysis showed that coculture with LM-MP decreases cell excitability and reduces voltage-gated Na+ currents but significantly enhances A-current and late afterhyperpolarization (AHP) and increases the expression of the four AHP-generating Ca2+-dependent K+ channel genes (KCNN), compared with control cells. In a separate experiment, differentiation of LM-MP cocultured CNS-NSC produced a significant increase in the numbers of cells that were immune reactive against the neurotransmitters nNOS, ChAT, and the neuropeptide VIP compared with CNS-NSC differentiated similarly in the presence of neonatal brain tissue. Our results show that the gut microenvironment induces CNS-NSC to produce neurons that share some of the characteristics of classical enteric neurons, further supporting the therapeutic use of these cells for gastrointestinal disorders.
Distension of the esophagogastric junction augments triggering of transient lower esophageal sphincter relaxation
Authors: van Wijk Michiel P. , Blackshaw L. Ashley , Dent John , Benninga Marc A. , Davidson Geoffrey P. , Omari Taher I.
Published: August 2011

Patients with gastroesophageal reflux disease show an increase in esophagogastric junction (EGJ) distensibility and in frequency of transient lower esophageal sphincter relaxations (TLESR) induced by gastric distension. The objective was to study the effect of localized EGJ distension on triggering of TLESR in healthy volunteers. An esophageal manometric catheter incorporating an 8-cm internal balloon adjacent to a sleeve sensor was developed to enable continuous recording of EGJ pressure during distension of the EGJ. Inflation of the balloon doubled the cross-section of the trans-sphincteric portion of the catheter from 5 mm OD (round) to 5 × 11 mm (oval). Ten healthy subjects were included. After catheter placement and a 30-min adaptation period, the EGJ was randomly distended or not, followed by a 45-min baseline recording. Subjects consumed a refluxogenic meal, and recordings were made for 3 h postprandially. A repeat study was performed on another day with EGJ distension status reversed. Additionally, in one subject MRI was performed to establish the exact position of the balloon in the inflated state. The number of TLESR increased during periods of EGJ distension with the effect being greater after a meal [baseline: 2.0(0.0–4.0) vs. 4.0(1.0–11.0), P=0.04; postprandial: 15.5(10.0–33.0) vs. 22.0(17.0–58.0), P=0.007 for undistended and distended, respectively]. EGJ distension augments meal-induced triggering of TLESR in healthy volunteers. Our data suggest the existence of a population of vagal afferents located at sites in/around the EGJ that may influence triggering of TLESR.
Absence of heat shock transcription factor 1 retards the regrowth of atrophied soleus muscle in mice
Authors: Yasuhara Kazuyuki , Ohno Yoshitaka , Kojima Atsushi , Uehara Kenji , Beppu Moroe , Sugiura Takao , Fujimoto Mitsuaki , Nakai Akira , Ohira Yoshinobu , Yoshioka Toshitada , Goto Katsumasa
Published: August 2011

Effects of heat shock transcription factor 1 (HSF1) gene on the regrowth of atrophied mouse soleus muscles were studied. Both HSF1-null and wild-type mice were subjected to continuous hindlimb suspension for 2 wk followed by 4 wk of ambulation recovery. There was no difference in the magnitude of suspension-related decrease of muscle weight, protein content, and the cross-sectional area of muscle fibers between both types of mice. However, the regrowth of atrophied soleus muscle in HSF1-null mice was slower compared with that in wild-type mice. Lower baseline expression level of HSP25, HSC70, and HSP72 were noted in soleus muscle of HSF1-null mice. Unloading-associated downregulation and reloading-associated upregulation of HSP25 and HSP72 mRNA were observed not only in wild-type mice but also in HSF1-null mice. Reloading-associated upregulation of HSP72 and HSP25 during the regrowth of atrophied muscle was observed in wild-type mice. Minor and delayed upregulation of HSP72 at mRNA and protein levels was also seen in HSF1-null mice. Significant upregulations of HSF2 and HSF4 were observed immediately after the suspension in HSF1-null mice, but not in wild-type mice. Therefore, HSP72 expression in soleus muscle might be regulated by the posttranscriptional level, but not by the stress response. Evidence from this study suggested that the upregulation of HSPs induced by HSF1-associated stress response might play, in part, important roles in the mechanical loading (stress)-associated regrowth of skeletal muscle.
FLT3 Ligand Enhances the Cancer Therapeutic Potency of Naked RNA Vaccines
Authors: Kreiter Sebastian , Diken Mustafa , Selmi Abderraouf , Diekmann Jan , Attig Sebastian , Hüsemann Yves , Koslowski Michael , Huber Christoph , Türeci Özlem , Sahin Ugur
Published: August 2011

Intranodal immunization with antigen-encoding naked RNA may offer a simple and safe approach to induce antitumor immunity. RNA taken up by nodal dendritic cells (DC) coactivates toll-like receptor (TLR) signaling that will prime and expand antigen-specific T cells. In this study, we show that RNA vaccination can be optimized by coadministration of the DC-activating Fms-like tyrosine kinase 3 (FLT3) ligand as an effective adjuvant. Systemic administration of FLT3 ligand prior to immunization enhanced priming and expansion of antigen-specific CD8+ T cells in lymphoid organs, T-cell homing into melanoma tumors, and therapeutic activity of the intranodal RNA. Unexpectedly, plasmacytoid DCs (pDC) were found to be essential for the adjuvant effect of FLT3 ligand and they were systemically expanded together with conventional DCs after treatment. In response to FLT3 ligand, pDCs maintained an immature phenotype, internalized RNA, and presented the RNA-encoded antigen for efficient induction of antigen-specific CD8+ T-cell responses. Coadministration of FLT3 ligand with RNA vaccination achieved remarkable cure rates and survival of mice with advanced melanoma. Our findings show how to improve the simple and safe strategy offered by RNA vaccines for cancer immunotherapy. Cancer Res; 71(19); 6132–42. ©2011 AACR.
microRNA-10b: A New Marker or the Marker of Pancreatic Ductal Adenocarcinoma?
Authors: Setoyama Tetsuro , Zhang Xinna , Natsugoe Shoji , Calin George A.
Published: August 2011

microRNA-10b (miR-10b) expression in pancreatic ductal adenocarcinoma (PDAC), as identified by in situ hybridization, is highly correlated with cancer diagnosis, therapy response, and prognosis. If these findings are further confirmed in prospective studies, miR-10b could be used to improve the management of PDAC and decrease the mortality rate of this deadly cancer. Clin Cancer Res; 17(17); 5527–9. ©2011 AACR.
Dual-Fluorescence Isogenic High-Content Screening for MUC16/CA125 Selective Agents
Authors: Rao Thapi D. , Rosales Nestor , Spriggs David R.
Published: August 2011

Most of the currently used cancer chemotherapies are based on compounds that inhibit general cellular mechanisms, such as DNA replication or tubulin function, and lack specificity in relation to features of the cancer cell. Recent advances in genomic studies have increased our knowledge of tumor cell biology, and a panoply of new targets have been postulated. This has provided an opportunity to develop and validate drugs that specifically target cancer cells through their unique genetic characteristics. Identification of MUC16/CA125 both as a marker and a driver of transformation led us to design a target-based high-content screen to identify and classify compounds that exhibit differential effect on MUC16-expressing cells. We developed a coculture assay in 384-well plate containing isogenic ovarian cancer cells that are positive or negative for the MUC16 protein. High-throughput screening of our small molecule pilot library led to the identification of compounds preferentially cytotoxic to MUC16+ or MUC16− cells, using a Preferential Score analysis. We compared screening results in both A2780 and SK-OV-3 ovarian cancer cells in single and coculture settings. We also identified compounds that were cytotoxic for both types of ovarian cancer cells regardless of the MUC16 status. Compounds that were preferentially targeting MUC16 cells were subsequently confirmed by caspase-induction assays. The isogenic, dual-color fluorescence strategy is an innovative approach that can effectively identify novel drug candidates, selectively targeting cancer cells that have unique molecular properties. Mol Cancer Ther; 10(10); 1939–48. ©2011 AACR.
2-Methoxy-5-Amino-N-Hydroxybenzamide Sensitizes Colon Cancer Cells to TRAIL-Induced Apoptosis by Regulating Death Receptor 5 and Survivin Expression
Authors: Stolfi Carmine , Caruso Roberta , Franzè Eleonora , Rizzo Angelamaria , Rotondi Angela , Monteleone Ivan , Fantini Massimo Claudio , Pallone Francesco , Monteleone Giovanni
Published: August 2011

TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis is a crucial event in the control of tumor growth. However, many cancer cells, including colon cancer cells, are resistant to TRAIL-driven cell death. We have recently shown that 2-methoxy-5-amino-N-hydroxybenzamide (herein termed 2-14), a novel derivative of mesalamine, induces endoplasmic reticulum stress in colon cancer cells. Because endoplasmic reticulum stress-induced signals regulate the expression of molecules involved in TRAIL-driven apoptosis, we examined whether 2-14 makes colon cancer cells sensitive to TRAIL. Colon cancer cells were cultured with 2-14 and/or TRAIL. Death receptor (DR) 4/DR5 were analyzed by real-time PCR and flow cytometry. TRAIL pathway–associated proteins and extracellular signal–regulated kinase (ERK) were assessed by Western blotting. The in vivo capability of 2-14 to sensitize colon cancer cells to TRAIL-induced apoptosis was evaluated in a syngenic colon cancer model in which CT26-derived grafts were induced in mice. 2-14 promoted ERK-dependent induction of DR5, thereby enhancing TRAIL-mediated caspase-8 activation and apoptosis. Analysis of TRAIL-related pro- and antiapoptotic factors and functional studies revealed that survivin is involved in the protection of colon cancer cells against TRAIL-driven apoptosis. Notably, 2-14 enhanced ubiquitination and proteasome-mediated degradation of survivin. These data were confirmed in a murine model of TRAIL-resistant colon cancer in which 2-14 upregulated DR5, reduced survivin expression, and synergized with TRAIL in inhibiting tumor growth. Similarly, intraperitoneal administration of 2-14 to mice upregulated DR5 and downregulated survivin in a model of colitis-associated colon cancer. These findings indicate that 2-14 acts as a sensitizer for TRAIL-induced apoptosis and suggest that 2-14 can be useful in the therapy for TRAIL-resistant colon cancer. Mol Cancer Ther; 10(10); 1969–81. ©2011 AACR.
Suppression of IRF4 by IRF1, 3, and 7 in Noxa Expression Is a Necessary Event for IFN-γ–Mediated Tumor Elimination
Authors: Piya Sujan , Moon Ae Ran , Song Peter I. , Hiscott John , Lin Rongtuan , Seol Dai-Wu , Kim Tae-Hyoung
Published: August 2011

IFN-γ plays a critical role in tumor immunosurveillance by affecting either immune cells or tumor cells; however, IFN-mediated effects on tumor elimination are largely unknown. In this study, we showed that IFN regulatory factors (IRF) modulated by IFNs up- and downregulated Noxa expression, a prodeath BH3 protein, in various cancer cells. Inhibition of Noxa expression using short hairpin RNA in tumor cells leads to resistance against lipopolysaccharide (LPS)-induced tumor elimination, in which IFN-γ is known as a critical effecter in mice. Chromatin immunoprecipitation analysis in both CT26 cells and SP2/0 cells, sensitive and resistant to LPS-induced tumor elimination, respectively, revealed that the responsiveness of IRF1, 3, 4, and 7 in the Noxa promoter region in response to IFN-γ might be crucial in LPS-induced tumor elimination. IRF1, 3, and 7 were upregulated by IFN-γ and activated Noxa expression, leading to the death of Noxa wild-type baby mouse kidney (BMK) cells but not of Noxa-deficient BMK cells. In contrast, IRF4 acts as a repressor for Noxa expression and inhibits cell death induced by IRF1, 3, or 7. Therefore, although IFN-γ alone are not able to induce cell death in tumor cells in vitro, Noxa induction by IFN-γ, which is regulated by the balance between its activators (IRF1, 3, and 7) and its repressor (IRF4), is crucial to increasing the susceptibility of tumor cells to immune cell-mediated cytotoxicity. Mol Cancer Res; 9(10); 1356–65. ©2011 AACR.
Plaque Rupture and Thrombosis Are Reduced by Lowering Cholesterol Levels and Crystallization With Ezetimibe and Are Correlated With Fluorodeoxyglucose Positron Emission Tomography
Authors: Patel Roshan , Janoudi Abed , Vedre Ameeth , Aziz Kusai , Tamhane Umesh , Rubinstein Jack , Abela Oliver G. , Berger Kevin , Abela George S.
Published: August 2011

Objective—

This study evaluated effects of lipid lowering with ezetimibe on plaque burden and associated cholesterol crystallization and inflammation in a rabbit model of plaque disruption and thrombosis.

Methods and Results—

Atherosclerotic rabbits (Group I, n=10 without; Group II, n=12 with ezetimibe, 1 mg/kg per day) were pharmacologically triggered for plaque disruption. Fluorodeoxyglucose positron emission tomography, RAM 11 macrophage staining, and serum inflammatory markers detected arterial inflammation. Serum and aortic wall cholesterol levels were measured, and thrombus area was planimetered. Cholesterol crystal density on aortic surface was scored (0 to +3) by scanning electron microscopy. Serum and aortic wall cholesterol, plaque area, and thrombosis area were significantly lower in Group II versus Group I (83.4±106.4 versus 608±386 mg/dL,
P
=0.002; 3.12±1.40 versus 9.39±5.60 mg/g,
P
=0.003; 10.84±1.6 versus 17.48±1.8 mm
2
,
P
<0.001; and 0.05±0.15 versus 0.72±0.58 mm
2
,
P
=0.01, respectively). There were significant correlations between crystal density and plaque area (
r
=0.75,
P
<0.003) and between crystal density and RAM 11 (
r
=0.82,
P
<0.001). Scanning electron microscopy demonstrated that there were fewer crystals in Group II versus Group I (+1.2±0.61 versus +2.4±0.63,
P
<0.001) and less inflammation detected by fluorodeoxyglucose positron emission tomography and RAM 11 (
P
<0.004 and
P
<0.04, respectively).

Conclusion—

Lowering cholesterol levels with ezetimibe reduced plaque burden, crystallization, and inflammation, preventing plaque disruption and thrombosis.
Short-Term Exposure to Exogenous Lipids in Premature Infants and Long-Term Changes in Aortic and Cardiac Function
Authors: Lewandowski Adam J. , Lazdam Merzaka , Davis Esther , Kylintireas Ilias , Diesch Jonathan , Francis Jane , Neubauer Stefan , Singhal Atul , Lucas Alan , Kelly Brenda , Leeson Paul
Published: August 2011

Objective—

Intravenous lipid use is associated with an acute hyperlipidemia, but long-term consequences have not been studied. We investigated whether elevated lipids in humans during the critical period of preterm neonatal life have a long-term impact on aortic and myocardial function relevant to adult disease.

Methods and Results—

We followed up 102 subjects born prematurely and now aged 23 to 28 years. Eighteen received intravenous lipids as neonates and were matched to controls with equivalent perinatal characteristics. Global and regional aortic stiffness and left ventricular function were assessed by cardiovascular magnetic resonance. Those who received intravenous lipids had greater aortic stiffness in early adulthood (
P
=0.0002), with greater stiffness in the abdominal aorta (
P
=0.012). The relationship was graded according to the elevation in neonatal cholesterol induced by intravenous lipids (
P
<0.0001) but not other metabolic parameters altered by the infusion. Peak systolic circumferential strain was also reduced in the lipid group (
P
=0.006), which, again, was proportional to neonatal cholesterol level (
P
<0.01).

Conclusion—

Aortic and myocardial function in young adulthood is associated with intralipid exposure during neonatal life for preterm infants, in a graded manner related to the rise in cholesterol. Circulating cholesterol during critical developmental periods may have long-term impacts on the human cardiovascular system.
Association of Atherosclerosis With Expression of the LILRB1 Receptor By Human NK and T-Cells Supports the Infectious Burden Hypothesis
Authors: Romo Neus , Fitó Montserrat , Gumá Mónica , Sala Joan , García Cosme , Ramos Rafel , Muntasell Aura , Masiá Rafel , Bruguera Jordi , Subirana Isaac , Vila Joan , de Groot Eric , Elosua Roberto , Marrugat Jaume , López-Botet Miguel
Published: August 2011

Objective—

The contribution of human cytomegalovirus (HCMV) to vascular disease may depend on features of the immune response not reflected by the detection of specific antibodies. Persistent HCMV infection in healthy blood donors has been associated with changes in the distribution of NK cell receptors (NKR). The putative relationship among HCMV infection, NKR distribution, subclinical atherosclerosis, and coronary heart disease was assessed.

Methods and Results—

NKR expression was compared in acute myocardial infarction (AMI) patients (
n
=70) and a population-based control sample (
n
=209). The relationship between NKR expression and carotid intima-media thickness (CIMT) in controls (
n
=149) was also studied. HCMV infection was associated with higher proportions of NKG2C+ and LILRB1+ NK and T-cells. In contrast, only LILRB1+ NK and CD56+ T-cells were found to be increased in AMI patients, independent of age, sex, conventional vascular risk factors, and HCMV seropositivity. Remarkably, LILRB1 expression in NK and T-cells significantly correlated with CIMT in controls.

Conclusion—

The association of overt and subclinical atherosclerotic disease with LILRB1+ NK and T-cells likely reflects a relationship between the immune challenge by infections and cardiovascular disease risk, without attributing a dominant role for HCMV. Our findings may lead to the identification of novel biomarkers of vascular disease.
Fibroblast Growth Factor Homologous Factor 13 Regulates Na
+
Channels and Conduction Velocity in Murine Hearts
Authors: Wang Chuan , Hennessey Jessica A. , Kirkton Robert D. , Wang Chaojian , Graham Victoria , Puranam Ram S. , Rosenberg Paul B. , Bursac Nenad , Pitt Geoffrey S.
Published: August 2011

Rationale:

Fibroblast growth factor homologous factors (FHFs), a subfamily of fibroblast growth factors (FGFs) that are incapable of functioning as growth factors, are intracellular modulators of Na
+
channels and have been linked to neurodegenerative diseases. Although certain FHFs have been found in embryonic heart, they have not been reported in adult heart, and they have not been shown to regulate endogenous cardiac Na
+
channels or to participate in cardiac pathophysiology.

Objective:

We tested whether FHFs regulate Na
+
channels in murine heart.

Methods and Results:

We demonstrated that isoforms of FGF13 are the predominant FHFs in adult mouse ventricular myocytes. FGF13 binds directly to, and colocalizes with, the Na
V
1.5 Na
+
channel in the sarcolemma of adult mouse ventricular myocytes. Knockdown of FGF13 in adult mouse ventricular myocytes revealed a loss of function of Na
V
1.5-reduced Na
+
current density, decreased Na
+
channel availability, and slowed Na
V
1.5-reduced Na
+
current recovery from inactivation. Cell surface biotinylation experiments showed ≈45% reduction in Na
V
1.5 protein at the sarcolemma after FGF13 knockdown, whereas no changes in whole-cell Na
V
1.5 protein or in mRNA level were observed. Optical imaging in neonatal rat ventricular myocyte monolayers demonstrated slowed conduction velocity and a reduced maximum capture rate after FGF13 knockdown.

Conclusion:

These findings show that FHFs are potent regulators of Na
+
channels in adult ventricular myocytes and suggest that loss-of-function mutations in FHFs may underlie a similar set of cardiac arrhythmias and cardiomyopathies that result from Na
V
1.5 loss-of-function mutations.
Loss of NB-3 Aggravates Cerebral Ischemia by Impairing Neuron Survival and Neurite Growth
Authors: Huang Xin , Sun Jia , Zhao Tong , Wu Kui-Wu , Watanabe Kazutada , Xiao Zhi-Cheng , Zhu Ling-Ling , Fan Ming
Published: August 2011

Background and Purpose—

NB-3 is a member of the F3/contactin family of neural recognition molecules, which are crucial for cell morphogenesis and motility. NB-3 is expressed in neurons and plays an important role in axonal extension and neuronal survival. However, the role of NB-3 in cerebral ischemic injury remains unknown.

Methods—

Adult male wild-type and NB-3 knockout mice were subjected to ischemic injury by unilateral middle cerebral carotid artery occlusion for 3 hours, 6 hours, and 12 hours. Ischemic infarction volumes were then determined by 2, 3, 5-triphenyltetrazolium chloride staining. Neurological dysfunction analysis was also performed. Primary culture of neuronal cells from wild-type and knockout animals was also used for analysis of neuronal survival and neurite outgrowth.

Results—

NB-3 expression in the ischemic hemisphere was decreased after transient middle cerebral artery occlusion (MCAO). NB-3-knockout mice developed a 2.6-fold larger infarct volume and exhibited increased neurological deficit scores after transient middle cerebral artery occlusion compared with control mice. Substrate with NB-3 promoted neuronal survival and neurite outgrowth in vitro, whereas neurite outgrowth and neuronal survival were significantly reduced in NB-3-deficient neurons. In addition, NB-3 deficiency renders neurons more susceptible to oxygen–glucose deprivation-induced damage and NB-3 as substrate could partially through homophilic mechanisms.

Conclusions—

These data demonstrate that NB-3 deficiency may aggravate brain damage after middle cerebral artery occlusion by impairing neuronal survival and neurite growth.
Ischemic Stroke and Transient Ischemic Attack After Head and Neck Radiotherapy
Authors: Plummer Chris , Henderson Robert D. , O'Sullivan John D. , Read Stephen J.
Published: August 2011

Background and Purpose—

Cerebrovascular disease can complicate head and neck radiotherapy and result in transient ischemic attack and ischemic stroke. Although the incidence of radiation vasculopathy is predicted to rise with improvements in median cancer survival, the pathogenesis, natural history, and management of the disease are ill defined.

Methods—

We examined studies on the epidemiology, imaging, pathogenesis, and management of medium- and large-artery intra- and extra-cranial disease after head and neck radiotherapy. Controlled prospective trials and larger retrospective trials from the last 30 years were prioritized.

Results—

The relative risk of transient ischemic attack or ischemic stroke is at least doubled by head and neck radiotherapy. Chronic radiation vasculopathy affecting medium and large intra- and extra-cranial arteries is characterized by increasing rates of hemodynamically significant stenosis with time from radiotherapy. Disease expression is the likely consequence of the combined radiation insult to the intima-media (accelerating atherosclerosis) and to the adventitia (injuring the vasa vasorum). Optimal medical treatment is not established. Carotid endarterectomy is confounded by the need to operate across scarred tissue planes, whereas carotid stenting procedures have resulted in high restenosis rates.

Conclusions—

Head and neck radiotherapy significantly increases the risk of transient ischemic attack and ischemic stroke. Evidence-based guidelines for the management of asymptomatic and symptomatic (medium- and large-artery) radiation vasculopathy are lacking. Long-term prospective studies remain a priority, as the incidence of the problem is anticipated to rise with improvements in postradiotherapy patient survival.
Mechanical Thrombectomy in Acute Embolic Stroke
Authors: Rohde Stefan , Haehnel Stefan , Herweh Christian , Pham Mirko , Stampfl Sibylle , Ringleb Peter A. , Bendszus Martin
Published: August 2011

Background and Purpose—

The purpose of this study was to evaluate the safety and technical feasibility of a new thrombectomy device (Revive; Micrus Endovascular) in the endovascular treatment of acute ischemic stroke.

Methods—

Ten patients with acute large vessel occlusions were treated with the Revive device between October 2010 and December 2010. Mean National Institutes of Health Stroke Scale on admission was 19.0; mean duration of symptoms was 172 minutes. Recanalization was assessed using the Thrombolysis In Cerebral Infarction score. Clinical outcome (National Institutes of Health Stroke Scale) after thrombectomy was determined on Day 1, at discharge, and at Day 30.

Results—

Vessel recanalization (Thrombolysis In Cerebral Infarction 2b or 3) was successful in all patients without device-related complications. Mean National Institutes of Health Stroke Scale 24 hours after the intervention, at discharge, and at Day 30 was 14.0, 11.5, and 5.1, respectively. At Day 30, 6 patients had a clinical improvement of >8 points or an National Institutes of Health Stroke Scale of 0 to 1, 1 patient showed minor improvement, and 3 patients had died. Symptomatic intracranial hemorrhage occurred in 2 patients, of which 1 was fatal.

Conclusions—

Thrombectomy with the Revive device in patients with stroke with acute large vessel occlusions demonstrated to be technically safe and highly effective. Clinical safety and efficacy have to be established in larger clinical trials.
Prestroke Glycemic Control Is Associated With the Functional Outcome in Acute Ischemic Stroke
Authors: Kamouchi Masahiro , Matsuki Takayuki , Hata Jun , Kuwashiro Takahiro , Ago Tetsuro , Sambongi Yoshiki , Fukushima Yoshihisa , Sugimori Hiroshi , Kitazono Takanari ,   for the FSR Investigators
Published: August 2011

Background and Purpose—

Diabetes mellitus is an established risk factor for stroke. However, it is uncertain whether prestroke glycemic control (PSGC) status affects clinical outcomes of acute ischemic stroke. The aim of this study was to elucidate the association between PSGC status and neurological or functional outcomes in patients with acute ischemic stroke.

Methods—

From the Fukuoka Stroke Registry (FSR), a multicenter stroke registry in Japan, 3627 patients with first-ever ischemic stroke within 24 hours after onset were included in the present analysis. The patients were categorized into 4 groups based on their PSGC status: excellent (hemoglobin [Hb] A1c on admission <6.2%), good (6.2–6.8%), fair (6.9–8.3%) and poor (≥8.4%). Study outcomes were neurological improvement (≥4 points decrease in the National Institutes of Health Stroke Scale [NIHSS] score during hospitalization or 0 points on NIHSS score at discharge), neurological deterioration (≥1 point increase in NIHSS score) and poor functional outcome (death or dependency at discharge, modified Rankin Scale 2–6).

Results—

The age- and sex-adjusted ORs for neurological improvement were lower, and those for neurological deterioration and a poor functional outcome were higher in patients with poorer PSGC status. After adjusting for multiple confounding factors, these trends were unchanged (all probability values for trends were <0.002). These findings were comparable in patients with noncardioembolic and cardioembolic infarctions.

Conclusions—

In ischemic stroke patients, HbA1c on admission was an independent significant predictor for neurological and functional outcomes.
Patients With Severe Asymptomatic Carotid Artery Stenosis Do Not Have a Higher Risk of Stroke and Mortality After Coronary Artery Bypass Surgery
Authors: Mahmoudi Michael , Hill Peter C. , Xue Zhenyi , Torguson Rebecca , Ali Gholam , Boyce Steven W. , Bafi Ammar S. , Corso Paul J. , Waksman Ron
Published: August 2011

Background and Purpose—

Stroke development is a major concern in patients undergoing coronary artery bypass grafting (CABG). Whether asymptomatic severe carotid artery stenosis (CAS) contributes to the development of stroke and mortality in such patients remains uncertain.

Methods—

A retrospective analysis of 878 consecutive patients with documented carotid duplex ultrasound who underwent isolated CABG in our institution from January 2003 to December 2009 was performed. Patients with severe CAS (n=117) were compared with those without severe CAS (n=761) to assess the rates of stroke and mortality during hospitalization for CABG. The 30-day mortality rate was also assessed.

Results—

Patients with severe CAS were older and had a higher prevalence of peripheral arterial disease and heart failure. Patients with severe CAS had similar rates of in-hospital stroke (3.4% versus 3.6%;
P
=1.0) and mortality (3.4% versus 4.2%;
P
=1.0) compared with patients without severe CAS. The 30-day rate of mortality was also similar between the 2 cohorts (3.4% versus 2.9%;
P
=0.51).

Conclusions—

Severe CAS alone is not a risk factor for stroke or mortality in patients undergoing CABG. The decision to perform carotid imaging and subsequent revascularization in association with CABG must be individualized and based on clinical judgment.
Graduating US Neurology Residents' Experience With Tissue-Type Plasminogen Activator for Acute Stroke
Authors: Fridman Vera , Raser Jonathan , Brizzi Kate , Cucchiara Brett
Published: August 2011

Background and Purpose—

A survey of graduating neurology residents conducted in 2000 showed that many residents had limited experience and comfort treating with tissue-type plasminogen activator (tPA). We examined changes in residents' experience during the past decade.

Methods—

A 12-item survey was sent to US neurology residents in their final year of training. Items examined residents' experience and confidence with assessment of the acute stroke patient and use of tPA for treatment. Questions were worded identically in the 2000 and 2010 surveys, and responses were compared between the two.

Results—

Of 491 residents, 286 (58%) responded. There was a significant increase from 2000 to 2010 in the percentage of residents who felt comfortable independently treating with tPA (73% versus 94%,
P
<0.001), who had observed administration of tPA (88% versus 99%,
P
<0.001), who had personally treated with tPA (80% versus 95%,
P
<0.001), and who had been involved in post-tPA care (89% versus 98%,
P
<0.001). There was a substantial increase in residents with formal training in using the National Institutes of Health Stroke Scale (65% versus 92%,
P
<0.001) and who had dedicated stroke teams at their institution (84% versus 93%,
P
=0.001).

Conclusions—

Neurology residents' experience and comfort treating acute ischemic stroke with tPA increased significantly between 2000 and 2010, as did resident exposure to stroke teams and formal training in the National Institutes of Health Stroke Scale.
The Ties that Bound: The Conception of Anglo-America, 1617-67
Authors:   Roper
Published: August 2011

This article sketches the development of the Anglo-American world in both colonial and imperial fashions between the establishment of tobacco cultivation in Virginia and the end of the Second Anglo-Dutch War. It argues that an imperial consciousness developed in the English-speaking world during the seventeenth century, especially in the American colonies, while, at the same time, enterprising colonists set up societies modeled closely on the metropolitan standard.
The Link between Rossby Wave Breakings and Weather Regime Transitions
Authors: Michel Clio , Rivière Gwendal
Published: August 2011

The link between Rossby wave breaking (RWB) and the four wintertime weather regimes over the North Atlantic domain is studied in this paper. Using the 40-yr ECMWF Re-Analysis (ERA-40) data, frequencies of occurrence of anticyclonic and cyclonic wave-breaking (AWB and CWB, respectively) events are computed. Each weather regime has its own characteristic pattern of RWB frequencies. CWB events are found to be most frequent for the Greenland anticyclone weather regime whereas AWB events occur more for the Atlantic ridge and the zonal regimes. Time-lagged composites show that the RWB events characterizing each weather regime occur more often during the formation of the regime rather than during its decay. This suggests a reinforcement of the weather regime by RWB. An exception is the blocking weather regime, which is destroyed by an increase of CWB events south of Greenland.

Weather regime transitions are then studied using the low-frequency streamfunction tendency budget. Two types of precursors for the transitions have been identified. One is related to linear propagation of low-frequency transient eddies and the other to nonlinear interactions among the low- and high-frequency transient eddies. The latter has been related to the anomalous frequencies of occurrence of RWB. Two transitions are more precisely analyzed. The transition from blocking to Greenland anticyclone is triggered by a decrease of AWB events over Europe as well as a strong CWB event south of Greenland. The zonal to blocking transition presents evidence of two distinct precursors: one is a low-frequency wave train coming from the subtropical western Atlantic and the other, which occurs later, is characterized by a decrease of AWB and CWB events over western Europe that cannot continue to maintain the westerlies in that region.