bluuebunny/crossref_metadata_2025 huggingface dataset:
Nod1 Ligands Induce Site-Specific Vascular Inflammation
Authors: Nishio Hisanori , Kanno Shunsuke , Onoyama Sagano , Ikeda Kazuyuki , Tanaka Tamami , Kusuhara Koichi , Fujimoto Yukari , Fukase Koichi , Sueishi Katsuo , Hara Toshiro
Published: February 2011

Objective—

The goal of this study was to investigate the effects of stimulants for a nucleotide-binding domain, leucine-rich repeat-containing (NLR) protein family on human artery endothelial cells and murine arteries.

Methods and Results—

Human coronary artery endothelial cells were challenged in vitro with microbial components that stimulate NLRs or Toll-like receptors. We found stimulatory effects of NLR and Toll-like receptor ligands on the adhesion molecule expression and cytokine secretion by human coronary artery endothelial cells. On the basis of these results, we examined the in vivo effects of these ligands in mice. Among them, FK565, 1 of the nucleotide-binding oligomerization domain (Nod)-1 ligands induced strong site-specific inflammation in the aortic root. Furthermore, coronary arteritis/valvulitis developed after direct oral administration or ad libitum drinking of FK565. The degree of the respective vascular inflammation was associated with persistent high expression of proinflammatory chemokine/cytokine and matrix metallopeptidase (
Mmp
) genes in each tissue in vivo by microarray analysis.

Conclusion—

This is the first coronary arteritis animal model induced by oral administration of a pure synthetic Nod1 ligand. The present study has demonstrated an unexpected role of Nod1 in the development of site-specific vascular inflammation, especially coronary arteritis. These findings might lead to the clarification of the pathogenesis and pathophysiology of coronary artery disease in humans.
Syndecan-4 Deficiency Limits Neointimal Formation After Vascular Injury by Regulating Vascular Smooth Muscle Cell Proliferation and Vascular Progenitor Cell Mobilization
Authors: Ikesue Masahiro , Matsui Yutaka , Ohta Daichi , Danzaki Keiko , Ito Koyu , Kanayama Masashi , Kurotaki Daisuke , Morimoto Junko , Kojima Tetsuhito , Tsutsui Hiroyuki , Uede Toshimitsu
Published: February 2011

Objective—

Syndecan-4 (Syn4) is a heparan sulfate proteoglycan and works as a coreceptor for various growth factors. We examined whether Syn4 could be involved in the development of neointimal formation in vivo.

Methods and Results—

Wild-type (WT) and Syn4-deficient (Syn4
−/−
) mice were subjected to wire-induced femoral artery injury.
Syn4
mRNA was upregulated after vascular injury in WT mice. Neointimal formation was attenuated in Syn4
−/−
mice, concomitantly with the reduction of Ki67-positive vascular smooth muscle cells (VSMCs). Basic-fibroblast growth factor– or platelet-derived growth factor-BB–induced proliferation, extracellular signal-regulated kinase activation, and expression of cyclin D1 and Bcl-2 were impaired in VSMCs from Syn4
−/−
mice. To examine the role of Syn4 in bone marrow (BM)–derived vascular progenitor cells (VPCs) and vascular walls, we generated chimeric mice by replacing the BM cells of WT and Syn4
−/−
mice with those of WT or Syn4
−/−
mice. Syn4 expressed by both vascular walls and VPCs contributed to the neointimal formation after vascular injury. Although the numbers of VPCs were compatible between WT and Syn4
−/−
mice, mobilization of VPCs from BM after vascular injury was defective in Syn4
−/−
mice.

Conclusion—

Syn4 deficiency limits neointimal formation after vascular injury by regulating VSMC proliferation and VPC mobilization. Therefore, Syn4 may be a novel therapeutic target for preventing arterial restenosis after angioplasty.
Soluble Jagged-1 Inhibits Neointima Formation by Attenuating Notch-Herp2 Signaling
Authors: Caolo Vincenza , Schulten Henny M. , Zhuang Zhen W. , Murakami Masahiro , Wagenaar Allard , Verbruggen Sanne , Molin Daniel G.M. , Post Mark J.
Published: February 2011

Objective—

Notch has been implicated in neointima formation as reflected by increased Notch/Jagged expression on vascular injury and the promigratory effect of Notch signaling on smooth muscle cells. Soluble Jagged-1 (sJag1) has been shown to inhibit Notch signaling in vitro; however, its capacity to suppress neointima formation remains unknown.

Methods and Results—

Balloon injury of rat carotid arteries induced Notch1, Notch3, and Jagged-1 expression at days 3 and 14 postinjury. Notch signaling was activated as shown by increased expression of the Notch target gene Herp2. Adenoviral sJag1 (Ad-sJag1) transfection reduced neointima formation in carotid artery and enhanced reendothelialization, whereas adenoviral full-length Jagged-1 (Ad-Fl-Jag1) or LacZ had no effect. Injury-induced Herp2 expression was absent in vessels treated with Ad-sJag1. Consistently, Herp2 expression was reduced in Ad-sJag1-infected or recombinant sJag1 –treated coronary artery smooth muscle cells (CASMCs). Ad-sJag1 had no effect on human umbilical endothelial cell behavior, but it significantly reduced proliferation and migration of CASMCs. Overexpression of Herp2 in sJag1-treated CASMCs rescued the migratory and proliferative capacity in vitro.

Conclusion—

Our results demonstrate that sJag1 can inhibit neointima formation after balloon injury by decreasing smooth muscle cell proliferation and migration through interference with Notch-Herp2 signaling.
Mean Platelet Volume May Represent a Predictive Parameter for Overall Vascular Mortality and Ischemic Heart Disease
Authors: Slavka Georg , Perkmann Thomas , Haslacher Helmuth , Greisenegger Stefan , Marsik Claudia , Wagner Oswald F. , Endler Georg
Published: February 2011

Objective—

An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets resulting from an increased platelet turnover, may represent a risk factor for overall vascular mortality, including myocardial infarction. We intended to identify patients at higher risk of dying from vascular disease in a large, hospital-based cohort.

Methods and Results—

A total of 206 554 first-ever admissions to the Allgemeines Krankenhaus Wien for determination of MPV between January 1996 and July 2003 were included. Primary end points were overall vascular mortality and death due to ischemic heart disease. Multivariate Cox regression adjusted for sex, age, and platelet count was applied for analysis. MPV values were categorized into quintiles, with the lowest quintile serving as the reference category. Compared with individuals with lower MPV (<8.7 fL), hazard ratios for overall vascular mortality gradually increased to 1.5 in the highest category (≥11.01 fL). The relationship of MPV to ischemic heart disease was even stronger and increased from 1.2 (8.71 to 9.60 fL category) to 1.8 in the highest category (≥11.01 fL).

Conclusion—

Our results indicate that patients with an increased MPV (≥11.01 fL) are at higher risk of death due to ischemic heart disease, with hazard ratios comparable to those reported for obesity or smoking.
Toll-Like Receptor 4 Is Involved in Human and Mouse Vein Graft Remodeling, and Local Gene Silencing Reduces Vein Graft Disease in Hypercholesterolemic APOE*3Leiden Mice
Authors: Karper Jacco C. , de Vries Margreet R. , van den Brand Ben T. , Hoefer Imo E. , Fischer Jens W. , Jukema J. Wouter , Niessen Hans W.M. , Quax Paul H.A.
Published: February 2011

Objective—

The goal of this study was to explore the role of Toll-like receptor 4 (TLR4) in vein graft remodeling and disease.

Methods and Results—

First, expression of TLR4 was analyzed in freshly isolated human saphenous veins (huSV), in freshly isolated huSV ex vivo perfused in an extracorporeal circulation, or in huSV used as coronary vein grafts. Marked induction of focal TLR4 expression was observed in perfused fresh huSV. Moreover, TLR4 was abundantly present in lesions in fresh huSV or in intimal hyperplasia in coronary vein grafts. Second, mouse venous bypass grafting was performed. In grafts of hypercholesterolemic APOE*3Leiden mice, increased TLR4 mRNA and protein was detected over time by reverse transcription–polymerase chain reaction and immunohistochemistry. Furthermore, the local presence of the endogenous TLR4 ligands heat shock protein 60, high-mobility group box 1, tenascin-C, and biglycan in the grafts was demonstrated. TLR4 deficiency in C3H-

Tlr4
LPS-d

(LPS indicates lipopolysaccharide) mice resulted in 48±12% less vein graft wall thickening (
P
=0.04) than in Balb/c controls. Moreover, local TLR4 gene silencing in hypercholesterolemic APOE*3Leiden mice using lentiviral short hairpin RNA against TLR4 administered perivascularly around vein grafts led to a 44±13% reduction of vessel wall thickening compared with controls (
P
=0.0059).

Conclusion—

These results indicate that TLR4 is involved in vein graft remodeling and can be used as a local therapeutic target against vein graft disease.
Divide and Conquer
Authors: Agnetti Giulio , Husberg Cathrine , Van Eyk Jennifer E.
Published: February 2011

Chronic heart failure is a worldwide cause of mortality and morbidity and is the final outcome of a number of different etiologies. This reflects both the complexity of the disease and our incomplete understanding of its underlying molecular mechanisms. One experimental approach to address this is to study subcellular organelles and how their functions are activated and synchronized under physiological and pathological conditions. In this review, we discuss the application of proteomic technologies to organelles and how this has deepened our perception of the cellular proteome and its alterations with heart failure. The use of proteomics to monitor protein quantity and posttranslational modifications has revealed a highly intricate and sophisticated level of protein regulation. Posttranslational modifications have the potential to regulate organelle function and interplay most likely by targeting both structural and signaling proteins throughout the cell, ultimately coordinating their responses. The potentials and limitations of existing proteomic technologies are also discussed emphasizing that the development of novel methods will enhance our ability to further investigate organelles and decode intracellular communication.
cGMP Signals Modulate cAMP Levels in a Compartment-Specific Manner to Regulate Catecholamine-Dependent Signaling in Cardiac Myocytes
Authors: Stangherlin Alessandra , Gesellchen Frank , Zoccarato Anna , Terrin Anna , Fields Laura Ashley , Berrera Marco , Surdo Nicoletta Concetta , Craig Margaret Anne , Smith Godfrey , Hamilton Graham , Zaccolo Manuela
Published: February 2011

Rationale:

cAMP and cGMP are intracellular second messengers involved in heart pathophysiology. cGMP can potentially affect cAMP signals via cGMP-regulated phosphodiesterases (PDEs).

Objective:

To study the effect of cGMP signals on the local cAMP response to catecholamines in specific subcellular compartments.

Methods and Results:

We used real-time FRET imaging of living rat ventriculocytes expressing targeted cAMP and cGMP biosensors to detect cyclic nucleotides levels in specific locales. We found that the compartmentalized, but not the global, cAMP response to isoproterenol is profoundly affected by cGMP signals. The effect of cGMP is to increase cAMP levels in the compartment where the protein kinase (PK)A-RI isoforms reside but to decrease cAMP in the compartment where the PKA-RII isoforms reside. These opposing effects are determined by the cGMP-regulated PDEs, namely PDE2 and PDE3, with the local activity of these PDEs being critically important. The cGMP-mediated modulation of cAMP also affects the phosphorylation of PKA targets and myocyte contractility.

Conclusions:

cGMP signals exert opposing effects on local cAMP levels via different PDEs the activity of which is exerted in spatially distinct subcellular domains. Inhibition of PDE2 selectively abolishes the negative effects of cGMP on cAMP and may have therapeutic potential.
Myocardin-Related Transcription Factor A Mediates OxLDL-Induced Endothelial Injury
Authors: Fang Fei , Yang Yuyu , Yuan Zhibin , Gao Yuqi , Zhou Jiliang , Chen Qi , Xu Yong
Published: February 2011

Rationale:

Atherosclerosis proceeds through a multistep reaction that begins with endothelial injury caused by a host of stress signals, among which oxidized low-density lipoprotein (oxLDL) plays a critical role. OxLDL disrupts normal functionality of the endothelium by upregulating adhesion molecules (eg, ICAM-1) and concomitantly downregulating endothelial nitric oxide synthase (eNOS) expression. The transcriptional modulator that mediates the cellular response to oxLDL remains largely obscure.

Objective:

Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, is responsible for the endothelial injury by oxLDL, and, if so, how MRTF-A promotes the proatherogenic agenda initiated by oxLDL.

Methods and Results:

OxLDL stimulated the expression of MRTF-A in endothelial cells as evidenced by Western blotting and immunofluorescence. Overexpression of MRTF-A synergistically enhanced the induction of ICAM-1 and suppression of eNOS by oxLDL. In contrast, disruption of MRTF-A, either by small interfering RNA or dominant negative mutation, abrogated the pathogenic program triggered by oxLDL. Finally, chromatin immunoprecipitation assays indicate that oxLDL preferentially augmented MRTF-A binding to ICAM-1 and eNOS promoters and that MRTF-A drove differential epigenetic alterations taking place on these promoters in response to oxLDL.

Conclusions:

Therefore, our data provide the first demonstration that MRTF-A is critically linked to pivotal pathophysiological events in the vascular endothelium.
Functionally Competent Cardiac Stem Cells Can Be Isolated From Endomyocardial Biopsies of Patients With Advanced Cardiomyopathies
Authors: D'Amario Domenico , Fiorini Claudia , Campbell Patricia M. , Goichberg Polina , Sanada Fumihiro , Zheng Hanqiao , Hosoda Toru , Rota Marcello , Connell John M. , Gallegos Robert P. , Welt Frederick G. , Givertz Michael M. , Mitchell Richard N. , Leri Annarosa , Kajstura Jan , Pfeffer Marc A. , Anversa Piero
Published: February 2011

Rationale:

Two categories of cardiac stem cells (CSCs) with predominantly myogenic (mCSC) and vasculogenic (vCSC) properties have been characterized in the human heart. However, it is unknown whether functionally competent CSCs of both classes are present in the myocardium of patients affected by end-stage cardiac failure, and whether these cells can be harvested from relatively small myocardial samples.

Objective:

To establish whether a clinically relevant number of mCSCs and vCSCs can be isolated and expanded from endomyocardial biopsies of patients undergoing cardiac transplantation or left ventricular assist device implantation.

Methods and Results:

Endomyocardial biopsies were collected with a bioptome from the right side of the septum of explanted hearts or the apical LV core at the time of left ventricular assist device implantation. Two to 5 biopsies from each patient were enzymatically dissociated, and, after expansion, cells were sorted for c-kit (mCSCs) or c-kit and KDR (vCSCs) and characterized. mCSCs and vCSCs constituted 97% and 3% of the c-kit population, respectively. Population doubling time averaged 27 hours in mCSCs and vCSCs; 5×10
6
mCSCs and vCSCs were obtained in 28 and 41 days, respectively. Both CSC classes possessed significant growth reserve as documented by high telomerase activity and relatively long telomeres. mCSCs formed mostly cardiomyocytes, and vCSCs endothelial and smooth muscle cells.

Conclusions:

The growth properties of mCSCs and vCSCs isolated from endomyocardial biopsies from patients with advanced heart failure were comparable to those obtained previously from larger myocardial samples of patients undergoing elective cardiac surgery.
Increased Risk of Hemorrhagic Transformation in Ischemic Stroke Occurring During Warfarin Anticoagulation
Authors: Pfeilschifter Waltraud , Spitzer Daniel , Czech-Zechmeister Bożena , Steinmetz Helmuth , Foerch Christian
Published: February 2011

Background and Purpose—

The prevalence of long-term oral anticoagulant therapy is rising. Treatment options for patients who have an ischemic stroke under oral anticoagulant therapy are limited, and clinical data on the risk of hemorrhagic transformation (HT) in this condition are scarce. We therefore aimed to establish a mouse model of ischemic stroke occurring during oral anticoagulant therapy to assess the frequency and characteristics of HT.

Methods—

C57BL/6 mice (n=59) were pretreated with warfarin. Untreated mice (n=32) served as controls. We performed a 3-hour transient filament occlusion of the right middle cerebral artery. In a first set of animals, ischemic lesion size and HT were evaluated macroscopically at 24 hours after middle cerebral artery occlusion. In a second set of mice, quantitative analysis of HT was performed at different time points after middle cerebral artery occlusion and in animals with different international normalized ratio levels using a photometric hemoglobin assay.

Results—

Oral anticoagulant therapy at the onset of ischemia led to HT in all anticoagulated mice, whereas only 14% of the control mice showed HT. Mean HT blood volume 24 hours after middle cerebral artery occlusion was 0.3±0.4 μL in controls, 4.2±1.7 μL in mice anticoagulated to a mean international normalized ratio of 1.9±0.5 (
P
<0.05 versus controls), and 5.2±2.7 μL in mice with an international normalized ratio of 2.9±0.9 (
P
<0.001 versus controls). Anticoagulated mice euthanized at the time point of reperfusion had less HT than mice euthanized after 21 hours of reperfusion (1.6±0.5 μL versus 5.9±3.6 μL,
P
<0.05).

Conclusions—

We present a mouse model of ischemic stroke occurring during oral anticoagulant therapy. Warfarin pretreatment dramatically increases the risk of HT 24 hours after middle cerebral artery occlusion. Reperfusion injury seems to be a critical component in this condition.
Reforms of Korea's Trade Adjustment Assistance Program for Its Bilateral Free Trade Agreements with the European Union and the United States
Authors: Cheong Inkyo , Cho Jungran
Published: February 2011

The Korean government introduced the trade adjustment assistance (TAA) program to facilitate structural adjustment under the implementation of its free trade agreements (FTAs). One big problem with the TAA program is that its criterion for eligibility for TAA support requires a 25 percent decrease in sales volume, and this does not reflect firms' business realities. The TAA program should be reformed to reflect that the TAA is a quid pro quo for the implementation of FTAs with large economies such as the United States and the EU.
The Korean Economic Adjustment to the World Financial Crisis
Authors: Yoon Deok Ryong
Published: February 2011

The global financial crisis hit the Korean economy in two ways. First, the sudden reversal of capital flow dried up the domestic and international liquidity. Second, the global contraction of demand reduced Korea's export by over 40 percent in the fourth quarter of 2008. Consequently, the Korean currency depreciated sharply and the economic growth rate fell drastically. Even though Korea could not prevent the 2008 crisis, it was the first OECD country to escape the negative economic growth zone, possibly because of three reasons. First, Korea might have had better initial conditions than other economies thanks to the reform measures after the 1997–98 Asian financial crisis. Second, the Korean government has had significant experience in dealing with crises. Third, Korea had an international network of cooperation to establish swap arrangements of US$ 90 billion to stabilize foreign exchange market. Even though the Korean economy has become more resilient to future financial crises by learning from the crisis in 1997, the small open economy still has limited capacity to stabilize the financial market. Korea now faces a new issue, which is to learn from the global crisis on how to stabilize the foreign exchange market.
Strategic Maneuvering in the 2008 Presidential Debates
Authors: Morris Eric , Johnson Jessica M.
Published: February 2011

Application of the pragma-dialectic perspective, and particularly, strategic maneuvering, to political argumentation remains sparse. To address the issue in the context of the 2008 campaigns, the clash strategies of Barack Obama and John McCain during the debates were coded using the same content analysis codebook as prior analyses of presidential debates, allowing comparison between 2008 and the other nine electoral cycles with general election debates. The 2008 debates included significant shifts in the candidates’ use of ritualistic discourse, direct statements to opponent, self-analysis, opponent analysis, policy statements, comparison, and cooption. Although structural elements continue to serve as a corrective to functional theory, it appeared that the political climate, more than format, explained these changes. The findings suggest that candidates engage in strategic maneuvering consistent with the focal-points perspective and that campaigns engage in competitive learning in an attempt to master format modifications.
Justice is a secret
Authors: Baxi Pratiksha
Published: February 2011

This article draws attention to the culture of compromise that underwrites rape prosecutions. This aspect of rape prosecutions has not been sufficiently discussed either within the women’s movement, the judiciary or the contemporary discourse on judicial reform in India. I argue that the socio-legal process encapsulated in the word ‘compromise’ (or samadhan, the coexisting Gujarati usage) is an exposition of how secrecy may be thought of as ‘indispensable to the operation of power rather than as an abuse of power’ (Taussig 1999: 57). Unlike other forms of out-of-court settlements described as mechanisms of alternate dispute resolution, plea-bargaining or mediation in courts of law, compromise is not legal in rape cases in India. The term ‘culture of compromise’ emphasises how a criminal trial becomes a site for contestation between the accused, the complainant and the prosecuting agencies over how to monopolise the framing of an out-of-court settlement.
Secondary Bone Tumours in the Dog
Authors: Goedegebuure S. A.
Published: February 2011

During a 2 1/2-year period 209 dogs with 218 malignant tumours were examined for skeletal metastases. There were 77 malignant tumours without visceral or skeletal metastases. Twenty-four (17%) of the 141 tumours with visceral metastases also had skeletal metastases. Ninety-eight of these tumours were of epithelial origin, and of these 21 (21.4%) had skeletal metastases. In 14 dogs, more than one bone had a metastatic tumour. The humerus, femur and vertebral column were most frequently involved. The lung was the most frequent site of metastatic tumours; then, in order, the liver, kidney and skeleton. The incidence of primary and secondary bone tumours was similar. Metastatic bone disease in the dog is far more common than is generally realized.
The Pregnant Syrian Hamster as a Model to Study Intravascular Trophoblasts and Associated Maternal Blood Vessel Changes
Authors: Burek J. D. , Goldberg B. , Hutchins G. , Strandberg J. D.
Published: February 2011

In pregnant Syrian hamsters (Mesocricetus auratus) used as an animal model for studying the migration of fetal trophoblasts and the associated changes in maternal blood vessels, intravascular trophoblasts migrated well beyond the blood vessels of the uterus and into the vessels of the mesometrium. They migrated beyond the decidua of the uterus, into the lumina of maternal uterine and mesometrial arteries, but not into veins. The arterial changes, which were often segmental, resembled those seen in the decidua and consisted of a replacement of normal smooth muscle cells by poorly differentiated stromal cells. Ultrastructurally, the trophoblasts were either above or below maternal endothelial cells. They occurred also as single or multiple layers within the lumina of arteries that lacked an endothelial lining. Apparent penetration of the elastic membrane by the fetal trophoblasts brought them into close apposition to maternal cells in the arterial wall. Histochemical studies showed heightened metabolic activity of the intravascular trophoblasts as suggested by strong histochemical reactions to nonspecific esterase, succinic dehydrogenase and the glycerophosphate dehydrogenase reactions. Thus, these metabolically active fetal trophoblasts actively migrate into the maternal arterial system, resulting in loss of endothelial cells and changes in the wall of the maternal arteries similar to those in the decidua at the uteroplacental junction.
Studies on the Pathogenesis of Swine Dysentery
Authors: Wilcock B. P. , Olander H. J.
Published: February 2011

Broth cultures of Treponema hyodysenteriae and colonic content from pigs with swine dysentery were tested for cytotoxicity in cell cultures, erythrocyte suspensions and in ligated segments of pig colon. Live cells of T. hyodysenteriae attached to the surface of cells in all cultures tested but did not penetrate them nor cause morphologic change detectable by light microscopy. Only live T. hyodysenteriae caused erythrolysis. Broth cultures or colonic content sterilized by filtration or by disruption with ultrasound had no visible effect on the cell cultures, erythrocyte suspensions or the mucosa of ligated colonic segments.
Fish Oil-induced Yellow Fat Disease in Rats
Authors: Danse L. H. J. C. , Stolwijk J. , Verschuren P. M.
Published: February 2011

In rats with “stage S/E“ yellow fat disease an injection of colloidal carbon resulted in a marked reduction in the number of circulating platelets. The death rate of rats with experimental Listeria monocytogenes infection, the number of bacteria in their spleens and the decrease of bacteria in their spleens on the days after infection were the same in rats with yellow fat disease as in controls. The fact that the rats died during the first few days after infection also may indicate that their immunological resistance to L. monocytogenes was not altered by yellow fat disease.
Late-Holocene sea-surface conditions offshore Newfoundland based on dinoflagellate cysts
Authors: Solignac Sandrine , Seidenkrantz Marit-Solveig , Jessen Catherine , Kuijpers Antoon , Gunvald Anja K. , Olsen Jesper
Published: February 2011

Dinoflagellate cysts and XRF core scanning data from two marine sediment cores from embayments north (Bonavista Bay) and south (Placentia Bay) of Newfoundland show significant changes in ocean and atmospheric conditions of the SW Labrador Sea region during the last 5700 years. Fresh and cold conditions, probably accompanied by seasonal sea ice, prevailed both north and south of Newfoundland from c. 5.7 to 4.0 cal. kyr BP. This may be linked to intensified Labrador Current export of cold meltwater and/or sea ice from the Arctic, presumably related to warmer conditions in the northernmost latitudes and the prevalence of strong (north)westerly winds. After c. 4.0 cal. kyr BP, sea-surface conditions warmed up and sea ice decreased northeast of Newfoundland, but conditions were still cold south of Newfoundland. This suggests a decrease in Arctic meltwater export and westerly wind strength. After 2.9—2.5 cal. kyr BP, only minor changes in sea-surface conditions affected the study sites. Sea-surface temperatures increased and sea ice decreased at both sites, which may be related to a more meridional atmospheric circulation pattern associated with the general Northern Hemisphere neoglacial cooling. In Placentia Bay the warmest part of the record corresponds to the Roman Warm Period, while the warmest part of the records in Bonavista Bay notably corresponds to the Dark Ages.
How dialogue creates opposite characters: An analysis of Arthur & George
Authors: Rossen-Knill Deborah F.
Published: February 2011

This article offers an analysis of the dialogue in Julian Barnes’s Arthur & George, drawing on relevance theory (Grice, 1989; Sperber and Wilson, 1995) and politeness theory (Brown and Levinson, 1987; Fraser, 1990; Lakoff, 1973; Leech, 1983; Spencer-Oatey, 2002). The analysis demonstrates how Arthur’s and George’s particular ability to use language shapes their social situations. George’s inability to make sense of implicature and recover interpersonal messages leads to social disaster; whereas, Arthur’s heightened sensitivity to language’s creative possibilities leads to exceptional social success. The analysis has the secondary effect of revealing the intimate and indivisible relationship among natural language ability, language use, and social identity.
Trade in Financial Services—Has the IMF been Involved Constructively?
Authors: Stern Robert M.
Published: February 2011

This paper considers the key policy issues related to liberalisation of trade in financial services that the International Monetary Fund (IMF) should be concerned with, and the role the IMF has played in advising on policies related to trade in financial services in its bilateral and multilateral surveillance and in conditionality attached to lending programmes. The IMF staff were generally aware of the literature and country experiences showing the benefits of financial liberalisation. But Fund advice in support of liberalisation can be best interpreted to be in support of country unilateral policy actions and the dynamics of the World Trade Organisation (WTO) accession process.
Post-Doha Trade Policy Options for a Small Country
Authors: Deardorff Alan V.
Published: February 2011

This paper uses a partial equilibrium model of two small countries, within a large world economy, implementing reciprocal tariff cuts on each other’s exports in a regional trade agreement (RTA) and compares the effects with unilateral most favoured nation (MFN) tariff cuts. The reciprocal cuts are shown to be more likely beneficial to a country if the partner country’s trade is larger. The welfare effects of a country’s own tariff cut on imports are also compared to the effects on its welfare of the partner country’s tariff cut on its exports. If tariff levels are low, the latter is seen to be larger than the former. Implications of the analysis are that, if multilateral trade liberalisation is unlikely, then small countries should seek to form RTAs with countries larger than themselves. In addition, to assure that they have something to offer in such arrangements, they should not go too far in unilaterally reducing their MFN tariffs.
Mapping commercial intertextuality: HBO’s True Blood
Authors: Hardy Jonathan
Published: February 2011

Corporate synergy, cross-media promotion and transmedia storytelling are increasingly prevalent features of media production today, yet they generate highly divergent readings. Criticism of synergistic corporate control and commercialism in some political economic accounts contrasts with celebrations of fan/prosumer agency, active audiences and resistant readings in others. This debate reviews the different approaches taken by political economists and culturalists in their analyses of commercial intertextuality. Tracing influential studies, it considers the tensions and affinities between divergent readings, and grounds for synthesis. Here, the article addresses the ordering of (inter)textual space, outlining the main forms of textual production along an axis from corporate to autonomous texts. Contemporary forms of cross-media/cross-platform intertextuality and online promotional strategies are examined through a case study of HBO’s True Blood. The article also assesses the implications of work on commercial intertextuality for (re)engagements between critical political economy and culturalist approaches.
Media, mythology and morphogenesis: Aliens™
Authors: Littau Karin
Published: February 2011

What do cross-media practices and Darwin teach us concerning the matter of adaptation? Traditional models of adaptation orbit the bipolar terms of source and target, imposing not only a linear but also a closed account of adapted and adaptation. By examining key texts from the Alien franchise — including the van Vogt stories (1939) and pre-versions of Alien such as Cahn’s The Terror from Beyond Space (1958) on which Scott’s 1979 film is arguably based, the Alien’s crossovers into the Predator franchise, games and comic books — two additional elements of adaptation are fore-grounded. The first concerns the nonlinear, developmental account of variation and descent amongst the versions and ur-texts in play in the series, which account is best modelled along lines suggested by Darwinian adaptation. The second highlights the inseparability of content from matter as regards the various media platforms in which these ‘evolutionary’ developments take place. The present article provides a model for thinking about adaptation as well as media history as an ecology of intermedial borrowings, joinings and convergences.
‘Where were you when the monster hit?’ Media convergence, branded security citizenship, and the trans-media phenomenon of Cloverfield
Authors: Wessels Emanuelle
Published: February 2011

This article uses the concept of media convergence to examine several aspects of the successful 2008 motion picture Cloverfield. I discuss implications of the film’s interaction in an increasingly convergent media landscape, such as its internet marketing campaigns, and interface with technological discourses of citizenship and surveillance. I explore the extent to which movies produced with digital technology, marketed through the internet, and increasingly viewed in private homes are best considered through media convergence literature. I investigate the extent to which this multi-platform, trans-media phenomenon, synergizing with numerous cross-promotional product marketing initiatives, constructs citizen-spectators through narratives of security, post-9/11 citizenship, and surveillance, and the extent to which consumer activity (such as purchasing cell phones) is implicated in this process. Lastly, I discuss concerns of labour and subjectivity pertinent to this media phenomenon, specifically how this film utilized unpaid audience labour in its construction, circulation, and construction of a trans-media presence.
Social network market: Storytelling on a Web 2.0 original literature site
Authors: Zhao Elaine Jing
Published: February 2011

This article looks at a Chinese Web 2.0 original literature site, Qidian, in order to show the co-evolution of market and non-market initiatives. The analytic framework of social network markets (Potts et al., 2008) is employed to analyse the motivations of publishing original literature works online and to understand the support mechanisms of the site, which encourage readers’ willingness to pay for user-generated content. The co-existence of socio-cultural and commercial economies and their impact on the successful business model of the site are illustrated in this case. This article extends the concept of social network markets by proposing the existence of a ripple effect of social network markets through convergence between fixed and mobile internet, between traditional and internet publishing, and between publishing and other cultural industries. It also examines the side effects of social network markets, and the role of market and non-market strategies in addressing the issues.
The CC genotype of the angiotensin II type I receptor gene independently associates with acute myocardial infarction in a Tunisian population
Authors: Mehri Sounira , Mahjoub Sinda , Finsterer Josef , Zaroui Amira , Mechmeche Rachid , Baudin Bruno , Hammami Mohamed
Published: February 2011

Acute myocardial infarction (AMI) is a multifactorial disease influenced by environmental and genetic factors. The aim of this study was to assess the association of angiotensin II type 1 receptor (ATR1) gene polymorphisms with AMI as well as to evaluate the role of serum angiotensin-converting enzyme (ACE) activity and that of cardiac troponin I (cTnI) in Tunisian AMI patients. One hundred and eighteen AMI patients were compared to 150 healthy controls. ATR1 genotypes were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The ATR1 A1166C polymorphism was significantly associated with AMI ( p = 0.024). CC genotype and C allele frequencies were associated with increased AMI risk [CC vs. AC and AA: OR = 2.06; p = 0.045; 95 % CI (1.02–4.18); C vs. A: OR = 1.68; p = 0.004; 95 % CI (1.17–2.41)]. By multivariate logistic regression analysis, CC genotype, hypertension, diabetes, serum ACE activity and peak-cTnI were significant independent predictors of AMI. Increased serum ACE activity and cTnI peak levels were associated with the CC genotype in AMI patients. In conclusion, the ATR1 A1166C polymorphism is associated with AMI and the CC genotype associated with increased ACE activity and cTnI levels appear to predispose for AMI risk.
Significance of pigment epithelium-derived factor levels with angiotensin II type 1 receptor blockers in patients with successful coronary stent implantation
Authors: Sugihara Makoto , Miura Shin-ichiro , Takamiya Yosuke , Kiya Yoshihiro , Arimura Tadaaki , Iwata Atsushi , Kawamura Akira , Nishikawa Hiroaki , Yamagishi Sho-ichi , Saku Keijiro
Published: February 2011

Pigment epithelium-derived factor (PEDF) and pentosidine have received growing attention as sensitive biomarkers of the progression of atherosclerosis. The present study was performed to evaluate the utility of these biomarkers for assessing the effects of angiotensin II type 1 receptor blockers (ARBs). Sixty-three patients with coronary artery disease (CAD) following successful stent implantation were divided into an ARB group ( n = 50), who initially received valsartan or olmesartan immediately following stent implantation, and a non-ARB group ( n = 13) according to their blood pressure (BP) at baseline. Measurement of BP and blood sampling was performed prior to (at baseline) and 6—8 months following stent implantation (at follow-up). There were no significant differences in the baseline characteristics between the groups. Although there were no differences in the percentage of diameter re-stenosis between the groups, the BP level in the ARB group at follow-up showed a significant reduction and reached the target BP. The levels of plasma PEDF were significantly increased at follow-up in the ARB group, but not in the non-ARB group, while there were no differences in the levels of pentosidine between the groups. Changes in BP (ΔBP = BP at follow-up minus BP at baseline) were not associated with ΔPEDF. In conclusion, PEDF may be a useful biomarker for assessing the effects of ARBs independent of a reduction in BP.
Sutureless Meshplasty in Lumbar Hernia
Authors: Garg Chaitanya P. , Sharma Praveen , Patel Gulab , Malik Pushpendra
Published: February 2011

Background. Lumbar hernia is a rare hernia arising through posterolateral abdominal wall defects. Different techniques of repair are reported in the literature. Methods. The authors present their experience of 4 lumbar hernias during a short span of 9 months. All surgical repairs were performed using synthetic mesh placed in the extraperitoneal space, below the muscular layers, using a sutureless tension-free technique. Results. The patients were 3 children and 1 adult, all males. All hernias were through superior triangle. Duration of surgery ranged between 60 and 80 minutes. There were no surgical complications. The mean hospital stay was 2.5 days. All patients are well on follow-up till date. Conclusions. Sutureless tension-free meshplasty of these rare hernias can be successfully performed with the posterior approach. This method of repair is easy, safe, and effective.
Fostering community understanding of sufficient benefit and early stopping for a phase 2B HIV prevention clinical trial in Africa
Authors: White Rhonda , Chileshe Modesta , Dawson Liza , Donnell Deborah , Hillier Sharon , Morar Neetha , Noguchi Lisa , Dixon Dennis
Published: February 2011

Background Most trials of interventions are designed to address the traditional null hypothesis of no benefit. VOICE, a phase 2B HIV prevention trial funded by NIH and conducted in Africa, is designed to assess if the intervention will prevent a substantial fraction of infections. Planned interim analysis may provide conclusive evidence against the traditional null hypothesis without establishing substantial benefit. At this interim point, the Data and Safety Monitoring Board would then face the dilemma of knowing the product has some positive effect, but perhaps not as great an effect as the protocol has declared necessary.

Purpose In March 2008, NIH program staff recommended that the VOICE protocol team discuss the stopping rules with stakeholders prior to initiating the protocol. The goals of the workshop were to inform community representatives about the potential ethical dilemma associated with stopping rules and engage in dialogue about these issues. We describe the resulting community consultation and summarize the outcomes.

Methods A 2-day workshop was convened with the goal of having a clear and transparent consultation with the stakeholders around the question, ‘Given emerging evidence that a product could prevent some infections, would the community support a decision to continue accruing to the trial?’ Participants included research staff and community stakeholders. Lectures with visual aids, discussions, and exercises using interactive learning tasks were used, with a focus on statistics and interpreting data from trials, particularly interim data.

Results Results of oral and written evaluations by participants were reviewed. The feedback was mostly positive, with some residual confusion regarding statistical concepts. However, discussions with attendees later revealed that not all felt prepared to engage fully in the workshop.

Limitations This was the presenters’ first experience facilitating a formal discussion with an audience that had no advanced science, research, or mathematics training. Community representatives’ concern regarding speaking for their communities without consulting them also created a challenge for the workshop.

Conclusions Open discussion around trial stopping rules requires that all discussants have an understanding of trial design concepts and feel a sense of empowerment to ask and answer questions. The VOICE CWG workshop was a first step toward the goal of open discussion regarding trial stopping rules and interim results for the study; however, ongoing education and dialogue must occur to ensure that all stakeholders fully participate in the process.
Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer’s disease
Authors: Xiong Chengjie , van Belle Gerald , Miller J Philip , Morris John C
Published: February 2011

Background Therapeutic trials of disease-modifying agents on Alzheimer’s disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials.

Purpose The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD.

Methods A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model.

Results Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally chosen.

Limitations The proposed method assumes that the only and immediate effect of treatment switch is on the rate of cognitive change.

Conclusions Crucial design parameters for the clinical trials of disease-modifying agents on AD can be optimally chosen. Government and industry officials as well as academia researchers should consider the optimum use of the clinical trials design for disease-modifying agents on AD in their effort to search for the treatments with the potential to modify the underlying pathophysiology of AD.
Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli
Authors: Chatterjee Madhumita , Huang Zhangsen , Zhang Wei , Jiang Lei , Hultenby Kjell , Zhu Linjing , Hu Hu , Nilsson Gunnar P. , Li Nailin
Published: February 2011

The present study characterized platelet secretion and surface expression of proangiogenic stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) and antiangiogenic PF4 and endostatin on activation. The angiogenic factors presented in randomly distributed granules in resting platelets, which were peripherized on activation. Confocal and immunogold electron microscopy demonstrated that SDF-1α/CXCL12 and PF4/CXCL4 mostly present in different granules. Platelet activation induced marked SDF-1α and endostatin but mild PF4 or no VEGF surface expression. PAR1-activating peptide (PAR1-AP), adenosine diphosphate (via P2Y1/P2Y12), and glycoprotein VI-targeting collagen-related peptide induced massive SDF-1α and VEGF but modest PF4 or no endostatin release. In contrast, PAR4-AP triggered marked PF4 and sole endostatin release but limited SDF-1α or VEGF secretion. Distinct platelet release of SDF-1α and endostatin involved different engagements of intracellular signaling pathways. In conclusion, different platelet stimuli evoke distinct secretion and surface expression of proangiogenic and antiangiogenic factors. PAR1, adenosine diphosphate, and glycoprotein VI stimulation favors proangiogenic, whereas PAR4 promotes antiangiogenic, factor release.