bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE DECOHERENCE-FREE SUBALGEBRA OF A QUANTUM MARKOV SEMIGROUP WITH UNBOUNDED GENERATOR
Authors: DHAHRI AMEUR , FAGNOLA FRANCO , REBOLLEDO ROLANDO 
Published: October 2010

Let [Formula: see text] be a quantum Markov semigroup on [Formula: see text] with a faithful normal invariant state ρ. The decoherence-free subalgebra [Formula: see text] of [Formula: see text] is the biggest subalgebra of [Formula: see text] where the completely positive maps [Formula: see text] act as homomorphisms. When [Formula: see text] is the minimal semigroup whose generator is represented in a generalised GKSL form [Formula: see text], with possibly unbounded H, Lℓ, we show that [Formula: see text] coincides with the generalised commutator of [Formula: see text] under some natural regularity conditions. As a corollary we derive simple sufficient algebraic conditions for convergence towards a steady state based on multiple commutators of H and Lℓ. We give examples of quantum Markov semigroups [Formula: see text], with h infinite-dimensional, having a non-trivial decoherence-free subalgebra.
Hippo Pathway Effector Yap Is an Ovarian Cancer Oncogene
Authors: Hall Chad A. , Wang Runsheng , Miao Jiangyong , Oliva Esther , Shen Xiaoyun , Wheeler Thomas , Hilsenbeck Susan G. , Orsulic Sandra , Goode Scott 
Published: October 2010

Abstract
The Hippo pathway regulates organ size and tumorigenesis in Drosophila and mammals and is altered in a variety of human cancers, yet it remains unclear if the Hippo pathway is of prognostic significance to cancer patients. Here we show that the key targets of Hippo signaling, transcriptional coactivators Yki and Yap, play a conserved role in promoting ovarian cancer in flies and humans, respectively. Whereas studies linking Yap to cancer in other tissues have focused on overall Yap levels, we show for the first time that subcellular levels of Yap show an exceptionally strong association with poor patient survival. Specifically, high levels of nuclear Yap (nYap), or low levels of cytoplasmic phosphorylated Yap (cpYap), associated with poor survival from ovarian cancer. Patients with both high nYap and low cpYap had ∼50% lower 5-year survival, and this combination is an independent prognostic marker for survival, with an exceptionally high hazard ratio of 7.8. We find that Yap2 is the predominantly expressed Yap isoform in both the ovarian surface epithelium (OSE) and epithelial ovarian cancers. Overexpression of Yap2 and phosphorylation-defective Yap2-5SA in immortalized OSE cells resulted in increased cell proliferation, resistance to cisplatin-induced apoptosis, faster cell migration, and anchorage-independent growth, whereas Yap knockdown resulted in increased sensitivity to cisplatin-induced apoptosis. Findings argue that the Hippo signaling pathway defines an important pathway in progression of ovarian cancer. Cancer Res; 70(21); 8517–25. ©2010 AACR.
Androgen-Induced TMPRSS2:ERG Fusion in Nonmalignant Prostate Epithelial Cells
Authors: Bastus Nuria Coll , Boyd Lara K. , Mao Xueying , Stankiewicz Elzbieta , Kudahetti Sakunthala C. , Oliver R. Tim D. , Berney Daniel M. , Lu Yong-Jie 
Published: October 2010

Abstract
Fusion genes play important roles in tumorigenesis. The identification of the high-frequency TMPRSS2 fusion with ERG and other ETS family genes in prostate cancer highlights the importance of fusion genes in solid tumor development and progression. However, the mechanisms leading to these fusions are unclear. We investigated whether androgen, through stimulating its receptor, could promote spatial genome reorganization and contribute to the generation of the TMPRSS2:ERG fusion. We show that treatment with androgen can induce the TMPRSS2:ERG fusion in both malignant and nonmalignant prostate epithelial cells. Although the fusion could be detected in malignant cells following 24-hour treatment, prolonged exposure to androgen was required to detect the fusion transcript in nonmalignant cells. We associated the fusion incidence with genetic factors, including androgen-induced gene proximity, androgen receptor exon1 CAG repeat length and expression of the PIWIL1 gene. This study demonstrates that fusions can be induced prior to malignant transformation and generation of the fusion is associated with both gene proximity and loss of the ability to prevent double-strand breaks. Cancer Res; 70(23); 9544–8. ©2010 AACR.
IL-2 Costimulation Enables Statin-Mediated Activation of Human NK Cells, Preferentially through a Mechanism Involving CD56+ Dendritic Cells
Authors: Gruenbacher Georg , Gander Hubert , Nussbaumer Oliver , Nussbaumer Walter , Rahm Andrea , Thurnher Martin 
Published: October 2010

Abstract
Statins are inhibitors of cholesterol biosynthesis and protein prenylation that also have been studied in cancer therapy and chemoprevention. With regard to natural killer (NK) cells, only inhibitory effects of statins such as suppression of granule exocytosis have been reported so far. In this study, we show that statins can cooperate with IL-2 to potently induce the activation of CD56dim NK cells in a synergistic, time- and dose-dependent fashion. Supplementation experiments revealed that the statin effect was specific to inhibition of their target hydroxymethylglutaryl coenzyme A reductase and that downstream depletion of geranylgeranyl pyrophosphate was responsible for cooperating with IL-2 in NK cell activation. Mechanistic studies revealed that CD56+HLA-DR+CD14+ dendritic cell (DC)-like accessory cells mediated the ability of statin to activate NK cells. In contrast, BDCA-1+ (CD1c+) myeloid DCs, which partially expressed CD56, were somewhat less potent. Conventional blood monocytes, which lack CD56, exhibited the lowest accessory cell capacity. NK cell IFN-γ production was IL-12 independent but required endogenous IL-18, IL-1β, and caspase-1 activity. Statins directly induced apoptosis in human cancer cell lines and cooperated with NK cell–derived IFN-γ to generate potent cytotoxic antitumor effects in vitro even in the presence of statin-mediated inhibitory effects on granule exocytosis. Our work reveals novel and unexpected immunomodulatory properties of statins, which might be harnessed for the treatment of cancer. Cancer Res; 70(23); 9611–20. ©2010 AACR.
Inflammatory and MicroRNA Gene Expression as Prognostic Classifier of Barrett's-Associated Esophageal Adenocarcinoma
Authors: Nguyen Giang Huong , Schetter Aaron J. , Chou David B. , Bowman Elise D. , Zhao Ronghua , Hawkes Jason E. , Mathé Ewy A. , Kumamoto Kensuke , Zhao Yiqiang , Budhu Anuradha , Hagiwara Nobutoshi , Wang Xin Wei , Miyashita Masao , Casson Alan G. , Harris Curtis C. 
Published: October 2010

Abstract
Purpose: Esophageal cancer is one of the most aggressive and deadly forms of cancer; highlighting the need to identify biomarkers for early detection and prognostic classification. Our recent studies have identified inflammatory gene and microRNA signatures derived from tumor and nontumor tissues as prognostic biomarkers of hepatocellular, lung, and colorectal adenocarcinoma. Here, we examine the relationship between expression of these inflammatory genes and micro RNA (miRNA) expression in esophageal adenocarcinoma and patient survival.
Experimental Design: We measured the expression of 23 inflammation-associated genes in tumors and adjacent normal tissues from 93 patients (58 Barrett's and 35 Sporadic adenocarcinomas) by quantitative reverse transcription-polymerase chain reaction. These data were used to build an inflammatory risk model, based on multivariate Cox regression, to predict survival in a training cohort (n = 47). We then determined whether this model could predict survival in a cohort of 46 patients. Expression data for miRNA-375 were available for these patients and was combined with inflammatory gene expression.
Results: IFN-γ, IL-1α, IL-8, IL-21, IL-23, and proteoglycan expression in tumor and nontumor samples were each associated with poor prognosis based on Cox regression [(Z-score)&gt;1.5] and therefore were used to generate an inflammatory risk score (IRS). Patients with a high IRS had poor prognosis compared with those with a low IRS in the training (P = 0.002) and test (P = 0.012) cohorts. This association was stronger in the group with Barrett's history. When combining with miRNA-375, the combined IRS/miR signature was an improved prognostic classifier than either one alone.
Conclusion: Transcriptional profiling of inflammation-associated genes and miRNA expression in resected esophageal Barrett's-associated adenocarcinoma tissues may have clinical utility as predictors of prognosis. Clin Cancer Res; 16(23); 5824–34. ©2010 AACR.
Increased 12/15-Lipoxygenase Enhances Cell Growth, Fibronectin Deposition, and Neointimal Formation in Response to Carotid Injury
Authors: Deliri Hamid , Meller Nahum , Kadakkal Ajay , Malhotra Rohit , Brewster Jordan , Doran Amanda C. , Pei Hong , Oldham Stephanie N. , Skaflen Marcus D. , Garmey James C. , McNamara Coleen A. 
Published: October 2010

Objective—
To determine whether increased 12/15-lipoxygenase (12/15LO) expression in vivo enhances neointimal formation in response to injury.

Methods and Results—

12/15LO expression in the vessel wall is increased in animal models of metabolic syndrome and diabetes mellitus. Increased expression of 12/15LO enhances cultured vascular smooth muscle cell (VSMC) proliferation, an effect mediated by the helix-loop-helix factor inhibitor of differentiation 3 (Id3). Carotid endothelial denudation was performed on apolipoprotein (Apo) E
−/−
, ApoE
−/−
/12/15LO
−/−
, C57BL/6, and 12/15LO-overexpressing transgenic mice. ApoE
−/−
/12/15LO
−/−
mice had attenuated and 12/15LO-overexpressing transgenic mice had enhanced neointimal formation compared with control mice. 12/15LO-overexpressing transgenic mice had greater postinjury carotid Id3 and Ki-67 expression, cell number, and fibronectin deposition compared with C57BL/6 mice. Loss of 12/15LO attenuated proliferation of cultured ApoE
−/−
VSMCs, whereas 12/15LO overexpression induced VSMC proliferation. Loss of Id3 enhanced immunoglobulin trascription factor (ITF)-2b binding to and activation of the p21
cip1
promoter and abrogated 12/15LO-induced VSMC proliferation.

Conclusion—

To our knowledge, these data are the first demonstration that increased expression of 12/15LO in the vessel wall enhances Id3-dependent cell proliferation, fibronectin deposition, and neointimal formation in response to injury. Results identify p21
cip1
as a potential target of the 12/15LO-Id3 pathway and suggest that modulation of this pathway may have therapeutic implications for targeting the increased risk of restenosis in patients with diabetes.
Sphingosine-1-Phosphate Receptor-2 Function in Myeloid Cells Regulates Vascular Inflammation and Atherosclerosis
Authors: Skoura Athanasia , Michaud Jason , Im Dong-Soon , Thangada Shobha , Xiong Yuquan , Smith Jonathan D. , Hla Timothy 
Published: October 2010

Objective—
Sphingomyelin deposition and metabolism occurs in the atherosclerotic plaque, leading to the formation of sphingosine-1-phosphate (S1P), which activates G protein–coupled receptors to regulate vascular and immune cells. The role of S1P receptors in atherosclerosis has not been examined.

Methods and Results—

We tested the hypothesis that S1P receptor-2 (S1PR2) regulates atherosclerosis.
Apoe
−/−
S1pr2
−/−
mice showed greatly attenuated atherosclerosis compared with the
Apoe
−/−
mice. Bone marrow transplant experiments indicate that S1PR2 function in the hematopoietic compartment is critical. S1PR2 is expressed in bone marrow–derived macrophages and in macrophage-like foam cells in atherosclerotic plaques. Reduced macrophage-like foam cells were found in the atherosclerotic plaques of
Apoe
−/−
S1pr2
−/−
mice, suggesting that S1PR2 retains macrophages in atherosclerotic plaques. Lipoprotein profiles, plasma lipids, and oxidized low-density lipoprotein uptake by bone marrow–derived macrophages were not altered by the
S1pr2
genotype. In contrast, endotoxin-induced inflammatory cytokine (interleukin [IL]-1β, IL-18) levels in the serum of S1PR2 knockout mice were significantly reduced. Furthermore, treatment of wild-type mice with S1PR2 antagonist JTE-013 suppressed IL-1β and IL-18 levels in plasma.

Conclusion—
These data suggest that S1PR2 signaling in the plaque macrophage regulates macrophage retention and inflammatory cytokine secretion, thereby promoting atherosclerosis.
Differential Endothelial Transcriptomics Identifies Semaphorin 3G as a Vascular Class 3 Semaphorin
Authors: Kutschera Simone , Weber Holger , Weick Anja , De Smet Frederik , Genove Guillem , Takemoto Minoru , Prahst Claudia , Riedel Maria , Mikelis Constantinos , Baulande Sylvain , Champseix Catherine , Kummerer Petra , Conseiller Emmanuel , Multon Marie-Christine , Heroult Melanie , Bicknell Roy , Carmeliet Peter , Betsholtz Christer , Augustin Hellmut G. 
Published: October 2010

Objective—
To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G]).

Methods and Results—
Semaphorins have been identified as axon guidance molecules. Yet, they have more recently also been characterized as attractive and repulsive regulators of angiogenesis. Through a transcriptomic screen, we identified Sema3G as a molecule of angiogenic endothelial cells. Sema3G-deficient mice are viable and exhibit no overt vascular phenotype. Yet, LacZ expression in the Sema3G locus revealed intense arterial vascular staining in the angiogenic vasculature, starting at E9.5, which was detectable throughout adolescence and downregulated in adult vasculature. Sema3G is expressed as a full-length 100-kDa secreted molecule that is processed by furin proteases to yield 95- and a 65-kDa Sema domain–containing subunits. Full-length Sema3G binds to NP2, whereas processed Sema3G binds to NP1 and NP2. Expression profiling and cellular experiments identified autocrine effects of Sema3G on endothelial cells and paracrine effects on smooth muscle cells.

Conclusion—
Although the mouse knockout phenotype suggests compensatory mechanisms, the experiments identify Sema3G as a primarily endothelial cell–expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners, respectively.
Differential Effects of Rosiglitazone and Metformin on Postprandial Lipemia in Patients With HIV-Lipodystrophy
Authors: van Wijk Jeroen P.H. , Hoepelman Andy I.M. , de Koning Eelco J.P. , Dallinga-Thie Geesje , Rabelink Ton J. , Cabezas Manuel Castro 
Published: October 2010

Objective—
To compare the effects of rosiglitazone (8 mg/d, n=19) and metformin (2 g/d, n=18) on postprandial lipemia in patients with HIV-lipodystrophy.

Methods and Results—

Lipodystrophy in HIV is associated with insulin resistance and disturbed postprandial triglyceride and free fatty acid (FFA) metabolism. We conducted an open randomized 6-month study with standardized 10-h oral fat-loading tests at baseline and after treatment. Rosiglitazone (−34%) and metformin (−37%) reduced homeostasis model assessment similarly (
P
<0.05). Rosiglitazone did not change the area under the curve for FFA and triglyceride; however, it did reduce the area under the curve for hydroxybutyric acid (a marker of hepatic FFA oxidation) by 25% (
P
<0.05). Rosiglitazone increased the area under the curve for remnantlike particle cholesterol by 40% (
P
<0.01) compared with baseline. Metformin did not change any of the postprandial measurements.

Conclusion—
Rosiglitazone improved insulin sensitivity and decreased postprandial hydroxybutyric acid levels in patients with HIV-lipodystrophy, suggesting improved FFA handling. Despite metabolic improvements, rosiglitazone caused a marked increase in postprandial remnantlike particle cholesterol, which may adversely affect cardiovascular risk. Metformin did not affect postprandial lipemia and could be used to treat insulin resistance in this population.
Annexin A5 Therapy Attenuates Vascular Inflammation and Remodeling and Improves Endothelial Function in Mice
Authors: Ewing Mark M. , de Vries Margreet R. , Nordzell Mariette , Pettersson Knut , de Boer Hetty C. , van Zonneveld Anton Jan , Frostegård Johan , Jukema J. Wouter , Quax Paul H.A. 
Published: October 2010

Objective—
Annexin A5 (AnxA5) has antithrombotic, antiapoptotic, and antiinflammatory properties; we investigated its effectiveness against vascular inflammation, remodeling, and dysfunction in accelerated atherosclerosis.

Methods and Results—

AnxA5 (1 mg/kg per day or vehicle) was investigated in vascular injury models in hypercholesterolemic apolipoprotein E (ApoE)3*Leiden mice. AnxA5 treatment reduced adhesion and infiltration of leukocytes by 71% to 69% (
P
=0.015,
P
=0.031) and macrophages by 51% to 87% (
P
=0.014,
P
=0.018), as well as monocyte chemotactic protein-1 and tumor necrosis factor-α expression in a femoral artery inflammation model (perivascular cuff for 3 days), indicating reduced vascular inflammation. In a vein graft model, 28 days of AnxA5 treatment reduced vein graft thickening (48%;
P
=0.006) and leukocyte infiltration (46%;
P
=0.003). In these mice, reduced plasma concentrations of IFN-γ (−72%;
P
=0.040), granulocyte colony–stimulating factor (−41%;
P
=0.010), and macrophage inflammatory protein-1β (MIP-1β) (−66%;
P
=0.020) were measured, indicating reduced systemic inflammation. An in vitro endothelial cell model shows the importance of AnxA5's anticoagulant properties in reducing vascular inflammation. Endothelium-mediated dilatation in hypercholesterolemic ApoE
(−/−)
mice was improved by 3 days of AnxA5 treatment, shown by improved systolic and diastolic blood pressure reductions in response to metacholine, which could be abolished by
l
-Nitro-Arginine-Methyl Ester (
l
-NAME), indicating nitric oxide involvement.

Conclusion—
AnxA5 reduced local vascular and systemic inflammation and vascular remodeling and improved vascular function, indicating that it has a therapeutic potential against atherosclerotic cardiovascular diseases.
Triggers of Ischemic Stroke
Authors: Guiraud Vincent , Amor Mejdi Ben , Mas Jean-Louis , Touzé Emmanuel 
Published: October 2010

Background and Purpose—Several studies have suggested that exposure to “triggers,” could precipitate the onset of ischemic stroke (IS). We performed a systematic review of the potential triggers of IS.Methods—Two independent reviewers identified studies published between January 1980 and June 2010 from MEDLINE and Embase. Where appropriate, odds ratios (ORs) were combined.Results—A total of 26 studies identified 12 potential triggers. Twenty-two studies used a case–control design, and hazard period durations ranged from 2 hours to 3 months. The majority of studies were dedicated to alcohol abuse (n=10) and clinical infection (n=12). There was a significant association between IS and alcohol abuse of >40 to 60 g within the preceding 24 hours (OR=2.66; 95% CI, 1.54 to 4.61) or >150 g within the previous week (OR=2.47; 95% CI, 1.52 to 4.02) and infection within the previous week (OR=2.91; 95% CI, 1.41 to 6.00) or within the previous month (OR=2.41; 95% CI, 1.78 to 3.27). Other triggers have been far less investigated. There was a significant association between IS and anger, heavy eating, negative or positive emotions, sudden posture change in response to a startling event, birthday, and psychological distress and no significant association with drug abuse or heavy physical exertion. Regarding methodological issues, patients were rarely blinded to study objectives, and interviewers were rarely blinded to patient status.Conclusions—Research on triggers of IS has been mainly focused on acute alcohol abuse and clinical infection. More research is needed on factors such as physical exertion or acute stress. Future studies should use more appropriate designs and examine different hazard periods.
Chinese Foreign Policy under Hu Jintao:The Struggle between Low-Profile Policy and Diplomatic Activism
Authors: Suisheng Zhao 
Published: October 2010

AbstractThis article explores a controversial issue of Chinese foreign policy: whether the Hu leadership has abandoned Deng Xiaoping’s taoguang yanghui policy — hiding one’s capabilities and biding one’s time — and reoriented Chinese foreign policy towards a more assertive, if not more aggressive, direction. This is controversial because while China in public still insists that it follows the taoguang yanghui policy established by Deng in the early 1990s; Chinese diplomacy has become increasingly active and assertive since Hu came to power, particularly since the 2008-2009 global economic crisis. This article argues that as a rising power, an active foreign policy has become a necessity rather than a luxury for China. This diplomatic activism marks a certain departure from the taoguang yanghui policy, but the Hu leadership is still juggling China’s taoguang yanghui policy with its emerging role as a global power. One defining tension in China’s foreign policy agenda is to find a balance between expanding China’s international influence and taking more international responsibility on the one hand and continuing to play down its pretence of being a global power and avoiding confrontation with the United States on the other.
Chinese Diplomacy towards the EU: Grand Vision but Hard to Manage
Authors: Gaenssmantel Frank 
Published: October 2010

AbstractThis article investigates the sudden rise and subsequent slow decline of the European Union (EU) in Chinese diplomacy between 2002 and 2007. China’s decision in 2003 to consider relations with the EU as ‘strategic’ in nature does not reflect a fundamental change of mind but rather a perception of favourable circumstances. China has a long track record of high expectations towards a united Europe. After the World Trade Organization (WTO) negotiations had created a positive image of a united and independent EU, the transatlantic rift over the Iraq War in 2002 and 2003 seemed to present an international environment that was conducive to stronger China‐EU ties. Subsequently, however, the difficulties of engaging with a complex entity like the EU have contributed to souring diplomatic relations. This development is traced for two major cases of Chinese foreign policy towards the EU: the quest for recognition as a market economy; and the push to have the EU’s arms embargo lifted. Over time, Chinese engagement with the EU on these issues has gone through different phases, reflecting repeated attempts to improve the diplomatic approach, to eliminate unsuccessful strategies and to react to EU feedback. China has not yet reached its goal on either issue. The article concludes by pointing to the specific difficulties that have emerged from the evolution of Chinese diplomacy towards the EU on these two cases.