bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous Thromboembolism Does Not Share Strong Familial Susceptibility With Ischemic Stroke
Authors: Zöller Bengt , Li Xinjun , Ohlsson Henrik , Sundquist Jan , Sundquist Kristina 
Published: September 2011

Background—
Coagulation allelic variants associated with venous thromboembolism (VTE) have been suggested to be involved in the pathogenesis of ischemic stroke. This nationwide study aimed at determining whether VTE shares familial susceptibility with ischemic stroke.

Method and Results—
The Swedish Multigeneration Register of 0- to 75-year-old subjects was linked to the Swedish Hospital Discharge Register and the Cause of Death Register for the period 1987 to 2007. Odds ratios (ORs) for VTE and ischemic stroke were determined in 2 ways: odds of ischemic stroke in offspring whose parents had been diagnosed with VTE, and odds of VTE in offspring whose parents had been diagnosed with ischemic stroke. The analyses were repeated for siblings and spouses. Offspring of parents with VTE (n=25 929) were at increased risk for ischemic stroke (n=5595): OR, 1.10 (95% confidence interval [CI], 1.06–1.14). Siblings of probands with VTE (n=45 132) had no increased risk of ischemic stroke (n=1716): OR, 1.05 (95% CI, 1.00–1.11). Spouses of probands with VTE (n=24 106) were at increased risk for ischemic stroke (n=940): OR, 1.18 (95% CI, 1.10–1.27). The risks for VTE in relatives of probands with ischemic stroke were OR, 1.15; 95% CI, 1.10–1.21 (offspring); OR, 1.07; 95% CI, 1.02–1.12 (siblings); and OR, 1.21; 95% CI, 1.11–1.32 (spouses).

Conclusions—
VTE does not share strong familial susceptibility with ischemic stroke in the Swedish population. Moreover, familial nongenetic factors contribute to the observed weak familial associations. The present study suggests that it is unlikely that strong shared disease-causing mutations exist to a large extent in the Swedish population.
Regional Patterns of Tropical Indo-Pacific Climate Change: Evidence of the Walker Circulation Weakening
Authors: Tokinaga Hiroki , Xie Shang-Ping , Timmermann Axel , McGregor Shayne , Ogata Tomomichi , Kubota Hisayuki , Okumura Yuko M. 
Published: September 2011

Regional patterns of tropical Indo-Pacific climate change are investigated over the last six decades based on a synthesis of in situ observations and ocean model simulations, with a focus on physical consistency among sea surface temperature (SST), cloud, sea level pressure (SLP), surface wind, and subsurface ocean temperature. A newly developed bias-corrected surface wind dataset displays westerly trends over the western tropical Pacific and easterly trends over the tropical Indian Ocean, indicative of a slowdown of the Walker circulation. This pattern of wind change is consistent with that of observed SLP change showing positive trends over the Maritime Continent and negative trends over the central equatorial Pacific. Suppressed moisture convergence over the Maritime Continent is largely due to surface wind changes, contributing to observed decreases in marine cloudiness and land precipitation there. Furthermore, observed ocean mixed layer temperatures indicate a reduction in zonal contrast in the tropical Indo-Pacific characterized by larger warming in the tropical eastern Pacific and western Indian Ocean than in the tropical western Pacific and eastern Indian Ocean. Similar changes are successfully simulated by an ocean general circulation model forced with the bias-corrected wind stress. Whereas results from major SST reconstructions show no significant change in zonal gradient in the tropical Indo-Pacific, both bucket-sampled SSTs and nighttime marine air temperatures (NMAT) show a weakening of the zonal gradient consistent with the subsurface temperature changes. All these findings from independent observations provide robust evidence for ocean–atmosphere coupling associated with the reduction in the Walker circulation over the last six decades.
Diffusion in Direct Democracy: The Effect of Political Information on Proposals for Tax and Expenditure Limits in the U.S. States
Authors: Seljan Ellen C. , Weller Nicholas 
Published: September 2011

AbstractMany theories of policy diffusion contend that the flow of information is the driving force in the diffusion process. Prior scholarship has identified at least two types of information: information about policy and information about political viability. Few empirical approaches have been able to distinguish between these separate mechanisms. The authors argue that an analysis of policy proposals can untangle political information from policy-based information. They employ their strategy with data on the proposal of tax and expenditure limits (TELs) in the U.S. states since 1970 through direct democracy. The authors find that states in close geographic proximity to states that have rejected TELs are significantly less likely to propose TELs themselves. Since this event does not reveal information about policy effectiveness, the authors conclude that information about political viability systematically diffuses from state to state at the proposal stage of policy making.
Latent KSHV infection increases the vascular permeability of human endothelial cells
Authors: Guilluy Christophe , Zhang Zhigang , Bhende Prasanna M. , Sharek Lisa , Wang Ling , Burridge Keith , Damania Blossom 
Published: September 2011

AbstractKaposi sarcoma–associated herpesvirus (KSHV) is associated with 3 different human malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Endothelial cells with latent KSHV infection display increased Rac1 activation and activation of its downstream modulator, p21-activated kinase 1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine phosphorylation of vascular endothelial (VE)–cadherin and β-catenin, whereas total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that KSHV-infected endothelial cells displayed increased permeability compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of reactive oxygen species (ROS) resulted in decreased permeability in the KSHV-infected endothelial cells. We further demonstrate that the KSHV K1 protein can activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1 activity in endothelial cells, resulting in the phosphorylation of VE-cadherin and β-catenin and leading to the disassembly of cell junctions and to increased vascular permeability of the infected endothelial cells.
Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation?
Authors: Ustun Celalettin , Miller Jeffrey S. , Munn David H. , Weisdorf Daniel J. , Blazar Bruce R. 
Published: September 2011

AbstractThe microenviroment of acute myelogenous leukemia (AML) is suppressive for immune effector cells. Regulatory T cells (Tregs) have been recognized as a contributor factor and may be recruited and exploited by leukemic cells to evade immunesurveillance. Studies have shown that the frequencies of marrow and blood Tregs are greater in patients with AML than in control patients. Although increased Tregs have been associated with a decreased risk of GVHD after allogeneic HCT and hence may impede the graft-versus-tumor effect, recent findings indicate that that this may not be the case. Because there is a need to improve outcomes of standard treatment (chemotherapy with or without allogeneic HCT) in AML, targeting Tregs present an outstanding opportunity in AML because discoveries may apply throughout its treatment. Here, we review data on the roles of Tregs in mediating immune system-AML interactions. We focused on in vitro, animal, and observational human studies of Tregs in AML biology, development, prognosis, and therapy in different settings (eg, vaccination and HCT). Manipulation of Tregs or other types of immunomodulation may become a part of AML treatment in the future.
Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies
Authors: Hwang Pei-Ing , Wu Huan-Bin , Wang Chin-Di , Lin Bai-Ling , Chen Cheng-Tao , Yuan Shinsheng , Wu Guani , Li Ker-Chau 
Published: September 2011

Abstract

Background
To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue.

Results
By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific G ene E xpression T emplates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.
Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity.

Conclusions
These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.
Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection
Authors: Paul Vivek Daniel , Sundarrajan Sudarson , Rajagopalan Sanjeev Saravanan , Hariharan Sukumar , Kempashanaiah Nanjundappa , Padmanabhan Sriram , Sriram Bharathi , Ramachandran Janakiraman 
Published: September 2011

AbstractBackgroundInterest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy.ResultsWe developed a recombinant lysis-deficientStaphylococcus aureusphage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized inS. aureusstrain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (cat) gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test thein vivoefficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenicS. aureusat a dose that results in 80% mortality (LD80). Treatment with the endolysin-deficient phage rescued mice from the fatalS. aureusinfection.ConclusionsA recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistantS. aureuswithout causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host. The recombinant phage effectively rescued mice from fatalS. aureusinfection. To our knowledge this is the first report of a lysis-deficient staphylococcal phage.
Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza
Authors: Almansa Raquel , Anton Andres , Ramirez Paula , Martin-Loeches Ignacio , Banner David , Pumarola Tomás , Xu Luoling , Blanco Jesús , Ran Longsi , Lopez-Campos Guillermo , Martin-Sanchez Fernando , Socias Lorenzo , Loza Ana , Andaluz David , Maravi Enrique , Gordón Mónica , Gallegos Maria C , Fernandez Victoria , León Cristobal , Merino Pedro , Marcos Maria Ángeles , Gandía Francisco , Bobillo Felipe , Resino Salvador , Eiros Jose Mª , Castro Carmen , Mateo Paula , Gonzalez-Rivera Milagros , Rello Jordi , de Lejarazu Raul Ortiz , Kelvin David J , Bermejo-Martin Jesus F 
Published: September 2011

Abstract

Background
Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.

Methods
Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.

Results
Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.

Conclusions
Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.
Association of COMT genotypes with S-COMT promoter methylation in growth-discordant monozygotic twins and healthy adults
Authors: Schreiner Felix , El-Maarri Osman , Gohlke Bettina , Stutte Sonja , Nuesgen Nicole , Mattheisen Manuel , Fimmers Rolf , Bartmann Peter , Oldenburg Johannes , Woelfle Joachim 
Published: September 2011

Abstract

Background
Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and estrogen metabolism. Recently, COMT haplotypes rather than the single polymorphism Val158Met have been reported to underlie differences in protein expression by modulating mRNA secondary structure. So far, studies investigating the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly focused on phenotypical aspects, and results have been controversial.

Methods
We assessed S-COMT promoter methylation in saliva and blood derived DNA with regard to early pre- and postnatal growth as well as to genotype for polymorphisms rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4 years), who were discordant for intrauterine development due to severe feto-fetal-transfusion syndrome. Methylation levels of two previously reported partially methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP HPLC) assay.

Results
Overall, we observed a high variability of S-COMT promoter methylation, which did not correlate with individual differences in the pre- or postnatal growth pattern. Within the twin pairs however we noted a distinct similarity that could be linked to underlying COMT genotypes. This association was subsequently confirmed in a cohort of 93 unrelated adult controls. Interestingly, 158Val-alleles were found at both ends of the epigenotypical range, which is in accordance with a recently proposed model of COMT haplotypes corresponding to a continuum of phenotypical variability.

Conclusion
The strong heritable component of S-COMT promoter methylation found in our study needs to be considered in future approaches that focus on interactions between COMT epigenotype and phenotype.
Alcohol consumption in tertiary education students
Authors: Reavley Nicola J , Jorm Anthony F , McCann Terence V , Lubman Dan I 
Published: September 2011

Abstract

Background
Heavy alcohol consumption among adolescents and young adults is an issue of significant public concern. With approximately 50% of young people aged 18-24 attending tertiary education, there is an opportunity within these settings to implement programs that target risky drinking. The aim of the current study was to survey students and staff within a tertiary education institution to investigate patterns of alcohol use, alcohol-related problems, knowledge of current National Health and Medical Research Council (NHMRC) guidelines for alcohol consumption and intentions to seek help for alcohol problems.

Methods
Students of an Australian metropolitan university (with staff as a comparison group) participated in a telephone interview. Questions related to knowledge of NHMRC guidelines, drinking behaviour, alcohol-related problems and help-seeking intentions for alcohol problems. Level of psychological distress was also assessed.

Results
Of the completed interviews, 774 (65%) were students and 422 (35%) were staff. While staff were more likely to drink regularly, students were more likely to drink heavily. Alcohol consumption was significantly higher in students, in males and in those with a history of earlier onset drinking. In most cases, alcohol-related problems were more likely to occur in students. The majority of students and staff had accurate knowledge of the current NHMRC guidelines, but this was not associated with lower levels of risky drinking. Psychological distress was associated with patterns of risky drinking in students.

Conclusions
Our findings are consistent with previous studies of tertiary student populations, and highlight the disconnect between knowledge of relevant guidelines and actual behaviour. There is a clear need for interventions within tertiary education institutions that promote more effective means of coping with psychological distress and improve help-seeking for alcohol problems, particularly among young men.
Solid-state dye-sensitized solar cells based on ZnO nanoparticle and nanorod array hybrid photoanodes
Authors: Lee Tao-Hua , Sue Hung-Jue , Cheng Xing 
Published: September 2011

Abstract
The effect of ZnO photoanode morphology on the performance of solid-state dye-sensitized solar cells (DSSCs) is reported. Four different structures of dye-loaded ZnO layers have been fabricated in conjunction with poly(3-hexylthiophene). A significant improvement in device efficiency with ZnO nanorod arrays as photoanodes has been achieved by filling the interstitial voids of the nanorod arrays with ZnO nanoparticles. The overall power conversion efficiency increases from 0.13% for a nanorod-only device to 0.34% for a device with combined nanoparticles and nanorod arrays. The higher device efficiency in solid-state DSSCs with hybrid nanorod/nanoparticle photoanodes is originated from both large surface area provided by nanoparticles for dye adsorption and efficient charge transport provided by the nanorod arrays to reduce the recombinations of photogenerated carriers.
A scalable multi-sink gradient-based routing protocol for traffic load balancing
Authors: Yoo Hongseok , Shim Moonjoo , Kim Dongkyun 
Published: September 2011

Abstract
Wireless sensor networks have been assumed to consist of a single sink and multiple sensor nodes which do not have mobility. In these networks, sensor nodes near the sink dissipate their energy so fast due to their many-to-one traffic pattern, and finally they die early. This uneven energy depletion phenomenon known as the hot spot problem becomes more serious as the number of sensor nodes (i.e., their scale) increases. Recently, multi-sink wireless sensor networks have been envisioned to solve the hot spot problem. Gradient routing protocols are known to be appropriate for the networks in that network traffic is evenly distributed to multiple sinks to prolong network lifetime and they are scalable. Each node maintains its gradient representing the direction toward a neighbor node to reach one of the sinks. In particular, existing protocols allow a sensor node to construct its gradient using the cumulative traffic load of a path for load balancing. However, they have a critical drawback that a sensor node cannot efficiently avoid using the path with the most overloaded node. Hence, this paper introduces a new Gradient routing protocol for LOad-BALancing (GLOBAL) with a new gradient model to maximize network lifetime.
The proposed gradient model considers both of the cumulative path load and the traffic load of the most overloaded node over the path in calculating each node's gradient value. Therefore, packets are forwarded over the least-loaded path, which avoids the most overloaded node. In addition, it is known that assigning a unique address to each sensor node causes much communication overhead. Since the overhead increases as the network scales, routing protocols using an address to indicate the receiver in forwarding a packet are not scalable. Thus, GLOBAL also includes an addressing-free data forwarding strategy. Through ns-2 simulation, we verify that GLOBAL achieves better performance than the shortest path routing and load-aware gradient routing ones.
Epithelial-Mesenchymal Transition in tumor microenvironment
Authors: Jing Yingying , Han Zhipeng , Zhang Shanshan , Liu Yan , Wei Lixin 
Published: September 2011

Abstract
The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and also in the tumor invasion process. In addition, EMT also causes disruption of cell-cell adherence, loss of apico-basal polarity, matrix remodeling, increased motility and invasiveness in promoting tumor metastasis. The tumor microenvironment plays an important role in facilitating cancer metastasis and may induce the occurrence of EMT in tumor cells. A large number of inflammatory cells infiltrating the tumor site, as well as hypoxia existing in a large area of tumor, in addition many stem cells present in tumor microenvironment, such as cancer stem cells (CSCs), mesenchymal stem cells (MSCs), all of these may be the inducers of EMT in tumor cells. The signaling pathways involved in EMT are various, including TGF-β, NF-κB, Wnt, Notch, and others. In this review, we discuss the current knowledge about the role of the tumor microenvironment in EMT and the related signaling pathways as well as the interaction between them.