bluuebunny/crossref_metadata_2025 huggingface dataset:
Active DNA Demethylation Mediated by DNA Glycosylases
Authors: Zhu Jian-Kang
Published: November 2009

Active DNA demethylation is involved in many vital developmental and physiological processes of plants and animals. Recent genetic and biochemical studies in Arabidopsis have demonstrated that a subfamily of DNA glycosylases function to promote DNA demethylation through a base excision-repair pathway. These specialized bifunctional DNA glycosylases remove the 5-methylcytosine base and then cleave the DNA backbone at the abasic site, resulting in a gap that is then filled with an unmethylated cytosine nucleotide by as yet unknown DNA polymerase and ligase enzymes. Evidence suggests that active DNA demethylation in mammalian cells is also mediated at least in part by a base excision repair pathway where the AID/Apobec family of deaminases convert 5-methylcytosine to thymine followed by G/T mismatch repair by the DNA glycosylase MBD4 or TDG. This review also discusses other possible mechanisms of active DNA demethylation, how genome DNA methylation status might be sensed to regulate the expression of demethylase genes, and the targeting of demethylases by small RNAs.
Regressive Evolution in Astyanax Cavefish
Authors: Jeffery William R.
Published: November 2009

A diverse group of animals, including members of most major phyla, have adapted to life in the perpetual darkness of caves. These animals are united by the convergence of two regressive phenotypes, loss of eyes and pigmentation. The mechanisms of regressive evolution are poorly understood. The teleost Astyanax mexicanus is of special significance in studies of regressive evolution in cave animals. This species includes an ancestral surface dwelling form and many con-specific cave-dwelling forms, some of which have evolved their recessive phenotypes independently. Recent advances in Astyanax development and genetics have provided new information about how eyes and pigment are lost during cavefish evolution; namely, they have revealed some of the molecular and cellular mechanisms involved in trait modification, the number and identity of the underlying genes and mutations, the molecular basis of parallel evolution, and the evolutionary forces driving adaptation to the cave environment.
Cohesin: Its Roles and Mechanisms
Authors: Nasmyth Kim , Haering Christian H.
Published: November 2009

The cohesin complex is a major constituent of interphase and mitotic chromosomes. Apart from its role in mediating sister chromatid cohesion, it is also important for DNA double-strand-break repair and transcriptional control. The functions of cohesin are regulated by phosphorylation, acetylation, ATP hydrolysis, and site-specific proteolysis. Recent evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.
The Kinetochore and the Centromere: A Working Long Distance Relationship
Authors: Przewloka Marcin R. , Glover David M.
Published: November 2009

Accurate chromosome segregation is a prerequisite for the maintenance of the genomic stability. Consequently, elaborate molecular machineries and mechanisms emerged during the course of evolution in order to ensure proper division of the genetic material. The kinetochore, an essential multiprotein complex assembled on mitotic or meiotic centromeres, is an example of such machinery. Recently considerable progress has been made in understanding their composition, the recruitment hierarchy of their components, and the principles of their regulation. However, these advances are accompanied by a growing number of unanswered questions about the function of the individual subunits and of how the structure of the different subcomplexes relates to function. Here we review our rapidly growing knowledge on interacting networks of structural and regulatory proteins of the metazoan mitotic kinetochore: its centromeric foundations, its structural core, its components that interact with spindle microtubules and the spindle assembly checkpoint.
Dynamism in gene expression across multiple studies
Authors: Morgan Alexander A. , Dudley Joel T. , Deshpande Tarangini , Butte Atul J.
Published: November 2009

In this study we develop methods of examining gene expression dynamics, how and when genes change expression, and demonstrate their application in a meta-analysis involving over 29,000 microarrays. By defining measures across many experimental conditions, we have a new way of characterizing dynamics, complementary to measures looking at changes in absolute variation or breadth of tissues showing expression. We show conservation in overall patterns of dynamism across three species (human, mouse, and rat) and show associations with known disease-related genes. We discuss the enriched functional properties of the sets of genes showing different patterns of dynamics and show that the differences in expression dynamics is associated with the variety of different transcription factor regulatory sites. These results can influence thinking about the selection of genes for microarray design and the analysis of measurements of mRNA expression variation in a global context of expression dynamics across many conditions, as genes that are rarely differentially expressed between experimental conditions may be the subject of increased scrutiny when they significantly vary in expression between experimental subsets.
Growth Inhibition of Re‐Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma‐Targeted Chemo‐Thermo‐Immunotherapy
Authors: Takada Tomoaki , Yamashita Toshiharu , Sato Makito , Sato Akiko , Ono Ichiro , Tamura Yasuaki , Sato Noriyuki , Miyamoto Atsushi , Ito Akira , Honda Hiroyuki , Wakamatsu Kazumasa , Ito Shosuke , Jimbow Kowichi
Published: November 2009

Melanogenesis substrate, N‐propionyl‐cysteaminylphenol (NPrCAP), is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP) upon exposure to an alternating magnetic field (AMF). This study tested if a chemo‐thermo‐immunotherapy (CTI therapy) strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M). We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re‐challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re‐challenge transplant. The heat‐generated therapeutic effect was more significant at a temperature of 43∘C than either 41∘C or 46∘C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re‐challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43∘C compared to that with 41∘C or 46∘C. CD8+T cells were infiltrated at the site of the re‐challenge melanoma transplant.
The Expand Probability Analysis of a Surrounding Large Truss-Board Antenna
Authors: Zhang Jianguo , Chen Jianjun , Hu Taibin
Published: November 2009

Successful unfolding in the space is the first step for a satellite antenna to work normally, so that it is important to study the movement reliability of a large deployable satellite antenna. By studying the movement principium, a mechanical analysis model of the deployment mechanism and calculating formulae for the internal forces of trusses were presented. From the performance function of the truss unfolding to meet, a movement reliability analysis model of the mechanism was also given. Synthetically considering the dimension errors and the impact of space environmental factors, we treated the mechanism's movement as a function of random variables and derived the reliability calculation formula by using the method of second-order moment. Finally, the movement probability of the deployment mechanism was simulated by the computer within whole spreading process. The trend of the computing results agrees with the truss model experiments, which shows that the method is reasonable and effective.
Slow Rotation of Concentric Spheres with Source at Their Centre in a Viscous Fluid
Authors: Srivastava Deepak Kumar
Published: November 2009

The problem of concentric pervious spheres carrying a fluid source at their centre and rotating slowly with different uniform angular velocities Ω1, Ω2 about a diameter has been studied. The analysis reveals that only azimuthal component of velocity exists, and the couple, rate of dissipated energy is found analytically in the present situation. The expression of couple on inner sphere rotating slowly with uniform angular velocity Ω1, while outer sphere also rotates slowly with uniform angular velocity Ω2, is evaluated. The special cases, like (i) inner sphere is fixed (i.e., Ω1 = 0), while outer sphere rotates with uniform angular velocity Ω2, (ii) outer sphere is fixed (i.e., Ω2 = 0), while inner sphere rotates with uniform angular velocity Ω1, and (iii) inner sphere rotates with uniform angular velocity Ω1, while outer sphere rotates at infinity with angular velocity Ω2, have been deduced.
Supercell Band Calculations and Correlation for High- Copper Oxide Superconductors
Authors: Jarlborg T.
Published: November 2009

First principle band calculations based on local versions of density functional theory (DFT), together with results from nearly free-electron models, can describe many typical but unusual properties of the high- copper oxides. The methods and a few of the most important results are reviewed. Some additional calculations are presented, and the problems with the commonly used approximate versions of DFT for oxides are discussed with a few ideas for corrections. It is concluded that rather modest corrections to the approximate DFT, without particular assumptions about strong correlation, can push the ground state towards antiferro magnetic (AFM) order. Spin fluctuations interacting with phonons are crucial for the mechanism of superconductivity in this scenario.
Fibrin network structure and clot mechanical properties are altered by incorporation of erythrocytes
Authors: Gersh Kathryn , Nagaswami Chandrasekaran , Weisel John
Published: November 2009

Although many in vitro fibrin studies are performed with plasma, in vivo clots and thrombi contain erythrocytes, or red blood cells (RBCs).To determine the effects of RBCs on fibrin clot structure and mechanical properties, we compared plasma clots without RBCs to those prepared with low (2 vol%), intermediate (5-10 vol%), or high (≥20 vol%) numbers of RBCs. By confocal microscopy, we found that low RBC concentrations had little effect on clot structure. Intermediate RBC concentrations caused heterogeneity in the fiber network with pockets of densely packed fibers alongside regions with few fibers. With high levels of RBCs, fibers arranged more uniformly but loosely around the cells. Scanning electron micrographs demonstrated an uneven distribution of RBCs throughout the clot and a significant increase in fiber diameter upon RBC incorporation. While permeability was not affected by RBC addition, at 20% or higher RBCs, the ratio of viscous modulus (G′′) to elastic modulus (G′) increased significantly over that of a clot without any RBCs. RBCs triggered variability in the fibrin network structure, individual fiber characteristics, and overall clot viscoelasticity compared to the absence of cells. These results are important for understanding in vivo clots and thrombi.
Chlamydia pneumoniae adversely modulates vascular cell properties by direct interaction with signalling cascades
Authors: Kern Jan , Maass Viola , Maass Matthias
Published: November 2009

Due to its dependence on intracellular development Chlamydia pneumoniae has developed numerous strategies to create an adequate environment within its host cells ensuring both chlamydial reproduction and target cell survival. The bacterium that has been related to atherogenesis due to its presence in vascular tissue is able to enter a persistent state of chronic infection in the vasculature that escapes antibiotic targeting. Ingestion of the bacterium results in severe modifications and reprogramming of signalling pathways and the metabolism of the host cell. Processes range from the prevention of direct lysosomal destruction of chlamydial inclusions to the inhibition of host cell apoptosis and an enhanced cellular glucose uptake to maintain energy-consuming mechanisms. Furthermore, infection regularly causes the development of a proinflammatory and proproliferative phenotype in the host cell in vitro, ex vivo and in vivo and own new findings suggest a detrimental proliferative loop within vascular cells upon a modified endothelin-1 axis demonstrating a potential for proatherosclerotic processes in early and progressed atherosclerosis. This review displays crucial mechanisms of Chlamydia pneumoniae-induced interactions with vascular host cell signalling cascades with an emphasis on mitogenic and inflammatory processes as well as target cell activation.
Thrombin generation as an intermediate phenotype for venous thrombosis
Authors: Segers Olivier , Oerle René van , Cate Hugo ten , Rosing Jan , Castoldi Elisabetta
Published: November 2009

In vitro thrombin generation, which reflects an individual’s plasma coagulation potential and has been shown to correlate with the risk of venous thromboembolism (VTE), might represent a useful intermediate phenotype for the genetic dissection of VTE. As a proof of principle, we have investigated whether the thrombin generation assay can detect changes in the haemostatic balance associated with common genetic variation affecting the level or function of coagulation factors and inhibitors. The study population consisted of 140 healthy individuals. Plasma levels of coagulation factors and inhibitors and thrombin generation parameters determined at low tissue factor (TF) ± thrombomodulin (TM) and at high TF ± activated protein C (APC) were available from a previous study. All individuals were genotyped for F5 Leiden, F2 G20210A and 19 additional single nucleotide polymorphisms (SNPs) in haemostasis-related genes. The association of each SNP with plasma levels of the corresponding proteins and with thrombin generation parameters (lag time, peak height and endogenous thrombin potential [ETP]) was evaluated by statistical analysis. Not only F5 Leiden and F2 G20210A, but also several other common SNPs, significantly affected thrombin generation parameters. In particular, FGA A1069G (Thr312Ala) decreased the ETP-APC, F2 A19911G increased the ETP-APC, F10 IVS2 C+517G decreased the ETP+APC, F12 C-46T decreased peak height at low TF, and TFPI T-287C and TFPI IVS7 T-33C decreased the ETP+APC. These results indicate that the thrombin generation assay is sensitive to genetic variation in haemostasis-related genes, which makes it a promising tool to identify novel genetic risk factors of VTE.
The influence of variation in the P2Y12 receptor gene on in vitro platelet inhibition with the direct P2Y12 antagonist cangrelor
Authors: van Werkum Jochem , Rude Goran , Leebeek Frank , Kruit Adrian , Hackeng Christian , ten Berg Jurriën , de Maat Moniek , Ruven Henk , Bouman Heleen
Published: November 2009

Novel P2Y12 inhibitors are in development to overcome the occurrence of atherothrombotic events associated with poor responsiveness to the widely used P2Y12 inhibitor clopidogrel. Cangrelor is an intravenously administered P2Y12 inhibitor that does not need metabolic conversion to an active metabolite for its antiplatelet action, and as a consequence exhibits a more potent and consistent antiplatelet profile as compared to clopidogrel. It was the objective of this study to determine the contribution of variation in the P2Y12 receptor gene to platelet aggregation after in vitro partial P2Y12 receptor blockade with the direct antagonist cangrelor. Optical aggregometry was performed at baseline and after in vitro addition of 0.05 and 0.25 μM cangrelor to the platelet-rich plasma of 254 healthy subjects. Five haplotype-tagging (ht)-SNPs covering the entire P2Y12 receptor gene were genotyped (rs6798347C>t, rs6787801T>c, rs9859552C>a, rs6801273A>g and rs2046934T>c [T744C]) and haplotypes were inferred. The minor c allele of SNP rs6787801 was associated with a 5% lower 20 μM ADP-induced peak platelet aggregation (0.05 μM cangrelor, p<0.05). Aa homozygotes for SNP rs9859552 showed 20% and 17% less inhibition of platelet aggregation with cangrelor when compared to CC homozygotes (0.05 and 0.25 μM cangrelor respectively; p<0.05). Results of the haplotype analyses were consistent with those of the single SNPs. Polymorphisms of the P2Y12 receptor gene contribute significantly to the interindividual variability in platelet inhibition after partial in vitro blockade with the P2Y12 antagonist cangrelor.
Hydration does not prevent orthostatic hypercoagulability
Authors: Brenner Benjamin , Masoud Muhannad , Sarig Galit , Jacob Giris
Published: November 2009

Prolonged standing activates the coagulation cascade by the activation of endothelial cells, and probably the haemoconcentration effect contributes to this "orthostatic hypercoagulability". It was the objective of this study to assess whether rehydration (haemodilution) prevents or attenuates orthostatic induced thrombin formation. Twelve healthy young subjects were studied during two separate visits. Haematocrit (Hct), total plasma protein, coagulation profile tests, including endothelial activation related factors, and protein C global pathway were studied at rest supine, and while standing at 15 and 30 minutes (min). During the second visit the study was repeated after intravenous 1.5 liter 0.9% saline. While in supine posture, intravenous rehydration resulted in Hct reduction of 14.2 ± 2% (haemodilution), a decrease of 11.5 ± 1.3% in total protein, as well as a significant dilutional effect on most of the coagulation parameters. Still standing for 30 min, with and without rehydration caused a comparable increase in tissue factor by 49.83 ± 13.6%, and 35.34 ± 8.55% (p>0.05), respectively and in von Willebrand factor (vWF) 9.5 ± 2.4% and 13.59 ± 2.17% (p>0.05), respectively. At 30 min standing, after intravenous rehydration, factor V and VIII activities, and fibrinogen rose by 22 ± 1.9%, 31.2 ± 6.2%, 9.15 ± 2.64%, (p<0.002 for all), respectively. Prothrombin fragments 1+2 elevated by 84.84 ± 15.3% (p<0.001). Comparable results were obtained with and without the rehydration. Additionally, protein C assay results decreased by 19.4 ±1.7% and 17.5 ± 2.6%, with and without fluids (p<0.05 for both). In healthy subjects, intravenous prophylactic rehydration with normal saline resulted in a haemodilution of all the coagulation parameters, but did neither attenuate nor prevent the orthostatic hypercoagulability.
The contribution of systems biology and reverse genetics to the understanding of Kaposi’s sarcoma-associated herpesvirus pathogenesis in endothelial cells
Authors: Konrad Andreas , Alkharsah Khaled , Jochmann Ramona , Thurau Mathias , Marquardt Gaby , Stürzl Michael , Schulz Thomas
Published: November 2009

Kaposi’s sarcoma-associated herpesvirus (KSHV) / human herpesvirus-8 is the causative agent of the endothelial cell-derived tumour Kaposi’s sarcoma. Herpesviruses possess large complex genomes which provide many options to regulate cellular physiology during the viral life cycle and in the course of tumourigenicity. Novel techniques of systems biology and reverse genetics are increasingly applied to dissect the complex interaction of KSHV with endothelial cells. This review will outline novel results and pitfalls of these technologies in the elucidation of KSHV pathogenicity.
Venous thromboembolism during pregnancy, postpartum or during contraceptive use
Authors: Blanco-Molina Ángeles , Rota Lidia , Micco Pierpaolo Di , Brenner Benjamin , Trujillo-Santos Javier , Ruiz-Gamietea Angeles , Monreal Manuel ,   the RIETE Investigators
Published: November 2009

Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17–1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66–1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28–1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.
Endothelium, venous thromboembolism and ischaemic cardiovascular events
Authors: Momi Stefania , Migliacci Rino , Gresele Paolo
Published: November 2009

The association between venous thromboembolism and arterial thrombosis has emerged as consistent clinical observation in the last few years. While several experimental, epidemiological and pharmacologic studies support this association, the initial pathophysiological mechanism linking these two clinical conditions remains to be established. This review discusses the pathophysiological bases and a number of experimental and clinical observations suggesting that the common link between venous thromboembolism and arterial thrombosis is represented by a dysfunctional endothelium.
Multi-screen electronic alerts to augment venous thromboembolism prophylaxis
Authors: Fiumara Karen , Piovella Chiara , Hurwitz Shelley , Piazza Gregory , Niles Clyde , Fanikos John , Paterno Marilyn , Labreche Matthew , Stevens Leslie-Ann , Baroletti Steven , Goldhaber Samuel
Published: November 2009

Venous thromboembolism (VTE) prophylaxis in high-risk patients is frequently underutilised. We previously devised a one-screen computer alert program that identified hospitalised patients at high risk for VTE who were not receiving prophylaxis and advised their physicians to prescribe prophylaxis. While this strategy reduced the 90-day incidence of symptomatic VTE by 41%, the majority of electronic alerts were ignored. We have now developed a serial three-screen alert computer program designed to educate physicians who initially declined to order prophylaxis after a single screen alert. Of a total cohort of 880, the responsible physicians for 425 patients received a single electronic alert, whereas 455 who declined prophylaxis after the first screen received the second and third screens of the novel three-screen alert. Our enhanced serial three-screen alert program generated VTE prophylaxis orders for 58.4% of the 455 patients whose physicians initially declined to order prophylaxis following the one-screen alert. There was no significant difference in symptomatic 90-day VTE rates between the two cohorts (2.8% for the one-screen vs. 2.2% for the three-screen, p=0.55). We conclude that our three-screen computer alert program can markedly increase prophylaxis among physicians who decline an initial single screen alert.
Percutaneous Coronary Intervention Outcomes in a Low-Volume Center
Authors: Kenney Kimberly M. , Marzo Mitchell C. , Ondrasik Nicholas R. , Wisenbaugh Thomas
Published: November 2009

Background—

American College of Cardiology (ACC) guidelines state that percutaneous coronary interventions (PCI) be performed at centers and by operators with high-volume (>400 yearly/center) whose historical and current risk-adjusted outcomes statistics are comparable to those reported in large registries. Tripler Army Medical Center is a low-volume treatment facility but has a geographic need and special mission requirement for providing this service.

Methods and Results—

We computed 30-day incidence of stent thrombosis, need for repeat revascularization, and all-cause mortality for all PCIs performed at Tripler from January 2002 through June 2008. The New York State Registry regression model was selected among 3 risk-adjustment models that we assessed in our patients. This model was used to compute expected mortality rate based on patient risk factors. The 30-day incidence of stent thrombosis and repeat revascularization was also determined, and the long-term incidence of these events was estimated with the Kaplan–Meier method as was survival. For all 546 PCI procedures, 30-day mortality was 1.47%, the incidence of stent thrombosis 2.1%, the incidence of any repeat revascularization 5.1%, and the combined event rate 5.9%. Based on risk factors used in the New York State Registry, our expected mortality was 1.93% and not significantly different from the observed rate. Although survival at 1 and 3 years appeared comparable with benchmarks at 94.6% and 89.3%, as did repeat revascularization rates at 13.0% and 21.4%, the incidence of stent thrombosis was regarded as high whether the definition included possible cases (3.2% and 3.9%) or only those regarded as definite or probable (2.7% and 3.1%). We did not identify any remediable risk factors for stent thrombosis, nor were we able to identify significant differences by year or by operator. However, visual inspection of a plot of deciles of New York State risk of death demonstrated 2 outlier cases among the 8 who died, who could have been considered candidates for thorough peer review.

Conclusion—

We recommend other low-volume interventional programs enter all patients undergoing PCI into a database, their own local registry even if not a national one such as the American College of Cardiology National Cardiovascular Data Registry, obtain information about survival and cardiac events during follow-up, compute and risk-adjust in-hospital or 30-day mortality, and use the objective assessment of risk in individual patients to identify outliers when outcome is adverse, and possibly as a means of triaging patients to appropriate therapy before choosing PCI.
Vision and Creation of the American Heart Association Pharmaceutical Roundtable Outcomes Research Centers
Authors: Peterson Eric D. , Spertus John A. , Cohen David J. , Hlatky Mark A. , Go Alan S. , Vickrey Barbara G. , Saver Jeffrey L. , Hinton Patricia C.
Published: November 2009

Background—

The field of outcomes research seeks to define optimal treatment in practice and to promote the rapid full adoption of efficacious therapies into routine clinical care. The American Heart Association (AHA) formed the AHA Pharmaceutical Roundtable (PRT) Outcomes Research Centers Network to accelerate attainment of these goals. Participating centers were intended to carry out state-of-the-art outcomes research in cardiovascular disease and stroke, to train the next generation of investigators, and to support the formation of a collaborative research network.

Program—

After a competitive application process, 4 AHA PRT Outcomes Research Centers were selected: Duke Clinical Research Institute; Saint Luke’s Mid America Heart Institute; Stanford University–Kaiser Permanente of Northern California; and University of California, Los Angeles. Each center proposed between 1 and 3 projects organized around a single theme in cardiovascular disease or stroke. Additionally, each center will select and train up to 6 postdoctoral fellows over the next 4 years, and will participate in cross-collaborative activities among the centers.

Conclusions—

The AHA PRT Outcomes Research Centers Network is designed to further strengthen the field of cardiovascular disease and stroke outcomes research by fostering innovative research, supporting high quality training, and encouraging center-to-center collaborations.
Impact of Implantable Cardioverter-Defibrillator, Amiodarone, and Placebo on the Mode of Death in Stable Patients With Heart Failure
Authors: Packer Douglas L. , Prutkin Jordan M. , Hellkamp Anne S. , Mitchell L. Brent , Bernstein Robert C. , Wood Freda , Boehmer John P. , Carlson Mark D. , Frantz Robert P. , McNulty Steve E. , Rogers Joseph G. , Anderson Jill , Johnson George W. , Walsh Mary Norine , Poole Jeanne E. , Mark Daniel B. , Lee Kerry L. , Bardy Gust H.
Published: November 2009

Background—

The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown.

Methods and Results—

SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death.

Conclusions—

ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients.

Clinical Trial Registration Information—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.
Endothelial Progenitor Cells Bind and Inhibit Platelet Function and Thrombus Formation
Authors: Abou-Saleh Haissam , Yacoub Daniel , Théorêt Jean-François , Gillis Marc-Antoine , Neagoe Paul-Eduard , Labarthe Benoit , Théroux Pierre , Sirois Martin G. , Tabrizian Maryam , Thorin Eric , Merhi Yahye
Published: November 2009

Background—Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation.

Methods and Results—Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride–induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow.

Conclusions—Peripheral blood mononuclear cell–derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential roles in regulating platelet function and thrombosis.
Aliskiren Monotherapy Does Not Cause Paradoxical Blood Pressure Rises
Authors: Stanton Alice V. , Gradman Alan H. , Schmieder Roland E. , Nussberger Juerg , Sarangapani Ramesh , Prescott Margaret F.
Published: November 2009

Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after ≥4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (>10 mm Hg;
P
=0.30) or diastolic (>5 mm Hg;
P
=0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%;
P
<0.001). None of the 536 patients with plasma renin activity data who received 300 mg of aliskiren exhibited an increase in systolic pressure >10 mm Hg that was associated with an increase in plasma renin activity >0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure.
Relationship between Lightning Activity over Peninsular India and Sea Surface Temperature
Authors: Tinmaker M. I. R. , Ali Kaushar , Beig G.
Published: November 2009

This paper presents a study of spatiotemporal variation of lightning activity over Peninsular India (8°–22°N, 72°–88°E) by using monthly satellite-based lightning flash grid (1° × 1°) data for a period of 10 yr (1998–2007). The data are examined in terms of spatial, annual, and seasonal distribution of the lightning activity. It is found that lightning activity is higher over south Peninsular India and eastern India. On a seasonal time scale, the lightning activity shows two maxima—first in the month of May and then in the month of September. The lightning activity in the monsoon period is noticed to be considerable because of the occurrence of the low-level jet and increase in the monsoon break period. During the postmonsoon, the activity is mainly due to the presence of the convective nature of the disturbed weather during the northeast monsoon season over most parts of the east coast of south Peninsular India. The relationship between lightning activity over Peninsular India and sea surface temperature in the bordering seas (Arabian Sea and Bay of Bengal) is also examined. The results disclose a significant link between them.
Generation of Infrasound by Evaporating Hydrometeors in a Cloud Model
Authors: Schecter David A. , Nicholls Melville E.
Published: November 2009

The dynamical core of the Regional Atmospheric Modeling System has been tailored to simulate the infrasound of vortex motions and diabatic cloud processes in a convective storm. Earlier studies have shown that the customized model (c-RAMS) adequately simulates the infrasonic emissions of generic vortex oscillations. This paper provides evidence that c-RAMS accurately simulates the infrasound associated with parameterized phase transitions of cloud moisture. Specifically, analytical expressions are derived for the infrasonic emissions of evaporating water droplets in dry and humid environments. The dry analysis considers two single-moment parameterizations of the microphysics, which have distinguishable acoustic signatures. In general, the analytical results agree with the numerical output of the model. An appendix briefly demonstrates the ability of c-RAMS to accurately simulate the infrasound of the entropy and mass sources generated by an equilibrating cloud of icy hydrometeors.
Noah LSM Snow Model Diagnostics and Enhancements
Authors: Livneh Ben , Xia Youlong , Mitchell Kenneth E. , Ek Michael B. , Lettenmaier Dennis P.
Published: November 2009

A negative snow water equivalent (SWE) bias in the snow model of the Noah land surface scheme used in the NCEP suite of numerical weather and climate prediction models has been noted by several investigators. This bias motivated a series of offline tests of model extensions and improvements intended to reduce or eliminate the bias. These improvements consist of changes to the model’s albedo formulation that include a parameterization for snowpack aging, changes to how pack temperature is computed, and inclusion of a provision for refreeze of liquid water in the pack. Less extensive testing was done on the performance of model extensions with alternate areal depletion parameterizations. Model improvements were evaluated through comparisons of point simulations with National Resources Conservation Service (NRCS) Snowpack Telemetry (SNOTEL) SWE data for deep-mountain snowpacks at selected stations in the western United States, as well as simulations of snow areal extent over the conterminous United States (CONUS) domain, compared with observational data from the NOAA Interactive Multisensor Snow and Ice Mapping System (IMS). The combination of snow-albedo decay and liquid-water refreeze results in substantial improvements in the magnitude and timing of peak SWE, as well as increased snow-covered extent at large scales. Modifications to areal snow depletion thresholds yielded more realistic snow-covered albedos at large scales.
Evaluation of GSMaP Precipitation Estimates over the Contiguous United States
Authors: Tian Yudong , Peters-Lidard Christa D. , Adler Robert F. , Kubota Takuji , Ushio Tomoo
Published: November 2009

Precipitation estimates from the Global Satellite Mapping of Precipitation (GSMaP) project are evaluated over the contiguous United States (CONUS) for the period of 2005–06. GSMaP combines precipitation retrievals from the Tropical Rainfall Measuring Mission satellite and other polar-orbiting satellites, and interpolates them with cloud motion vectors derived from infrared images from geostationary satellites, to produce a high-resolution dataset. Four other satellite-based datasets are also evaluated concurrently with GSMaP, to provide a better perspective. The new Climate Prediction Center (CPC) unified gauge analysis is used as the reference data. The evaluation shows that GSMaP does well in capturing the spatial patterns of precipitation, especially for summer, and that it has better estimation of precipitation amount over the eastern than over the western CONUS. Meanwhile, GSMaP shares many of the challenges common to other satellite-based products, including that it underestimates in winter and overestimates in summer. In winter, GSMaP has on average one-half less precipitation over the western region and one-third less over the eastern region, whereas in summer it has about three-quarters and one-quarter more estimated precipitation over the two respective regions, respectively. Most of the summer overestimates (winter underestimates) are from an excessive (insufficient) number of strong events (>20 mm day−1). Overall, GSMaP’s performance is comparable to other satellite-based products, with slightly better probability of detection during summer, and the different satellite-based estimates as a group have better agreement among themselves during summer than during winter.
Democratization in the Arab World
Authors: Mohapatra Aswini K.
Published: November 2009

The article argues that the Turkish experience with democracy may not offer a ‘model’ for democratization of the Arab states in West Asia and North Africa. It begins with a brief account of institutional and political changes in Turkey since the establishment of the modern Turkish Republic. It also explains how historical and structural conditions conducive to Turkey’s progression to democracy are absent in much of the Arab world. It concludes that the Turkish experience is sui generis and cannot be replicated by any other state in the region. Nevertheless, it does provide an example for Arab liberal reformers, currently campaigning for democracy and political pluralism in the region.
Palestinian Politics in the Post-Arafat Period
Authors: Pradhan Bansidhar
Published: November 2009

The article examines the key developments in Palestinian politics in the post-Arafat era, including the decision of Hamas to participate in the democratic political process. Even though the issue of succession was settled with much more ease than expected, the divisions within the Palestinian movement came to the fore with the electoral victory of Hamas in the January 2006 legislative elections. The subsequent power struggle between Fatah and Hamas completely fragmented the Palestinian community. The author argues that the external actors—particularly the US and Israel—are mostly, though not entirely, responsible for such political fragmentation and the subsequent weakening of the Palestinian movement.
Horizontal Transmission of Mutans Streptococci in Children
Authors: Doméjean S. , Zhan L. , DenBesten P.K. , Stamper J. , Boyce W.T. , Featherstone J.D.
Published: November 2009

It has not been established whether transmission of mutans streptococci occurs between unrelated children older than 4 years of age. The aim of the study was to investigate the possible transmission of mutans streptococci genotypes from child to child in kindergarten. We studied 96 children (ages 5–6 yrs) in three San Francisco Bay Area public schools. Mutans streptococci colonies from each child were isolated from selective culture on Mitis Salivarius Sucrose Bacitracin agar. We used arbitrary primed polymerase chain reactions to determine the mutans streptococci genotypes. Two children (not siblings) in each of the three schools (6%) shared an identical amplitype of S. mutans, unique to each pair. The 19 S. sobrinus amplitypes were found in 12 children, and all were unique to each child. The presence of matching genotypes of S. mutans demonstrates horizontal transmission of this species between unrelated children aged 5–6 years.
Exploratory Work on the Spinning Condition of the Structure of Staple-core Twin-spun Yarns
Authors: Matsumoto Yo-ichi , Kanai Hiroyuki , Morooka Hideo , Kimura Hirokazu , Fukushima Kazunari
Published: November 2009

In order to design and develop novel-spun yarns with good functionality, we investigated how to construct a core-sheath structure adapted from a multilayered structure of triplet-spun yarn and/or made from a twin-spun yarn with core-staple fibers using an experimental ring-spinning frame. The results were follows: (1) staple-core twin-spun yarn, a new yarn, could be made by applying the production method of triplet-spun yarn and/or combining the production methods of core-spun yarn and twin-spun yarn into one twisting process; (2) by adopting three rovings made from fibers of differing length and fineness, the resulting triplet-spun yarn had the core-sheath structure within an adequate spinning condition; (3) for the construction of core-sheath structure, it is important that there be a difference between spinning tensions at the center and the two sides of the drafted fiber strands or drafted strand lengths from the front roller nip to the point of yarn formation by controlling the distance of the supply rovings and the yarn’s twist factor.
Prediction Method for Temporal Change in Fiber Orientation on Cylindrical Braided Preforms
Authors: Nishimoto Hiroyuki , Ohtani Akio , Nakai Asami , Hamada Hiroyuki
Published: November 2009

An advantage of braided fabrics is that the fiber bundle orientation angle, called the “braiding angle,” can be changed. Because the braiding angle affects the fabric’s mechanical properties, changing the angle is an important means of adjusting the stiffness distribution as required. However, when the braiding angle is changing from an initial braiding angle to a targeted braiding angle designated by the longitudinal velocity of the mandrel, some delay occurs before the actual braiding angle reaches the targeted braiding angle. Previously, several models have been developed in order to predict braiding angles, although a prediction method for a temporal change in braiding angle caused by the mandrel velocity change has not been presented. In order to obtain the temporal change in braiding angle under unsteady-state conditions, this paper presents a step response model in braiding angle on a cylindrical braided fabric. Furthermore, the method is verified with the experimental data. As a consequence, the model has proved effective for predicting fiber orientation on a cylindrical braided preform under unsteady-state conditions.
Informal Civil—Military Relations in Latin America: Why Politicians and Soldiers Choose Unofficial Venues
Authors: Pion-Berlin David
Published: November 2009

This study examines the phenomenon of informal civil—military relations. Informal behaviors are those that normally do not occur within the chain of command, are not mandated by law, and do not conform to official procedures. Politicians and soldiers discover that formal, institutional routines are sometimes too constraining and that they can advance their interests more effectively by amending, circumventing, or violating those routines. The party most aggrieved by the rules of the game initiates an informal solution. Whether the other side goes along depends on how divergent its preferences are with the aggrieved party. Greatly divergent preferences result in unilateral informalities, less divergent but still negotiable positions yield bilateral-conflictive encounters, and convergent preferences result in cooperative ventures. Case studies on Chile, Argentina, and Bolivia exemplify three different kinds of informal encounters and their impacts on civilian policy choices and military interests.