bluuebunny/crossref_metadata_2025 huggingface dataset:
In VitroGrowth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali
Authors: Crompton Peter D. , Miura Kazutoyo , Traore Boubacar , Kayentao Kassoum , Ongoiba Aissata , Weiss Greta , Doumbo Safiatou , Doumtabe Didier , Kone Younoussou , Huang Chiung-Yu , Doumbo Ogobara K. , Miller Louis H. , Long Carole A. , Pierce Susan K.
Published: November 2009

Immunity to the asexual blood stage ofPlasmodium falciparumis complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a correspondingin vitrocorrelate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth ofP. falciparum in vitro. In humans, naturally acquired and vaccine-inducedP. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95;P= 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85;P= 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as anin vitrocorrelate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity.
INTERPRETATION OF HANDWRITTEN SINGLE-STROKE GRAFFITI USING SUPPORT VECTOR MACHINES
Authors: LAM H. K. , PRADA J.
Published: November 2009

This paper presents the graffiti interpretation of one-stroke handwritten digits (0 to 9) and commands (backspace, carriage return and space) using support vector machines (SVMs). A number of SVM-based graffiti interpreters are proposed for the recognition of graffiti. The performance of the proposed SVM-based graffiti interpreters subject to various kernel functions and parameters are investigated. Simulation and experimental results are presented to show the applicability and the merits of various graffiti interpreters.
A VECTOR MATRIX REAL TIME RECURSIVE BACKPROPAGATION ALGORITHM FOR RECURRENT NEURAL NETWORKS THAT APPROXIMATE MULTI-VALUED PERIODIC FUNCTIONS
Authors: STUBBERUD PETER
Published: November 2009

Unlike feedforward neural networks (FFNN) which can act as universal function approximators, recursive, or recurrent, neural networks can act as universal approximators for multi-valued functions. In this paper, a real time recursive backpropagation (RTRBP) algorithm in a vector matrix form is developed for a two-layer globally recursive neural network that has multiple delays in its feedback path. This algorithm has been evaluated on two GRNNs that approximate both an analytic and nonanalytic periodic multi-valued function that a feedforward neural network is not capable of approximating.
FUZZY OPERATOR TREES FOR MODELING RATING FUNCTIONS
Authors: YI YU , FOBER THOMAS , HÜLLERMEIER EYKE
Published: November 2009

We introduce a new method for modeling rating (utility) functions which employs techniques from fuzzy set theory. The main idea is to build a hierarchical model, called a fuzzy operator tree (FOT), by recursively decomposing a rating criterion into sub-criteria, and to combine the evaluations of these sub-criteria by means of suitable aggregation operators. Apart from the model conception itself, we propose an evolutionary method for model calibration that fits the parameters of an FOT to exemplary ratings. The possibility to adapt an FOT to a given set of data makes the approach also interesting from a machine learning point of view. The performance of the approach is evaluated by means of a suitable experimental study.
ANNEALED CHAOTIC LEARNING FOR TIME SERIES PREDICTION IN IMPROVED NEURO-FUZZY NETWORK WITH FEEDBACKS
Authors: VAIRAPPAN CATHERINE , GAO SHANGCE , TANG ZHENG , TAMURA HIROKI
Published: November 2009

A new version of neuro-fuzzy system of feedbacks with chaotic dynamics is proposed in this work. Unlike the conventional neuro-fuzzy, improved neuro-fuzzy system with feedbacks is better able to handle temporal data series. By introducing chaotic dynamics into the feedback neuro-fuzzy system, the system has richer and more flexible dynamics to search for near-optimal solutions. In the experimental results, performance and effectiveness of the presented approach are evaluated by using benchmark data series. Comparison with other existing methods shows the proposed method for the neuro-fuzzy feedback is able to predict the time series accurately.
A TWO-STATE ANT COLONY ALGORITHM FOR SOLVING THE MINIMUM GRAPH BISECTION PROBLEM
Authors: WANG RONG-LONG , OKAZAKI KOZO
Published: November 2009

The graph bisection problem is an important problem in printed circuit board layout and communication networks. Since it is known to be NP-complete, approximation algorithm have been considered. In this paper, we propose a so-called two-state ant colony algorithm for efficiently solving the problem. In the proposed algorithm two kinds of pheromone and two kinds of heuristic information are introduced to reinforce the search ability. The proposed algorithm is tested on a large number of instances and is compared with a heuristic algorithm and a genetic algorithm. The experimental results show that the proposed approach is superior to its competitors.
Genetic Control of Programmed Cell Death During Animal Development
Authors: Conradt Barbara
Published: November 2009

The elimination of unwanted cells by programmed cell death is a common feature of animal development. Genetic studies in the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse have not only revealed the molecular machineries that cause the programmed demise of specific cells, but have also allowed us to get a glimpse of the types of pathways that regulate these machineries during development. Rather than serving as a broad overview of programmed cell death during development, this review focuses on recent advances in our understanding of the regulation of specific programmed cell death events during nematode, fly, and mouse development. Recent studies have revealed that many of the regulatory pathways involved play additional important roles in development, which confirms that the programmed cell death fate is an integral aspect of animal development.
Regulation of the cGMP-cPKG pathway and large-conductance Ca2+-activated K+ channels in uterine arteries during the ovine ovarian cycle
Authors: Khan Liaqat H. , Rosenfeld Charles R. , Liu Xiao-tie , Magness Ronald R.
Published: November 2009

The follicular phase of the ovine ovarian cycle demonstrates parallel increases in ovarian estrogens and uterine blood flow (UBF). Although estrogen and nitric oxide contribute to the rise in UBF, the signaling pathway remains unclear. We examined the relationship between the rise in UBF during the ovarian cycle of nonpregnant sheep and changes in the uterine vascular cGMP-dependent pathway and large-conductance Ca2+-activated K+ channels (BKCa). Nonpregnant ewes ( n = 19) were synchronized to either follicular or luteal phase using a vaginal progesterone-releasing device (CIDR), followed by intramuscular PGF2α, CIDR removal, and treatment with pregnant mare serum gonadotropin. UBF was measured with flow probes before tissue collection, and second-generation uterine artery segments were collected from nine follicular and seven luteal phase ewes. The pore-forming α- and regulatory β-subunits that constitute the BKCa, soluble guanylyl cyclase (sGC), and cGMP-dependent protein kinase G (cPKG) isoforms (cPKG1α and cPKG1β) were measured by Western analysis and cGMP levels by RIA. BKCa subunits were localized by immunohistochemistry. UBF rose >3-fold ( P < 0.04) in follicular phase ewes, paralleling a 2.3-fold rise in smooth muscle cGMP and 32% increase in cPKG1α ( P < 0.05). sGC, cPKG1β, and the BKCa α-subunit were unchanged. Notably, expression of β1- and β2-regulatory subunits rose 51 and 79% ( P ≤ 0.05), respectively. Increases in endogenous ovarian estrogens in follicular-phase ewes result in increases in UBF associated with upregulation of the cGMP- and cPKG-dependent pathway and increased vascular BKCa β/α-subunit stoichiometry, suggesting enhanced BKCa activation contributes to the follicular phase rise in UBF.
Neonatal growth and regeneration of β-cells are regulated by the Wnt/β-catenin signaling in normal and diabetic rats
Authors: Figeac Florence , Uzan Benjamin , Faro Monique , Chelali Noura , Portha Bernard , Movassat Jamileh
Published: November 2009

Wnt/β-catenin signaling is critical for a variety of fundamental cellular processes. Here, we investigated the implication of the Wnt/β-catenin signaling in the in vivo regulation of β-cell growth and regeneration in normal and diabetic rats. To this aim, TCF7L2, the distal effector of the canonical Wnt pathway, was knocked down in groups of normal and diabetic rats by the use of specific antisense morpholino-oligonucleotides. In other groups of diabetic rats, the Wnt/β-catenin pathway was activated by the inhibition of its negative regulator GSK-3β. GSK-3β was inactivated by either LiCl or anti-GSK-3β oligonucleotides. The β-cell mass was evaluated by morphometry. β-cell proliferation was assessed in vivo and in vitro by BrdU incorporation method. In vivo β-cell neogenesis was estimated by the evaluation of PDX1-positive ductal cells and GLUT2-positive ductal cells and the number of β cells budding from the ducts. We showed that the in vivo disruption of the canonical Wnt pathway resulted in the alteration of normal and compensatory growth of β-cells mainly through the inhibition of β-cell proliferation. Conversely, activation of the Wnt pathway through the inhibition of GSK-3β had a significant stimulatory effect on β-cell regeneration in diabetic rats. In vitro, GSK-3β inactivation resulted in the stimulation of β-cell proliferation. This was mediated by the stabilization of β-catenin and the induction of cyclin D. Taken together, our results demonstrate the involvement of the canonical Wnt signaling in the neonatal regulation of normal and regenerative growth of pancreatic β-cells. Moreover, we provide evidence that activation of this pathway by pharmacological maneuvers can efficiently improve β-cell regeneration in diabetic rats. These findings might have potential clinical applications in the regenerative therapy of diabetes.
Dynamic insulin sensitivity index: importance in diabetes
Authors: Pillonetto Gianluigi , Caumo Andrea , Cobelli Claudio
Published: November 2009

The classical minimal model (MM) index of insulin sensitivity, SI, does not account for how fast or slow insulin action takes place. In a recent work, we proposed a new dynamic insulin sensitivity index, SID, which is able to take into account the dynamics of insulin action as well. The new index is a function of two MM parameters, namely SI and p2, the latter parameter governing the speed of rise and decay of insulin action. We have previously shown that in normal glucose tolerant subjects SID provides a more comprehensive picture of insulin action on glucose metabolism than SI. The aim of this study is to show that resorting to SID rather SI is even more appropriate when studying diabetic patients who have a low and slow insulin action. We analyzed insulin-modified intravenous glucose tolerance test studies performed in 10 diabetic subjects and mixed meal glucose tolerance test studies exploiting the triple tracer technique in 14 diabetic subjects. We derived both SI and SID resorting to Bayesian and Fisherian identification strategies. The results show that SID is estimated more precisely than SI when using the Bayesian approach. In addition, the less labor-intensive Fisherian approach can still be used to obtain reliable point estimates of SID but not of SI. These results suggest that SID yields a comprehensive, precise, and cost-effective assessment of insulin sensitivity in subjects with impaired insulin action like impaired glucose tolerant subjects or diabetic patients.
Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney
Authors: Dunbar Donald R. , Khaled Hiba , Evans Louise C. , Al-Dujaili Emad A. S. , Mullins Linda J. , Mullins John J. , Kenyon Christopher J. , Bailey Matthew A.
Published: November 2009

We investigated the effects on urinary steroid and electrolyte excretion and renal gene expression of chronic infusions of ACTH in the mouse. ACTH caused a sustained increase in corticosteroid excretion; aldosterone excretion was only transiently elevated. There was an increase in the excretion of deoxycorticosterone, a weak mineralocorticoid, to levels of physiological significance. Nevertheless, we observed neither antinatriuresis nor kaliuresis in ACTH-treated mice, and plasma renin activity was not suppressed. We identified no changes in expression of mineralocorticoid target genes. Water turnover was increased in chronic ACTH-treated mice, as were hematocrit and hypertonicity: volume contraction is consistent with high levels of glucocorticoid. ACTH-treated mice exhibited other signs of glucocorticoid excess, such as enhanced weight gain and involution of the thymus. We identified novel ACTH-induced changes in 1) genes involved in vitamin D ( Cyp27b1, Cyp24a1, Gc) and calcium ( Sgk, Calb1, Trpv5) metabolism associated with calciuria and phosphaturia; 2) genes that would be predicted to desensitize the kidney to glucocorticoid action ( Nr3c1, Hsd11b1, Fkbp5); and 3) genes encoding transporters of enzyme systems associated with xenobiotic metabolism and oxidative stress. Although there is evidence that ACTH-induced hypertension is a function of physiological cross talk between glucocorticoids and mineralocorticoids, the present study suggests that the major changes in electrolyte and fluid homeostasis and renal function are attributable to glucocorticoids. The calcium and organic anion metabolism pathways that are affected by ACTH may explain some of the known adverse effects associated with glucocorticoid excess.
Protection ofSalvia miltiorrhizaeto the Spleen and Thymus of Rats with Severe Acute Pancreatitis or Obstructive Jaundice
Authors: Xiping Zhang , Chuyang Li , Jie Zhang , Yuefang Ruan , Meili Ma
Published: November 2009

Objective. To investigate the therapeutic effects and mechanism ofSalvia miltiorrhizaein the treatment of SAP and OJ.Methods. A total of 288 rats were used for SAP- and OJ-associated experiments. The rats were randomly divided into sham-operated group, model control group and treated group. The mortality rates of rats, contents of endotoxin andPLA2in blood, patholodgical changes of different indexes in spleen and thymus were observed.Results. The contents of endotoxin and PLA2 in treated group were significantly lower than those in model control group.The pathological severity scores of spleen and thymus of SAP rats as well as that of spleen of OJ rats in treated groups were significantly lower than those in model control groups (P<.05). The staining intensity as well as the product of the staining intensity and positive rate of Bax protein of spleen in model control group were significantly higher than those in treated groups (P<.01) , and the apoptosis index of spleen in treated group was significantly lower than that in model control group (P<.01).Conclusion.Salvia miltiorrhizaeexerts protective effects on the spleen and thymus of SAP rats and spleen of OJ rats.
About the Use of the HdHr Algorithm Group in Integrating the Movement Equation with Nonlinear Terms
Authors: Bottura Heitor Miranda , Rigitano Antonio Carlos
Published: November 2009

This work summarizes the HdHr group of Hermitian integration algorithms for dynamic structural analysis applications. It proposes a procedure for their use when nonlinear terms are present in the equilibrium equation. The simple pendulum problem is solved as a first example and the numerical results are discussed. Directions to be pursued in future research are also mentioned.
Exploring Cortical Attentional System by Using fMRI during a Continuous Perfomance Test
Authors: Tana M. G. , Montin E. , Cerutti S. , Bianchi A. M.
Published: November 2009

Functional magnetic resonance imaging (fMRI) was performed in eight healthy subjects to identify the localization, magnitude, and volume extent of activation in brain regions that are involved in blood oxygen level-dependent (BOLD) response during the performance of Conners' Continuous Performance Test (CPT). An extensive brain network was activated during the task including frontal, temporal, and occipital cortical areas and left cerebellum. The more activated cluster in terms of volume extent and magnitude was located in the right anterior cingulate cortex (ACC). Analyzing the dynamic trend of the activation in the identified areas during the entire duration of the sustained attention test, we found a progressive decreasing of BOLD response probably due to a habituation effect without any deterioration of the performances. The observed brain network is consistent with existing models of visual object processing and attentional control and may serve as a basis for fMRI studies in clinical populations with neuropsychological deficits in Conners' CPT performance.
Browder's Convergence for Uniformly Asymptotically Regular Nonexpansive Semigroups in Hilbert Spaces
Authors: López Acedo Genaro , Suzuki Tomonari
Published: November 2009

We give a sufficient and necessary condition concerning a Browder's convergence type theorem for uniformly asymptotically regular one-parameter nonexpansive semigroups in Hilbert spaces.
Enzymatic and mRNA Transcript Response of Ovine 6-Phosphogluconate Dehydrogenase (6PGD) in Respect to Different Milk Yield
Authors: Trivizaki Stamatina , Laliotis George P. , Bizelis Iosif , Charismiadou Maria A. , Rogdakis Emmanuel
Published: November 2009

Ovine 6-phosphogluconate dehydrogenase (6PGD) is an enzyme of the pentose phosphate pathway, providing the necessary compounds of NADPH for the synthesis of fatty acids. Much of research has been conducted both on enzymatic level and on molecular level. However, to our knowledge, any correlation between enzymatic activity and 6PGD gene expression pattern related to different physiological stages has not been yet reported. With this report, we tried to highlight if any correlation between enzymatic activity and expression of ovine 6PGD gene exists, in respect to different milk yield. According to the determined enzymatic activities and adipocytes characteristics, ewes with low milk production possessed a greater (P≤.001) 6PGD activity and larger adipocytes than the highly productive ewes. Although 6PGD expression pattern was higher in low milk yield ewes than in ewes with high milk production, this difference was not found statistically significant. Thus, 6PGD gene expression pattern was not followed by so rapid and great/sizeable changes as it was observed for its respective enzymatic activity, suggesting that other mechanisms such as post translation regulation may be involved in the regulation of the respective gene.
Safety, pharmacokinetics and pharmacodynamics of single doses of rivaroxaban – an oral, direct factor Xa inhibitor – in elderly Chinese subjects
Authors: Jiang Ji , Hu Yufang , Zhang Jianyan , Yang Jueling , Mueck Wolfgang , Kubitza Dagmar , Bauer Richard , Meng Ling , Hu Pei
Published: November 2009

Rivaroxaban is a novel, oral, direct factor Xa (FXa) inhibitor for the prevention and treatment of thromboembolic disorders. The aim of this study was to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy, elderly Chinese subjects. In this single-centre, single-blind, placebo-controlled, parallel-group, dose-escalation study, 79 subjects, aged 59–74 years (mean 62.8), were randomised to receive once-daily oral doses of rivaroxaban 5, 10, 20, 30 or 40 mg. Rivaroxaban was well tolerated: there was a low incidence of treatment-emergent adverse events and all events were of mild intensity. Rivaroxaban was absorbed rapidly, reaching maximum plasma concentrations within 2–4 hours. The PK of rivaroxaban were dose dependent over the dose range tested. Maximal inhibition of FXa occurred 2–3 hours after dosing and returned to baseline after 24–48 hours, reflecting rivaroxaban plasma concentrations. Inhibition of FXa was associated with dose-dependent effects on global clotting tests. There were no clinically relevant differences in rivaroxaban plasma concentrations between male and female subjects. In conclusion, rivaroxaban was well tolerated and was found to have predictable PK and PD in healthy, elderly Chinese subjects.
A fusion protein with improved thrombolytic effect and low bleeding risk
Authors: Wang Lisheng , Zhang Qinglin , Qin Yide , Wu Chutse , Wang Xiudong , Zhang Guangman , Yu Aiping
Published: November 2009

To resolve the therapeutic dilemma between efficacy of thrombolysis and bleeding risk associated with the use of a combination of thrombolytic and anticoagulant treatments, we created a fusion protein. Staphylokinase was fused to the N-terminus of hirudin using thrombin recognition sequence as linker peptide, resulting in a fusion protein STH.We hypothesised that STH would be cleaved by thrombin at the thrombus site, releasing staphylokinase and hirudin to perform bifunctionally, and attenuating bleeding risk. SDS-PAGE andWestern blot analyses indicated that the linker peptide could be specially recognised and cleaved by thrombin. Amidolytic and thromboelastogram assays showed that the N-terminus of hirudin in STH was blocked by staphylokinase and linker peptide, impeding hirudin’s anticoagulant activity. Once cleaved, STH displayed 35.7% of the anticoagulant activity of equimolar hirudin and exhibited anticoagulant effects in the fibrin clot lysis assay.Thrombin-binding and fibrin clot lysis assays showed that the C-terminus of hirudin retained its high affinity for thrombin. Moreover, STH showed improved thrombolytic effects and a lower bleeding risk in animals. Thus, STH may have the capacity to perform bifunctionally and release anticoagulant activity in a thrombus-targeted manner in vivo, which may reduce the bleeding risk that often accompanies high thrombolytic efficacy in the treatment of thromboembolic diseases.
Different expression of proteins in platelets from aspirin-resistant and aspirin-sensitive patients
Authors: Macaya Carlos , Azcona Luis , Modrego Javier , Mahillo Estela , Bernardo Esther , Fernández-Ortiz Antonio , López-Farré Antonio , Mateos-Cáceres Petra
Published: November 2009

The aim of the present study was to analyse differences in the protein expression profile between platelets from aspirin (ASA)-resistant patients and ASA-sensitive patients. We analysed platelets from 51 clinically stable coronary ischaemic patients taking ASA (100 mg/day) divided into ASA-resistant (n=25) and ASA-sensitive (n=26) based on a platelet functionality test (PFA-100). Proteins associated with cytoskeleton, energetic metabolism, oxidative stress, inflammation and cell survival were analysed by two-dimensional electrophoresis and mass spectrometry. The expression of two gelsolin precursor isotypes and one F-acting capping protein isotype was decreased in ASA-resistant platelets (p<0.05). The expression of glyceraldehyde 3-phosphate dehydrogenase was increased in the ASA-resistant platelets (1751.1 ± 220.6 vs. 4273.3 ± 971.7, 95% confidence interval [CI] 1815.11 to 4061.2, p=0.001). It was accompanied by a reduced expression and activity of 1,6-bisphosphate aldolase in platelets without changes in the content of pyruvate. A reduced expression of gluthathione-S-transferase and the protein disulfide isomerase isotype 1 was found in ASA-resistant platelets. The protein expression of the chloride intracellular channel isotype 1 was increased in ASA-resistant platelets (21.3 ± 3.8 vs. 48.8 ± 6.0, CI 29.5 to 45.95, p=0.03) while the expression of two HSP60 and two HSP71 isotypes was decreased. No changes were observed in proteins associated with inflammation. In conclusion, ASA-resistant and ASA-sensitive platelets are different in terms of the level of expression of proteins associated with mechanisms such as energetic metabolism, cytoskeleton, oxidative stress and cell survival which may be associated with their different ability to respond to ASA.
Genetic manipulation of endothelial cells by viral vectors
Authors: Lindemann Dirk , Schnittler Hans
Published: November 2009

The need for uncovering molecular mechanisms in endothelial cell biology has tremendously increased in the last decades as it became more and more clear that the endothelium is an important target in nearly all diseases and treatments (drug delivery) and plays a central role in regeneration processes. One of the critical methods generally applied in cell biology research to uncover structural and functional aspects is the modulation of protein expression by over-expression, expression of mutant variants or gene silencing. This strategy, however, requires genetic manipulation of the respective cells. The classical gene transfer by chemical transfection techniques works pretty well in a large variety of cultured cells but fails for most endothelial cell types. Insufficient transfection rates and gene expression levels as well as the sensitivity of the endothelium against chemical transfection reagents limits utilisation of this technique for endothelial cell biology research. This holds true not only for primary endothelial cell cultures and endothelial cells in vivo but also for endothelial cell lines, e.g. endothelioma cells. The development of viral vectors originally designed for gene therapy approaches has significantly improved the methodological spectrum in endothelial cell research. Two viral vector systems, based on retroviruses and adenoviruses, deliver transgenic information highly efficient into both cultured endothelial cells and in endothelial cells in vivo, respectively. This review aims to give a comprehensive overview of these two vector systems that appear to be reliable and efficient tools for gene delivery into endothelial cell types.
Effects of Statin Therapy According to Plasma High-Sensitivity C-Reactive Protein Concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
Authors: McMurray John J.V. , Kjekshus John , Gullestad Lars , Dunselman Peter , Hjalmarson Åke , Wedel Hans , Lindberg Magnus , Waagstein Finn , Grande Peer , Hradec Jaromir , Kamenský Gabriel , Korewicki Jerzy , Kuusi Timo , Mach François , Ranjith Naresh , Wikstrand John
Published: November 2009

Background—

We examined whether the antiinflammatory action of statins may be of benefit in heart failure, a state characterized by inflammation in which low cholesterol is associated with worse outcomes.

Methods and Results—

We compared 10 mg rosuvastatin daily with placebo in patients with ischemic systolic heart failure according to baseline high sensitivity-C reactive protein (hs-CRP) <2.0 mg/L (placebo, n=779; rosuvastatin, n=777) or ≥2.0 mg/L (placebo, n=1694; rosuvastatin, n=1711). The primary outcome was cardiovascular death, myocardial infarction, or stroke. Baseline low-density lipoprotein was the same, and rosuvastatin reduced low-density lipoprotein by 47% in both hs-CRP groups. Median hs-CRP was 1.10 mg/L in the lower and 5.60 mg/L in the higher hs-CRP group, with higher hs-CRP associated with worse outcomes. The change in hs-CRP with rosuvastatin from baseline to 3 months was −6% in the low hs-CRP group (27% with placebo) and −33.3% in the high hs-CRP group (−11.1% with placebo). In the high hs-CRP group, 548 placebo-treated (14.0 per 100 patient-years of follow-up) and 498 rosuvastatin-treated (12.2 per 100 patient-years of follow-up) patients had a primary end point (hazard ratio of rosuvastatin to placebo, 0.87; 95% confidence interval, 0.77 to 0.98;
P
=0.024). In the low hs-CRP group, 175 placebo-treated (8.9 per 100 patient-years of follow-up) and 188 rosuvastatin-treated (9.8 per 100 patient-years of follow-up) patients experienced this outcome (hazard ratio, 1.09; 95% confidence interval, 0.89 to 1.34;
P
>0.2;
P
for interaction=0.062). The numbers of deaths were as follows: 581 placebo-treated (14.1 per 100 patient-years of follow-up) and 532 rosuvastatin-treated (12.6 per 100 patient-years) patients in the high hs-CRP group (hazard ratio, 0.89; 95% confidence interval, 0.79 to 1.00;
P
=0.050) and 170 placebo-treated (8.3 per 100 patient-years) and 192 rosuvastatin-treated (9.7 per 100 patient-years) patients in the low hs-CRP group (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43;
P
=0.14;
P
for interaction=0.026).

Conclusion—

In this retrospective hypothesis-generating study, we found a significant interaction between hs-CRP and the effect of rosuvastatin for most end points whereby rosuvastatin treatment was associated with better outcomes in patients with hs-CRP ≥2.0 mg/L.

Clinical Trial Registration Information—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
Priming With Angiopoietin-1 Augments the Vasculogenic Potential of the Peripheral Blood Stem Cells Mobilized With Granulocyte Colony-Stimulating Factor Through a Novel Tie2/Ets-1 Pathway
Authors: Kim Min-Seok , Lee Choon-Soo , Hur Jin , Cho Hyun-Jai , Jun Soo-In , Kim Tae-Youn , Lee Sae-Won , Suh Jung-Won , Park Kyung-Woo , Lee Hae-Young , Kang Hyun-Jae , Lee Dong-Soo , Koh Gou-Young , Nakagami Hironori , Morishita Ryuichi , Park Young-Bae , Kim Hyo-Soo
Published: November 2009

Background—

The low engraftment rate of stem/progenitor cells infused via the intracoronary route to the ischemic myocardium is one of the most important factors limiting the efficacy of cell therapy. We investigated the concept of priming peripheral blood stem cells enriched by granulocyte colony-stimulating factor mobilization and apheresis (
mob
PBSCs) with angiopoietin-1 (Ang1), to enhance the engraftment into the ischemic tissue and neovasculogenic potential.

Methods and Results—

The expression of Tie2, the Ang1 receptor, was significantly higher in
mob
PBSCs than naïve peripheral blood mononuclear cells (19.2±3.0% versus 1.2±0.8% versus 1.2±0.2%;
P
<0.001 for
mob
PBSCs from acute myocardial infarction (AMI) patients with granulocyte colony-stimulating factor treatment for 3 days versus peripheral blood mononuclear cells from AMI patients versus peripheral blood mononuclear cells from stable angina patients). After 4 hours of cartilage oligomeric matrix protein (COMP)-Ang1 stimulation,
mob
PBSCs committed to the endothelial lineage with the induction of CD31 and VE-cadherin expression, mediated by Tie2/Ets-1 pathway. Priming of
mob
PBSCs with COMP-Ang1 induced the expression of α4β1 and α5β1 integrins, which are also Ets-1 downstream molecules, leading to enhanced adhesion to endothelial cells or fibronectin. In a rabbit ear ischemia/reperfusion model, priming of
mob
PBSCs with COMP-Ang1 improved first-pass engraftment to the distal vascular bed after intraarterial delivery. In a murine ischemic hind-limb model, intravascular delivery of primed
mob
PBSCs enhanced both engraftment and neovascularization.

Conclusions—

The short-term priming with COMP-Ang1 may be a feasible and promising option to activate
mob
PBSCs by enhancing differentiation and adhesiveness and to improve the efficacy of cell therapy for ischemic diseases.
Lack of Glutathione Peroxidase 1 Accelerates Cardiac-Specific Hypertrophy and Dysfunction in Angiotensin II Hypertension
Authors: Ardanaz Noelia , Yang Xiao-Ping , Cifuentes M. Eugenia , Haurani Mounir J. , Jackson Kyle W. , Liao Tang-Dong , Carretero Oscar A. , Pagano Patrick J.
Published: November 2009

Glutathione peroxidase 1 (Gpx1) plays an important role in cellular defense by converting hydrogen peroxide and organic hydroperoxides to nonreactive products, and Gpx1
−/−
mice, which are characterized by reduced tissue glutathione peroxidase activity, are known to exhibit enhanced oxidative stress. Peroxides participate in tissue injury, as well as the hypertrophy of cultured cells, yet the role of Gpx1 to prevent end organ damage in cardiovascular tissue is not clear. We postulated that Gpx1 deletion would potentiate both aortic and cardiac hypertrophy, as well as mean arterial blood pressure, in response to angiotensin II (AngII). Our results show that short-term AngII markedly increased left ventricular mass, myocyte cross-sectional area, and interventricular septum thickness and decreased shortening fraction in Gpx1
−/−
mice as compared with wild-type animals. On the other hand, AngII resulted in a similar increase in mean arterial blood pressure in wild-type and Gpx1
−/−
mice. Collagen deposition increased in response to AngII, but no differences were found between strains. Vascular hypertrophy increased to the same extent in Gpx1
−/−
and wild-type mice. Collectively, our results indicate that Gpx1 deficiency accelerates cardiac hypertrophy and dysfunction but has no effect on vascular hypertrophy and mean arterial blood pressure and suggest a major role for Gpx1 in cardiac dysfunction in AngII-dependent hypertension.
Sex Differences in Pulse Pressure Trends With Age Are Cross-Cultural
Authors: Skurnick Joan H. , Aladjem Mordechay , Aviv Abraham
Published: November 2009

Sex differences in systolic and diastolic blood pressure levels and trends with age have been consistently observed in both industrialized and unindustrialized populations. However, the impact of sex on pulse pressure, an index of vascular aging, in unindustrialized populations has not been addressed. The objective of this report was to characterize sex differences in aging trends of pulse pressure within unindustrialized populations. Using PubMed and Medline, we identified 60 articles with blood pressure data from unacculturated or partially acculturated populations. Data on 27 populations from 22 articles were included for analysis, on the basis of adequate description of study design and blood pressure measurement. Blood pressure means of adult age groups were modeled by linear and polynomial regression. The pulse pressure levels of women were lower than those of men in early adulthood and higher in older ages. Women had a steeper, steady increase in pulse pressure with age than men (
P
<0.001), whereas men had a stronger curvilinear upswing in pulse pressure with age (
P
=0.006). Partially acculturated populations had higher pulse pressures than unacculturated populations. Sex had a stronger effect on pulse pressure than acculturation. Pulse pressure trajectories of unindustrialized populations were slightly attenuated compared with those seen in National Health and Nutritional Examination Surveys III and IV of the US population. A sex effect on pulse pressure trends with age prevails across unacculturated and acculturated populations. Accordingly, the biological principles of arterial aging, as expressed in pulse pressure, are the same in all humans, regardless of demography.
Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications
Authors: Cooper-DeHoff Rhonda M. , Wen Sheron , Beitelshees Amber L. , Zineh Issam , Gums John G. , Turner Stephen T. , Gong Yan , Hall Karen , Parekh Vishal , Chapman Arlene B. , Boerwinkle Eric , Johnson Julie A.
Published: November 2009

We assessed adverse metabolic effects of atenolol and hydrochlorothiazide among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes mellitus. Intervention included randomization to 25 mg of hydrochlorothiazide or 100 mg of atenolol monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and uric acid levels were measured at baseline and after monotherapy and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose ≥100 mg/dL (impaired fasting glucose), triglyceride ≥150 mg/dL, high-density lipoprotein ≤40 mg/dL for men or ≤50 mg/dL for women, or new-onset diabetes mellitus according to the presence or absence of abdominal obesity. Abdominal obesity was present in 167 (58%) of 395 patients. Regardless of strategy, in those with abdominal obesity, 20% had impaired fasting glucose at baseline compared with 40% at the end of study (
P
<0.0001). Proportion with triglycerides ≥150 mg/dL increased from 33% at baseline to 46% at the end of study (
P
<0.01). New-onset diabetes mellitus occurred in 13 patients (6%) with and in 4 patients (2%) without abdominal obesity. Baseline levels of glucose, triglyceride, and high-density lipoprotein predicted adverse outcomes, and predictors for new-onset diabetes mellitus after monotherapy in those with abdominal obesity included hydrochlorothiazide strategy (odds ratio: 46.91 [95% CI: 2.55 to 862.40]), female sex (odds ratio: 31.37 [95% CI: 2.10 to 468.99]), and uric acid (odds ratio: 3.19 [95% CI: 1.35 to 7.52]). Development of adverse metabolic effect, including new-onset diabetes mellitus associated with short-term exposure to hydrochlorothiazide and atenolol was more common in those with abdominal obesity.
Intercomparison of Variational Data Assimilation and the Ensemble Kalman Filter for Global Deterministic NWP. Part II: One-Month Experiments with Real Observations
Authors: Buehner Mark , Houtekamer P. L. , Charette Cecilien , Mitchell Herschel L. , He Bin
Published: November 2009

An intercomparison of the Environment Canada variational and ensemble Kalman filter (EnKF) data assimilation systems is presented in the context of producing global deterministic numerical weather forecasts. Five different variational data assimilation approaches are considered including four-dimensional variational data assimilation (4D-Var) and three-dimensional variational data assimilation (3D-Var) with first guess at the appropriate time (3D-FGAT). Also included among these is a new approach, called Ensemble-4D-Var (En-4D-Var), that uses 4D ensemble background-error covariances from the EnKF. A description of the experimental configurations and results from single-observation experiments are presented in the first part of this two-part paper. The present paper focuses on results from medium-range deterministic forecasts initialized with analyses from the EnKF and the five variational data assimilation approaches for the period of February 2007. All experiments assimilate exactly the same full set of meteorological observations and use the same configuration of the forecast model to produce global deterministic medium-range forecasts.

The quality of forecasts in the short (medium) range obtained by using the EnKF ensemble mean analysis is slightly degraded (improved) in the extratropics relative to using the 4D-Var analysis with background-error covariances similar to those used operationally. The use of the EnKF flow-dependent error covariances in the variational system (4D-Var or 3D-FGAT) leads to large (modest) forecast improvements in the southern extratropics (tropics) as compared with using covariances similar to the operational system (a gain of up to 9 h at day 5). The En-4D-Var approach leads to (i) either improved or similar forecast quality when compared with the 4D-Var experiment similar to the currently operational system, (ii) slightly worse forecast quality when compared with the 4D-Var experiment with EnKF error covariances, and (iii) generally similar forecast quality when compared with the EnKF experiment.
India’s Economic Diplomacy at the World Trade Organization
Authors: Tripathi Rahul
Published: November 2009

India has adopted a policy of pragmatic engagement with multilateral economic organizations in recent years. In the context of India’s economic diplomacy at the World Trade Organization (WTO), where it is seen as one of the major voices of dissent from the developing world, a shift in its traditional posturing is clearly evident. This article seeks to interpret the shift both in the context of structural changes within the WTO and the changing goals of India’s economic policy. In view of the stalemate at the Doha round of negotiations, the article argues that multi-lateral organizations like the WTO need to recognize the role of domestic lobbies and transnational civil society networks in shaping the aspirations of emerging economies like India.
Education, Income, and Support for Suicide Bombings: Evidence from Six Muslim Countries
Authors: Najeeb Shafiq M. , Sinno Abdulkader H.
Published: November 2009

The authors examine the effect of educational attainment and income on support for suicide bombing among Muslim publics in six predominantly Muslim countries that have experienced suicide bombings: Indonesia, Jordan, Lebanon, Morocco, Pakistan, and Turkey. The authors make two contributions. First, they present a conceptual model, which has been lacking in the literature. Second, they consider attitudes toward two different targets of suicide bombings: civilians within the respondent’s country and Western military and political personnel in Iraq. The authors find that the effect of educational attainment and income on support for suicide bombings varies across countries and targets.The findings therefore draw attention to the difficulties of making generalizations about Muslim countries and the importance of distinguishing between targets of suicide bombings.
Oral Biofilms: Emerging Concepts in Microbial Ecology
Authors: Filoche S. , Wong L. , Sissons C.H.
Published: November 2009

Oral biofilms develop under a range of different conditions and different environments. This review will discuss emerging concepts in microbial ecology and how they relate to oral biofilm development and the treatment of oral diseases. Clues to how oral biofilms develop may lie in other complex systems, such as interactions between host and gut microbiota, and even in factors that affect biofilm development on leaf surfaces. Most of the conditions under which oral biofilms develop are tightly linked to the overall health and biology of the host. Advances in molecular techniques have led to a greater appreciation of the diversity of human microbiota, the extent of interactions with the human host, and how that relates to inter-individual variation. As a consequence, plaque development may no longer be thought of as a generic process, but rather as a highly individualized process, which has ramifications for the treatment of the diseases it causes.
Some Early Problems with Verbs
Authors: Crystal David
Published: November 2009

The paper reviews some of the problems which arise in teaching verbs to language-handicapped children, first with reference to different types of input structure, then with reference to the question of selecting verbs to teach early in a programme. It outlines a set of criteria for choosing verbs, and proposes a technique for evaluating them.
Sharing and Owning of Musical Works
Authors: Nill Alexander , Geipel Andreas
Published: November 2009

Markets for musical works are based on a compromise between sharing and owning. By empowering consumers and aspiring artists, new digital technology and the Internet threaten to change this compromise. The new technologies allow consumers to make and to disseminate—legally and illegally—copies of musical works that are virtually the same in quality as the original. Facing falling or stagnant sales, established entities of the music industry—recording companies, producers, and distributors— are fighting back with increased lobbying for ever tighter copyright laws and stricter enforcement. The authors analyze contemporary copyright protection for musical works by illuminating the interplay of new technologies, public policy, protection awarded to artists, and outcomes for all stakeholders in markets for musical works throughout history from a societal, jurisprudential, and ethical perspective. Little support has been found for the music industry’s call for more legal protection of the status quo. A new balance between sharing and owning that shifts power from the industry and its established stars to consumers and aspiring artists is not likely to translate ‘‘to the day the music died.’’
Medicalization and Marketing
Authors: Brennan Ross , Eagle Lynne , Rice David
Published: November 2009

Medicalization is the process by which aspects of the human condition, formerly considered nonmedical, are brought within the medical realm. Medical sociologists have asserted that medicalization is a prevalent contemporary sociocultural phenomenon that is actively promoted by pharmaceutical company marketing strategies and that has widespread negative societal effects. Medicalization has not been investigated from a business, marketing management, or macromarketing perspective. One of the principal implications of the medicalization thesis is that pharmaceutical marketing frequently acts to reduce human welfare. The central purposes of this article are to explain what evidence and argumentation has been deployed in medical sociology to implicate marketing practices in medicalization and to argue for the relevance of medicalization to the field of macromarketing. Medicalization is an intellectually robust concept of potential use when conducting macromarketing investigations into ethical and quality-of-life (QOL) aspects of the health care industries and quality of death and dying issues.
The Earth Charter in Higher Education for Sustainability
Authors: Weakland Joseph P. , Corcoran Peter Blaze
Published: November 2009

A central challenge of sustainable development is to provide material sufficiency for the human population while preserving the integrity of Earth’s biosphere. Current modes of economic production and consumption accomplish neither of these ethical imperatives. Institutions of higher education must show leadership in the transition to sustainable ways of life. The Earth Charter is a people’s declaration of ethical principles for securing a just, peaceful, humane and sustainable future. The document can serve as a valuable resource for tertiary educators. The Earth Charter provides an inclusive definition of sustainability, emphasising the interrelated concepts of ecological integrity; social and economic justice; and democracy, nonviolence and peace. It can help us resolve the tension between educating for sustainability while creating learning spaces for contestation and critical inquiry. The Earth Charter also valorises the principle of intergenerational equity, challenging us to create human livelihoods that secure the continued full flourishing of all life for generations to come.