bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Adhesion-Inhibitory Antibodies against PlacentalPlasmodium falciparumParasites by Using Single Domains of VAR2CSA
Authors: Nielsen Morten A. , Pinto Vera V. , Resende Mafalda , Dahlbäck Madeleine , Ditlev Sisse B. , Theander Thor G. , Salanti Ali
Published: March 2009

In areas of endemicity pregnancy-associated malaria is an important cause of maternal anemia, stillbirth, and delivery of low-birth-weight children. The syndrome is precipitated by the accumulation ofPlasmodium falciparum-infected erythrocytes in the placenta, mediated through an interaction between a parasite protein expressed on erythrocytes named variant surface antigen 2-chondroitin sulfate A (VAR2CSA) and CSA on syncytiotrophoblasts. VAR2CSA is a large polymorphic protein consisting of six Duffy binding-like (DBL), domains and with current constraints on recombinant protein production it is not possible to produce entire VAR2CSA recombinant proteins. Furthermore, the presence of polymorphisms has raised the question of whether it is feasible to define VAR2CSA antigens eliciting broadly protective antibodies. Thus, the challenge for vaccine development is to define smaller parts of the molecule which induce antibodies that inhibit CSA binding of different parasite strains. In this study, we produced a large panel of VAR2CSA proteins and raised antibodies against these antigens. We show that antibodies against the DBL4 domain effectively inhibit parasite binding. As the inhibition was not limited to homologous parasite strains, it seems feasible to base a protective malaria vaccine on a single VAR2CSA DBL domain.
Cytolethal Distending Toxin PromotesHelicobacter cinaedi-Associated Typhlocolitis in Interleukin-10-Deficient Mice
Authors: Shen Z. , Feng Y. , Rogers A. B. , Rickman B. , Whary M. T. , Xu S. , Clapp K. M. , Boutin S. R. , Fox J. G.
Published: March 2009

Helicobacter cinaedicolonizes a wide host range, including rodents, and may be an emerging zoonotic agent. Colonization parameters, pathology, serology, and inflammatory responses to wild-typeH. cinaedi(WTHc) were evaluated in B6.129P2-IL-10tm1Cgn(IL-10−/−) mice for 36 weeks postinfection (WPI) and in C57BL/6 (B6) mice for 12 WPI. Because cytolethal distending toxin (CDT) may be a virulence factor, IL-10−/−mice were also infected with thecdtBHcandcdtB-NHcisogenic mutants and evaluated for 12 WPI. Consistent with other murine enterohepatic helicobacters, WTHcdid not cause typhlocolitis in B6 mice, but mild to severe lesions developed at the cecocolic junction in IL-10−/−mice, despite similar colonization levels of WTHcin the cecum and colon of both B6 and IL-10−/−mice. WTHcandcdtBmutants also colonized IL-10−/−mice to a similar extent, but infection with eithercdtBmutant resulted in attenuated typhlocolitis and hyperplasia compared to infection with WTHc(P< 0.03), and only WTHcinfection caused dysplasia and intramucosal carcinoma. WTHcandcdtBHcmutant infection of IL-10−/−mice elevated mRNA expression of tumor necrosis factor alpha, inducible nitric oxide synthase, and gamma interferon in the cecum, as well as elevated Th1-associated serum immunoglobulin G2abcompared to infection of B6 mice (P< 0.05). Although no hepatitis was noted, liver samples were PCR positive at various time points for WTHcor thecdtBHcmutant in approximately 33% of IL-10−/−mice and in 10 to 20% of WTHc-infected B6 mice. These results indicate that WTHccan be used to model inflammatory bowel disease in IL-10−/−mice and that CDT contributes to the virulence ofH. cinaedi.
Bacillus anthracisEdema Toxin Suppresses Human Macrophage Phagocytosis and Cytoskeletal Remodeling via the Protein Kinase A and Exchange Protein Activated by Cyclic AMP Pathways
Authors: Yeager Linsey A. , Chopra Ashok K. , Peterson Johnny W.
Published: March 2009

Bacillus anthracis, the etiological agent of anthrax, is a gram-positive spore-forming bacterium. It produces edema toxin (EdTx), a powerful adenylate cyclase that increases cyclic AMP (cAMP) levels in host cells. Because other cAMP-increasing agents inhibit key macrophage (MΦ) functions, such as phagocytosis, it was hypothesized that EdTx would exhibit similar suppressive activities. Our previous GeneChip data showed that EdTx downregulated MΦ genes involved in actin cytoskeleton remodeling, including protein kinase A (PKA). To further examine the role of EdTx during anthrax pathogenesis, we explored the hypothesis that EdTx treatment leads to deregulation of the cAMP-dependent PKA system, resulting in impaired cytoskeletal functions essential for MΦ activity. Our data revealed that EdTx significantly suppressed human MΦ phagocytosis of Ames spores. Cytoskeletal changes, such as decreased cell spreading and lowered F-actin content, were also observed for toxin-treated MΦs. Further, EdTx altered the protein levels and activity of PKA and exchange protein activated by cAMP (Epac), a recently identified cAMP-binding molecule. By using PKA- and Epac-selective cAMP analogs, we confirmed the involvement of both pathways in the inhibition of MΦ functions elicited by EdTx-generated cAMP. These results suggested that EdTx weakened the host immune response by increasing cAMP levels, which then signaled via PKA and Epac to cripple MΦ phagocytosis and interfered with cytoskeletal remodeling.
Resistance ofCapnocytophaga canimorsusto Killing by Human Complement and Polymorphonuclear Leukocytes
Authors: Shin Hwain , Mally Manuela , Meyer Salome , Fiechter Chantal , Paroz Cécile , Zaehringer Ulrich , Cornelis Guy R.
Published: March 2009

Capnocytophaga canimorsusis a bacterium of the canine oral flora known since 1976 to cause rare but severe septicemia and peripheral gangrene in patients that have been in contact with a dog. It was recently shown that these bacteria do not elicit an inflammatory response (H. Shin, M. Mally, M. Kuhn, C. Paroz, and G. R. Cornelis, J. Infect. Dis. 195:375-386, 2007). Here, we analyze their sensitivity to the innate immune system. Bacteria from the archetype strain Cc5 were highly resistant to killing by complement. There was little membrane attack complex (MAC) deposition in spite of C3b deposition. Cc5 bacteria were as resistant to phagocytosis by human polymorphonuclear leukocytes (PMNs) asYersinia enterocoliticaMRS40, endowed with an antiphagocytic type III secretion system. We isolated Y1C12, a transposon mutant that is hypersensitive to killing by complement via the antibody-dependent classical pathway. The mutation inactivated a putative glycosyltransferase gene, suggesting that the Y1C12 mutant was affected at the level of a capsular polysaccharide or lipopolysaccharide (LPS) structure. Cc5 appeared to have several polysaccharidic structures, one being altered in Y1C12. The structure missing in Y1C12 could be purified by classical LPS purification procedures and labeled by tritiated palmitate, indicating that it is more likely to be an LPS structure than a capsule. Y1C12 bacteria were also more sensitive to phagocytosis by PMNs than wild-type bacteria. In conclusion, a polysaccharide structure, likely an LPS, protectsC. canimorsusfrom deposition of the complement MAC and from efficient phagocytosis by PMNs.
Campylobacter jejuni
Glycosylation Island Important in Cell Charge, Legionaminic Acid Biosynthesis, and Colonization of Chickens
Authors: Howard Sarah L. , Jagannathan Aparna , Soo Evelyn C. , Hui Joseph P. M. , Aubry Annie J. , Ahmed Imran , Karlyshev Andrey , Kelly John F. , Jones Michael A. , Stevens Mark P. , Logan Susan M. , Wren Brendan W.
Published: March 2009

Previously, we identified five genes (Cj1321 to Cj1326, of which Cj1325 and Cj1326 are a single gene) in the O-linked flagellin glycosylation island that are highly prevalent in
Campylobacter jejuni
isolates from chickens. We report mutagenesis, functional, and structural data to confirm that this locus, and Cj1324 in particular, has a significant contributory role in the colonization of chickens by
C. jejuni
. A motile ΔCj1324 mutant with intact flagella was considerably less hydrophobic and less able to autoagglutinate and form biofilms than the parent strain, 11168H, suggesting that the surface charge of flagella of Cj1324-deficient strains was altered. The physical and functional attributes of the parent were restored upon complementation. Structural analysis of flagellin protein purified from the ΔCj1324 mutant revealed the absence of two legionaminic acid glycan modifications that were present in the parent strain, 11168H. These glycoform modifications were shown to be prevalent in chicken isolates and confirm that differences in the highly variable flagellin glycosylation locus can relate to the strain source. The discovery of molecular mechanisms influencing the persistence of
C. jejuni
in poultry aids the rational design of approaches to control this problematic pathogen in the food chain.
Antibody-Enhanced, Fc Gamma Receptor-Mediated Endocytosis of
Clostridium difficile
Toxin A
Authors: He Xiangyun , Sun Xingmin , Wang Jufang , Wang Xiaoning , Zhang Quanshun , Tzipori Saul , Feng Hanping
Published: March 2009

Toxin A (TcdA) and toxin B (TcdB) are major virulence factors of
Clostridium difficile
. These two toxins intoxicate cultured cells by similar mechanisms, and TcdB generally is more potent than TcdA in cultured cells. The exact reason for this difference is unclear. Here, we report that the cellular effects of TcdA can be substantially enhanced via an opsonizing antibody through Fc gamma receptor I (FcγRI)-mediated endocytosis. A TcdA-specific monoclonal antibody, A1H3, was found to significantly enhance the cytotoxicity of TcdA to macrophages and monocytes. The A1H3-dependent enhancement of glucosyltransferase activity, cytoskeleton disruption, and tumor necrosis factor alpha production induced by TcdA was further demonstrated using RAW 264.7 cells. Subsequent experiments indicated that the interaction of FcγRI with A1H3 underlays the antibody-dependent enhancement of the cellular effects of TcdA. While blocking FcγRII and FcγRIII with anti-CD16/32 antibodies did not affect the TcdA-mediated glucosylation of Rac1 in RAW 264.7 cells, presaturation of FcγRI with anti-CD64 antibodies in THP1 cells significantly reduced this activity. Incubation of a TcdA-A1H3 immune complex with recombinant mouse CD64 completely abrogated the A1H3-mediated enhancement of the glucosyltransferase activity of TcdA in RAW 264.7 cells. Moreover, expression of FcγRI in CHO cells strikingly enhanced the sensitivity of these cells to TcdA complexed with A1H3. We showed that the presence of A1H3 facilitated cell surface recruitment of TcdA, contributing to the antibody-dependent, FcγRI-mediated enhancement of TcdA activity. Finally, studies using chlorpromazine and endosomal acidification inhibitors revealed an important role of the endocytic pathway in the A1H3-dependent enhancement of TcdA activity.
Size distribution as a measure of dispersant performanceA paper submitted to the Journal of Environmental and Engineering Science.
Authors: Mukherjee Biplab , Wrenn Brian A.
Published: March 2009

Study of the chemical dispersion of crude oil using size distribution methods can provide important information needed for oil-spill response strategy, which is lacking in the more commonly used mass–concentration methods. Therefore, identification of a reliable method or methods that can provide accurate information regarding droplet size and the mass of oil dispersed is necessary. This research compared four such methods. Gravimetric analysis of the oil mass dispersed was biased low due to loss of volatile components, whereas UV spectroscopy provided accurate results. Size–distribution data obtained using an optical particle counter (OPC) produced accurate estimates of oil mass dispersed, but microscopic examination produced inaccurate and poorly reproducible estimates. Although size–distribution metrics (e.g., estimates of the mean diameter of the size distribution) produced by the two methods were similar, microscopic examination gave unreliable estimates of the number concentration of dispersed oil droplets due to the relatively small number of observations relative to the OPC.
NONCOMMUTATIVE BLACK HOLES, THE FINAL APPEAL TO QUANTUM GRAVITY: A REVIEW
Authors: NICOLINI PIERO
Published: March 2009

We present the state of the art regarding the relation between the physics of Quantum Black Holes and Noncommutative Geometry. We start with a review of models proposed in the literature for describing deformations of General Relativity in the presence of noncommutativity, seen as an effective theory of Quantum Gravity. We study the resulting metrics, proposed to replace or at least to improve the conventional black hole solutions of Einstein's equation. In particular, we analyze noncommutative-inspired solutions obtained in terms of quasiclassical noncommutative coordinates: indeed because of their surprising new features, these solutions enable us to circumvent long standing problems with Quantum Field Theory in Curved Space and to cure the singular behavior of gravity at the centers of black holes. As a consequence, for the first time, we get a complete description of what we may call the black hole SCRAM, the shut down of the emission of thermal radiation from the black hole: in place of the conventional scenario of runaway evaporation in the Planck phase, we find a zero temperature final state, a stable black hole remnant, whose size and mass are determined uniquely in terms of the noncommutative parameter θ. This result turns out to be of vital importance for the physics of the forthcoming experiments at the LHC, where mini black hole production is foreseen in extreme energy hadron collisions. Because of this, we devote the final part of this review to higher-dimensional solutions and their phenomenological implications for TeV Gravity.
FRACTURE BEHAVIOR FOR A LONG CENTER SLANT CRACKED RECTANGULAR SLAB OF SUPERCONDUCTOR UNDER ELECTROMAGNETIC FORCE
Authors: GAO ZHI WEN , ZHOU YOU HE
Published: March 2009

This paper presents a theoretical analysis to the fracture behavior of the large single-domain YBCO superconductor with a center slant crack under electromagnetic force. The stress intensity factors are obtained by using the coupled finite element and infinite element numerical method. Numerical results are computed for two activation processes. For the zero-field cooling (ZFC) magnetization processes, the stress intensity factors increase as the applied field becomes large during field descent. For the field cooling (FC) magnetization processes, the stress intensity factors are obvious differences between the two cases when bfc> 1 and bfc≤ 1. In addition, the predicted crack growth is the Mode-I fracture mainly. In this case, the numerical results developed in the present work are considered to be available for providing quantitative predictions of the fracture mechanism of superconductor both in theory and applications.
SYNTHESIS OF ZINC OXIDE NANOPARTICLES BY THE REACTION OF ZINC METAL WITH ETHANOL
Authors: SHAH M. A.
Published: March 2009

A novel approach has been described for the synthesis of zinc oxide nanoparticles by a very simple reaction of zinc metal with ethanol at 200°C. The diameters of the nanoparticles range from 50–200 nm. The reaction involves the cleavage of C–O bond of the alcohol, which occurs readily on the zinc metal surface. Addition of ethylenediamine to the reaction yields nanorods, thus acting as a shape-directing agent. A plausible mechanism is proposed for the formation of these nanostructures and it is expected that this synthetic technique can be extended to obtain other metal oxides.
OPTIMUM EXPERIMENTAL CONDITION IN OXYGEN GAS-ASSISTED LOW POWER Nd:YAG LASER CUTTING
Authors: BAHAR M. , GOLNABI H.
Published: March 2009

The optimum condition for the reactive gas-assisted Nd:YAG laser cuttings is described in this article. The cut kerf width is investigated for a laser power range of 50–170 W and a gas pressure of 1–6 bar for steel and mild steel materials. Variation of sample thickness, material type, gas pressure and the laser power on the cut width and slot quality are considered in this study. An overall 338 experiments at different experimental conditions are performed and the kerf results are compared. Optimum conditions for the steel and mild steel materials with a thickness range of 1–2 mm are obtained. The optimum condition for the steel cutting results in a minimum kerf width of 0.2 mm at a laser power of 67 W, cutting speed of 7.1 mm/s and an oxygen pressure of 4 bar. A similar investigation for the mild steel-cutting results in a minimum kerf width of 0.3 mm at the same laser power of 67 W, cutting speed of 9.5 mm/s, and an oxygen pressure of 1 bar. Comparison of the results for the two material types indicates that for cutting mild steel, a lower oxygen gas is required for the optimum condition while the kerf width is a little higher for this case. For the same pressure, workpiece thickness, and cutting speed, the threshold power is lower for the mild steel in comparison with the steel. For the case of steel, it is possible to have a lower kerf width and a better kerf quality.
MOLECULAR BIOCIRCUITS
Authors: LIPAN OVIDIU
Published: March 2009

Systems biology aims to describe gene regulatory networks at both experimental and theoretical levels. Mathematical formalisms used at present to describe the behavior of genetic networks range from stochastic to deterministic. The stochastic approach is further subdivided and moves from Langevin to the Master equation. This review presents the Master equation approach.
FERROMAGNETISM IN Fe-DOPED ZnO THIN FILMS
Authors: ZHAO R. B. , HOU D. L. , WEI Y. Y. , ZHOU Z. Z. , PAN C. F. , ZHEN C. M. , TANG G. D.
Published: March 2009

Zn 1-x Fe x O (x = 0.04, 0.06, 0.08, 0.10, 0.12) thin films were grown on Si substrates using reactive magnetron sputtering. X-ray diffraction analyses show that the samples have wurtzite structures with the c-axis orientation. X-ray photoelectron spectroscopy results indicate that the Fe ions are in a +2 charge state in the films. Magnetization measurements indicate that room temperature ferromagnetism is present in films annealed in vacuum while films annealed in air were non-magnetic. The presence of oxygen vacancies in these films may mediate exchange coupling of the dopant ions, resulting in room temperature ferromagnetism.
ULTRATHIN Al FILM ON THE W(100) SURFACE
Authors: CHOI D. S. , KIM D. H.
Published: March 2009

We have investigated Al adsorption on the W (100) surface using LEED and low energy Ion Scattering Spectroscopy (ISS). We observe a p(2 × 1) double domain LEED image for the 1.0 ML Al/W (100) surface at annealing temperature 850°C. We also measured the Al adsorption site at the Al/W (100) — p(2 × 1) surface using ISS. It is found that Al atoms adsorbed at 0.7±0.1 Å aside from the center of the bridge sites with a zigzag structure — one atom adsorbs at the right-hand side and next atom at the left-hand side along the [100] direction. The height of the adsorbed Al atoms is determined to be 1.75±0.15 Å above the W surface layer.
Muscle-specific differences in the response of mitochondrial proteins to β-GPA feeding: an evaluation of potential mechanisms
Authors: Williams Deon B. , Sutherland Lindsey N. , Bomhof Marc R. , Basaraba Susan A. U. , Thrush A. Brianne , Dyck David J. , Field Catherine J. , Wright David C.
Published: March 2009

β-Guanadinopropionic acid (β-GPA) feeding leads to reductions in skeletal muscle phosphagen concentrations and has been used as a tool with which to study the effects of energy charge on skeletal muscle metabolism. Supplementing standard rodent diets with β-GPA leads to increases in mitochondrial enzyme content in fast but not slow-twitch muscles from male rats. Given this apparent discrepancy between muscle types we used β-GPA feeding as a model to study signaling pathways involved in mitochondrial biogenesis. We hypothesized that β-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle. Despite similar reductions in high-energy phosphate concentrations, 6 wk of β-GPA feeding led to increases in mitochondrial proteins in triceps but not soleus muscles. Differences in the response of mitochondrial proteins to β-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPARγ coactivator (PGC)-1α and -1β. The protein content and expression of the nuclear corepressor RIP140 was reduced in triceps but not soleus muscle. Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1α and -1β in both soleus and triceps muscles. The lack of an effect of β-GPA feeding on mitochondrial proteins in the soleus muscles could be related to a fiber type-specific effect of β-GPA on RIP140 protein content.
Empirical Reduced‐Order Modeling for Boundary Feedback Flow Control
Authors: Djouadi Seddik M. , Camphouse R. Chris , Myatt James H.
Published: March 2009

This paper deals with the practical and theoretical implications of model reduction for aerodynamic flow‐based control problems. Various aspects of model reduction are discussed that apply to partial differential equation‐ (PDE‐) based models in general. Specifically, the proper orthogonal decomposition (POD) of a high dimension system as well as frequency domain identification methods are discussed for initial model construction. Projections on the POD basis give a nonlinear Galerkin model. Then, a model reduction method based on empirical balanced truncation is developed and applied to the Galerkin model. The rationale for doing so is that linear subspace approximations to exact submanifolds associated with nonlinear controllability and observability require only standard matrix manipulations utilizing simulation/experimental data. The proposed method uses a chirp signal as input to produce the output in the eigensystem realization algorithm (ERA). This method estimates the system′s Markov parameters that accurately reproduce the output. Balanced truncation is used to show that model reduction is still effective on ERA produced approximated systems. The method is applied to a prototype convective flow on obstacle geometry. AnH∞feedback flow controller is designed based on the reduced model to achieve tracking and then applied to the full‐order model with excellent performance.
Limit Cycle Prediction Based on Evolutionary Multiobjective Formulation
Authors: Katebi M. , Tawfik H. , Katebi S. D.
Published: March 2009

This paper is concerned with an evolutionary search for limit cycle operation in a class of nonlinear systems. In the first part, single input single output (SISO) systems are investigated and sinusoidal input describing function (SIDF) is extended to those cases where the key assumption in its derivation is violated. Describing function matrix (DMF) is employed to take into account the effects of higher harmonic signals and enhance the accuracy of predicting limit cycle operation.
In the second part, SIDF is extended to the class of nonlinear multiinput multioutput (MIMO) systems containing separable nonlinear elements of any general form. In both cases linearized harmonic balance equations are derived and the search for a limit cycle is formulated as a multiobjective problem. Multiobjective genetic algorithm (MOGA) is utilized to search the space of parameters of theoretically possible limit cycle operations. Case studies are presented to demonstrate the effectiveness of the proposed approach.
Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and Cerebrospinal Levels of Orally Administered Ivermectin
Authors: Rose Charles E. , Paciullo Christopher A. , Kelly David R. , Dougherty Mark J. , Fleckenstein Lawrence L.
Published: March 2009

Strongyloides stercoralisaffects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment forStrongyloides stercoralisinfection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations.
Novel Use of Cardiac Pacemakers in Heart Failure to Dynamically Manipulate the Respiratory System Through Algorithmic Changes in Cardiac Output
Authors: Baruah Resham , Manisty Charlotte H. , Giannoni Alberto , Willson Keith , Mebrate Yoseph , Baksi A. John , Unsworth Beth , Hadjiloizou Nearchos , Sutton Richard , Mayet Jamil , Francis Darrel P.
Published: March 2009

Background—

Alternation of heart rate between 2 values using a pacemaker generates oscillations in end-tidal CO
2
(et-CO
2
). This study examined (a) whether modulating atrioventricular delay can also do this, and (b) whether more gradual variation of cardiac output can achieve comparable changes in et-CO
2
with less-sudden changes in blood pressure.

Methods and Results—

We applied pacemaker fluctuations by adjusting heart rate (by 30 bpm) or atrioventricular delay (between optimal and nonoptimal values) or both, with period of 60 s in 19 heart failure patients (age 73�11, EF 29�12%). The changes in cardiac output, by either heart rate or atrioventricular delay or both, were made either as a step (“square wave”) or more gradually (“sine wave”). We obtained changes in cardiac output sufficient to engender comparable oscillations in et-CO
2
(
P
=NS) in all 19 patients either by manipulation of heart rate (14), or by atrioventricular delay (2) or both (3). The square wave produced 191% larger and 250% more sudden changes in blood pressure than the sine wave alternations (22.4�11.7 versus 13.6�4.5 mm Hg,
P
<0.01 and 19.8�10.0 versus 7.9�3.2 mm Hg over 5 s,
P
<0.01), but peak-to-trough et-CO
2
elicited was only 45% higher (0.45�0.18 versus0.31�0.13 kPa,
P
=0.01).

Conclusion—

This study shows that cardiac output is the key to dynamically manipulating the respiratory system with pacing sequences. When manipulating respiration by this route, a sine wave pattern may be preferable to a square wave, because it minimizes sudden blood pressure fluctuations.
Infarct Tissue Heterogeneity Assessed With Contrast-Enhanced MRI Predicts Spontaneous Ventricular Arrhythmia in Patients With Ischemic Cardiomyopathy and Implantable Cardioverter-Defibrillator
Authors: Roes Stijntje D. , Borleffs C. Jan Willem , van der Geest Rob J. , Westenberg Jos J.M. , Marsan Nina Ajmone , Kaandorp Theodorus A.M. , Reiber Johan H.C. , Zeppenfeld Katja , Lamb Hildo J. , de Roos Albert , Schalij Martin J. , Bax Jeroen J.
Published: March 2009

Background—

The relation between infarct tissue heterogeneity on contrast-enhanced MRI and the occurrence of spontaneous ventricular arrhythmia (or sudden cardiac death) is unknown. Therefore, the study purpose was to evaluate the predictive value of infarct tissue heterogeneity assessed with contrast-enhanced MRI on the occurrence of spontaneous ventricular arrhythmia with subsequent implantable cardioverter-defibrillator (ICD) therapy (as surrogate of sudden cardiac death) in patients with previous myocardial infarction.

Methods and Results—

Ninety-one patients (age, 65�11 years) with previous myocardial infarction scheduled for ICD implantation underwent cine MRI to evaluate left ventricular function and volumes and contrast-enhanced MRI for characterization of scar tissue (infarct gray zone as measure of infarct tissue heterogeneity, infarct core, and total infarct size). Appropriate ICD therapy was documented in 18 patients (20%) during a median follow-up of 8.5 months (interquartile range, 2.1 to 20.3). Multivariable Cox proportional hazards analysis revealed that infarct gray zone was the strongest predictor of the occurrence of spontaneous ventricular arrhythmia with subsequent ICD therapy (hazard ratio, 1.49/10 g; CI, 1.01 to 2.20; χ
2
=4.0;
P
=0.04).

Conclusions—

Infarct tissue heterogeneity on contrast-enhanced MRI is the strongest predictor of spontaneous ventricular arrhythmia with subsequent ICD therapy (as surrogate of sudden cardiac death) among other clinical and MRI variables, that is, total infarct size and left ventricular function and volumes, in patients with previous myocardial infarction.
Collagen-Targeting Vascular Endothelial Growth Factor Improves Cardiac Performance After Myocardial Infarction
Authors: Zhang Jing , Ding Liang , Zhao Yannan , Sun Wenjie , Chen Bing , Lin Hang , Wang Xia , Zhang Lujie , Xu Biao , Dai Jianwu
Published: March 2009

Background—

Vascular endothelial growth factor (VEGF) is an important active protein for the induction of angiogenesis and improvement in cardiac function after myocardial ischemia; however, the lack of a delivery system targeted to the injured myocardium reduces the local therapeutic efficacy of VEGF and increases its possible adverse effects.

Methods and Results—

We produced a fusion protein (CBD-VEGF) consisting of VEGF and a collagen-binding domain (CBD). The fusion protein specifically bound to type I collagen in vitro. In addition, CBD-VEGF promoted human umbilical vein endothelial cell proliferation after binding to collagen, which indicates that it retained both growth factor activity and collagen-binding ability. When implanted subcutaneously in rats, collagen membranes loaded with CBD-VEGF were significantly vascularized. After it was injected into rats with acute myocardial infarction, CBD-VEGF was largely retained in the cardiac extracellular matrix, in which collagen I was rich. Four weeks after VEGF or CBD-VEGF was injected into the infarct border zone, cardiac function detected by echocardiography and hemodynamics was preserved in the CBD-VEGF group. Administration of CBD-VEGF also induced reduction of scar size, whereas native VEGF did not have these effects. In addition, a significant increase in the number of capillary vessels in infarcted hearts was found in the CBD-VEGF group.

Conclusions—

The injection of CBD-VEGF improved cardiac function in rats with induced acute myocardial infarction. This could potentially provide a new treatment option for myocardial infarction.
Stress Doppler Echocardiography in Relatives of Patients With Idiopathic and Familial Pulmonary Arterial Hypertension
Authors: Grünig Ekkehard , Weissmann Sylvia , Ehlken Nicola , Fijalkowska Anna , Fischer Christine , Fourme Thierry , Galié Nazzareno , Ghofrani Ardeschir , Harrison Rachel E. , Huez Sandrine , Humbert Marc , Janssen Bart , Kober Jaroslaw , Koehler Rolf , Machado Rajiv D. , Mereles Derliz , Naeije Robert , Olschewski Horst , Provencher Steeve , Reichenberger Frank , Retailleau Kathleen , Rocchi Guido , Simonneau Gérald , Torbicki Adam , Trembath Richard , Seeger Werner
Published: March 2009

Background—

This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (
BMPR2
) gene.

Methods and Results—

TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (F
io
2
=12%; ≈4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects. Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of control subjects but 31.6% of relatives (
P
<0.0001) exceeded the 90% quantile of mean maximal TRV seen in control subjects. Hypoxia revealed hypertensive TRV in 26% of relatives (
P
=0.0029). Among control subjects, TRV at rest was not related to age, sex, body mass index, systemic blood pressure, smoking status, or heart rate. Within kindreds identified as harboring deleterious mutations of the
BMPR2
gene, a hypertensive TRV response occurred significantly more often compared with those without detected mutations.

Conclusions—

Pulmonary hypertensive response to exercise and hypoxia in idiopathic/familial PAH relatives appears as a genetic trait with familial clustering, being correlated to but not caused by a
BMPR2
mutation. The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies.
Associations of Gestational Weight Gain With Offspring Body Mass Index and Blood Pressure at 21 Years of Age
Authors: Mamun Abdullah A. , O'Callaghan Michael , Callaway Leonie , Williams Gail , Najman Jake , Lawlor Debbie A.
Published: March 2009

Background—

Maternal weight gain in pregnancy is positively associated with offspring body mass index (BMI) and obesity risk in childhood, but whether this increased risk extends into adulthood or results in increases in other cardiovascular risk factors such as elevated blood pressure (BP) is unclear.

Methods and Results—

We used a population-based birth cohort of 2432 individuals (50% male) born in Brisbane, Australia, between 1981 and 1983 to prospectively examine the association between maternal gestational weight gain (GWG) and offspring BMI and BP at 21 years. On average, each mother gained 14.8 kg (SD, 5.1 kg) during her pregnancy. At 21 years of age, offspring mean BMI, systolic BP, and diastolic BP were 24.2 kg/m
2
(SD, 4.9 kg/m
2
), 116.4 mm Hg (SD, 14.5 mm Hg), and 67.7 mm Hg (SD, 8.5 mm Hg), respectively. Offspring BMI was on average 0.3 kg/m
2
(95% confidence interval, 0.1 to 0.4 kg/m
2
) higher for each 0.1-kg/wk greater GWG after adjustment for potential confounding factors. Systolic BP also was greater (0.2 mm Hg per 0.1 kg; 95% confidence interval, −0.2 to 0.6) in offspring whose mothers had higher GWG. Although this association was not statistically significant, it was consistent in magnitude with the association of maternal GWG with offspring BMI and of offspring BMI with BP.

Conclusions—

Our findings show that greater GWG is associated with greater offspring BMI into early adulthood and that this may translate into higher systolic BP in offspring. Further large studies are required to confirm an effect of GWG on a range of offspring cardiovascular risk factors.
Arterial and Aortic Valve Calcification Abolished by Elastolytic Cathepsin S Deficiency in Chronic Renal Disease
Authors: Aikawa Elena , Aikawa Masanori , Libby Peter , Figueiredo Jose-Luiz , Rusanescu Gabriel , Iwamoto Yoshiko , Fukuda Daiju , Kohler Rainer H. , Shi Guo-Ping , Jaffer Farouc A. , Weissleder Ralph
Published: March 2009

Background—

Clinical studies have demonstrated that 50% of individuals with chronic renal disease (CRD) die of cardiovascular causes, including advanced calcific arterial and valvular disease; however, the mechanisms of accelerated calcification in CRD remain obscure, and no therapies can prevent disease progression. We recently demonstrated in vivo that inflammation triggers cardiovascular calcification. In vitro evidence also indicates that elastin degradation products may promote osteogenesis. Here, we used genetically modified mice and molecular imaging to test the hypothesis in vivo that cathepsin S (catS), a potent elastolytic proteinase, accelerates calcification in atherosclerotic mice with CRD induced by 5/6 nephrectomy.

Methods and Results—

Apolipoprotein-deficient (apoE
−/−
)/catS
+/+
(n=24) and apoE
−/−
/catS
−/−
(n=24) mice were assigned to CRD and control groups. CRD mice had significantly higher serum phosphate, creatinine, and cystatin C levels than those without CRD. To visualize catS activity and osteogenesis in vivo, we coadministered catS-activatable and calcification-targeted molecular imaging agents 10 weeks after nephrectomy. Imaging coregistered increased catS and osteogenic activities in the CRD apoE
−/−
/catS
+/+
cohort, whereas CRD apoE
−/−
/catS
−/−
mice exhibited less calcification. Quantitative histology demonstrated greater catS-associated elastin fragmentation and calcification in CRD apoE
−/−
/catS
+/+
than CRD apoE
−/−
/catS
−/−
aortas and aortic valves. Notably, catS deletion did not cause compensatory increases in RNA levels of other elastolytic cathepsins or matrix metalloproteinases. Elastin peptide and recombinant catS significantly increased calcification in smooth muscle cells in vitro, a process further amplified in phosphate-enriched culture medium.

Conclusions—

The present study provides direct in vivo evidence that catS-induced elastolysis accelerates arterial and aortic valve calcification in CRD, providing new insight into the pathophysiology of cardiovascular calcification.
Trends in All-Cause and Cardiovascular Disease Mortality Among Women and Men With and Without Diabetes Mellitus in the Framingham Heart Study, 1950 to 2005
Authors: Preis Sarah Rosner , Hwang Shih-Jen , Coady Sean , Pencina Michael J. , D'Agostino Ralph B. , Savage Peter J. , Levy Daniel , Fox Caroline S.
Published: March 2009

Background—

Despite population declines in all-cause mortality, women with diabetes mellitus may have experienced an increase in mortality rates compared with men.

Methods and Results—

We examined change in all-cause, cardiovascular, and non-cardiovascular disease mortality rates among Framingham Heart Study participants who attended examinations during an “earlier” (1950 to 1975; n=930 deaths) and a “later” (1976 to 2001; n=773 deaths) time period. Diabetes mellitus was defined as casual glucose ≥200 mg/dL, fasting plasma glucose ≥126 mg/dL, or treatment. Among women, the hazard ratios (HRs) for all-cause mortality in the later versus the earlier time period were 0.59 (95% confidence interval, 0.50 to 0.70;
P
<0.0001) for those without diabetes mellitus and 0.48 (95% confidence interval, 0.32 to 0.71;
P
=0.002) for those with diabetes mellitus. Similar results were observed in men. Among women and men, the HR of cardiovascular disease mortality declined among those with and without diabetes mellitus. Non-cardiovascular disease mortality declined among women without diabetes mellitus (HR, 0.76;
P
=0.01), whereas no change was observed among women with diabetes mellitus or among men with or without diabetes mellitus. Individuals with versus those without diabetes mellitus were at increased risk of all-cause mortality in the earlier (HR, 2.44;
P
<0.0001) and later (HR, 1.95;
P
<0.0001) time periods.

Conclusions—

Reductions in all-cause mortality among women and men with diabetes mellitus have occurred over time. However, mortality rates among individuals with diabetes mellitus remain ≈2-fold higher compared with individuals without diabetes mellitus.
Nanoparticle-Mediated Delivery of Nuclear Factor κB Decoy Into Lungs Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension
Authors: Kimura Satoshi , Egashira Kensuke , Chen Ling , Nakano Kaku , Iwata Eiko , Miyagawa Miho , Tsujimoto Hiroyuki , Hara Kaori , Morishita Ryuichi , Sueishi Katsuo , Tominaga Ryuji , Sunagawa Kenji
Published: March 2009

Pulmonary arterial hypertension (PAH) is an intractable disease of the small pulmonary artery that involves multiple inflammatory factors. We hypothesized that a redox-sensitive transcription factor, nuclear factor κB (NF-κB), which regulates important inflammatory cytokines, plays a pivotal role in PAH. We investigated the activity of NF-κB in explanted lungs from patients with PAH and in a rat model of PAH. We also examined a nanotechnology-based therapeutic intervention in the rat model. Immunohistochemistry results indicated that the activity of NF-κB increased in small pulmonary arterial lesions and alveolar macrophages in lungs from patients with PAH compared with lungs from control patients. In a rat model of monocrotaline-induced PAH, single intratracheal instillation of polymeric nanoparticles (NPs) resulted in delivery of NPs into lungs for ≤14 days postinstillation. The NP-mediated NF-κB decoy delivery into lungs prevented monocrotaline-induced NF-κB activation. Blockade of NF-κB by NP-mediated delivery of the NF-κB decoy attenuated inflammation and proliferation and, thus, attenuated the development of PAH and pulmonary arterial remodeling induced by monocrotaline. Treatment with the NF-κB decoy NP 3 weeks after monocrotaline injection improved the survival rate as compared with vehicle administration. In conclusion, these data suggest that NF-κB plays a primary role in the pathogenesis of PAH and, thus, represent a new target for therapeutic intervention in PAH. This nanotechnology platform may be developed as a novel molecular approach for treatment of PAH in the future.
Mechanisms of Impaired Potassium Handling With Dual Renin-Angiotensin-Aldosterone Blockade in Chronic Kidney Disease
Authors: Preston Richard A. , Afshartous David , Garg Dyal , Medrano Sergio , Alonso Alberto B. , Rodriguez Rolando
Published: March 2009

The combination of an aldosterone receptor antagonist added to an angiotensin-converting enzyme inhibitor has been demonstrated to reduce cardiovascular and renal end points in hypertensive humans but can produce hyperkalemia in the common clinical setting of impaired renal function. We investigated the effects of dual therapy on acute and chronic potassium handling in hypertensive humans with renal impairment by conducting a randomized crossover clinical trial of 4 weeks of 40 mg lisinopril/25 mg spironolactone versus placebo in 18 participants with a glomerular filtration rate of 25 to 65 mL/min. Study end points, following an established protocol, were hourly determinations of dynamic renal potassium excretion (mmol/h) and serum potassium (mmol/L) after 35 mmol oral potassium challenge in addition to ambulatory potassium concentration. After 4 weeks, ambulatory potassium concentration was 4.87 mmol/L with lisinopril/spironolactone versus 4.37 with placebo (
P
<0.001). Lisinopril/spironolactone produced only a modest 0.44 mmol/h reduction in stimulated potassium excretion (
P
=0.03) but a substantial 0.67 mmol/L increase in serum potassium (
P
<0.001) in response to 35 mmol potassium; these findings are consistent with impaired extrarenal/transcellular potassium disposition. We found the increase in serum potassium after an oral potassium challenge to be a strong predictor of the increase in ambulatory potassium with lisinopril/spironolactone. Our study suggests that dual renin-angiotensin-aldosterone blockade may impair extrarenal/transcellular potassium disposition in addition to reducing potassium excretion in humans with renal impairment, and that acute changes in dynamic potassium handling are predictive of chronic changes in ambulatory potassium concentration with dual renin-angiotensin-aldosterone blockade.
Response Sensitivity and Parameter Importance in Composites Manufacturing
Authors: Bebamzadeh A. , Haukaas T. , Vaziri R. , Poursartip A. , Fernlund G.
Published: March 2009

In this article we derive, implement, and verify equations to compute the sensitivity of responses from numerical simulation of composites manufacturing. The responses considered are part temperature and degree of cure, as well as process-induced deformation of the cured part. The `direct differentiation method' (DDM) is used, which entails a one-time investment of effort to differentiate the governing response equations analytically. The implementation of the derivative equations facilitates efficient and accurate computation of response sensitivities in all subsequent analyses. This article extends the DDM methodology developed earlier for mechanical problems. Novel `shape sensitivity' equations and efficient implementation techniques are also included. In order to verify the implementations, the model predictions are compared with those obtained from the less efficient finite difference approach. A comprehensive example is presented where the usefulness and interpretation of response sensitivities are emphasized. It is observed that the responses are particularly sensitive to certain model parameters, for which further data gathering and model improvement efforts should be focused.
Harlem Undercover
Authors: Robertson Stephen
Published: March 2009

In 1928, the Committee of Fourteen, New York City's leading private antivice organization, employed a black teacher to conduct a five-month undercover investigation of Harlem's night-life. It had been ten years since the committee had subjected the neighborhood to such intensive surveillance. Typically explained as the result of racism, that neglect also reflected white investigators' increasing inability to gather information in Harlem. This article explores the work of investigators and the racial dynamics of undercover investigations to show how those difficulties grew from the congregation of waves of new black migrants in the neighborhood and, as Prohibition drew whites to Harlem, blacks' retreat into private spaces, buffet flats, for their leisure. It uses the rich snapshot offered by the black investigator's reports to reveal how, in the 1920s, black prostitutes, rather than being successfully regulated, blended into these new black spaces.
Taking Chances in the Face of Threat: Romantic Risk Regulation and Approach Motivation
Authors: Cavallo Justin V. , Fitzsimons Gráinne M. , Holmes John G.
Published: March 2009

Four studies examine the hypothesis that goals adopted by high and low self-esteem people (HSEs and LSEs) to manage risk in romantic relationships may reflect global shifts in approach motivation and subsequently affect risk taking in nonsocial domains. In Studies 1 and 2, threats to participants' romantic relationships heightened HSEs' self-reported general approach motivation while lowering LSEs' approach motivation. In Studies 2 through 4, HSEs exhibited riskier decision making (i.e., a greater tendency to pursue rewards and ignore risks) in nonsocial domains following a relationship threat manipulation whereas LSEs made more conservative decisions. These results suggest that the romantic risk regulation may be inherently linked to a broader approach and avoidance system and that specific risk regulation behaviors may be driven by global motivational shifts to a greater degree than previously theorized.
Evaluating One Performance Among Others: The Influence of Rank and Degree of Exposure to Comparison Referents
Authors: Chambers John R. , Windschitl Paul D.
Published: March 2009

Three studies examined the influence of comparison-referent exposure (i.e., the frequency with which one views comparison referents) on evaluations of the ability of a target person (either oneself or another person). In Experiment 1, participants performed a task and then viewed performances of both upward and downward referents. Participants who saw more performances by the upward referents than the downward referents evaluated their own performances less favorably did than participants who saw more performances by the downward referents than the upward referents. Experiment 2 produced similar findings, showing that comparison exposure also influences people's evaluations about someone other than themselves. In Experiment 3, comparison-exposure effects were significantly reduced when participants were instructed to think deliberatively about the comparison information, consistent with the idea that people typically rely on imprecise representations of comparison information even when they are capable of forming more precise representations from memory if motivated to do so.