bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of expanding polyurethane resin to remediate expansive soil foundations
Authors: Buzzi Olivier , Fityus Stephen , Sloan Scott W.
Published: May 2010

Injection of expansive polyurethane resin can be used to remediate differential settlement issues. The resin is injected incrementally under a structure to achieve a desired foundation level, forming a composite resin–clay material. This solution is not well documented in the literature and some questions arise on the long-term performance of this solution. As injection is usually carried out in a settled soil mass that is dry and dessicated, rehydration of the soil after injection may lead to swelling of the leveled foundation and overlifting of the structure. Experimental research undertaken to investigate this rehydration issue and determine if there is a risk of overlifting in the long term is presented here. In situ and laboratory testing was performed to investigate the most fundamental aspects of the problems. This included the in situ injection of resin, study of resin propagation in the soil mass, influence of resin on the hydraulic conductivity of the soil mass, and large-scale swelling tests. The results suggest that, even though the resin cannot prevent the rehydration of the soil mass, the risk of overlifting in the long term is limited.
A constitutive model for gravelly soils considering shear-induced volumetric deformation
Authors: Chu Bin-Lin , Jou Yeun-Wen , Weng Meng-Chia
Published: May 2010

This study elucidates the deformational behavior of gravelly soils by analyzing how hydrostatic pressure and pure shearing affect deformational behavior. A series of drained, triaxial compression tests have been performed using large specimens made of gravelly soils, where the grain-size distribution curve was based on the field condition. The volumetric and shear deformations of gravelly soils have been determined by performing experiments with controlled stress paths — hydrostatic pressure was applied first followed by pure shearing. A simple and innovative constitutive model is also proposed. The proposed model is characterized by the following features of gravelly soils: (i) significant shear-induced volumetric deformation prior to failure, (ii) modulus stiffening under hydrostatic loading and degradation under shearing, and (iii) stress-induced anisotropy. In the proposed model, deformational moduli K and G vary according to the stress state. The stiffening and degradation of these moduli result in diverse deformational behavior of gravelly soils. In addition, an anisotropic factor, β, is introduced to represent stress-induced anisotropy. Moreover, the proposed model only requires eight material parameters; each of which can be obtained easily from experiments.
Development of small molecules targeting the Wnt pathway for the treatment of colon cancer: a high-throughput screening approach
Authors: Chen Wei , Chen Minyong , Barak Larry S.
Published: May 2010

Wnt proteins play major roles in development and differentiation, and abnormalities in their regulation are believed to contribute to the formation of many cancers, including colorectal malignancies. As a result, there has been an interest in identifying small molecule inhibitors of Wnt signaling as tool compounds for research or as precursors to new generations of anticancer drugs. Advancements in robotic technology along with reductions in the costs of equipment, chemical libraries, and information handling have made high-throughput drug discovery programs possible in an academic setting. In this minireview we discuss the most plausible protein targets for inhibiting Wnt signaling in colon cancer therapy, list small molecule Wnt inhibitors that have been identified through recent drug discovery efforts, and provide our laboratory's strategy for identifying novel Wnt signaling antagonists using high-throughput screening. In particular, we summarize the results of a screen of over 1,200 drug and druglike compounds we recently completed in which niclosamide was identified as a Wnt pathway antagonist.
Protective role of α-actinin-3 in the response to an acute eccentric exercise bout
Authors: Vincent Barbara , Windelinckx An , Nielens Henri , Ramaekers Monique , Van Leemputte Marc , Hespel Peter , Thomis Martine A.
Published: May 2010

The ACTN3 gene encodes for the α-actinin-3 protein, which has an important structural function in the Z line of the sarcomere in fast muscle fibers. A premature stop codon (R577X) polymorphism in the ACTN3 gene causes a complete loss of the protein in XX homozygotes. This study investigates a possible role for the α-actinin-3 protein in protecting the fast fiber from eccentric damage and studies repair mechanisms after a single eccentric exercise bout. Nineteen healthy young men (10 XX, 9 RR) performed 4 series of 20 maximal eccentric knee extensions with both legs. Blood (creatine kinase; CK) and muscle biopsy samples were taken to study differential expression of several anabolic (MyoD1, myogenin, MRF4, Myf5, IGF-1), catabolic (myostatin, MAFbx, and MURF-1), and contraction-induced muscle damage marker genes [cysteine- and glycine-rich protein 3 (CSRP3), CARP, HSP70, and IL-6] as well as a calcineurin signaling pathway marker (RCAN1). Baseline mRNA content of CSRP3 and MyoD1 was 49 ± 12 and 67 ± 25% higher in the XX compared with the RR group ( P = 0.01–0.045). However, satellite cell number was not different between XX and RR individuals. After eccentric exercise, XX individuals tended to have higher serum CK activity ( P = 0.10) and had higher pain scores than RR individuals. However, CSRP3 ( P = 0.058) and MyoD1 ( P = 0.08) mRNA expression tended to be higher after training in RR individuals compared with XX α-actinin-3-deficient subjects. This study suggests a protective role of α-actinin-3 protein in muscle damage after eccentric training and an improved stress-sensor signaling, although effects are small.
The series-elastic shock absorber: tendons attenuate muscle power during eccentric actions
Authors: Roberts Thomas J. , Azizi Emanuel
Published: May 2010

Elastic tendons can act as muscle power amplifiers or energy-conserving springs during locomotion. We used an in situ muscle-tendon preparation to examine the mechanical function of tendons during lengthening contractions, when muscles absorb energy. Force, length, and power were measured in the lateral gastrocnemius muscle of wild turkeys. Sonomicrometry was used to measure muscle fascicle length independently from muscle-tendon unit (MTU) length, as measured by a muscle lever system (servomotor). A series of ramp stretches of varying velocities was applied to the MTU in fully activated muscles. Fascicle length changes were decoupled from length changes imposed on the MTU by the servomotor. Under most conditions, muscle fascicles shortened on average, while the MTU lengthened. Energy input to the MTU during the fastest lengthenings was −54.4 J/kg, while estimated work input to the muscle fascicles during this period was only −11.24 J/kg. This discrepancy indicates that energy was first absorbed by elastic elements, then released to do work on muscle fascicles after the lengthening phase of the contraction. The temporary storage of energy by elastic elements also resulted in a significant attenuation of power input to the muscle fascicles. At the fastest lengthening rates, peak instantaneous power input to the MTU reached −2,143.9 W/kg, while peak power input to the fascicles was only −557.6 W/kg. These results demonstrate that tendons may act as mechanical buffers by limiting peak muscle forces, lengthening rates, and power inputs during energy-absorbing contractions.
Thickness determination of SmCo films on silicon substrates utilizing X-ray diffraction
Authors: Vander Isaac , Zuneska R. W. , Cadieu F. J.
Published: May 2010

This paper presents a nondestructive measurement technique for the determination of the film thicknesses of Co and SmCo based magnetic films deposited by sputtering on single-crystal silicon (100) substrates. X-ray diffraction of Cu Kα radiation has been used to measure the intensity of the (400) reflection from bare silicon substrates and as attenuated by sputter coated Co and SmCo based films on Si substrates. A four-axis research diffractometer allowed the substrate orientation to be fine adjusted to maximize the (400) diffraction intensity. The thickness of SmCo based films was in a range from 0.05 to 5 μm. Co film thicknesses on Si could be measured to a few tens of nanometers. The accuracy of the thickness measurements depends on the effective mass attenuation coefficient of the film material. For the materials considered, the thicknesses determined by the X-ray attenuation method agree within at least several percent to values determined by other methods.
Laboratory-based characterization of heteroepitaxial structures: Advanced experiments not needing synchrotron radiation
Authors: Zaumseil P. , Giussani A. , Schroeder T.
Published: May 2010

It is demonstrated that a complex X-ray characterization of semiconductor films epitaxially grown on metal oxide buffer layers and Si(111) substrates is possible using laboratory-based equipment. This is demonstrated with epi-germanium on Pr2O3 as buffer material. Pole figure measurements prove that epi-Ge layers are nearly single crystalline with exactly the same in-plane orientation (type A) as the Si(111) substrate, while the lattice of the oxide layer is 180° rotated around the [111] surface normal (type B). Only a small fraction (less than 0.6 vol %) of the epi-Ge exhibits type B rotation twins. The main structural defects are microtwin lamellas lying in {111} planes 70.5° inclined to the wafer surface. The different in-plane orientation of the Si substrate and epi-Ge on one side and the Pr2O3 buffer layer on the other side allows a very sensitive analysis of strain and defects even for a 10-nm oxide layer buried under a 100-nm Ge. The epi-Ge layers are nearly fully relaxed and the Pr2O3 buffer layer is compressively strained. Due to the existing defects the Ge (111) planes are tilted in a characteristic pattern relative to the Si substrate.
X-ray diffraction imaging of dislocation generation related to microcracks in Si wafers
Authors: Wittge J. , Danilewsky A. , Allen D. , McNally P. , Li Z. J. , Baumbach T. , Gorostegui-Colinas E. , Garagorri J. , Elizalde M. R. , Jacques D. , Fossati M. C. , Bowen D. K. , Tanner B. K.
Published: May 2010

The nucleation of dislocations at indents in silicon following rapid thermal annealing (RTA) has been examined by X-ray diffraction imaging (topography). For indentation loads below 200 mN, no slip bands were generated from the indent sites following RTA at 1000 °C under spike conditions. Upon plateau annealing at 1000 °C, slip dislocations were propagated from some indents but not all. Slip was also observed from edge defects not associated with indentation. For 500-mN indentation load, large scale dislocation sources were generated from the indent sites propagating on two of the four {111} slip planes. These dislocations multiplied into macroscopic-scale slip bands. A significant change in morphology was observed in the 60° dislocation segments after the screw segment reached the rear surface of the wafer. Dislocations changed line direction and in some cases appeared to leave the Peierls trough during glide.
Stress analysis on Canadian naval platforms using a portable miniature X-ray diffractometer
Authors: Farrell S. P. , MacGregor L. W. , Porter J. F.
Published: May 2010

Strain field distribution in a naval platform under dry-dock conditions is complex and represents the cumulative response from residual stress (“locked in” during fabrication of materials and formation of the structure) and static loading stress (e.g., dry-dock loading). The magnitude and distribution of stress fields are a significant concern for the Canadian Navy, where the superposition of applied stresses on residual stresses may adversely affect the performance, safe operational envelope, and service life of naval platforms. Stress analysis was conducted on Canada’s VICTORIA Class submarines using a portable miniature X-ray diffractometer (mXRD) under dry-dock conditions. This paper introduces the concept of “residential stress” as it applies to submarine platforms and discusses the methodology for performing stress analysis with a portable mXRD. The evolution of residential stress during routine pressure hull repairs to Canada’s VICTORIA Class submarines is discussed. In particular, the recent replacement of the diesel exhaust hull and back-up valves on one of the submarines, as well as a pressure hull plate extraction-insertion-weld procedure on another, is discussed.
Serotonin Receptor 3A Expression in Normal and Neoplastic B Cells
Authors: Rinaldi Andrea , Chiaravalli Anna Maria , Mian Michael , Zucca Emanuele , Tibiletti Maria Grazia , Capella Carlo , Bertoni Francesco
Published: May 2010

Chromosome 11q21–qter is a very gene-rich region and is often targeted by genomic aberrations in a variety of human cancers, including B cell lymphoid neoplasms. In order to identify genes which could be deregulated in diffuse large B cell lymphomas (DLBCL), we analyzed the expression levels of genes mapped on chromosome 11q21–qter across a series of publicly available DLBCL expression data sets. We identified HTR3A, the gene coding for 5-hydroxytryptamine receptor 3A, as the most frequently differentially expressed. Since HTR3A expression had not been previously characterized in normal and neoplastic B cells, we evaluated its expression by real-time PCR and by immunohistochemistry. The gene is expressed by B cells and it seems to be regulated during the mature B cell differentiation, being overexpressed during the germinal center phase. Lymphomas derived from germinal center B cells maintain the expression, with the level of expression varying among different patients.
Constitutive Suppression of PRL-3 Inhibits Invasion and Proliferation of Gastric Cancer Cell in vitro and in vivo
Authors: Matsukawa Yasuko , Semba Shuho , Kato Hirotaka , Koma Yu-ichiro , Yanagihara Kazuyoshi , Yokozaki Hiroshi
Published: May 2010

Objective: Overexpression of phosphatase of regenerating liver-3 (PRL-3) has been implicated in tumor progression and metastasis of gastric carcinoma. Here we examined what alterations occur in the phenotype of gastric cancer cells in vitro and in vivo when PRL-3 expression is knocked down. Methods: We constructed a small interfering RNA (siRNA)-expressing vector which stably interfered with PRL-3 expression and was transfected into SH101-P4 cells, which express the highest PRL-3 mRNA levels among 13 gastric cancer cell lines. The new SH101-P4 subclones, in which PRL-3 was stably reduced, were established and their in vitro growth, motility and abilities of liver metastasis from the injected spleen were analyzed in vivo. Results: PRL-3 knockdown effectively suppressed invasion and growth of SH101-P4 cells in vitro. Liver metastasis in vivo was significantly decreased when PRL-3 expression was suppressed. The primary tumor size in the injected spleen tended to be smaller in PRL-3 knockdown clones than in the controls. These findings suggest that PRL-3 expression may contribute not only to the establishment of metastasis but also to the growth of primary foci of human gastric cancer. Therefore, PRL-3 may be one of the target molecules in gastric cancer therapy.
Capacity-Building in Human Genetics for Developing Countries: Initiatives and Perspectives in Sub-Saharan Africa
Authors: Wonkam A. , Muna W. , Ramesar R. , Rotimi C.N. , Newport M.J.
Published: May 2010

Background: Stakeholders who are committed to bridge the gap in genetics services need to be aware of current initiatives in sub-Saharan Africa. Methods: We reviewed selected experiences from African geneticists that led to specific recommendations. Results: The initiation of prenatal diagnosis of sickle cell anaemia founded the first medical genetic service in Cameroon. There remains a need for international collaborative effort to overcome the lack of human, technical and financial resources around the practice of medical genetics in Africa. The African Society of Human Genetics, Wellcome Trust and NIH have recently proposed a model on how to fully engage Africa in genomics. It includes a ‘Health and disease’ phase I: use of the case-control design to study genetic and epidemiological determinants of 7 important diseases in Africa, and a ‘Genetic variation’ phase II: comprehensive documentation of genetic variations in 100 carefully selected ethnic groups across Africa. The strategy would require the development of: (1) clinical phenotyping centres, (2) molecular phenotyping centres, (3) genotyping and sequencing capability, (4) data centres, and (5) a bio-repository in Africa. Conclusions: Governments and international health agencies need to recognise that genetics is important to the global medical community. The initiatives of African geneticists need advocacy and encouragement from the international community.
Pharmacokinetics and Pharmacodynamics of Subcutaneous Injection and Intravenous Infusion of Recombinant Human Interleukin-12 and Recombinant Human Interleukin-12 Combined with Hepatitis B Surface Antigen in Cynomolgus Monkeys
Authors: Li Rubing , Deng Fengjun , Fu Yonghang , Zhang Yijun , Wan Huayin , Zhou Dan , Gu Jingliang , Xu Jiangping
Published: May 2010

Background/Aims: Interleukin-12 (IL-12) is a cytokine that plays an important role in cell-mediated immunity and shows great potential as a therapeutic agent for the treatment of tumors and infectious diseases. Methods: We investigated the pharmacokinetics (PK) and pharmacodynamics of recombinant human IL-12 (rhIL-12) and rhIL-12 combined with hepatitis B surface antigen (HBsAg) after administration by subcutaneous (s.c.) injection or intravenous infusion in cynomolgus monkeys. Results: After s.c. injection of rhIL-12 at doses of 0.15–1.5 µg/kg, the monkey’s metabolism showed linear kinetic characteristics. The intramuscular injection of HBsAg vaccine did not affect the pharmacokinetic profile of rhIL-12. In monkeys administered rhIL-12 in a continuous dosing fashion, serum rhIL-12 was undetectable, probably due to the neutralizing effect of anti-rhIL-12 antibodies. In monkeys receiving high-dose s.c. injection of rhIL-12, the Tmax for serum rhIL-12 concentration was 4–8 h, and the Tmax for serum interferon-γ (IFN-γ) concentration was 24–72 h. However, in monkeys receiving continuous dosing of rhIL-12, serum IFN-γ concentration was very low or even undetectable. Conclusion: We found that the PK of rhIL-12 was dose-dependent and its pharmacological effects appeared after Tmax and lasted much longer than mean retention time.
Reduced Kidney Function Estimated by Cystatin C and Clinical Outcomes in Hypertensive Patients with Coronary Artery Disease: Association with Homocysteine and Other Cardiovascular Risk Factors
Authors: Dzielinska Zofia , Januszewicz Andrzej , Wiecek Andrzej , Prejbisz Aleksander , Zielinski Tomasz , Chudek Jerzy , Makowiecka-Ciesla Magdalena , Demkow Marcin , Tyczynski Pawel , Januszewicz Magdalena , Ruzyllo Witold , Naruszewicz Marek
Published: May 2010

Aims: To evaluate the association between serum cystatin C and homocysteine concentrations, cardiovascular risk factors and cardiovascular events in hypertensive patients with coronary artery disease (CAD). Methods: 260 patients with hypertension and CAD (mean age 56.9 ± 9.3) were included. During a mean 40-month follow-up the combined end-point of death from all causes, non-fatal myocardial infarction and stroke or coronary revascularization was assessed. Results: Subjects in the highest serum cystatin C quartile (>103.4 nmol/l) as compared with the lowest were older, were characterized by a higher frequency of multivessel CAD, higher levels of homocysteine (13.2 ± 5.2 vs. 11.4 ± 4.2 µmol/l; p < 0.01), fibrinogen and high-sensitivity C-reactive protein and by an increased intima-media thickness. Combined end-point occurred twice as frequently in the 4th quartile of serum cystatin C as compared with the 1st quartile (10.8 vs. 20.3%; p = 0.11). In an univariate analysis, but not in a multivariate model, cystatin C concentration predicted the combined end-point (Exp(B) = 1.096; p < 0.05). Conclusion: In hypertensive patients with CAD, serum cystatin C level was independently associated with the extent of CAD, homocysteine plasma level and traditional vascular risk factors. However, serum cystatin C concentration did not independently predict the combined end-point.
Development of a high-throughput ELISA assay for platelet function testing using platelet-rich plasma or whole blood
Authors: Broos Katleen , Fontayne Alexandre , Szántó Tímea , Ruan Changgeng , Nurden Alan , Vanhoorelbeke Karen , Deckmyn Hans , Salles Isabelle
Published: May 2010

Platelets play an essential role in the development of cardiovascular diseases and are the target of several agents that can inhibit their function. Despite the existence of a wide array of techniques to study platelet function, an assay to evaluate several platelet signalling pathways in a high-throughput fashion, combined with minimal blood volume and handling is still needed. We have developed a sensitive assay in the form of a sandwich ELISA where monoclonal antibodies against P-selectin or αIIbβ3 and GPIbα were used to capture and detect platelets, respectively, in the presence of five different agonists [ADP, TRAP (thrombin receptor agonist), U46619 (thromboxane A2 analogue), collagen-related-peptide, and arachidonic acid]. Binding of platelets to the antibodies increased dose-dependently with the concentration of either agonist, while binding of ADP-activated platelets was abrogated when inhibitors of platelet activation were concomitantly added. The test showed good sample reproducibility in 15 healthy donors with conserved platelet response to agonists throughout the assay. Healthy subjects could be identified as normal-, hypo- or hyper-responders for each agonist, which for most cases (73%) was confirmed upon retesting. Finally, we demonstrated that the platelet ELISA assay can not only be used in platelet-rich plasma but also in whole blood; it now awaits large scale studies to assess its full screening and diagnostic values.
Idraparinux versus standard therapy in the treatment of deep venous thrombosis in cancer patients: A subgroup analysis of the Van Gogh DVT trial
Authors: Cohen Alexander , Davidson Bruce , Decousus Herve , Gallus Alexander , Gent Michael , Piovella Franco , Prins Martin , Raskob Gary , Büller Harry , van Doormaal Frederiek
Published: May 2010

Standard treatment with heparin followed by vitamin K antagonists is frequently complicated by bleeding and recurrent venous thromboembolism (VTE) in cancer patients with VTE. To compare the efficacy, safety and overall survival of long-term idraparinux treatment to standard therapy in cancer patients we conducted a post-hoc analysis in the subgroup of non-active and active cancer patients included in the Van Gogh DVT clinical trial. The cancer patients with deep venous thrombosis (DVT) and without pulmonary embolism (PE) were randomised to standard treatment or a once-weekly subcutaneous injection of idraparinux (2.5 mg), a synthetic pentasaccharide. 421 cancer patients were included. A total of 220 patients received idraparinux and 201 were allocated to standard therapy for three months (8%) or six months (92%). A recurrent VTE was observed during the first six months in 2.5% (n=5) of the idraparinux recipients compared to 6.4% (n=12) in the standard therapy group (hazard ratio 0.39, 95% confidence interval [CI]; 0.14–1.11). The rate of bleeding was comparable (odds ratio 0.89, 95% CI; 0.50–1.59). The outcomes were similar at three months after randomisation in all patients. Of the idraparinux recipients, 22.7% (n=50) died during the study period compared to 48 patients (23.9%) in the standard treatment group (hazard ratio 0.99, 95% CI; 0.66–1.48). In conclusion, no significant safety or survival differences were observed between cancer patients with DVT treated with idraparinux for six months compared to standard therapy. Fewer recurrent VTEs were observed in the idraparinux group; however, this was not statistically significant and also because of study limitations this should be interpreted with caution.
Structure/Function Relationships of Apolipoprotein A-I Mimetic Peptides
Authors: D'Souza Wilissa , Stonik John A. , Murphy Andrew , Demosky Steven J. , Sethi Amar A. , Moore Xiao L. , Chin-Dusting Jaye , Remaley Alan T. , Sviridov Dmitri
Published: May 2010

Rationale
:

Apolipoprotein (apoA)-I mimetic peptides are a promising type of antiatherosclerosis therapy, but how the structural features of these peptides relate to the multiple antiatherogenic functions of HDL is poorly understood.

Objective
:

To establish structure/function relationships of apoA-I mimetic peptides with their antiatherogenic functions.

Methods and Results
:

Twenty-two bihelical apoA-I mimetic peptides were investigated in vitro for the capacity and specificity of cholesterol efflux, inhibition of inflammatory response of monocytes and endothelial cells, and inhibition of low-density lipoprotein (LDL) oxidation. It was found that mean hydrophobicity, charge, size of hydrophobic face, and angle of the link between the helices are the major factors determining the efficiency and specificity of cholesterol efflux. The peptide with optimal parameters was more effective and specific toward cholesterol efflux than human apoA-I. Charge and size of hydrophobic face were also the major factors affecting antiinflammatory properties, and the presence of cysteine and histidine residues was the main factor determining antioxidant properties. There was no significant correlation between capacities of the peptides to support individual functions; each function had its own optimal set of features.

Conclusions
:

None of the peptides was equally effective in all the antiatherogenic functions tested, suggesting that different functions of HDL may have different mechanisms and different structural requirements. The results do suggest, however, that rationalizing the design of apoA-I mimetic peptides may improve their therapeutic value and may lead to a better understanding of mechanisms of various antiatherogenic functions of HDL.
Inhibition of Delta-Like-4–Mediated Signaling Impairs Reparative Angiogenesis After Ischemia
Authors: Al Haj Zen Ayman , Oikawa Atsuhiko , Bazan-Peregrino Miriam , Meloni Marco , Emanueli Costanza , Madeddu Paolo
Published: May 2010

Rationale
:

Notch signaling regulates vascular development. However, the implication of the Notch ligand Delta-like 4 (Dll4) in postischemic angiogenesis remains unclear.

Objective
:

We investigated the role of Dll4/Notch signaling in reparative angiogenesis using a mouse model of ischemia.

Methods and Results
:

We found Dll4 weakly expressed in microvascular endothelial cells of normoperfused muscles. Conversely, Dll4 is upregulated following ischemia and localized at the forefront of sprouting capillaries. We analyzed the effect of inhibiting endogenous Dll4 by intramuscular injection of an adenovirus encoding the soluble form of Dll4 extracellular domain (
Ad-sDll4
). Dll4 inhibition caused the formation of a disorganized, low-perfused capillary network in ischemic muscles. This structural abnormality was associated to delayed blood flow recovery and muscle hypoxia and degeneration. Analysis of microvasculature at early stages of repair revealed that Dll4 inhibition enhances capillary sprouting in a chaotic fashion and causes excessive leukocyte infiltration of ischemic muscles. Furthermore, Dll4 inhibition potentiated the elevation of the leukocyte chemoattractant CXCL1 (chemokine [C-X-C motif] ligand 1) following ischemia, without altering peripheral blood levels of stromal cell–derived factor-1 and monocyte chemoattractant protein-1. In cultured human monocytes, Dll4 induces the transcription of Notch target gene
Hes-1
and inhibits the basal and tumor necrosis factor-α–stimulated production of interleukin-8, the human functional homolog of murine CXCL1. The inhibitory effect of Dll4 on interleukin-8 was abolished by DAPT, a Notch inhibitor, or by coculturing activated human monocytes with
Ad-sDll4
–infected endothelial cells.

Conclusions
:

Dll4/Notch interaction is essential for proper reparative angiogenesis. Moreover, Dll4/Notch signaling regulates sprouting angiogenesis and coordinates the interaction between inflammation and angiogenesis under ischemic conditions.
High-Molecular-Weight Adiponectin and Incident Ischemic Stroke in Postmenopausal Women
Authors: Ogorodnikova Alexandra D. , Wassertheil-Smoller Sylvia , Mancuso Peter , Sowers MaryFran R. , Rajpathak Swapnil N. , Allison Matthew A. , Baird Alison E. , Rodriguez Beatriz , Wildman Rachel P.
Published: May 2010

Background and Purpose—

Although low levels of adiponectin are associated with coronary heart disease and cardiovascular disease risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke.

Methods—

We examined the relationship between baseline high-molecular-weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case–control study nested within the Women’s Health Initiative Observational Study. Included were 855 incident ischemic stroke cases and 855 control subjects matched for age, race–ethnicity, date of entry into the cohort, and follow-up time. ORs of incident ischemic stroke associated with baseline HMW adiponectin levels were calculated using conditional logistic regression modeling adjusting for body mass index, type 2 diabetes, hypertension, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, physical activity, C-reactive protein, and aspirin use.

Results—

Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher body mass index, waist circumference, glucose, and insulin levels and lower high-density lipoprotein cholesterol levels. The distribution of incident stroke cases by HMW adiponectin quartiles was 49.9%, 50.5%, 50.7%, and 48.9%, respectively (
P
=0.96). Multivariable-adjusted ORs of stroke associated with the top 3 quartiles of HMW adiponectin versus the first quartile were 0.99 (95% CI, 0.71 to 1.37), 1.37 (0.99 to 1.91), and 1.25 (0.88 to 1.79), respectively (
P
trend=0.14).

Conclusion—

Despite moderate associations between HMW adiponectin and cardiovascular disease risk factors, we found no evidence of an association between HMW adiponectin levels and incident ischemic stroke in these postmenopausal women.
Weight of the Obesity Epidemic
Authors: Towfighi Amytis , Zheng Ling , Ovbiagele Bruce
Published: May 2010

Background and Purpose—

Recent US nationally representative data revealed that among individuals aged 45 to 54 years, women’s stroke prevalence was double that of men’s. The purpose of this study was to determine if the sex disparity existed previously.

Methods—

We assessed sex-specific stroke and vascular risk factor prevalence among individuals aged 35 to 64 years who participated in the National Health and Nutrition Examination Surveys (NHANES), a cross-sectional, nationally representative survey conducted in 2 waves: 1988 to 1994 (n=7234) and 1999 to 2004 (n=6499).

Results—

Women aged 35 to 54 years who participated in NHANES from 1999 to 2004 were 3 times more likely to have experienced a stroke compared with similarly aged women in NHANES 1988 to 1994 (1.8% versus 0.6%,
P
=0.003), but stroke prevalence among men did not change (0.9% versus 1.0%, nonsignificant). Among women, the prevalence of obesity (15.2% versus 17.9%,
P
=0.08), morbid obesity (12.8% versus 17.5%,
P
=0.003), abdominal obesity (47.4% versus 58.9%,
P
<0.0001), hypertriglyceridemia (22.91% versus 26.78%,
P
=0.035), and hypertension (33.04% versus 37.43%,
P
=0.03) was lower in NHANES 1988 to 1994 compared with the more recent NHANES wave. Higher waist circumference was the only independent stroke risk factor for women aged 35 to 54 years in NHANES 1999 to 2004 (OR per 15-cm increase in waist circumference=1.02, 95% CI 1.00 to 1.04).

Conclusions—

Stroke prevalence among women aged 35 to 54 years has tripled over the past 2 decades, at the same time remaining stable among men. Prevalence of obesity and 3 metabolic syndrome components increased; they may be key factors in the increase in women’s stroke prevalence.
Antihypertensive Drug Use and Adherence After Stroke
Authors: Khan Nadia A. , Yun Lingsong , Humphries Karin , Kapral Moira
Published: May 2010

Background and Purpose—

The majority of stroke fatalities occur in elderly women. We compared prescribing and adherence to antihypertensive therapies shown to reduce fatal and nonfatal stroke recurrence among elderly women and men with acute stroke.

Methods—

Using the Registry of the Canadian Stroke Network, we identified all patients ≥66 years of age discharged home from 11 tertiary care centers with acute stroke (July 1, 2003, through March 31, 2006) in Ontario, Canada. Stroke cases were linked to the Ontario Drug Benefits Database and evaluated for prescription claims for thiazide diuretic, angiotensin converting enzyme inhibitor, beta blocker, angiotensin receptor blocker, or calcium channel blocker within 1 year of discharge from hospital. One-year adherence was assessed using the proportion of days covered with suboptimal adherence defined as a proportion of days covered <0.8.

Results—

A total of 3571 patients (51.6% women) ≥66 years of age with acute stroke were discharged home, with 87.6% of women and 84.7% of men treated with antihypertensive therapy within 1 year of stroke. Men were more likely than women to be prescribed angiotensin converting enzyme inhibitor monotherapy but just as likely to be prescribed angiotensin converting enzyme inhibitor/diuretic combination. Women were more likely to be prescribed all other classes of antihypertensive therapy. Suboptimal adherence occurred in 32% of patients receiving thiazide diuretics, 25% for angiotensin converting enzyme inhibitors, and 38% for angiotensin converting enzyme inhibitor/diuretic combination. There were no sex differences in adherence to these antihypertensive therapies. Patients who died after stroke had lower adherence to antihypertensive therapy compared with those who survived.

Conclusions—

In a cohort of elderly stroke patients, women were generally just as likely or more likely than men to receive antihypertensive prescriptions after stroke. Drug adherence was similarly poor in women and men.
Retinal Vascular Caliber and Brachial Flow-Mediated Dilation
Authors: Nguyen Thanh T. , Islam F. M. Amirul , Farouque H. M. Omar , Klein Ronald , Klein Barbara E. K. , Cotch Mary Frances , Herrington David M. , Wong Tien Yin
Published: May 2010

Background and Purpose—

Retinal vascular caliber changes have been shown to predict stroke, but the underlying mechanism of this association is unknown. We examined the relationship between retinal vascular caliber with brachial flow-mediated dilation (FMD), a measure of systemic endothelial function.

Methods—

The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of persons 45 to 84 years of age residing in 6 US communities free of clinical cardiovascular disease at baseline. Brachial FMD data were collected at baseline (July 2000 to June 2002), and retinal vascular caliber was measured from digital retinal photographs at the second examination, immediately after the first (August 2002 to January 2004). Data were available for 2851 participants for analysis.

Results—

The mean brachial FMD was 4.39±2.79%. After adjusting for age and gender, brachial FMD was reduced in persons with wider retinal venular caliber (changes in FMD −0.25, 95% CI, −0.36, − 0.13;
P
<0.001, per SD increase in venular caliber). This relationship persists after adjusting for systolic blood pressure, serum total cholesterol, use of lipid-lowering and antihypertensive medication, body mass index, current smoking status, and hemoglobinA
1C
(−0.18; 95% CI −0.30, − 0.06;
P
=0.004, per SD increase in venular caliber). Brachial FMD was not associated with retinal arteriolar caliber.

Conclusions—

Persons with wider retinal venules have reduced brachial FMD, independent of other vascular risk factors. This suggests that retinal venular caliber, previously shown to predict stroke, may be a marker of underlying systemic endothelial dysfunction.
Isoflurane Posttreatment Reduces Neonatal Hypoxic–Ischemic Brain Injury in Rats by the Sphingosine-1-Phosphate/Phosphatidylinositol-3-Kinase/Akt Pathway
Authors: Zhou Yilin , Lekic Tim , Fathali Nancy , Ostrowski Robert P. , Martin Robert D. , Tang Jiping , Zhang John H.
Published: May 2010

Background and Purpose—

Isoflurane, administered before or during cerebral ischemia, has been shown to exhibit neuroprotection in animal models of ischemic stroke. However, the underlying mechanism remains to be elucidated. In the present study, we determined whether isoflurane posttreatment provides neuroprotection after neonatal hypoxia–ischemia (HI) in rats and evaluated the role of the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathway in this volatile anesthetic-mediated neuroprotection.

Methods—

HI was induced in postnatal day 10 (P10) rat pups by unilateral carotid ligation and 2 hours of hypoxia. For treatment, 2% isoflurane was administered immediately after HI for 1 hour. As pharmacological interventions, the sphingosine-1-phosphate antagonist VPC23019, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid antagonist naloxone was administered before HI. Isoflurane posttreatment was evaluated for effects on infarct volume at 48 hours after HI and brain atrophy and neurological outcomes at 4 weeks after HI. The expression of phosphorylated Akt and cleaved caspase-3 was determined by Western blotting and immunofluorescence analysis.

Results—

Isoflurane posttreatment significantly reduced infarct volume at 48 hours after HI. VPC23019 or wortmannin abrogated the neuroprotective effect of isoflurane, whereas naloxone did not inhibit the isoflurane-induced neuroprotection. Isoflurane posttreatment significantly preserved phosphorylated Akt expression and decreased cleaved caspase-3 levels. These effects were reversed by VPC23019 and wortmannin, respectively. Isoflurane also confers long-term neuroprotective effects against brain atrophy and neurological deficits at 4 weeks after HI.

Conclusions—

Isoflurane posttreatment provides lasting neuroprotection against hypoxic–ischemic brain injury in neonatal rats. Activation of the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathway may play a key role in isoflurane posttreatment-induced neuroprotection.
Effectiveness of Virtual Reality Using Wii Gaming Technology in Stroke Rehabilitation
Authors: Saposnik Gustavo , Teasell Robert , Mamdani Muhammad , Hall Judith , McIlroy William , Cheung Donna , Thorpe Kevin E. , Cohen Leonardo G. , Bayley Mark
Published: May 2010

Background and Purpose—

Hemiparesis resulting in functional limitation of an upper extremity is common among stroke survivors. Although existing evidence suggests that increasing intensity of stroke rehabilitation therapy results in better motor recovery, limited evidence is available on the efficacy of virtual reality for stroke rehabilitation.

Methods—

In this pilot, randomized, single-blinded clinical trial with 2 parallel groups involving stroke patients within 2 months, we compared the feasibility, safety, and efficacy of virtual reality using the Nintendo Wii gaming system (VRWii) versus recreational therapy (playing cards, bingo, or “Jenga”) among those receiving standard rehabilitation to evaluate arm motor improvement. The primary feasibility outcome was the total time receiving the intervention. The primary safety outcome was the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, was evaluated with the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at 4 weeks after intervention.

Results—

Overall, 22 of 110 (20%) of screened patients were randomized. The mean age (range) was 61.3 (41 to 83) years. Two participants dropped out after a training session. The interventions were successfully delivered in 9 of 10 participants in the VRWii and 8 of 10 in the recreational therapy arm. The mean total session time was 388 minutes in the recreational therapy group compared with 364 minutes in the VRWii group (
P
=0.75). There were no serious adverse events in any group. Relative to the recreational therapy group, participants in the VRWii arm had a significant improvement in mean motor function of 7 seconds (Wolf Motor Function Test, 7.4 seconds; 95% CI, −14.5, −0.2) after adjustment for age, baseline functional status (Wolf Motor Function Test), and stroke severity.

Conclusions—

VRWii gaming technology represents a safe, feasible, and potentially effective alternative to facilitate rehabilitation therapy and promote motor recovery after stroke.
On the Dynamics of Two-Dimensional Hurricane-like Concentric Rings Vortex Formation
Authors: Martinez Y. , Brunet G. , Yau M. K.
Published: May 2010

Despite the fact that asymmetries in hurricanes (e.g., spiral rainbands, polygonal eyewalls, and mesovortices) have long been observed in radar and satellite imagery, many aspects of their dynamics remain unsolved, particularly in the formation of the secondary eyewall. The underlying associated dynamical processes need to be better understood to advance the science of hurricane intensity forecasting. To fill this gap, a simple 2D barotropic “dry” model is used to simulate a hurricane-like concentric rings vortex. The empirical normal mode (ENM) technique, together with Eliassen–Palm (EP) flux calculations, are used to isolate wave modes from the model datasets to investigate their impact on the changes in the structure and intensity of the simulated hurricane-like vortex.

From the ENM diagnostics, it is shown that asymmetric disturbances outside a strong vortex ring with a large vorticity skirt may relax to form concentric rings of enhanced vorticity that contain a secondary wind maximum. The fact that the critical radius for some of the leading modes is close to the location where the secondary ring of enhanced vorticity develops suggests that a wave–mean flow interaction mechanism based on vortex Rossby wave (VRW) dynamics may explain important dynamical aspects of concentric eyewall genesis (CEG).
The Impact of North Atlantic–Arctic Multidecadal Variability on Northern Hemisphere Surface Air Temperature
Authors: Semenov Vladimir A. , Latif Mojib , Dommenget Dietmar , Keenlyside Noel S. , Strehz Alexander , Martin Thomas , Park Wonsun
Published: May 2010

The twentieth-century Northern Hemisphere surface climate exhibits a long-term warming trend largely caused by anthropogenic forcing, with natural decadal climate variability superimposed on it. This study addresses the possible origin and strength of internal decadal climate variability in the Northern Hemisphere during the recent decades. The authors present results from a set of climate model simulations that suggest natural internal multidecadal climate variability in the North Atlantic–Arctic sector could have considerably contributed to the Northern Hemisphere surface warming since 1980. Although covering only a few percent of the earth’s surface, the Arctic may have provided the largest share in this. It is hypothesized that a stronger meridional overturning circulation in the Atlantic and the associated increase in northward heat transport enhanced the heat loss from the ocean to the atmosphere in the North Atlantic region and especially in the North Atlantic portion of the Arctic because of anomalously strong sea ice melt. The model results stress the potential importance of natural internal multidecadal variability originating in the North Atlantic–Arctic sector in generating interdecadal climate changes, not only on a regional scale, but also possibly on a hemispheric and even a global scale.
Global Distribution and Characteristics of Diurnally Varying Low-Level Jets
Authors: Rife Daran L. , Pinto James O. , Monaghan Andrew J. , Davis Christopher A. , Hannan John R.
Published: May 2010

This study documents the global distribution and characteristics of diurnally varying low-level jets (LLJs), including their horizontal, vertical, and temporal structure, with a special emphasis on highlighting the underlying commonalities and unique qualities of the various nocturnal jets. Two tools are developed to accomplish this goal. The first is a 21-yr global reanalysis performed with the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) using a horizontal grid spacing of 40 km. A unique characteristic of the reanalysis is the availability of hourly three-dimensional output, which permits the full diurnal cycle to be analyzed. Furthermore, the horizontal grid spacing of 40 km better resolves many physiographic features that host LLJs than other widely used global reanalyses. This makes possible a detailed examination of the systematic onset and cessation of the jets, including time–height representations of the diurnal cycle. The second tool is an index of nocturnal LLJ (NLLJ) activity based upon the vertical structure of the wind’s temporal variation, where the temporal variation is defined in local time. The first available objectively constructed global maps of recurring NLLJs are created from this index, where the various NLLJs can be simultaneously viewed at or near their peak time. These maps not only highlight all of the locations where NLLJs are known to recur, but they also reveal a number of new jets.

The authors examine the basic mechanisms that give rise to the NLLJs identified in four disparate locations, each having a profound influence on the regional climate. The first, the extensively studied Great Plains NLLJ, is used to confirm the veracity of the global analysis and the index of NLLJ activity. It also provides context for three of the many newly identified NLLJs: 1) Tarim Pendi in northwest China; 2) Ethiopia in eastern Africa; and 3) Namibia–Angola in southwest Africa. Jets in these four regions illustrate the variety of physiographic and thermal forcing mechanisms that can produce NLLJs.