bluuebunny/crossref_metadata_2025 huggingface dataset:
A Numerical Study of Energy Separation in a Jet Flow
Authors: Han Bumsoo , Goldstein R. J.
Published: April 2007

Redistribution of the total energy of a fluid in motion, which is called “energy separation,” has been observed in various flow situations. Understanding the underlying mechanism of this interesting phenomenon has been limited due to lack of the temporal information on flow and temperature fields. In the present study, numerical simulation of a viscous circular jet was performed to provide detailed temporal information on pressure, vorticity, and total temperature fields. Nondimensionalized governing equations, including mass, momentum, and total energy conservation equations, were simultaneously solved by an equal-order linear finite element and fractional four-step method. The results show that the formation and transport of vortices induce a pressure fluctuation in the flow field. The fluid, which flows through the disturbed pressure field, exchanges pressure work with the surroundings, and gains or loses total energy. This work exchange leads to higher and lower total temperature regions than the surroundings. In addition to the presence and movement of the vortices, the results indicate that the vortex-pairing process significantly intensifies the pressure fluctuation and corresponding total temperature difference. This implies that the vortex-pairing process is a very important process in intensifying energy separation and might explain the enhancement of energy separation in a jet using acoustic excitation.
Numerical Simulation for Under-Floor Air Distribution System With Swirl Diffusers
Authors: Wang Xiuling , Pepper Darrell W.
Published: April 2007

A finite volume renormalization group (RNG) k-ε turbulent model was employed to simulate an under-floor air distribution (UFAD) system consisting of eight swirl diffusers. Mesh generation was conducted using PRO/E and GAMBIT. Computational fluid dynamics (CFD) results using FLUENT show both flow and thermal patterns for an instrumented laboratory room (Building Technology Laboratory-BTL) located at the University of Nevada Las Vegas. Simulation results are presented using symmetrical boundary settings for the BTL. Stratification heights and clear zones are discussed. The application of CFD simulation provides insightful analyses in UFAD design and placement.
Pressure-Based Finite-Volume Methods in Computational Fluid Dynamics
Authors: Acharya S. , Baliga B. R. , Karki K. , Murthy J. Y. , Prakash C. , Vanka S. P.
Published: April 2007

Pressure-based finite-volume techniques have emerged as the methods of choice for a wide variety of industrial applications involving incompressible fluid flow. In this paper, we trace the evolution of this class of solution techniques. We review the basics of the finite-volume method, and trace its extension to unstructured meshes through the use of cell-based and control-volume finite-element schemes. A critical component of the solution of incompressible flows is the issue of pressure-velocity storage and coupling. The development of staggered-mesh schemes and segregated solution techniques such as the SIMPLE algorithm are reviewed. Co-located storage schemes, which seek to replace staggered-mesh approaches, are presented. Coupled multigrid schemes, which promise to replace segregated-solution approaches, are discussed. Extensions of pressure-based techniques to compressible flows are presented. Finally, the shortcomings of existing techniques and directions for future research are discussed.
Multiple-Dose Escalation Study of the Safety, Pharmacokinetics, and Biologic Activity of Oral AMD070, a Selective CXCR4 Receptor Inhibitor, in Human Subjects
Authors: Stone Nimalie D. , Dunaway Shelia B. , Flexner Charles , Tierney Camlin , Calandra Gary B. , Becker Stephen , Cao Ying-Jun , Wiggins Ilene P. , Conley Jeanne , MacFarland Ron T. , Park Jeong-Gun , Lalama Christina , Snyder Sally , Kallungal Beatrice , Klingman Karin L. , Hendrix Craig W.
Published: April 2007

AMD070 is an oral CXCR4 antagonist with in vitro activity against X4-tropic human immunodeficiency virus type 1. Thirty fasting healthy male volunteers received oral doses of AMD070 ranging from a single 50-mg dose to seven 400-mg doses given every 12 h (q12h). Nine subjects received a 200-mg dose during fasting and prior to a meal. Subjects were monitored for safety and pharmacokinetics. AMD070 was well tolerated, without serious adverse events. Transient headaches (13 subjects) and neurocognitive (8 subjects) and gastrointestinal (7 subjects) symptoms were the most common complaints. Seven subjects had sinus tachycardia, and two were symptomatic. AMD070 plasma concentrations peaked 1 to 2 h after patient dosing. The estimated terminal half-life ranged from 11.2 to 15.9 h among cohorts. Dose proportionality was not demonstrated. Less than 1% of the drug appeared unchanged in the urine. Food reduced the maximum concentration of drug in serum and the area under the concentration-time curve from 0 to 24 h by 70% and 56%, respectively (
P
≤ 0.01). A dose-dependent elevation of white blood cells (WBC) demonstrated a maximum twofold increase over baseline (95% confidence interval, 2.0- to 2.1-fold) in an
E
max
model. In healthy volunteers, AMD070 was well tolerated and demonstrated mixed-order pharmacokinetics, and food reduced drug exposure. AMD070 induced a dose-related elevation of WBC which was attributed to CXCR4 blockade. Using leukocytosis as a surrogate marker for CXCR4 inhibition, this dose-response relationship suggests that the doses used in this study were active in vivo, though not maximal, throughout the dosing interval. Trough concentrations with the 400-mg dose q12h exceeded the antiviral in vitro 90% effective concentration of AMD070.
Defining Limits of Treatment with Humanized Neutralizing Monoclonal Antibody for West Nile Virus Neurological Infection in a Hamster Model
Authors: Morrey John D. , Siddharthan Venkatraman , Olsen Aaron L. , Wang Hong , Julander Justin G. , Hall Jeffery O. , Li Hua , Nordstrom Jeffrey L. , Koenig Scott , Johnson Syd , Diamond Michael S.
Published: April 2007

A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal antibody, hE16, was previously shown to improve the survival of WNV-infected hamsters when it was administered intraperitoneally (i.p.), even after the virus had infected neurons in the brain. In this study, we evaluated the therapeutic limit of hE16 for the treatment of WNV infection in hamsters by comparing single-dose peripheral (i.p.) therapy with direct administration into the pons through a convection-enhanced delivery (CED) system. At day 5 after infection, treatments with hE16 by the peripheral and the CED routes were equally effective at reducing morbidity and mortality. In contrast, at day 6 only the treatment by the CED route protected the hamsters from lethal infection. These experiments suggest that hE16 can directly control WNV infection in the central nervous system. In support of this, hE16 administered i.p. was detected in a time-dependent manner in the serum, cerebrospinal fluid (CSF), cerebral cortex, brain stem, and spinal cord in CSF. A linear relationship between the hE16 dose and the concentration in serum was observed, and maximal therapeutic activity occurred at doses of 0.32 mg/kg of body weight or higher, which produced serum hE16 concentrations of 1.3 μg/ml or higher. Overall, these data suggest that in hamsters hE16 can ameliorate neurological disease after significant viral replication has occurred, although there is a time window that limits therapeutic efficacy.
AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN
Authors: Serrano-Gómez Diego , Martínez-Nuñez Rocío T. , Sierra-Filardi Elena , Izquierdo Nuria , Colmenares María , Pla Jesús , Rivas Luis , Martinez-Picado Javier , Jimenez-Barbero Jesús , Alonso-Lebrero José Luis , González Salvador , Corbí Angel L.
Published: April 2007

AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of
Candida
,
Aspergillus
, and
Leishmania
to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV
trans
-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and
1
D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.
Production of High-Affinity Human Monoclonal Antibody Fab Fragments to the 19-Kilodalton C-Terminal Merozoite Surface Protein 1 ofPlasmodium falciparum
Authors: Cheng Xun-Jia , Hayasaka Hitoshi , Watanabe Katsuomi , Tao Yan-Lin , Liu Jin-Ye , Tsukamoto Hideo , Horii Toshihiro , Tanabe Kazuyuki , Tachibana Hiroshi
Published: April 2007

A combinatorial immunoglobulin gene library was constructed from peripheral blood lymphocytes of eight patients infected withPlasmodium falciparumand was screened for the production of human monoclonal antibody Fab fragments to the C-terminal 19-kDa fragment ofP. falciparummerozoite surface protein 1 (MSP-119). Three Fab clones recognized recombinant MSP-119under nonreducing conditions. Indirect immunofluorescence microscopy demonstrated that three Fab clones stained the surfaces of late trophozoites/schizonts and merozoites of the FCR3 and 3D7 strains, suggesting the Fabs' reactivities to a conserved epitope. Sequence analysis of the heavy-chain genes revealed that the closest germ line V segments were VH1-8 and VH7-81, with 91% to 98% homology. The closest germ line D segment was D3-10, and the closest germ line J segment was JH4 or JH5, with 90% to 97% homology. In the light-chain genes, the closest germ line V segment was A27 for the Jκ2, Jκ4, and Jκ5 segments. The dissociation constants of these Fab fragments for recombinant MSP-119ranged from 1.09 × 10−9to 2.66 × 10−9M. The binding of the three Fab fragments to MSP-119was competitively inhibited by the anti-MSP-119mouse monoclonal antibody 12.8, which inhibits erythrocyte invasion by merozoites. However, the human Fab fragment with the highest affinity did not inhibit in vitro growth ofP. falciparum. This is the first report of gene analysis and bacterial expression of human monoclonal antibodies toP. falciparumMSP-119. The combinatorial immunoglobulin gene library derived from malaria patients provides a potential tool for producing high-affinity human antibodies specific forP. falciparum.
Vacuolating Cytotoxin in
Helicobacter pylori
Water-Soluble Proteins Upregulates Chemokine Expression in Human Eosinophils via Ca
2+
Influx, Mitochondrial Reactive Oxygen Intermediates, and NF-κB Activation
Authors: Kim Jung Mogg , Kim Joo Sung , Lee Jin Young , Kim Yeong-Jeon , Youn Ho-Joo , Kim In Young , Chee Young Joon , Oh Yu-Kyoung , Kim Nayoung , Jung Hyun Chae , Song In Sung
Published: April 2007

Helicobacter pylori
-infected gastric mucosa is characterized by infiltration of inflammatory cells such as neutrophils and eosinophils. However, little information is available on the relationship between
H. pylori
virulence factors and chemokine expression in eosinophils. This study investigates the role of vacuolating cytotoxin (VacA) in chemokine expression from human eosinophils. Eosinophils were isolated from the peripheral blood of healthy volunteers using a magnetic cell separation system. VacA
+
H. pylori
water-soluble proteins (WSP) induced higher expression of interleukin-8, growth-related oncogene alpha, monocyte chemotactic protein 1, and RANTES (regulated on activation, normal, T-cell expressed and secreted) than Vac
−
WSP in human eosinophils, as assessed by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Purified VacA not only increased chemokine expression but also activated p65/p50 NF-κB heterodimers and phosphorylated IκB kinase (IKK) α/β signals in human eosinophils. Inhibition of NF-κB and IKK significantly decreased the chemokine expression in VacA-stimulated eosinophils. Furthermore, VacA-induced NF-κB activation and chemokine release from eosinophils were dependent on Ca
2+
influx and mitochondrial generation of reactive oxygen intermediates (ROI). These results suggest that NF-κB and IKK signals via Ca
2+
influx and mitochondrial ROI play a role in the up-regulation of chemokine expression in eosinophils stimulated with
H. pylori
VacA.
Regulation of P-Fimbrial Phase Variation Frequencies in
Escherichia coli
CFT073
Authors: Holden Nicola , Totsika Makrina , Dixon Lynn , Catherwood Kirsteen , Gally David L.
Published: April 2007

Adherence of uropathogenic
Escherichia coli
to host tissue is required for infection and is mediated by fimbriae, such as pyelonephritis-associated pili (Pap). Expression of P fimbriae is regulated by phase variation, and to date, phase transition frequencies have been measured only for
pap
regulatory region constructs integrated into the
E. coli
K-12 chromosome. The aim of this work was to measure P phase transition frequencies in clinical isolates for the first time, including frequencies for the sequenced strain
E. coli
CFT073. P fimbriation and associated phase transition frequencies were measured for two
E. coli
clinical isolates and compared with levels for homologous
pap
constructs in
E. coli
K-12. Fimbriation and off-to-on transition frequencies were always higher in the clinical isolate. It was concluded that the regulatory inputs controlling
papI
expression are likely to be different in
E. coli
CFT073 and
E. coli
K-12 as (i) phase variation could be stimulated in
E. coli
K-12 by induction of
papI
and (ii) the level of expression of a
papI
::
gfp

+

fusion was higher in
E. coli
CFT073 than in
E. coli
K-12. Furthermore, phase transition frequencies for the two
E. coli
CFT073
pap
clusters were shown to be different depending on the culture conditions, indicating that there is a hierarchy of expression depending on signal inputs.
Consensus statement on injury definitions and data collection procedures for studies of injuries in rugby union
Authors: Fuller Colin W , Molloy Michael G , Bagate Christian , Bahr Roald , Brooks John H M , Donson Hilton , Kemp Simon P T , McCrory Paul , McIntosh Andrew S , Meeuwisse Willem H , Quarrie Kenneth L , Raftery Martin , Wiley Preston
Published: April 2007

Wide variations in the definitions and methodologies used for studies of injuries in rugby union have created inconsistencies in reported data and made interstudy comparisons of results difficult. The International Rugby Board established a Rugby Injury Consensus Group (RICG) to reach an agreement on the appropriate definitions and methodologies to standardise the recording of injuries and reporting of studies in rugby union. The RICG reviewed the consensus definitions and methodologies previously published for football (soccer) at a meeting in Dublin in order to assess their suitability for and application to rugby union. Following this meeting, iterative draft statements were prepared and circulated to members of the RICG for comment; a follow-up meeting was arranged in Dublin, at which time all definitions and procedures were finalised. At this stage, all authors confirmed their agreement with the consensus statement. The agreed document was presented to and approved by the International Rugby Board Council. Agreement was reached on definitions for injury, recurrent injury, non-fatal catastrophic injury, and training and match exposures, together with criteria for classifying injuries in terms of severity, location, type, diagnosis and causation. The definitions and methodology presented in this consensus statement for rugby union are similar to those proposed for football. Adoption of the proposals presented in this consensus statement should ensure that more consistent and comparable results will be obtained from studies of injuries within rugby union.
INTEGRATIVE COMPUTER-AIDED DIAGNOSTIC WITH BREAST THERMOGRAM
Authors: NG E. Y. K. , KEE E. C.
Published: April 2007

Thermography is a non-invasive and non-contact imaging technique widely used in the medical arena. This paper investigates the analysis of thermograms with the use of biostatistical methods and Artificial Neural Networks (ANN). It is desired that through these approaches, highly accurate diagnosis using thermography techniques can be established.

The proposed advanced technique is a multipronged approach comprising of Linear Regression (LR), Radial Basis Function Network (RBFN) and Receiver Operating Characteristics (ROC). It is a novel and integrative technique that can be used to analyze complicated and large numerical data. In this study, the advanced technique will be used to analyze breast cancer thermogram for diagnosis purposes.

The use of LR shows the correlation between the variables and the actual health status (healthy or cancerous) of the subject, which is decided by using mammography. This is important when selecting the variables to be used as inputs, in particular, for building the neural network.

For ANN, RBFN is applied. Based on the various inputs fed into the network, RBFN will be trained to produce the desired outcome, which is either positive for cancerous or negative for healthy cases. When this is done, the RBFN algorithm will possess the ability to predict the outcome when there are new input variables. The advantages of using RBFN include fast training, superior classification and decision making abilities as compared to other networks such as back-propagation.

Next, ROC is used to evaluate the accuracy, sensitivity and specificity of the outcome of RBFN Test files. The best results obtained are an accuracy (score) rate of 80.95%, with 81.2% sensitivity and 88.2% specificity. For breast cancer diagnosis, clinical examination by experienced doctors has an accuracy rate of approximately 60–70%. Hence, the proposed method has a higher accuracy rate than the existing practice.

Through the use of Bio-statistical methods and ANN, improvements are made in thermography application with regard to achieving a higher level of accuracy rate in diagnosis as compared to clinical examination. It has now become possible to use thermography as a powerful adjunct tool for breast cancer detection, together with mammography for diagnosis purposes.
DEVELOPMENT OF A LASER CONFOCAL ENDOMICROSCOPE FOR IN VIVO FLUORESCENCE IMAGING
Authors: THONG PATRICIA S. P. , KHO K. W. , ZHENG W. , HARRIS M. , SOO K. C. , OLIVO M.
Published: April 2007

Malignancies of the oral cavity are conventionally diagnosed by white light endoscopy, biopsy and histopathology. However, it is often difficult to distinguish between benign lesions and premalignant or early lesions. There is a need for a more definitive, non-invasive technique for diagnosis of oral cavity lesions. A laser confocal endomicroscope offers non-invasive surface and subsurface imaging of tissue. We investigated its potential for fluorescence imaging of the oral cavity using hypericin, fluorescein and aminolevulinic acid. Fluorescence imaging was carried out both in vivo and on resected tissue samples of the oral cavity in both humans and animal models. Good structural images of the oral cavity were obtained. Morphological differences between normal and lesion tissue can be distinguished. The use of Pharmasolve® enhanced the subsurface depth from which images can be obtained. Our results show that laser confocal fluorescence endomicroscopy has great potential for the diagnosis of oral cavity malignancies.
VOLUME VISUALIZATION FOR SURGICAL PLANNING SYSTEM
Authors: FATT CHAN CHEE , KASSIM IRWAN , LO CHARLES , NG IVAN , KEONG KWOH CHEE
Published: April 2007

The 3D volume visualization is to overcome the difficulties of the 2D imaging by using computer technology. A volume visualization approach has been successfully implemented for Surgical Planning System in National Neuroscience Institute (NNI). The system allows surgeons to plan a surgical approach on a set of 2D image slices and process into volume models and visualise them in 3D rapidly and interactively on PC. In our implementation, we have applied it in neurosurgical planning. The surgeon can visualize objects of interest like tumor and surgical path, and verify that the surgical plan avoids the critical features and the planning of the surgical path can thus be optimal.
MEASUREMENT OF INTRAMENISCAL FORCES AND STRESSES BY TWO DIFFERENT MINIATURE TRANSDUCERS
Authors: GOH P. K. , FUSS F. K. , YANAI T. , RITCHIE A. C. , LIE D. T. T. , TJIN S. C.
Published: April 2007

Injuries to the knee joint are common and often have an adverse impact on a patient's quality of life. It is therefore important to understand the load transfer mechanism of the knee, especially with regard to the loading of the menisci in different positions and under different conditions.

To date, only contact pressure between joint surfaces and menisci, as well as circumferential strain, have been measured by pressure sensors and strain gauges. Therefore, the aim of this study was to investigate the spread of axial load within the menisci and the effect of the knee flexion angle on the axial load within the menisci.

Intrameniscal forces were measured with Fiber Bragg Grating (FBG) sensors and conductive rubber sensors in porcine knee joint specimens. The changes in pressure were measured under different loading conditions. Measurement of the intrameniscal pressure is feasible. Although, there is some existence of variations in readings, some trends can be inferred. From the overall trend, it was observed that higher stress occurs at lateral central and lateral posterior regions. As the occurrences of injuries are mainly at the medial meniscus, this may imply that the level of stress is secondary to the mobility of the meniscus in incidents of injuries. It was found that the posterior meniscofemoral ligament plays a crucial role in the mechanics of the lateral meniscus.
Angiotensin-Converting Enzyme
I/D
and α-Adducin
Gly460Trp
Polymorphisms
Authors: Li Yan , Zagato Laura , Kuznetsova Tatiana , Tripodi Grazia , Zerbini Gianpaolo , Richart Tom , Thijs Lutgarde , Manunta Paolo , Wang Ji-Guang , Bianchi Giuseppe , Staessen Jan A.
Published: April 2007

The angiotensin-converting enzyme (
ACE
)
I/D
and the α-adducin (
ADD1
)
Gly460Trp
polymorphisms are associated with cardiovascular risk factors. In a prospective population study and in cell models, we investigated the combined effects of these 2 polymorphisms. We randomly recruited 1287 white subjects (women: 50.0%; mean age: 55.9 years). We obtained outcomes from registries and repeat examinations (median 3). Over 9.0 years (median), 178 fatal or nonfatal cardiovascular events occurred. In
ADD1 Trp
allele carriers, the multivariate-adjusted hazard ratios associated with
ACE DD
versus
I
were 1.72 (
P
=0.007) for total mortality, 2.35 (
P
=0.02) for cardiovascular mortality, 2.02 (
P
=0.005) for all cardiovascular events, and 2.59 (
P
=0.03) for heart failure. In contrast, these hazard ratios did not reach significance in
ADD1 GlyGly
homozygotes (0.08≤
P
≤0.90). The positive predictive value and attributable risk associated with
ACE DD
homozygosity combined with mutated
ADD1
were 36.2% and 10.3%, respectively. To clarify our epidemiological observations, we investigated the effects of mutated human
ADD1
on the membrane-bound ACE activity in fibroblasts from 51 volunteers and in transfected human embryonic kidney cells (31 experiments). In fibroblasts (5.10 versus 3.63 nanomoles of generated hippuric acid per milligram of protein per minute;
P
=0.0021) and human embryonic kidney cells (1.086 versus 0.081 nmol/mg per minute;
P
=0.017), the membrane-bound ACE activity increased in the presence but not absence of the
ADD1 Trp
allele. In conclusion, the combination of
ACE DD
homozygosity and mutated
ADD1
worsened cardiovascular prognosis to a similar extent as classic risk factors, possibly because of increased membrane-bound ACE activity in subjects carrying the
ADD1 Trp
allele.
Childhood Growth and Hypertension in Later Life
Authors: Eriksson Johan G. , Forsén Tom J. , Kajantie Eero , Osmond Clive , Barker David J.P.
Published: April 2007

Few studies have examined the effects of both prenatal and postnatal growth on hypertension. We report on hypertension in 2003 people aged 62 years who were randomly selected from the Helsinki birth cohort and examined in a clinic. Their heights and weights had been recorded serially up to age 11 years. A total of 644 had already been diagnosed with hypertension. Compared with normotensive people, they were obese and insulin resistant. At birth they were thin and short, and they gained weight slowly up to age 2 years; thereafter they grew rapidly so that at age 11 years their body size was around the average. The odds ratio associated with each kilogram of birthweight was 0.42 (95% CI: 0.32 to 0.56); with each 10 kg of current weight it was 1.85 (95% CI: 1.66 to 2.05). The blood pressures of another 802 people were classified as hypertensive under current definitions. They were overweight and had an atherogenic lipid profile. At birth they were short, and after birth they grew slowly so that at age 11 years they were short and thin. The odds ratio associated with each kilogram of weight at age 2 years was 0.75 (95% CI: 0.68 to 0.84); with each 10 kg of current weight it was 1.42 (95% CI: 1.28 to 1.57). We conclude that 2 different paths of childhood growth precede the development of hypertension. We suggest that they lead to hypertension through different biological mechanisms and may respond differently to medication.
Long-Term Trandolapril Treatment Is Associated With Reduced Aortic Stiffness
Authors: Mitchell Gary F. , Dunlap Mark E. , Warnica Wayne , Ducharme Anique , Arnold J. Malcolm O. , Tardif Jean-Claude , Solomon Scott D. , Domanski Michael J. , Jablonski Kathleen A. , Rice Madeline M. , Pfeffer Marc A.
Published: April 2007

The Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial evaluated angiotensin-converting enzyme inhibition with trandolapril versus placebo added to conventional therapy in patients with stable coronary disease and preserved left ventricular function. The PEACE hemodynamic substudy evaluated effects of trandolapril on pulsatile hemodynamics. Hemodynamic studies were performed in 300 participants from 5 PEACE centers a median of 52 months (range, 25 to 80 months) after random assignment to trandolapril at a target dose of 4 mg per day or placebo. Central pulsatile hemodynamics and carotid–femoral pulse wave velocity were assessed by using echocardiography, tonometry of the carotid and femoral arteries, and body surface transit distances. Patients randomly assigned to trandolapril tended to be older (mean±SD: 64.2±7.9 versus 62.9±7.7 years;
P
=0.14), with a higher body mass index (28.5±4.0 versus 27.8±3.9 kg/m
2
;
P
=0.09) and lower ejection fraction (57.1±8.1% versus 58.7±8.4%;
P
<0.01). At the time of the hemodynamic substudy, the trandolapril group had lower mean arterial pressure (93.1±10.2 versus 96.3±11.3 mm Hg;
P
<0.01) and lower carotid-femoral pulse wave velocity (geometric mean [95% CI]: 10.4 m/s [10.0 to 10.9 m/s] versus 11.2 m/s [10.7 to 11.8 m/s];
P
=0.02). The difference in carotid–femoral pulse wave velocity persisted (
P
<0.01) in an analysis that adjusted for baseline characteristics and follow-up mean pressure. In contrast, there was no difference in aortic compliance, characteristic impedance, augmentation index, or total arterial compliance. Angiotensin-converting enzyme inhibition with trandolapril produced a modest reduction in carotid–femoral pulse wave velocity, a measure of aortic wall stiffness, beyond what would be expected from blood pressure lowering or differences in baseline characteristics alone.
Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice
Authors: VanTeeffelen Jurgen W.G.E. , Brands Judith , Jansen Carin , Spaan Jos A.E. , Vink Hans
Published: April 2007

The endothelial glycocalyx is a hydrated mesh of polysaccharides and adsorbed plasma proteins that forms the true interface between the flowing blood and the endothelium. We hypothesized in the present study that competitive binding of heparin to glycocalyx-associated proteins would affect glycocalyx barrier properties and mechanotransduction of shear stress to the endothelium. In anesthetized mice, the clearance of 70-kDa dextrans from the circulation was increased (
P
<0.05 versus saline) 1 hour after heparin (1.25 U) and glycocalyx degradation with hyaluronidase (35 U; amount cleared in 30 minutes after saline: 11±5%; after heparin: 45±8%; after hyaluronidase: 30±3%). Clearance of 40-kDa dextrans increased (
P
<0.05 versus saline) to a lesser extent after both treatments (saline: 46±3%; heparin: 60±5%; hyaluronidase: 60±2%). The dilator response of second-order arterioles in cremaster muscle during reactive hyperemia was reduced for ≤90 minutes after heparin as reflected by a decrease (
P
=0.008) in t
50
of diameter recovery, and this effect was associated with a diminished NO bioavailability. Infusion of hyaluronidase resulted in reductions (
P
<0.05) in baseline and peak reactive hyperemic diameter, whereas, despite an increase in wall shear rate at the beginning of reactive hyperemia, t
50
of diameter recovery was not affected. In conclusion, our data in mice show that a heparin challenge is associated with increased vascular leakage of dextrans and impaired arteriolar vasodilation during reactive hyperemia. Our data suggest that protein–heparan sulfate interactions are important for a functional glycocalyx.
Proinflammatory Profile Within the Grossly Normal Aged Human Aortic Wall
Authors: Wang Mingyi , Zhang Jing , Jiang Li-Qun , Spinetti Gaia , Pintus Gianfranco , Monticone Robert , Kolodgie Frank D. , Virmani Renu , Lakatta Edward G.
Published: April 2007

Studies in animal models demonstrate that angiotensin II and its downstream signaling molecules, that is, matrix metalloproteinases and monocyte chemoattractant protein-1, increase within the diffusely thickened intima of central arteries with aging. Whether such age-related changes occur within the human arterial wall is unknown. We harvested “grossly normal thoracic aortas” from 5 young (20±3 years) and 5 old white males (65±6 years) at necropsy, after death from traumatic causes. The intimae of older samples were markedly and diffusely thickened compared with younger intimae and contained increased levels of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor type 1, matrix metalloproteinases 2/9, monocyte chemoattractant protein-1, and collagen I and III proteins. In situ activities of metalloproteinases 2/9 were also significantly enhanced within old, normal aortas. The thickened intima of older aortas also contained a 5-fold increase in the embryonic form of smooth muscle myosin heavy chain–labeled cells than that of younger aortas, and these fetal-type cells were colocalized with angiotensin II protein staining. The ability of isolated smooth muscle cells to invade an artificial basement membrane in response to a monocyte chemoattractant protein-1 gradient increased with age. Furthermore, angiotensin II increased the invasive capacity of young smooth muscle cells, and this effect was reduced by a metalloproteinase inhibitor or an angiotensin II receptor blocker. Thus, in the absence of lipid infiltration, the aged human aortic wall exhibits a proinflammatory profile that renders it a fertile substrate for the development of arterial disease, for example, atherosclerosis and hypertension.
Differential Effects of 17β-Estradiol on Function and Expression of Estrogen Receptor α, Estrogen Receptor β, and GPR30 in Arteries and Veins of Patients With Atherosclerosis
Authors: Haas Elvira , Meyer Matthias R. , Schurr Ulrich , Bhattacharya Indranil , Minotti Roberta , Nguyen Hung H. , Heigl Andres , Lachat Mario , Genoni Michele , Barton Matthias
Published: April 2007

Venous complications have been implicated in the adverse effects of hormone replacement therapy. This study investigated acute effects of the natural estrogen, 17β-estradiol, on function, estrogen receptors/GPR30 expression, and kinase activation in vascular rings and cultured smooth muscle cells from arteries and veins of patients with coronary artery disease. Changes in vascular tone of internal mammary arteries and saphenous veins exposed to the steroid were recorded. 17β-Estradiol caused concentration-dependent, endothelium-independent relaxation in arteries (P<0.05 versus solvent control) but not in veins (Pnot significant). 17β-Estradiol enhanced contractions to endothelin-1 in veins but not in arteries. The novel membrane estrogen receptor GPR30 was detected in both vessels. Moreover, gene expression of estrogen receptor β was 10-fold higher than that of estrogen receptor α or GPR30 (P<0.05). Expression of all 3 of the receptors was reduced after exposure to 17β-estradiol in arteries but not in veins (P<0.05). Basal phosphorylation levels of extracellular signal-regulated kinase were higher in venous than in arterial smooth muscle cells and were increased by 17β-estradiol in arterial cells only. In summary, this is the first study to report that, in human arteries but not in veins, 17β-estradiol acutely affects vascular tone, estrogen receptor expression, including GPR30, and extracellular signal-regulated kinase phosphorylation. These data indicate that effects of natural estrogens in humans differ between arterial and venous vascular beds, which may contribute to the vascular risks associated with menopause or hormone therapy.
Rabbi David Fränckel, Moses Mendelssohn, and the Beginning of the Berlin Haskalah: Reattributing a Patriotic Sermon (1757)
Authors: Freudenthal Gad
Published: April 2007

On December 10, 1757 R. David Fränckel (1707–1762), Chief Rabbi of Berlin Jewry, delivered in German a sermon on the occasion of Frederick the Great's victory at Leuthen. Scholarly consensus has ascribed this sermon to Moses Mendelssohn (1729–1796), and it is included in the authoritative edition of Mendelssohn's Complete Works (Jubiläumsausgabe). Drawing on an earlier sermon by Fränckel that has only recently come to light, this paper argues that the "Leuthen Sermon" was in truth authored by Fränckel himself, in Hebrew, and that Mendelssohn only translated it into German. This re-attribution affords a better appreciation of Fränckel's important role in the emergence of the Berlin Haskalah. It is also suggested that Fränckel's thought was closer to Mendelssohn's than hitherto realized, and that Fränckel played a greater role in Mendelssohn's intellectual development than previously thought. The Appendix points out that Fränckel's sermon enjoyed a world-wide success: the German version was reprinted a considerable number of times in Germany; and an English translation was published in London and was reprinted in the New World by both Jews and Christians.
Ubi Lenin, Ibi Jerusalem: Illusions and Defeats of Jewish Communists in Polish-Jewish, Post-world War II Literature
Authors: Mincer Laura Quercioli
Published: April 2007

On the basis of an analysis of literary texts by Polish-Jewish authors, the character of the Communist Jews, their motivations and relations to Jewish and Polish culture is described. This topic involves at the same time the forms of Jewish self-representation and self-consciousness, and the role played by Polonized Jews within Polish society. The article opens with a brief sketch of the possible affinities between Jewish Messianism and revolutionary utopia.
Combining Spatial Statistical and Ensemble Information in Probabilistic Weather Forecasts
Authors: Berrocal Veronica J. , Raftery Adrian E. , Gneiting Tilmann
Published: April 2007

Forecast ensembles typically show a spread–skill relationship, but they are also often underdispersive, and therefore uncalibrated. Bayesian model averaging (BMA) is a statistical postprocessing method for forecast ensembles that generates calibrated probabilistic forecast products for weather quantities at individual sites. This paper introduces the spatial BMA technique, which combines BMA and the geostatistical output perturbation (GOP) method, and extends BMA to generate calibrated probabilistic forecasts of whole weather fields simultaneously, rather than just weather events at individual locations. At any site individually, spatial BMA reduces to the original BMA technique. The spatial BMA method provides statistical ensembles of weather field forecasts that take the spatial structure of observed fields into account and honor the flow-dependent information contained in the dynamical ensemble. The members of the spatial BMA ensemble are obtained by dressing the weather field forecasts from the dynamical ensemble with simulated spatially correlated error fields, in proportions that correspond to the BMA weights for the member models in the dynamical ensemble. Statistical ensembles of any size can be generated at minimal computational cost. The spatial BMA technique was applied to 48-h forecasts of surface temperature over the Pacific Northwest in 2004, using the University of Washington mesoscale ensemble. The spatial BMA ensemble generally outperformed the BMA and GOP ensembles and showed much better verification results than the raw ensemble, both at individual sites, for weather field forecasts, and for forecasts of composite quantities, such as average temperature in National Weather Service forecast zones and minimum temperature along the Interstate 90 Mountains to Sound Greenway.
African Easterly Waves during 2004—Analysis Using Objective Techniques
Authors: Berry Gareth , Thorncroft Chris , Hewson Tim
Published: April 2007

African easterly waves (AEWs) are identified in numerical model analyses using an objective technique based on the 700-hPa streamfunction field. This method has been developed to (i) reduce the amount of manual data interpretation, (ii) reduce the likelihood of unrelated phenomena being identified as AEWs, and (iii) facilitate completely objective comparisons between AEWs with different structures on multiple scales, in order to describe their variability. Results show this method performs well when compared to methods of AEW identification used in previous studies. The objective technique is used to analyze all AEWs that originated over tropical North Africa during July–September (JAS) 2004. Results indicate that the “average” AEW in this period bears a close resemblance to composite structures from previous research. However, there is marked variability in the characteristics and ultimate fate of AEWs. Most AEWs of JAS 2004 are first identified east of the Greenwich meridian and develop as they move westward. Mature structures over the African continent varied, ranging from isolated potential vorticity maxima confined equatorward of the objectively defined African easterly jet to broad cross-jet structures symptomatic of both baroclinic and barotropic growth. As many as 80% of the cases fell into the second category. After leaving the West African coast, 45% of the AEWs in JAS 2004 were associated with tropical cyclogenesis in either the Atlantic or Pacific Ocean basins.
Probabilistic Evaluation of the Dynamics and Predictability of the Mesoscale Convective Vortex of 10–13 June 2003
Authors: Hawblitzel Daniel P. , Zhang Fuqing , Meng Zhiyong , Davis Christopher A.
Published: April 2007

This study examines the dynamics and predictability of the mesoscale convective vortex (MCV) of 10–13 June 2003 through ensemble forecasting. The MCV of interest developed from a preexisting upper-level disturbance over the southwest United States on 10 June and matured as it traveled northeastward. This event is of particular interest given the anomalously strong and long-lived nature of the circulation. An ensemble of 20 forecasts using a 2-way nested mesoscale model with horizontal grid increments of 30 and 10 km are employed to probabilistically evaluate the dynamics and predictability of the MCV. Ensemble mean and spread as well as correlations between different forecast variables at different forecast times are examined. It is shown that small-amplitude large-scale balanced initial perturbations may result in very large ensemble spread, with individual solutions ranging from a very strong MCV to no MCV at all. Despite similar synoptic-scale conditions, the ensemble MCV forecasts vary greatly depending on intensity and coverage of simulated convection, illustrating the critical role of convection in the development and evolution of this MCV. Correlation analyses reveal the importance of a preexisting disturbance to the eventual development of the MCV. It is also found that convection near the center of the MCV the day after its formation may be an important factor in determining the eventual growth of a surface vortex and that a stronger midlevel vortex is more conducive to convection, especially on the downshear side, consistent with the findings of previous MCV studies.
Influence of Tropical Cyclones on Humidity Patterns over Southern Baja California, Mexico
Authors: Farfán Luis M. , Fogel Ira
Published: April 2007

The influence of tropical cyclone circulations in the distribution of humidity and convection over northwestern Mexico is investigated by analyzing circulations that developed in the eastern Pacific Ocean from 1 July to 21 September 2004. Documented cases having some impact over the Baja California Peninsula include Tropical Storm Blas (13–15 July), Hurricane Frank (23–25 August), Hurricane Howard (2–6 September), and Hurricane Javier (15–20 September). Datasets are derived from geostationary satellite imagery, upper-air and surface station observations, as well as an analysis from an operational model. Emphasis is given to circulations that moved within 800 km of the southern part of the peninsula. The distribution of precipitable water is used to identify distinct peaks during the approach of these circulations and deep convection that occurred for periods of several days over the southern peninsula and Gulf of California. Hurricane Howard is associated with a significant amount of precipitation, while Hurricane Javier made landfall across the central peninsula with a limited impact on the population in the area. An examination of the large-scale environment suggests that advection of humid air from the equatorial Pacific is an important element in sustaining tropical cyclones and convection off the coast of western Mexico.
The Impact of Convective Momentum Transport on Tropical Cyclone Track Forecasts Using the Emanuel Cumulus Parameterization
Authors: Hogan Timothy F. , Pauley Randal L.
Published: April 2007

The influence of convective momentum transport (CMT) on tropical cyclone (TC) track forecasts is examined in the Navy Operational Global Atmospheric Prediction System (NOGAPS) with the Emanuel cumulus parameterization. Data assimilation and medium-range forecast experiments show that for 35 tropical cyclones during August and September 2004 the inclusion of CMT in the cumulus parameterization significantly improves the TC track forecasts. The tests show that the track forecasts are very sensitive to the magnitude of the Emanuel parameterization’s convective momentum transport parameter, which controls the CMT tendency returned by the parameterization. While the overall effect of this formulation of CMT in NOGAPS data assimilation/medium-range forecasts results in the surface pressure of tropical cyclones being less intense (and more consistent with the analysis), the parameterization is not equivalent to a simple diffusion of winds in the presence of convection. This is demonstrated by two data assimilation/medium-range forecast tests in which a vertical diffusion algorithm replaces the CMT. Two additional data assimilation/medium-range forecast experiments were conducted to test whether the skill increase primarily comes from the CMT in the immediate vicinity of the tropical cyclones. The results show that the inclusion of the CMT calculation in the vicinity of the TC makes the largest contribution to the increase in forecast skill, but the general contribution of CMT away from the TC also plays an important role.
Antecedent Upstream Air Trajectories Associated with Northwest Flow Snowfall in the Southern Appalachians
Authors: Perry L. Baker , Konrad Charles E. , Schmidlin Thomas W.
Published: April 2007

Northwest flow snow (NWFS) events are common occurrences at higher elevations and on windward slopes in the southern Appalachians. Low temperatures and considerable blowing and drifting of snow, coupled with significant spatial variability of snowfall, substantially increase societal impacts. This paper develops a synoptic classification of NWFS events in the southern Appalachians using 72-h antecedent upstream (backward) air-trajectory analyses. Hourly observations from first-order stations and daily snowfall data from cooperative observer stations are used to define snowfall events. NCEP–NCAR reanalysis data are utilized to identify NWFS events on the basis of 850-hPa northwest flow (270°–360°) at the event maturation hour. The NOAA Hybrid Single-Particle Lagrangian Integrated Trajectory tool is used to calculate 72-h backward air trajectories at the event maturation hour and composite trajectories are mapped in a geographic information systems format. Analyses of vertical soundings are coupled with NCEP–NCAR reanalysis data to determine the synoptic characteristics associated with each trajectory class. Significant variability of trajectories and synoptic patterns is evident from the analyses, resulting in four distinct backward air-trajectory classes. Trajectories with a Great Lakes connection result in higher composite mean and maximum snowfall totals along portions of the higher-elevation windward slopes when compared with other northwest trajectories, but little effect of the Great Lakes is noted at lower elevations and on leeward slopes.