bluuebunny/crossref_metadata_2025_split huggingface dataset:
Far‐Field R‐Wave Reduction with a Novel Lead Design: Experimental and Human Results
Authors: DE VOOGT WILLEM , VAN HEMEL NORBERT , WILLEMS ALBERT , VISSER JAAP , CHITRE YOUGANDH , BORNZIN GENE , HELLAND JOHN 
Published: August 2005

Introduction: The purpose of this study was to examine a bipolar screw‐in lead (NL), specially designed to reduce unwanted far‐field R‐wave (FFRW) signal detection in an acute human setting. The results were compared with animal experiments.
Methods: The newly designed lead with a center‐to‐center distance between the anode and cathode electrodes of 3.23 mm, corresponding to an inter‐electrode spacing of 1.1 mm was implanted in nine canines with a follow‐up of 6 months. Sensing of P waves, FFRW signals, pacing threshold, and impedance was measured at regular intervals. As a result of the positive outcome with the animal study, an acute human experiment was performed. In patients scheduled for conventional dual chamber pacemaker implantation, the NL was compared to a Tendril® Model 1388T bipolar screw‐in lead (St. Jude Medical, CRMD, Sylmar, CA).
Results: Utilizing a tip‐to‐ring distance of 1.1 mm, the optimum P wave to FFRW ratio was found in animal experiments. In the acute human tests in 15 patients, the mean P‐wave voltage of the 1388T lead of 3.30 ± 1.54 mV was slightly larger than that of the NL, at 2.55 ± 1.11 mV, but did not differ significantly (P = 0.13). The FFRW voltage of the 1388T lead was 0.62 ± 0.37 mV and was significantly greater from that of the NL, at 0.10 ± 0.08 mV (P < 0.0001). Pacing thresholds and pacing impedances were comparable.
Conclusion: Animal testing results were reproducible in the acute human test setting. The lead reduced the paced FFRW signal amplitudes significantly, allowing for high atrial sensitivity settings but without sensing the FFRW. A robust P‐wave signal could be retained.
Temporal Relationship of Implantable Cardioverter Defibrillator Discharges and Environmental Physical Activity
Authors: STOUPEL ELIYAH , KUSNIEC JAIRO , MAZUR ALEXANDER , ZABARSKY RONIT , GOLOVCHINER GREGORY , ABRAMSON EVGENY , STRASBERG BORIS , BATTLER ALEXANDER 
Published: August 2005

Background: Studies by our group have shown an inverse relationship between sudden death and cardiac rhythm disturbances and environmental levels of geomagnetic activity (GMA). The aim of this study was to use the precise data provided by automatic implantable cardioverter defibrillators (ICDs) regarding the onset of ventricular fibrillation and ventricular tachycardia to link these events to GMA level.
Patients and Methods: The study group included 25 patients (22 men; 22 with ischemic cardiomyopathy) aged 28–81 years in whom an ICD had been implanted between 1995 and 2004. Patients were referred to the cardiac intensive care unit after each event that induced one or more discharges. The number of events and the day on which they occurred were recorded. Data on GMA and other cosmophysical parameters were obtained from the U.S. National Geophysical and Space Service Centers and the Russian Academy of Sciences. GMA levels, graded from I (quiet) to IV (stormy) in the middle latitutes, were recorded for 1974–2003 (10,954 days) and for each day on which an ICD discharge occurred.
Results: A total of 402 discharges were recorded on 137 days during the study period. Forty‐six percent of the discharges took place on days of GMA I, compared with 38%– II, 13%– III, and 3%– IV. The daily distribution of GMA was as follows: level I – 35.2%, II – 37.3%, III – 21.86%, IV – 5.61%. Comparison of ICD discharge days and actual multiyear levels of GMA (in percent) yielded a ratio of 1.326 for GMA I, 1.076 – II, 0.459 – III, 0.390 – IV. There was a significant inverse correlation between GMA level and number of discharges (r =−0.97, P = 0.03) and days of treatment (r =−0.96, P = 0.039), and a significant difference between ICD discharges on days of GMA I and GMA II–IV (χ2= 5.05, P = 0.02).
Conclusion: The higher number of ICD discharges on days of lowest GMA may be explained by a possible antiarrhythmic effect of GMA. Environmental arrhythmogenic factors that act inversely to GMA may be activated at times of low GMA.
Clinical pharmacological profile of etoposide in elderly patients with lung cancer
Authors: MIYAZAKI Mitsuru , FUJIWARA Yasushiro , OGURI Tetsuya , TAKAHASHI Toshiaki , OHUNE Terumasa , SUMIYOSHI Hidetaka , KOHNO Nobuoki , EGORIN Merrill J 
Published: August 2005

AbstractTo clarify the clinical pharmacological profile of etoposide in the elderly, we carried out prospective therapeutic drug monitoring in 14 patients with advanced lung cancer aged 75 or more years. The patients received 50 mg etoposide as oral capsules for 21 consecutive days during the first course, and intravenous etoposide for 3 days during the second course of palliative treatment. Plasma and urine samples were collected on days 1 and 21 of the first course and day 1 of the second course, and etoposide concentrations were measured using high‐performance liquid chromatography. We compared these data with those obtained from 17 adult patients under 75 years old who participated in our previous study of combined oral etoposide/carboplatin chemotherapy. Within the elderly group, no significant differences in the area under the concentration‐versus‐time curve, elimination half‐life, plasma clearance, urinary excretion or bioavailability of oral etoposide were observed between day 1 and day 21. However, the mean (±SD) elimination half‐lives for elderly and adult patients were 10.3 ± 1.9 h and 5.8 ± 2.5 h, respectively, while the mean (±SD) bioavailabilities were 62.8 ± 27.5% and 37.4 ± 15.4%; both were significantly increased in the elderly patients. Our previously proposed limited sampling model was validated using the elderly data set and proved to be unbiased and precise. In conclusion, although no accumulation of oral etoposide was observed in elderly patients, there were age‐dependent changes in its pharmacokinetics, especially in bioavailability.
Biochemotherapy for the treatment of metastatic melanoma: the experience of a tertiary oncology center
Authors: JOHN Thomas , CEBON Jonathan S , DAVIS Ian D 
Published: August 2005

AbstractBackground:  Malignant melanoma is generally resistant to cytotoxic chemotherapy. The addition of cytokines such as interleukin‐2 (IL‐2) and Interferon‐α (IFNα) to cytotoxic chemotherapy has been reported to result in significant improvement in response rates and time to treatment progression. There have also been reports of long‐term survival in a subset of patients who achieved a complete remission. While this treatment has promised significant improvement in tumor response, to date this has not translated into an increase in median overall survival in adequately powered randomized phase III studies. The Joint Ludwig Austin Oncology unit operates a clinic for patients with advanced malignant melanoma. On the basis of early encouraging reports, we have treated selected patients, over a 5‐year period, using a combination biochemotherapy regimen. Here, we report our experience with the treatment regimen.Methods:  Records from patients treated with biochemotherapy were examined for baseline characteristics, prior treatments and sites of disease. Outcomes measured included response, toxicity, hospitalization and survival.Results:  Between 1999 and 2003, 14 patients were treated at the Austin Hospital. There were four partial responses (PR) and two disease stabilizations lasting 7 months (SD). The overall clinical benefit (PR + SD) was 42.8% (6/14). The regimen was toxic with significant hematological and constitutional toxicity, although no treatment related deaths occurred. Patient survival with Stage 4 disease ranged from 2 to 60 months.Conclusions:  These results are consistent with published data from other institutions. Because this is palliative treatment, results in significant toxicity and has failed to result in a survival benefit when tested in randomized studies we do not feel that off‐study treatment with this regimen is justified. Further studies are needed into mechanisms of resistance and response prediction to determine whether any subgroups of patients with metastatic melanoma might benefit from this treatment.
Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects
Authors: López-Bermejo Abel , Castro Antoni , Broch Montserrat , Peñarroja Georgina , Vendrell Joan , Vázquez Gabriel , Ricart Wifredo , Fernández-Real José-Manuel 
Published: August 2005

SummaryRecent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n=40) compared to control nondiabetic subjects (n=100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r= −0.21, p=0.03, and r=−0.21, p=0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD14 and EDVD, r=−0.23, p=0.023; C-reactive protein and EDVD, r=−0.21, p=0.03; sCD14 and C-reactive protein, r=0.30, p=0.002). In contrast, sCD14 was positively associated with EDVD in type 2 diabetic patients (r= 0.37, p=0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r=0.62, p=0.001, n=22). EDVD also correlated with cyclic GMP (r=0.47, p=0.03, n=22). In summary, circulating sCD14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.
Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt
Authors: Katkade Vaibhav , Soyombo Abigail A. , Isordia-Salas Irma , Bradford Harlan N. , Gaughan John P. , Colman Robert W. , Panetti Tracee S. 
Published: August 2005

SummaryDomain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the PI3-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response to VEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3α.HKa and D5 inhibit phosphorylation of Akt and GSK-3α after stimulation withVEGF and S1P. Inhibitors of Akt and PI3-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters PI3-kinase- Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.
CpG methylation of the PAI-1 gene 5’-flanking region is inversely correlated with PAI-1 mRNA levels in human cell lines
Authors: Skeldal Sune , Krogdahl Annelise , Sørensen Jens Ahm , Andreasen Peter A. , Gao Shan 
Published: August 2005

SummaryThe physiological and pathophysiological functions of PAI-1 are related to its expression by specific cell types in normal and diseased tissues. We analysed the contribution of DNA methylation to the variation in PAI-1 mRNA levels in five cell lines. We found varying frequencies of methylation of 25 CpGs in the -805/+152 region of the PAI-1 gene in Bowes, MCF-7 and U937 cells, while little or no methylation was detected in Hep2 and HT-1080 cells. The methylation frequency was inversely correlated with PAI-1 mRNA level within its 20-fold range in Bowes, MCF-7,U937,and Hep2 cells, while the lack of methylation in both Hep2 and HT- 1080 cells suggested another mechanism behind the 150-fold higher level in HT-1080 cells than in Hep2 cells. However, all cell lines exhibited a high frequency of methylation of 10 CpGs in a CpG island at about -1800. Treatment with 5-aza-2‘-deoxycytidine led up to circa a 40-fold increase in the PAI-1 mRNA level and a strong decrease in the frequency of methylation in the -805/+152 region in Bowes, MCF-7 and U937. The histone deacetylase inhibitor trichostatin A induced a several fold increase of the PAI-1 mRNA level in cells with a high methylation frequency of the -805/+152 region. As compared with matched normal tissue, three samples of oral squamous cell carcinomas displayed decreased frequencies of methylation of the PAI-1 5' flanking region and increased levels of PAI-1 mRNA. These results for the first time implicate DNA methylation and histone acetylation in regulation of the PAI-1 gene, and indicate that without proper CpG islands in 5’-flanking region, trancription may be regulated by methylation of less dense CpGs in the 5’-flanking region rather than methylation of upstream CpG island.
Explicit Filtering and Reconstruction Turbulence Modeling for Large-Eddy Simulation of Neutral Boundary Layer Flow
Authors: Chow Fotini Katopodes , Street Robert L. , Xue Ming , Ferziger Joel H. 
Published: August 2005

AbstractStandard turbulence closures for large-eddy simulations of atmospheric flow based on finite-difference or finite-volume codes use eddy-viscosity models and hence ignore the contribution of the resolved subfilter-scale stresses. These eddy-viscosity closures are unable to produce the expected logarithmic region near the surface in neutral boundary layer flows. Here, explicit filtering and reconstruction are used to improve the representation of the resolvable subfilter-scale (RSFS) stresses, and a dynamic eddy-viscosity model is used for the subgrid-scale (SGS) stresses. Combining reconstruction and eddy-viscosity models yields a sophisticated (and higher order) version of the well-known mixed model of Bardina et al.; the explicit filtering and reconstruction procedures clearly delineate the contribution of the RSFS and SGS motions. A near-wall stress model is implemented to supplement the turbulence models and account for the stress induced by filtering near a solid boundary as well as the effect of the large grid aspect ratio. Results for neutral boundary layer flow over a rough wall using the combined dynamic reconstruction model and the near-wall stress model show excellent agreement with similarity theory logarithmic velocity profiles, a significant improvement over standard eddy-viscosity closures. Stress profiles also exhibit the expected pattern with increased reconstruction level.
Cyclogenetic Perturbations and Analysis Errors Decomposed into Singular Vectors
Authors: Snyder Chris , Hakim Gregory J. 
Published: August 2005

Abstract
Singular vectors (SVs) have been applied to cyclogenesis, to initializing ensemble forecasts, and in predictability studies. Ideally, the calculation of the SVs would employ the analysis error covariance norm at the initial time or, in the case of cyclogenesis, a norm based on the statistics of initial perturbations, but the energy norm is often used as a more practical substitute.
To illustrate the roles of the choice of norm and the vertical structure of initial perturbations, an upper-level wave with no potential vorticity perturbation in the troposphere is considered as a typical cyclogenetic perturbation or analysis error, and this perturbation is then decomposed by its projection onto each energy SV. All calculations are made, for simplicity, in the context of the quasigeostrophic Eady model (i.e., for a background flow with constant vertical shear and horizontal temperature gradient). Viewed in terms of the energy SVs, the smooth vertical structure of the typical perturbation, as well as its evolution, results from strong cancellation between the growing and decaying SVs, most of which are highly structured and tilted in the vertical.
A simpler picture, involving less cancellation, follows from decomposition of the typical perturbation into SVs using an alternative initial norm, which is based on the relation between initial norms and the statistics of initial perturbations together with the empirical assumption that the initial perturbations are not dominated by interior potential vorticity. Differences between the energy SVs and those based on the alternative initial norm can be understood by noting that the energy norm implicitly assumes initial perturbations with second-order statistics given by the covariance matrix whose inverse defines the energy norm. Unlike the “typical” perturbation, perturbations with those statistics have large variance of potential vorticity in the troposphere and fine vertical structure.
Finally, a brief assessment is presented of the extent to which the upper wave, and more generally the alternative initial norm, is representative of cyclogenetic perturbations and analysis errors. There is substantial evidence supporting deep perturbations with little vertical structure as frequent precursors to cyclogenesis, but surrogates for analysis errors are less conclusive: operational midlatitude analysis differences have vertical structure similar to that of the perturbations implied by the energy norm, while short-range forecast errors and analysis errors from assimilation experiments with simulated observations are more consistent with the alternative norm.
A Large-Eddy Simulation Study of Anisotropy in Fair-Weather Cumulus Cloud Fields
Authors: Hinkelman Laura M. , Stevens Bjorn , Evans K. Franklin 
Published: August 2005

AbstractCauses of anisotropy in fair-weather cumulus cloud fields were investigated using quantitative measures of anisotropy and a large-eddy simulation (LES) model. Case six of the Global Energy and Water Cycle Experiment (GEWEX) Cloud System Study Working Group 1 was used as the standard model scenario. This case represents radiatively forced development of cumulus clouds over the southern Great Plains. Cloud formation under a variety of environmental conditions was simulated and the degree of anisotropy in the output fields was calculated as a function of spatial scale. Wind shear was found to be the single greatest factor in the development of both vertically tilted and horizontally stretched cloud structures. Other factors included mean wind speed, initial water vapor mixing ratio, and the magnitude of the surface forcing.
The Impact of Zonal Propagation and Seeding on the Eddy–Mean Flow Equilibrium of a Zonally Varying Two-Layer Model
Authors: Zurita-Gotor Pablo , Chang Edmund K. M. 
Published: August 2005

Abstract
This paper investigates the role of zonal propagation for the equilibration of zonally varying flow. It is hypothesized that there exist two ideal limits, for very small or very large group speed. In the first limit the eddies equilibrate locally with the forcing, while in the second limit the equilibration can only be understood in a global sense. To understand these two limits and to assess which is more relevant for the extratropical troposphere, a series of idealized experiments that involves changing the magnitude of the uniform zonal wind is performed. The results of the idealized model experiments suggest that the actual troposphere is likely to be in a transition regime between the two limits, but perhaps closer to the global than the local limit.
Near the global limit, both the eddy amplitude and local baroclinicity over the baroclinic zone are strongly affected by the amount of upstream seeding. When the propagation speed is reduced relative to the control run, the zonal mean eddy activity decreases because the residence time increases more over the stable part of the channel than along the baroclinic zone. With the decrease in upstream seeding, the local supercriticality along the baroclinic zone increases, although the increase is moderate. The decrease in seeding and increase in baroclinicity partially offset the effects of each other, leading to only small changes in the maximum eddy amplitude downstream of the baroclinic zone.
Changes in upstream seeding can also be achieved by enhanced damping. When the eddies are locally damped, the baroclinicity is also enhanced downstream of the damping region due to reduced eddy fluxes. For typical parameters, the recovery of the eddy amplitude occurs over very long distances. Based on these idealized results, it is argued that the coexistence of enhanced baroclinicity and weaker eddy amplitude over the Pacific storm track, as compared to the Atlantic storm track, is consistent with the effects of strong eddy damping over Asia.
A Polarized Delta-Four-Stream Approximation for Infrared and Microwave Radiative Transfer: Part I
Authors: Liou K. N. , Ou S. C. , Takano Y. , Liu Q. 
Published: August 2005

Abstract
The delta-four-stream polarized (vector) thermal radiative transfer has been formulated and numerically tested specifically for application to satellite data assimilation in cloudy atmospheres. It is shown that for thermal emission in the earth’s atmosphere, the [I, Q] component of the Stokes vector can be decoupled from the [U, V] component and that the solution of the vector equation set involving the four-stream approximation can be expressed in an analytic form similar to the scalar case. Thus, the computer time requirement can be optimized for the simulation of forward radiances and their derivatives. Computations have been carried out to illustrate the accuracy and efficiency of this method by comparing radiance and polarization results to those computed from the exact doubling method for radiative transfer for a number of thermal infrared and microwave frequencies. Excellent agreement within 1% is shown for the radiance results for all satellite viewing angles and cloud optical depths. For polarization, differences between the two are less than 5% if brightness temperature is used in the analysis. On balance of the computational speed and accuracy, the four-stream approximation for radiative transfer appears to be an attractive means for the simulation of cloudy radiances and polarization for research and data assimilation purposes.