bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Age-Related Changes in the Nitric Oxide Pathway in the Arteries of Rats and the Intervention Effect of Dehydroepiandrosterone
Authors: Wu Saizhu , Ruan Yunjun , Yin Mengzhuo , Lai Wenyan
Published: March 2007

Background: Aging, especially the aging of blood vessels, is a dangerous independent factor in the occurrence and development of cardiovascular and cerebrovascular diseases. However, the cellular and molecular pathologic mechanisms underlying the aging of blood vessels remain unclear. Purpose: To observe changes in the nitric oxide (NO) pathway and the interventional effects of dehydroepiandrosterone (DHEA) in the artery during the aging process. Methods: Male Wistar rats were divided into 3 experimental groups of 6 rats each: group 1, adult control 12-month-old rats fed conventional fodder; group 2, 18-month-old rats fed conventional fodder, and group 3, 18-month-old rats that received 1 mg/kg/ DHEA in their fundamental fodder when they were 12 months old. The thoracic aorta was chosen. Endothelial NO synthase protein was measured using the Western blot method, the amount of NO using the Griess method, the amount of cGMP using radioimmunoassay, and the activity of superoxide dismutase (SOD) and the amount of malonyldialdehyde (MDA) using colorimetry. Result: Compared with the adult group, in the aortas of 18-month-old rats the protein expression of endothelial NO synthase (eNOS) is lower; the activity of SOD is lower but the amount of MDA is higher; the amounts of NO and cGMP are lower, but after DHEA intervention these changes are apparently ameliorated in the aged group. Conclusion: During the aging process in rat arteries, the expression of eNOS is lowered, the function of oxidation resistance is weakened, and the response of the vascular smooth muscle to NO is apparently decreased. DHEA is able to ameliorate the function of NO-related signal pathways and delay the aging process of the blood vessels.
Apolipoprotein E Genotypes in Hospitalized Elderly Patients with Vascular Dementia
Authors: Orsitto Giuseppe , Seripa Davide , Panza Francesco , Franceschi Marilisa , Cascavilla Leandro , Placentino Giuliana , Matera Maria Giovanna , Paris Francesco , Capurso Cristiano , Solfrizzi Vincenzo , Dallapiccola Bruno , Pilotto Alberto
Published: March 2007

Background: Polymorphism in the apolipoprotein E (APOE) gene is the major genetic risk factor associated with late-onset Alzheimer’s Disease (AD). However, it is still unclear if a relationship exists between the APOE Ε4 allele and vascular dementia (VaD) in elderly subjects. Objectives: To evaluate the prevalence of APOE alleles in elderly patients with VaD compared to AD patients and to control subjects with no cognitive impairment (NoCI). Patients and Methods: We evaluated 396 consecutive patients aged ≧65 years with definite or suspected cognitive impairment with a clinical (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Depression Scale), functional (Activities of Daily Living, Instrumental Activities of Daily Living), comorbidity (Cumulative Illness Rating Scale) and instrumental (CT scan, NMR) assessment. Diagnosis of dementia was made according to NINCDS-ADRDA and NINDS-AIREN Work Group and the DSM-IV. APOE genotypes were analyzed by a recently described method resulting in positive/negative chain reaction products for each APOE genotype. Statistical analysis was carried out using the Pearson χ2, the Kruskal-Wallis test and the ANOVA post hoc comparisons. Results: A total of 287 elderly patients (males = 138, females = 149, mean age = 77.8 ± 6.9 years, range = 65–98) with diagnoses of VaD (n = 97), AD (n = 82) or NoCI (n = 108) were included in the study. A significantly higher APOE Ε4 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects, while no differences were found between VaD patients and subjects with NoCI (AD = 24.3%, VaD = 10.3, NoCI = 8.7, p < 0.05). Furthermore, a significantly lower APOE Ε3 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects but not between VaD and NoCI patients (AD = 71.3%, VaD = 80.9, NoCI = 83.4, p < 0.05). No significant differences were observed in the APOE Ε2 allele (VaD = 8.8%, AD = 4.4, NoCI = 7.9, p = n.s.) among the 3 groups. Conclusions: In this population, the frequency of the APOE Ε4 allele is lower in VaD than in AD.
Spontaneous Ovulation in a True Hermaphrodite with Normal Male Phenotype and a Rare 46,XX/47,XXY Klinefelter’s Mosaic Karyotype
Authors: Kanaka-Gantenbein Ch. , Papandreou E. , Stefanaki K. , Fryssira H. , Kolialexi A. , Sophocleous C. , Mavrou A. , Kitsiou-Tzeli S. , Chrousos G. P.
Published: March 2007

Background: Most true hermaphrodite patients – characterized by the presence of both ovarian and testicular tis- sue – demonstrate ambiguous genitalia and are diagnosed at birth, most commonly bearing a 46,XX karyotype. Patient and Methods: We report on a 13-year-old boy presenting with left scrotal hemorrhage. He had a left inguinal hernia, a palpable testis in the right, normal male external genitalia and significant gynecomastia. During operation, the left gonad and adjacent tissue were removed for histological examination, which revealed the presence of a normal ovary, rich in follicles and a ruptured corpus luteum, suggestive of spontaneous ovulation, with a normal ipsilateral adnexa and semi-uterus. Biopsy of the right gonad revealed a dysgenetic testicle. Endocrinological assessment postoperatively depicted high FSH, pubertal testosterone and low estradiol levels. Cytogenetic analysis in peripheral blood lymphocytes and FISH of the right gonad revealed a 46,XX (70–60%)/47,XXY (30–40%) karyotype, respectively, while molecular analysis verified the presence of SRY and azoospermia factor genes. Conclusion: The importance of full histological, cytogenetic and molecular investigation and of interdisciplinary approach in every single patient with sex differentiation disorders is highlighted by this rare case of spontaneous ovulation in a true hermaphrodite with normal male external genitalia and Klinefelter mosaicism.
Targeted Mutation Reveals Essential Functions of the Homeodomain Transcription Factor
Shox2
in Sinoatrial and Pacemaking Development
Authors: Blaschke Rüdiger J. , Hahurij Nathan D. , Kuijper Sanne , Just Steffen , Wisse Lambertus J. , Deissler Kirsten , Maxelon Tina , Anastassiadis Konstantinos , Spitzer Jessica , Hardt Stefan E. , Schöler Hans , Feitsma Harma , Rottbauer Wolfgang , Blum Martin , Meijlink Frits , Rappold Gudrun , Gittenberger-de Groot Adriana C.
Published: March 2007

Background—

Identifying molecular pathways regulating the development of pacemaking and coordinated heartbeat is crucial for a comprehensive mechanistic understanding of arrhythmia-related diseases. Elucidation of these pathways has been complicated mainly by an insufficient definition of the developmental structures involved in these processes and the unavailability of animal models specifically targeting the relevant tissues. Here, we report on a highly restricted expression pattern of the homeodomain transcription factor
Shox2
in the sinus venosus myocardium, including the sinoatrial nodal region and the venous valves.

Methods and Results—

To investigate its function in vivo, we have generated mouse lines carrying a targeted mutation of the
Shox2
gene. Although heterozygous animals did not exhibit obvious defects, homozygosity of the targeted allele led to embryonic lethality at 11.5 to 13.5 dpc.
Shox2
−/−
embryos exhibited severe hypoplasia of the sinus venosus myocardium in the posterior heart field, including the sinoatrial nodal region and venous valves. We furthermore demonstrate aberrant expression of connexin 40 and connexin 43 and the transcription factor Nkx2.5 in vivo specifically within the sinoatrial nodal region and show that
Shox2
deficiency interferes with pacemaking function in zebrafish embryos.

Conclusions—

From these results, we postulate a critical function of
Shox2
in the recruitment of sinus venosus myocardium comprising the sinoatrial nodal region.
Early and Sustained Benefit on Event-Free Survival and Heart Failure Hospitalization From Fixed-Dose Combination of Isosorbide Dinitrate/Hydralazine
Authors: Taylor Anne L. , Ziesche Susan , Yancy Clyde W. , Carson Peter , Ferdinand Keith , Taylor Malcolm , Adams Kirkwood , Olukotun Adeoye Y. , Ofili Elizabeth , Tam S. William , Sabolinski Michael L. , Worcel Manuel , Cohn Jay N.
Published: March 2007

Background—

We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality.

Methods and Results—

Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (
P
<0.001) and a 39% reduction in the risk for first hospitalization for HF (
P
<0.001). These benefits appeared to emerge early (at ≈50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (
P
=0.012).

Conclusions—

FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.
Circulating Adipocyte–Fatty Acid Binding Protein Levels Predict the Development of the Metabolic Syndrome
Authors: Xu Aimin , Tso Annette W.K. , Cheung Bernard M.Y. , Wang Yu , Wat Nelson M.S. , Fong Carol H.Y. , Yeung Dennis C.Y. , Janus Edward D. , Sham Pak C. , Lam Karen S.L.
Published: March 2007

Background—

Adipocyte–fatty acid binding protein (A-FABP), a major cytoplasmic protein in adipocytes, plays a central role in the development of diabetes and atherosclerotic cardiovascular disease in experimental animals. We have previously shown that A-FABP is present in the bloodstream and that its circulating levels correlate with metabolic risk factors in a cross-sectional study. In the present study, we further evaluated the prospective association of A-FABP with the metabolic syndrome (MetS) as defined by the updated National Cholesterol Education Program criteria.

Methods and Results—

In the present study, 495 nondiabetic adults from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study were prospectively followed up for 5 years. The relationship of serum A-FABP with the MetS and its components was investigated. At baseline, high A-FABP levels were associated with the MetS (odds ratio, 4.0; 95% CI, 1.5 to 10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, the homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin,
P
=0.005). On long-term follow-up, subjects with higher baseline A-FABP levels had progressively worse cardiometabolic risk profile and increasing risk of the MetS. Among 376 subjects without the MetS at baseline, 50 had developed it at 5 years. Apart from the homeostasis model assessment index for insulin resistance (
P
=0.001), baseline A-FABP was the only independent predictor of the development of the MetS during the 5-year follow-up (odds ratio, 4.7; 95% CI, 1.8 to 11.9; highest versus lowest sex-specific tertile,
P
=0.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of the MetS even after adjustment for each of its individual components.

Conclusions—

Circulating A-FABP predicts the development of the MetS independently of adiposity and insulin resistance.
The Impact of Valve Surgery on 6-Month Mortality in Left-Sided Infective Endocarditis
Authors: Tleyjeh Imad M. , Ghomrawi Hassan M.K. , Steckelberg James M. , Hoskin Tanya L. , Mirzoyev Zaur , Anavekar Nandan S. , Enders Felicity , Moustafa Sherif , Mookadam Farouk , Huskins W. Charles , Wilson Walter R. , Baddour Larry M.
Published: March 2007

Background—

The role of valve surgery in left-sided infective endocarditis has not been evaluated in randomized controlled trials. We examined the association between valve surgery and all-cause 6-month mortality among patients with left-sided infective endocarditis.

Methods and Results—

A total of 546 consecutive patients with left-sided infective endocarditis were included. To minimize selection bias, propensity score to undergo valve surgery was used to match patients in the surgical and nonsurgical groups. To adjust for survivor bias, we matched the follow-up time so that each patient in the nonsurgical group survived at least as long as the time to surgery in the respective surgically-treated patient. We also used valve surgery as a time-dependent covariate in different Cox models. A total of 129 (23.6%) patients underwent surgery within 30 days of diagnosis. Death occurred in 99 of the 417 patients (23.7%) in the nonsurgical group versus 35 deaths among the 129 patients (27.1%) in the surgical group. Eighteen of 35 (51%) patients in the surgical group died within 7 days of valve surgery. In the subset of 186 cases (93 pairs of surgical versus nonsurgical cases) matched on the logit of their propensity score, diagnosis decade, and follow-up time, no significant association existed between surgery and mortality (adjusted hazard ratio, 1.3; 95% confidence interval, 0.5 to 3.1). With a Cox model that incorporated surgery as a time-dependent covariate, valve surgery was associated with an increase in the 6-month mortality with an adjusted hazard ratio of 1.9 (95% confidence interval, 1.1 to 3.2). Because the proportionality hazard assumption was violated in the time-dependent analysis, we performed a partitioning analysis. After adjustment for early (operative) mortality, surgery was not associated with a survival benefit (adjusted hazard ratio, 0.92; 95% confidence interval, 0.48 to 1.76).

Conclusions—

The results of our study suggest that valve surgery in left-sided infective endocarditis is not associated with a survival benefit and could be associated with increased 6-month mortality, even after adjustment for selection and survivor biases as well as confounders. Given the disparity between the results of our study and those of other observational studies, well-designed prospective studies are needed to further evaluate the role of valve surgery in endocarditis management.
Voltage-Dependent Calcium Currents Are Enhanced in Nucleus of the Solitary Tract Neurons Isolated From Renal Wrap Hypertensive Rats
Authors: Tolstykh Gleb , de Paula Patricia M. , Mifflin Steve
Published: March 2007

The nucleus of the solitary tract (NTS) is the central site of termination of baroreceptor afferents. We hypothesize that changes occur in voltage-gated calcium channels (VGCCs) within NTS neurons as a consequence of hypertension. Whole-cell patch-clamp recordings were obtained from adult normotensive (109±2 mm Hg; n=6 from 6 sham-operated and 31 nonsurgically treated) and hypertensive (158±6 mm Hg; n=24) rats. In some experiments, 4-(4-[dihexadecylamino]styryl)-N-methylpyridinium iodide was applied to the aortic nerve to visualize NTS neurons receiving baroreceptor synaptic contacts. Ba
2+
currents (500 ms; −80 mV prepotential; 500 ms voltage steps in 5-mV increments to +15mV) peaked between −20 and −10 mV and were blocked by 100 μm of Cd
2+
. Peak VGCCs were not different comparing non-4-(4-[dihexadecylamino]styryl)-N-methylpyridinium iodide-labeled and 4-(4- [dihexadecylamino]styryl)-N-methylpyridinium iodide-labeled NTS neurons in hypertensive and normotensive rats. The peak VGCC was significantly greater in cells from hypertensive compared with normotensive rats for both non–DiA-labeled (
P
=0.02) and DiA-labeled (
P
=0.04) neurons. To separate high-voltage activated (HVA) and low-voltage activated (LVA) components of VGCCs, voltage ramps (−110 mV to +30 mV over 50 ms) were applied from a holding potential of −60 mV (LVA channels inactivated) and a holding potential of −100 mV (both LVA and HVA currents activated). HVA currents were subtracted from HVA+LVA currents to yield the LVA current. Peak LVA currents were not different between hypertensive (8.9±0.8 pA/pF) and normotensive (7.8±0.6 pA/pF) groups of NTS neurons (
P
=0.27). These results demonstrate that 4 weeks of renal wrap hypertension induce an increase in Ca
2+
influx through HVA VGCCs in NTS neurons receiving arterial baroreceptor inputs.
Essential Role of Endothelial Nitric Oxide Synthase in Vascular Effects of Erythropoietin
Authors: d’Uscio Livius V. , Smith Leslie A. , Santhanam Anantha V. , Richardson Darcy , Nath Karl A. , Katusic Zvonimir S.
Published: March 2007

Erythropoietin (EPO) fosters tissue oxygenation by stimulating erythropoiesis. More recently, EPO has been recognized as a tissue-protective cytokine. In this study, we tested the hypothesis that endothelial NO synthase (eNOS) plays a key role in the vascular protective effect of EPO. A murine model of wire-induced injury of carotid artery was used to examine the effect of EPO on endothelial repair and arterial wall architecture. Recombinant human EPO (1000 U/kg, SC, biweekly) was administered for 2 weeks in wild-type and eNOS-deficient mice after which reactivity of isolated carotid arteries was studied in vitro, and the vasculature was histologically assessed. Injured arteries exhibited impairment of endothelium-dependent relaxations to acetylcholine (
P
<0.05). This was associated with increased medial cross-sectional area (
P
<0.05). EPO upregulated expression of phosphorylated Ser1177-eNOS and normalized the vasodilator response to acetylcholine (
P
<0.05). Furthermore, EPO prevented the injury-induced increase in medial cross-sectional area (
P
<0.05). The vascular protective effects of EPO were abolished in eNOS-deficient mice. Most notably, EPO significantly increased systolic blood pressure and enhanced medial thickening of injured carotid arteries in eNOS-deficient mice (
P
<0.05). Our results demonstrate that EPO prevents aberrant remodeling of the injured carotid artery. The protective effects of EPO are critically dependent on activation of eNOS.
Impact of Smoking and Smoking Cessation on Arterial Stiffness and Aortic Wave Reflection in Hypertension
Authors: Jatoi Noor A. , Jerrard-Dunne Paula , Feely John , Mahmud Azra
Published: March 2007

Cigarette smoking is an important modifiable cardiovascular risk factor and pathophysiological mechanisms may include a stiff vascular tree. Although smokers have stiffer arteries, whether smoking cessation is associated with reduced arterial stiffness is not known. We compared never-treated patients with essential hypertension (n=554) aged 18 to 80 years (56% females) classified as current smokers (n=150), ex-smokers (n=136), and nonsmokers (n=268). Ex-smokers were categorized into <1 year, >1 and <10 years, and >10 years of smoking cessation. Measurements included aortic stiffness, assessed as pulse wave velocity (Complior), wave reflection (augmentation index [AIx]), and transit time (T
R
) (Sphygmocor). Current and ex-smokers had significantly higher pulse wave velocity and AIx compared with nonsmokers (pulse wave velocity for current smokers: 10.7±0.2; ex-smokers: 10.6±0.2; nonsmokers: 9.9±0.1 m/s;
P
<0.001; AIx for current smokers: 31±1; ex-smokers: 30±1; nonsmokers: 27±0.8%;
P
<0.05), whereas T
R
was lower in current and ex-smokers compared with nonsmokers (T
R
for current smokers: 131±1.0; ex-smokers: 135±1; nonsmokers: 137±0.8 m/s;
P
<0.0001). There was a significant linear relationship between smoking status and pulse wave velocity (
P
<0.001), AIx (
P
<0.001), and T
R
(
P
<0.001), even after adjusting for age, sex, mean arterial pressure, heart rate, and body mass index. In ex-smokers, duration of smoking cessation had a significant linear relationship with improvement in pulse wave velocity (
P
<0.001), AIx (
P
<0.001), and T
R
(
P
<0.001), with arterial stiffness parameters returning to nonsignificant levels after a decade of smoking cessation.
Direct Insertion of MODIS Radiances in a Global Aerosol Transport Model
Authors: Weaver Clark , da Silva Arlindo , Chin Mian , Ginoux Paul , Dubovik Oleg , Flittner Dave , Zia Aahmad , Remer Lorraine , Holben Brent , Gregg Watson
Published: March 2007

In this paper results are presented from a simple offline assimilation system that uses radiances from the Moderate Resolution Imaging Spectroradiometer (MODIS) channels that sense atmospheric aerosols over land and ocean. The MODIS information is directly inserted into the Goddard Chemistry and Aerosol Radiation Transport model (GOCART), which simulates the following five aerosol types: dust, sea salt, black carbon, organic carbon, and sulfate. The goal is to produce three-dimensional fields of these aerosol types for radiative forcing calculations.

Products from this assimilation system are compared with ground-based measurements of aerosol optical depth (AOD) from the Aerosol Robotic Network (AERONET). Insertion of MODIS radiances draws the GOCART model closer to the AERONET AOD. However, there are still uncertainties with surface reflectivity over moderately bright surfaces and with the amount of absorbing aerosol.

Also described is the assimilation cycle. The forward model takes the aerosol information from the GOCART model and calculates radiances based on optical parameters of the aerosol type, satellite viewing angle, and the particle growth from relative humidity. Because the GOCART model is driven by previously assimilated meteorology, these forward model radiances can be directly compared with the observed MODIS level-2 radiances. The offline assimilation system simply adjusts the aerosol loading in the GOCART model so that the observed minus forward model radiances agree. Minimal change is made to the GOCART aerosol vertical distribution, size distribution, and the ratio of the five different aerosol types. The loading in the GOCART model is updated with new MODIS observations every 6 h. Since the previously assimilated meteorology provides surface wind speed, radiance sensitivity to wind speed over rough ocean is taken into account. Over land the dark target approach, also used by the MODIS–atmosphere group retrieval, is used. If the underlying land surface is deemed dark enough, the surface reflectances at the 0.47- and 0.66-μm wavelengths are constant multiples of the observed 2.13-μm reflectance. Over ocean the assimilation AOD compares well with AERONET, over land less so. The results herein are also compared with AERONET-retrieved single-scattering albedo. This research is part of an ongoing effort at NASA Goddard to integrate aerosols into the Goddard Modeling and Assimilation Office (GMAO) products.
A Mechanism for the Poleward Propagation of Zonal Mean Flow Anomalies
Authors: Lee Sukyoung , Son Seok-Woo , Grise Kevin , Feldstein Steven B.
Published: March 2007

Observational studies have shown that tropospheric zonal mean flow anomalies frequently undergo quasi-periodic poleward propagation. A set of idealized numerical model runs is examined to investigate the physical mechanism behind this poleward propagation.

This study finds that the initiation of the poleward propagation is marked by the formation of negative zonal wind anomalies in the Tropics. These negative anomalies arise from meridional overturning/breaking of waves that originate in midlatitudes. This wave breaking homogenizes the potential vorticity (PV) within the region of negative zonal wind anomalies, and also leads to the formation of positive zonal wind anomalies in the subtropics. Subsequent equatorward radiation of midlatitude waves is halted, which results in wave breaking at the poleward end of the homogenized PV region. This in turn generates new positive and negative zonal wind anomalies, which enables a continuation of the poleward propagation. The shielding of the homogenized PV region from equatorward wave propagation allows the model’s radiative relaxation to reestablish undisturbed westerlies in the Tropics, while extratropical westerly anomalies arise from eddy vorticity fluxes.

The above process indicates that the poleward zonal mean anomaly propagation is caused by an orchestrated combination of linear Rossby wave propagation, nonlinear wave breaking, and radiative relaxation. The importance of the meridional wave propagation and breaking is consistent with the fact that the poleward propagation occurs only in the parameter space of the model where the PV gradient is of moderate strength. Implications for predictability are briefly discussed.
Interaction between Near-Annual and ENSO Modes in a CGCM Simulation: Role of the Equatorial Background Mean State
Authors: Dewitte Boris , Cibot Carole , Périgaud Claire , An Soon-Il , Terray Laurent
Published: March 2007

A 260-yr-long coupled general circulation model (CGCM) simulation is used to investigate the interaction between ENSO mode and near-annual variability and its sensitivity to the equatorial background mean stratification and seasonal cycles. Although the thermocline mean vertical structure of the model favors the high-order baroclinic modes that are associated with the slow time scales of the coupled variability, the simulated ENSO oscillates at a dominant quasi-biennial frequency. Biases of the climatological velocity field are favorable to the dominance of the zonal advective feedback over the thermocline feedback, the model exhibiting an overenergetic westward seasonal zonal current in the central-western equatorial Pacific, and an upwelling rate that is about half the observations. This sets the conditions for the enhancement of a near-annual mode that is observed to oscillate at an 8-month period in the model. Using an intermediate coupled model of the tropical Pacific where the climatological fields are prescribed to the ones derived from the CGCM, it is demonstrated that the quasi-biennial ENSO variability simulated by the CGCM is mostly due to the biases in the climatological currents of the CGCM. These biases favor the dominance of the fast “zonal advective feedback” over the slow “thermocline feedback” in the coupled system and enhance a fast coupled basin mode. This fast mode differs from the theoretical Pacific Ocean basin mode in that, besides mean temperature advection by the zonal current anomalies, it is also driven by anomalous temperature advection by the total current. Results suggest that the near-annual mode destabilizes the ENSO mode to produce overenergetic quasi-biennial oscillations in the model. It also contributes to the ENSO asymmetry and the cold bias of the CGCM mean state by nonlinear accumulation of temperature zonal advection, which works toward the cold in the western Pacific more than the warm in the east. It is suggested that the model equilibrium results from the interaction between the ENSO mode, the near-annual mode, and the mean state.
Anidulafungin Does Not Require Dosage Adjustment in Subjects With Varying Degrees of Hepatic or Renal Impairment
Authors: Dowell James A. , Stogniew Martin , Krause David , Damle Bharat
Published: March 2007

Two open‐label studies assessed the effects of hepatic and renal impairment on anidulafungin pharmacokinetics. A single 50‐mg dose was administered intravenously to subjects with varying degrees of hepatic or renal insufficiency or with end‐stage renal disease; all were matched to normal healthy controls. Anidulafungin was well tolerated. AUC, CL, Cmax, tmax, t1/2, and Vss between renally impaired subjects and controls were not significantly different (P .05), and no measurable amounts of drug were found in dialysate. The same pharmacokinetic parameters were also not affected (P .05) by mild or moderate hepatic insufficiency, with respective mean AUCs of 50.6 ± 11.7 μg·h/mL and 68.6 ± 14.5 μg·h/mL, compared to 70.0 ± 13.4 μg·h/mL in controls. Statistically significant decreases (P < 05) of AUC (33% change) and Cmax (36% change) in severely hepatically impaired subjects compared to controls—most likely secondary to ascites and edema—were not clinically relevant. Anidulafungin can be safely administered to patients with any degree of hepatic or renal impairment without dosage adjustment and without regard to hemodialysis schedules.
Pharmacokinetics of a Rivastigmine Transdermal Patch Formulation in Healthy Volunteers: Relative Effects of Body Site Application
Authors: Lefèvre Gilbert , Sędek Greg , Huang Hsun‐Lun Aaron , Saltzman Marc , Rosenberg Mitchell , Kiese Beate , Fordham Peter
Published: March 2007

A patch formulation of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, is under development. The current objective was to evaluate the pharmacokinetic profile and patch adhesiveness following application at the upper back, chest, abdomen, thigh, and upper arm. In a single‐dose, open‐label, crossover study with 40 (42.5% men) healthy subjects, a 10‐cm2 patch containing 18 mg rivastigmine was applied to each body site. Median tmax was 16 hours for all sites except the thigh (22 hours). Exposure levels and Cmax were highest at the upper back, chest, and upper arm sites. Adhesiveness was greatest when applied to the thigh, followed by the abdomen, upper arm, chest, and upper back, although no statistically significant correlations with pharmacokinetic parameters were found, except at the chest (P = .02). Pharmacokinetic profiles and adhesiveness of the upper back, chest, and upper arm, coupled with low rates of erythema at these sites, suggest their suitability for clinical use.
Fostering internationally referenced vocational knowledge
Authors: Munro John
Published: March 2007

This article examines the issue of fostering vocational knowledge from an international perspective. It is based on the belief that 21 st-century students would benefit from a study of human endeavour that has an intercultural foundation. It identifies the aspects of knowledge that may be seen to comprise vocational knowledge and uses one international curriculum, the International Baccalaureate Diploma Programme, to examine the extent to which the knowledge outcomes match the competencies. It proposes a possible curriculum framework for fostering vocational knowledge. The pedagogic implications for teaching the types of competencies are discussed.
Standing out: how new firms in emerging markets build reputation
Authors: Rindova Violina P. , Petkova Antoaneta P. , Kotha Suresh
Published: March 2007

While strategy and organizational researchers increasingly recognize that observers' perceptions and beliefs about firms have a substantive effect on firms' access to resources and performance, the processes through which these perceptions form are not well understood. To address this question, we examined how three new firms - Amazon.com, barnesandnoble.com and CDNow - that entered the emerging e-commerce domain in the mid-1990s built their initial reputations in the media. Given the limited theory and empirical evidence about the process of reputation accumulation by new firms in emerging markets, we used the case study method to develop inductively a model that relates the visible external actions of the three firms to the patterns of media coverage they accumulated. Patterns of media coverage are likely to both reflect and affect the process of reputation accumulation, as the media constitute an influential audience of critics, who first form their own perceptions and opinions, thereby reflecting the process of reputation accumulation, and then disseminate these perceptions and opinions to the public, thereby influencing the perceptions and opinions of other stakeholder audiences. Our analysis indicates that the pattern of market actions of new firms influences the pattern of media coverage they receive in terms of levels (visibility), content (strategic character), tenor (favorability) and distinction (esteem).The observed inter-firm differences in these characteristics of received coverage suggest that reputation may be better understood as a composite construct and that firms' reputational assets may vary in their composition. Our study offers an inductively developed process model that relates the market actions of new firms to the accumulation of the different components of their initial reputations in the media.
Leading a Community of Learners
Authors: Starratt Robert J.
Published: March 2007

This article attempts to provide a foundational understanding of school learning as moral activity as well as intellectual activity. It first develops a distinction between general ethics and professional ethics, and provides an initial explanation of the moral good involved in learning. The moral good of learning is then connected to the fundamental moral agenda of learners, namely, to find, own and engage their true, authentic selves. The article takes up the distortion of the learning process in schools due to a misguided epistemology of knowledge inherited from the Enlightenment and suggests an epistemology more in tune with the sociology of knowledge and contemporary physics. This enables a clearer foundational connection of learning with authentic human development. There follows a description of what teaching for that kind of learning might look like. The article concludes with some implications for leadership of such learning.
Ethical School Leadership
Authors: Stefkovich Jacqueline , Begley Paul T.
Published: March 2007

This article explores the alternate ways ethical school leadership in the best interests of students is conceptualized in the educational leadership literature from several foundational perspectives including philosophy, psychology, critical theory and case law. Perspectives which are grounded solely in theory are differentiated from those grounded in research and practical field applications. An argument is made for the merits of applying multiple ethical perspectives. The findings of existing research on the valuation processes of school principals and their ethical leadership practices are also discussed with a particular focus on their explicit or implicit interpretations of the meaning of `best interests of students'. A genuine regard for student best interests emerges as a major influence on principal leadership practices in two ways: principal valuation processes are heavily oriented towards rational consequentialist orientations; the best interests of students figures prominently as a meta-organizer and ultimate influence on their decision making.
Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance
Authors: Izawa Takashi , Ishimaru Naozumi , Moriyama Keiji , Kohashi Masayuki , Arakaki Rieko , Hayashi Yoshio
Published: March 2007

Although receptor activator of nuclear factor (NF)–κB ligand (RANKL) signaling has been shown to prolong the survival of mature dendritic cells (DCs), the association of RANKL pathway with Fas-mediated apoptosis is obscure. Here, we found that bone marrow–derived DCs (BMDCs) from the Fas-deficient strain MRL/lpr mice, could survive much longer than normal DCs. The expressions of Bcl-x and Bcl-2 and the nuclear transport of NF-κB of RANKL-stimulated BMDCs from MRL/lpr mice were significantly up-regulated. By contrast, Fas expression of BMDCs from normal C57BL/6 and MRL+/+ mice was increased by RANKL stimulation, and an enhanced DC apoptosis was found when stimulated with both RANKL and anti-Fas mAb, which was associated with activation of caspase-3 and caspase-9. Furthermore, the expression of FLIPL, an inhibitory molecule against Fas-mediated apoptosis, in normal DCs was significantly decreased by RANKL and anti-Fas mAb. Indeed, the adoptive transfer of RANKL-stimulated DCs resulted in rapid acceleration of autoimmunity in MRL/lpr recipients. These findings indicate that the crosstalk between RANKL and Fas signaling in DCs might control immune tolerance.
The 2004 Niigata Ken Chuetsu, Japan, Earthquake
Authors: Scawthorn Charles , Rathje Ellen M.
Published: March 2007

The 23 October 2004 Niigata Ken Chuetsu, Japan, earthquake ( Mw=6.6) was the most significant earthquake to affect Japan since the 1995 Kobe earthquake, killing 48 people and injuring 4,160. Hundreds of major landslides destroyed entire upland villages and, together with permanent ground deformations, caused extensive damage to roads, rail lines and other lifelines, resulting in major economic disruption and an estimated cost of U.S. $40 billion. Two reconnaissance teams supported by EERI surveyed the earthquake damage soon after the event, employing new technologies such as handheld global positioning systems, satellite imagery, and light detection and ranging, which facilitated more rapid and detailed data collection than was possible in previous earthquake damage surveys.
Performance of Transportation Systems during the 2004 Niigata Ken Chuetsu, Japan, Earthquake
Authors: Ashford Scott A. , Kawamata Yohsuke
Published: March 2007

With the possible exception of the Shinkansen railway, transportation structures for the most part performed well in the Niigata Ken Chuetsu earthquake. There were no collapses. The damage appeared limited and repairable, indicating generally good performance despite the severe ground motions in the epicentral region. The reconnaissance team visited every bridge structure crossing the Uono and Shinano rivers in the epicentral region. All but two of the highway bridges inspected were open for at least limited traffic, and those two appeared to be open for emergency vehicles. Significant damage was observed on the Shinkansen high-speed railway, as well as on some local railway lines, but all appeared repairable. A historic first was the earthquake's derailment of a high-speed Shinkansen train.
Seismology and Strong Ground Motions in the 2004 Niigata Ken Chuetsu, Japan, Earthquake
Authors: Mori Jim , Somerville Paul
Published: March 2007

The Niigata Ken Chuetsu earthquake was a shallow, moderate-sized event producing strong shaking and considerable land failure damage across a significant region of Niigata Prefecture in central Japan. Moment tensor solutions indicate the main shock as being pure reverse faulting on a fault striking 30° east of north, roughly parallel to the mapped active faults and to the structural trends of the region, with nodal planes that dip down to the west at about 50° and down to the east at about 40°. The main shock was followed by an unusual number of large aftershocks. An extensive field investigation identified only minor surface faulting. Hanging wall effects accompanied by unusually high accelerations were observed, with peak horizontal accelerations of 1.75 g recorded at Tohkamachi and 1.33 g recorded at Ojiya.
Geotechnical Aspects of the 2004 Niigata Ken Chuetsu, Japan, Earthquake
Authors: Rathje Ellen M. , Kelson Keith , Ashford Scott A. , Kawamata Yohsuke , Towhata I. , Kokusho T. , Bardet J. P.
Published: March 2007

The Niigata Ken Chuetsu earthquake induced significant geotechnical and geologic failures throughout the affected region. The most prevalent geotechnical observations from this earthquake are related to ground failure, including landslides in natural ground, failures of highway embankments and residential earth fills, and limited liquefaction in alluvial deposits. The absence of considerable levee deformations and surface faulting was noted. This paper documents the geotechnical aspects of the Niigata Ken Chuetsu earthquake as related to earth structures, liquefaction, and surface faulting; landslides are discussed in an accompanying paper.
Terrestrial-LIDAR Visualization of Surface and Structural Deformations of the 2004 Niigata Ken Chuetsu, Japan, Earthquake
Authors: Kayen Robert , Pack Robert T. , Bay James , Sugimoto Shigetoshi , Tanaka Hajime
Published: March 2007

Following the 23 October 2004 Niigata Ken Chuetsu, Japan, Mw 6.6 earthquake, LIDAR (light detection and ranging) technology was used to create ultra high-resolution three-dimensional digital terrain models of the earthquake damage. Two reconnaissance teams traveled with tripod-mounted LIDAR that allowed for the rapid collection of post-earthquake failure geometries of ground, structures, and lifelines prior to modification by post-disaster recovery efforts and natural processes, with range accuracies of approximately 2.5 cm and targets illuminated up to 400–700 m from the sensor. LIDAR offers several benefits: (1) detailed failure morphologies of damaged ground and structures, measured remotely and in a way not feasible by conventional means; (2) exploration and visualization of damage on a computer screen is enabled, in orientations and scales that were previously impossible, providing better definition of the failure surfaces, deformation patterns, and morphologies required for understanding failure modes; and (3) archived ultra-high-resolution data for evaluation of analytical and numerical models of deformation. High-resolution images and movies of LIDAR data can be viewed at http://walrus.wr.usgs.gov/geotech/Niigata/ and the online pages of Earthquake Spectra.
Lifeline Aspects of the 2004 Niigata Ken Chuetsu, Japan, Earthquake
Authors: Scawthorn Charles , Miyajima Masakatsu , Ono Yusuke , Kiyono Junji , Hamada Masanori
Published: March 2007

After landslides, damage to lifelines was the next most notable feature of the 23 October 2004 Niigata Ken Chuetsu, Japan, earthquake ( Mw=6.6). Roads and highways sustained damage at over 6,000 locations; rail lines, water systems, and wastewater systems sustained major damage; and over 300,000 customers lost electric power. Nagaoka's water supply was disrupted by the failure of electric power, which illustrates lifeline interaction, and Ojiya's water treatment plant almost lost its intake of raw water. Nagaoka's 1,079- km-long water system sustained damage at 287 locations, and Ojiya's 329- km-long water system sustained damage at 102 locations. In 2,672 km of wastewater piping, damage was sustained at over 9,000 locations, with manhole settlement or uplift at over 1,300 locations. The pattern of refugees was strongly influenced by the availability of lifeline services—primarily, electric power.
Expression of Bone Morphogenetic Proteins and their Receptors in the Bone Marrow Megakaryocytes of GATA-1low Mice
Authors: Garimella Rama , Kacena Melissa A. , Tague Sarah E. , Wang Jinxi , Horowitz Mark C. , Anderson H. Clarke
Published: March 2007

The mechanism of osteosclerosis associated with myelofibrosis in megakaryocyte (MK)-related myeloproliferative disorders is largely unknown. However, growth factors released from the bone marrow cells, including from MKs, have been implicated in myelofibrosis, osteosclerosis, and angiogenesis. GATA-1 is a transcription factor required for normal MK development. GATA-1 deficiency in mice (GATA-1low) leads to increased megakaryocytic proliferation, followed by osteosclerosis and myelofibrosis. In this study we investigated the expression of bone morphogenetic proteins (BMPs) and BMP receptors and their possible role in the development of osteosclerosis in the MKs of 12-month-old GATA-1low mice by immunohistochemistry, cytomorphometry, and quantitative real-time PCR. Marrow MKs from both wild-type and GATA-1low mice showed moderate to intense staining for BMP-2, −4, and −6 and BMPR-IA and BMPR-II, whereas splenic MKs showed no BMP immunostaining. Presence of BMP protein in the bone marrow of GATA-1low mice was more than that seen in controls, owing to an increased number of MKs and osteoblasts. The osteosclerosis seen in GATA-1low mice appeared not to be due to a reduced number of functional osteoclasts because the number of tartrate-resistant acid phosphatase-positive osteoclasts was greater in GATA-1low mice than in controls. Our findings demonstrate the presence of significant amounts of BMP-2, −4, and −6 along with their receptors in bone marrow MKs of WT and GATA-1low mice. The increased levels of BMPs appear to be a result of increased numbers of MKs in GATA-1low mice and may, in part, account for the stimulation of osteoblastic activity and resulting osteosclerosis.
Effects of TNF-α on Leukocyte Adhesion Molecule Expressions in Cultured Human Lymphatic Endothelium
Authors: Sawa Yoshihiko , Sugimoto Yukitaka , Ueki Takeshi , Ishikawa Hiroyuki , Sato Atuko , Nagato Toshikazu , Yoshida Shigemitsu
Published: March 2007

TNF-α alters leukocyte adhesion molecule expression of cultured endothelial cells like human umbilical vein endothelial cells (HUVEC). This study was designed to investigate the changes in vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) expression with TNF-α stimulation in cultured human neonatal dermal lymphatic endothelial cells (HNDLEC). The real-time quantitative PCR analysis on HNDLEC showed that TNF-α treatment leads to increases of VCAM-1 and ICAM-1 mRNAs to the 10.8- and 48.2-fold levels of untreated cells and leads to a reduction of PECAM-1 mRNA to the 0.42-fold level of untreated cells. Western blot and immunohistochemical analysis showed that TNF-α leads to VCAM-1 and ICAM-1 expressions that were inhibited by antiserum to human TNF receptor or by AP-1 inhibitor nobiletin. In flow cytometry analysis, the number of VCAM-1- and ICAM-1-positive cells increased, and PECAM-1-positive cells decreased with TNF-α treatment. Regarding protein amounts produced in cells and amounts expressed on the cell surface, VCAM-1 and ICAM-1 increased in HNDLEC and HUVEC, and PECAM-1 decreased in HNDLEC in a TNF-α concentration-dependent manner. VCAM-1, ICAM-1, and PECAM-1 protein amounts in TNF-α-stimulated cells were lower in HNDLEC than in HUVEC. This suggests that the lymphatic endothelium has the TNF-α-induced signaling pathway, resulting in increased VCAM-1 and ICAM-1 expression to a weaker extent than blood endothelium and PECAM-1 reduction to a stronger extent than blood endothelium.
Bayes'sche Methodik zur lokalen Fusion heterogener Informationsquellen (Bayesian Methodology for the Local Fusion of Heterogeneous Information Sources)
Authors: Beyerer Jürgen , Sander Jennifer , Werling Stefan
Published: March 2007

Bei der Fusion heterogener Informationsquellen muss deren unterschiedlicher Abstraktionsgrad und deren unterschiedliche Natur (Formalisierung) überwunden werden. Essenzielle Forderungen an eine Fusionsmethodik sind die Fähigkeiten zur Transformation, Fusion und Fokussierung. Es wird gezeigt, dass die Bayes’sche Wahrscheinlichkeitstheorie in einer Degree-of-Belief-Deutung jede dieser Forderungen erfüllt. Um ihren hohen Rechenaufwand entscheidend zu verringern, wird anschließend ein lokaler Bayes’scher Fusionsansatz vorgestellt. Dieser kann in Anlehnung an kriminalistische Ermittlungen mittels einer agentenbasierten Fusionsarchitektur umgesetzt werden.