bluuebunny/crossref_metadata_2025 huggingface dataset:
Non–Small Cell Lung Cancers with Kinase Domain Mutations in the Epidermal Growth Factor Receptor Are Sensitive to Ionizing Radiation
Authors: Das Amit K. , Sato Mitsuo , Story Michael D. , Peyton Michael , Graves Robert , Redpath Stella , Girard Luc , Gazdar Adi F. , Shay Jerry W. , Minna John D. , Nirodi Chaitanya S.
Published: October 2006

Non–small cell lung cancers (NSCLCs) bearing mutations in the tyrosine kinase domain (TKD) of the epidermal growth factor receptor (EGFR) often exhibit dramatic sensitivity to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Ionizing radiation (IR) is frequently used in the treatment of NSCLC, but little is known how lung tumor–acquired EGFR mutations affect responses to IR. Because this is of great clinical importance, we investigated and found that clonogenic survival of mutant EGFR NSCLCs in response to IR was reduced 500- to 1,000-fold compared with wild-type (WT) EGFR NSCLCs. Exogenous expression of either the L858R point mutant or the ΔE746-E750 deletion mutant form of EGFR in immortalized human bronchial epithelial cells, p53 WT NSCLC (A549), or p53-null NSCLC (NCI-H1299) resulted in dramatically increased sensitivity to IR. We show that the majority of mutant EGFR NSCLCs, including those that contain the secondary gefitinib resistance T790M mutation, exhibit characteristics consistent with a radiosensitive phenotype, which include delayed DNA repair kinetics, defective IR-induced arrest in DNA synthesis or mitosis, and pronounced increases in apoptosis or micronuclei. Thus, understanding how activating mutations in the TKD domain of EGFR contribute to radiosensitivity should provide new insight into effective treatment of NSCLC with radiotherapy and perhaps avoid emergence of single agent drug resistance. (Cancer Res 2006; 66(19): 9601-07)
Role of Extracellular Superoxide Dismutase in the Mouse Angiotensin Slow Pressor Response
Authors: Welch William J. , Chabrashvili Tinatin , Solis Glenn , Chen Yifan , Gill Pritmohinder S. , Aslam Shakil , Wang Xiaoyan , Ji Hong , Sandberg Kathryn , Jose Pedro , Wilcox Christopher S.
Published: October 2006

Low rates of angiotensin II (Ang II) infusion raise blood pressure, renal vascular resistance (RVR), NADPH oxidase activity, and superoxide. We tested the hypothesis that these effects are ameliorated by extracellular superoxide dismutase (EC-SOD). EC-SOD knockout (−/−) and wild type (+/+) mice were equipped with blood pressure telemeters and infused subcutaneously with Ang II (400 ng/kg per minute) or vehicle for 2 weeks. During vehicle infusion, EC-SOD −/− mice had significantly (
P
<0.05) higher MAP (+/+: 107±3 mm Hg versus −/−: 114±2 mm Hg; n=11 to 14), RVR, lipid peroxidation, renal cortical p22
phox
expression, and NADPH oxidase activity. Ang II infusion in EC-SOD +/+ mice significantly (
P
<0.05) increased MAP, RVR, p22
phox
, NADPH oxidase activity, and lipid peroxidation. Ang II reduced SOD activity in plasma, aorta, and kidney accompanied by reduced renal EC-SOD expression. During Ang II infusion, both groups had similar values for MAP (+/+ Ang II: 125±3 versus −/− Ang II: 124±3 mmHg;
P
value not significant), RVR, NADPH oxidase activity, and lipid peroxidation. SOD activity in the kidneys of Ang II–infused mice was paradoxically higher in EC-SOD −/− mice (+/+: 8.8±1.2 U/mg protein
−1
versus −/−: 13.7±1.6 U/mg protein
−1
;
P
<0.05) accompanied by a significant upregulation of mRNA and protein for Cu/Zn-SOD. In conclusion, EC-SOD protects normal mice against oxidative stress by attenuating renal p22
phox
expression, NADPH oxidase activation, and the accompanying renal vasoconstriction and hypertension. However, during an Ang II slow pressor response, renal EC-SOD expression is reduced and, in its absence, renal Cu/Zn-SOD is upregulated and may prevent excessive Ang II–induced renal oxidative stress, renal vasoconstriction, and hypertension.
β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension
Authors: Pojoga Luminita , Kolatkar Nikheel S. , Williams Jonathan S. , Perlstein Todd S. , Jeunemaitre Xavier , Brown Nancy J. , Hopkins Paul N. , Raby Benjamin A. , Williams Gordon H.
Published: October 2006

Two genetic variants of the β-2 adrenergic receptor, 46G>A and 79C>G, affect agonist-mediated receptor downregulation and vascular reactivity. We determined whether these variants were associated with hypertension, per se, blood pressure response to dietary sodium, 2 forms of salt-sensitive hypertension (low renin and nonmodulation), and the activity of the renin–angiotensin–aldosterone system. Included are 280 hypertensive and 65 normotensive white subjects who had the 2 β-2 adrenergic receptor genotypes available. Of all subjects, 171 hypertensive and 48 normotensive subjects had complete data for intermediate phenotyping and blood pressure evaluation on high- and low-sodium balance. The β-2 adrenergic receptor variants were not associated with hypertension per se. However, among hypertensive subjects, the change (from low to high sodium balance) in mean arterial pressure differed significantly by genotype and by diplotype. Compared with all of the other diplotypes combined, 46AA/79CC was associated with a greater change in blood pressure. Furthermore, this diplotype was associated with low-renin (LR) hypertension (identifying 32% of the LR hypertensives), higher plasma aldosterone, and lower plasma renin and serum potassium levels. In conclusion, the 46AA/79CC diplotype is associated with greater blood pressure response to dietary sodium and higher odds of LR hypertension. We propose that the mechanism for the observed association is inadequate suppression of aldosterone with salt intake, implicating the β-2 adrenergic receptor in the regulation of aldosterone secretion. This hypothesis was confirmed in isolated glomerulosa cells, where β-2 adrenergic receptor stimulation increased aldosterone secretion, whereas blockade reduced the stimulated aldosterone response. Importantly, this association could only be detected with an intermediate and not a distant phenotype.
Genetic Determinants of Systolic and Pulse Pressure in an Intercross Between Normotensive Inbred Rats
Authors: Llamas Bastien , Lau Catherine , Cupples William A. , Rainville Marie-Line , Souzeau Emmanuelle , Deschepper Christian F.
Published: October 2006

By continuous monitoring of abdominal aortic blood pressure via telemetry in conscious rats, we have observed that systolic, diastolic, and pulse pressures of male Brown–Norway rats were all significantly lower than that of male Wistar–Kyoto rats, despite the fact that all of the values in both strains were within normotensive ranges. Further analyses performed in 166 animals from the progeny of an F2 intercross between Brown–Norway and Wistar–Kyoto rats revealed that, despite a high correlation between systolic blood pressure and diastolic blood pressure, there was no correlation between pulse pressure and diastolic blood pressure, and the value of the correlation between systolic blood pressure and pulse pressure was lower than that of systolic blood pressure with diastolic blood pressure. Two major and highly significant (
P
<0.001) quantitative trait loci linked to pulse pressure were found on chromosome 4 (
Pp1
) and 16 (
Pp2).
Only suggestive quantitative trait loci were found for systolic blood pressure, but the strongest one (
Sbp1
) had the same peak and linkage probability profile as
Pp1.
Altogether, these data show that genetic determinants affecting pulse pressure in normotensive animals are either stronger or independent from the ones affecting systolic blood pressure and are of interest in light of evidence showing that pulse pressure is highly heritable in humans and that elevated pulse pressure is a predictor of cardiovascular risk.
Autonomic Cardiovascular Responses to Heme Oxygenase Inhibition in Conscious Rats
Authors: Hirakawa Haruhisa , Hayashida Yoshiaki
Published: October 2006

Carbon monoxide (CO) is produced in the course of heme degradation from biliverdin by heme oxygenase (HO) in various tissues, including the central nervous system. Recent studies suggest the inhibition of HO activity increases arterial pressure mediated by the autonomic nervous system. The present study was designed to investigate the autonomic regulation of cardiovascular responses to inhibition of endogenous CO production by the HO inhibitor Zinc deuteroporphyrin 2, 4-bis glycol (ZnDPBG) by using direct sympathetic nerve recordings in conscious, chronically instrumented rats. ZnDPBG induced increases in mean arterial pressure (MAP) (
P
<0.05) and renal sympathetic nerve activity (RSNA) (
P
<0.05) but no significant change in heart rate (
P
>0.05) in intact rats. In atropine-treated rats, ZnDPBG also induced increases in MAP (
P
<0.05) and RSNA (
P
<0.05) but no change in heart rate (
P
>0.05). In sinoaortic denervated rats, ZnDPBG induced increases in MAP (
P
<0.05), heart rate (
P
<0.05), and RSNA (
P
<0.05). ZnDPBG shifted the baroreflex curve for RSNA upward and to the right, which was characterized by increases in the maximum and minimum response and midpoint pressure without altering the maximum gain. These results indicate that inhibition of HO activity within the central nervous system causes sympathoexcitation, resulting in an increase in arterial pressure. We conclude that the CO/HO system plays an important role in cardiovascular regulation by modulating sympathetic tone.
NO Differentially Regulates Neurotransmission to Premotor Cardiac Vagal Neurons in the Nucleus Ambiguus
Authors: Kamendi Harriet , Dergacheva Olga , Wang Xin , Huang Zheng-Gui , Bouairi Evguenia , Gorini Christopher , Mendelowitz David
Published: October 2006

NO is involved in the neural control of heart rate, and NO synthase expressing neurons and terminals have been localized in the nucleus ambiguus where parasympathetic cardiac vagal preganglionic neurons are located; however, little is known about the mechanisms by which NO alters the activity of premotor cardiac vagal neurons. This study examines whether the NO donor sodium nitroprusside ([SNP] 100 μmol/L) and precursor,
l
-arginine (10 mmol/L), modulate excitatory and inhibitory synaptic neurotransmission to cardiac vagal preganglionic neurons. Glutamatergic, GABAergic, and glycinergic activity to cardiac vagal neurons was examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation in rats. Both SNP, as well as
l
-arginine, increased the frequency of GABAergic neurotransmission to cardiac vagal preganglionic neurons but decreased the amplitude of GABAergic inhibitory postsynaptic currents. In contrast, both
l
-arginine and SNP inhibited the frequency of glutamatergic and glycinergic synaptic events in cardiac vagal preganglionic neurons. SNP and
l
-arginine also decreased glycinergic inhibitory postsynaptic current amplitude, and this response persisted in the presence of tetrodotoxin. Inclusion of the NO synthase inhibitor 7-nitroindazole (100 μmol/L) prevented the
l
-arginine–evoked responses. These results demonstrate that NO differentially regulates excitatory and inhibitory neurotransmission, facilitating GABAergic and diminishing glutamatergic and glycinergic neurotransmission to cardiac vagal neurons.
Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis
Authors: Mahrholdt Heiko , Wagner Anja , Deluigi Claudia C. , Kispert Eva , Hager Stefan , Meinhardt Gabriel , Vogelsberg Holger , Fritz Peter , Dippon Juergen , Bock C. -Thomas , Klingel Karin , Kandolf Reinhard , Sechtem Udo
Published: October 2006

Background—

Enteroviruses and adenoviruses have been considered the most common causes of viral myocarditis, but parvovirus B19 (PVB19) and human herpesvirus 6 (HHV6) are increasingly found in endomyocardial biopsy samples.

Methods and Results—

Consequently, our aim was to evaluate the prevalence and clinical presentation of cardiac PVB19 and/or HHV6 infection in a cohort of myocarditis patients and to follow its clinical course. In addition, we sought to demonstrate patterns of myocardial damage and to determine predictors for chronic heart failure. Our study design consisted of a cardiovascular magnetic resonance protocol as well as endomyocardial biopsies in the myocardial region affected as indicated by cardiovascular magnetic resonance. One hundred twenty-eight patients were enrolled by clinical criteria. In the group of myocarditis patients (n=87), PVB19 (n=49), HHV6 (n=16), and combined PVB19/HHV6 infections (n=15) were detected most frequently. The remaining patients were diagnosed with healing myocarditis (n=15) or did not have myocarditis (n=26). Patients with PVB19 presented in a manner similar to that of myocardial infarction; most had typical subepicardial late gadolinium enhancement in the lateral wall and recovered within months. Conversely, patients with HHV6 and especially with HHV6/PVB19 myocarditis presented with new onset of heart failure, had septal late gadolinium enhancement, and frequently progressed toward chronic heart failure.

Conclusions—

Our data indicate that PVB19 and HHV6 are the most important causes for viral myocarditis in Germany and that the clinical presentation is related to the type of virus. Furthermore, clinical presentation, type of virus, and pattern of myocardial damage are related to the clinical course.
T-Cell Immunity to Subclinical Cytomegalovirus Infection Reduces Cardiac Allograft Disease
Authors: Tu Wenwei , Potena Luciano , Stepick-Biek Pamela , Liu Lanxiang , Dionis Kira Y. , Luikart Helen , Fearon William F. , Holmes Tyson H. , Chin Clifford , Cooke John P. , Valantine Hannah A. , Mocarski Edward S. , Lewis David B.
Published: October 2006

Background—

Asymptomatic cytomegalovirus (CMV) replication is frequent after cardiac transplantation in recipients with pretransplantation CMV infection. How subclinical viral replication influences cardiac allograft disease remains poorly understood, as does the importance of T-cell immunity in controlling such replication.

Methods and Results—

Thirty-nine cardiac recipients who were pretransplantation CMV antibody positive were longitudinally studied for circulating CMV-specific CD4 and CD8 T-cell responses, CMV viral load in blood neutrophils, and allograft rejection during the first posttransplantation year. Nineteen of these recipients were also analyzed for changes of coronary artery intimal, lumen, and whole-vessel area. All recipients received early prophylactic therapy with ganciclovir. No recipients developed overt CMV disease. Those with detectable levels of CMV-specific CD4 T cells in the first month after transplantation were significantly protected from high mean and peak posttransplantation viral load (
P
<0.05), acute rejection (
P
<0.005), and loss of allograft coronary artery lumen (
P
<0.05) and of whole-vessel area (
P
<0.05) compared with those who lacked this immune response. The losses of lumen and vessel area were both significantly correlated with the time after transplantation at which a CD4 T-cell response was first detected (
P
<0.05) and with the cumulative graft rejection score (
P
<0.05).

Conclusions—

The early control of subclinical CMV replication after transplantation by T-cell immunity may limit cardiac allograft rejection and vascular disease. Interventions to increase T-cell immunity might be clinically useful in limiting these adverse viral effects.
Implications of the Failure to Identify High-Risk Electrocardiogram Findings for the Quality of Care of Patients With Acute Myocardial Infarction
Authors: Masoudi Frederick A. , Magid David J. , Vinson David R. , Tricomi Albert J. , Lyons Ella E. , Crounse Laurie , Ho P. Michael , Peterson Pamela N. , Rumsfeld John S.
Published: October 2006

Background—

The impact of misinterpretation of the ECG in patients with acute myocardial infarction (AMI) in the emergency department (ED) setting is not well known. Our goal was to assess the prevalence of the failure to identify high-risk ECG findings in ED patients with AMI and to determine whether this failure is associated with lower-quality care.

Methods and Results—

In a retrospective cohort study of consecutive patients presenting to 5 EDs in California and Colorado from July 1, 2000, through June 30, 2002, with confirmed AMI (n=1684), we determined the frequency of the failure by the treating provider to identify significant ST-segment depressions, ST-segment elevations, or T-wave inversions on the presenting ECG. In multivariable models, we assessed the relationship between missed high-risk ECG findings and evidence-based therapy in the ED after adjustment for patient characteristics and site of care. High-risk ECG findings were not documented in 201 patients (12%). The failure to identify high-risk findings was independently associated with a higher odds of not receiving treatment among ideal candidates for aspirin (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.51 to 2.94), β-blockers (OR, 1.85; 95% CI, 1.14 to 3.03), and reperfusion therapy (OR, 7.69; 95% CI, 3.57 to 16.67). Among patients with missed high-risk ECG findings, in-hospital mortality was 7.9% compared with 4.9% among those without missed findings (
P
=0.1).

Conclusions—

The failure to identify high-risk ECG findings in patients with AMI results in lower-quality care in the ED. Systematic processes to improve ECG interpretation may have important implications for patient treatment and outcomes.
Midkine Plays a Protective Role Against Cardiac Ischemia/Reperfusion Injury Through a Reduction of Apoptotic Reaction
Authors: Horiba Mitsuru , Kadomatsu Kenji , Yasui Kenji , Lee Jong-Kook , Takenaka Hiroharu , Sumida Arihiro , Kamiya Kaichiro , Chen Sen , Sakuma Sadatoshi , Muramatsu Takashi , Kodama Itsuo
Published: October 2006

Background—

Midkine (MK) is a heparin-binding growth factor involved in diverse biological phenomena, eg, neural survival, carcinogenesis, and tissue repair. MK could have a protective action against ischemia/reperfusion (I/R) injury in the heart, because MK was shown to have cytoprotective activity in cultured neurons and tumor cells. We investigated this hypothesis in mice with and without genetic MK deletion.

Methods and Results—

Myocardial injury after I/R was produced by transient occlusion of coronary arteries. In wild-type (
Mdk
+/+
) mice, MK expression was increased after I/R in the periinfarct area. Infarct size/area at risk 24 hours after I/R in MK-deficient (
Mdk
−/−
) mice was larger than in
Mdk
+/+
mice (55.4±9.1% versus 32.1±5.3%,
P
<0.05). Terminal dUTP nick end-labeling–positive myocyte population in the periinfarct area in
Mdk
−/−
mice was higher than in
Mdk
+/+
mice (6.8±0.9% versus 3.2±0.6%,
P
<0.05). Left ventricular fractional shortening 24 hours after I/R in
Mdk
−/−
mice was significantly less than that in
Mdk
+/+
mice (34.3±4.4% versus 50.8±2.1%,
P
<0.05). Supplemental application of MK protein to left ventricle of
Mdk
−/−
mice at the time of I/R resulted in reduction of the infarct size. Application of exogenous MK to cultured cardiomyocytes resulted in increased Bcl-2 expression and decreased apoptosis after hypoxia/reoxygenation.

Conclusions—

These results suggest that MK plays a protective role against I/R injury, most likely through a prevention of apoptotic reaction. MK is a potentially important new molecular target for treatment of ischemic heart disease.
Percutaneous Implantation of the CoreValve Self-Expanding Valve Prosthesis in High-Risk Patients With Aortic Valve Disease
Authors: Grube Eberhard , Laborde Jean C. , Gerckens Ulrich , Felderhoff Thomas , Sauren Barthel , Buellesfeld Lutz , Mueller Ralf , Menichelli Maurizio , Schmidt Thomas , Zickmann Bernfried , Iversen Stein , Stone Gregg W.
Published: October 2006

Background—

The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve).

Methods and Results—

Symptomatic high-risk patients with an aortic valve area <1 cm
2
were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2±10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4±3.0 mm Hg;
P
<0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital.

Conclusions—

Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.
China's Elite Politics and Sino-American Rapprochement, January 1969–February 1972
Authors: Xia Yafeng
Published: October 2006

Western scholars have long assumed that Mao Zedong and Zhou Enlai encountered opposition within the Chinese leadership when they sought to improve relations with the United States in the late 1960s and early 1970s. Formerly secret documents and first-hand accounts published in China over the last two decades cast doubt on this assumption. Drawing on newly available Chinese sources, this article examines China's policymaking process vis-à-vis the United States during the crucial period from January 1969 to February 1972. The article shows that the highest Chinese officials (especially Mao, Lin Biao, and Zhou) agreed that improvements in U.S.-China relations would be desirable to offset the threat from the Soviet Union.
Properties of El Niño–Southern Oscillation in Different Equilibrium Climates with HadCM3
Authors: Toniazzo Thomas
Published: October 2006

The ENSO variability in three long, stable, steady-state integrations of the Third Hadley Centre Coupled Ocean–Atmosphere GCM (HadCM3) is analyzed, relevant to climatic conditions of the Last Glacial Maximum (LGM), of the preindustrial period [control (CTL)], and of a greenhouse stabilization scenario (GHS) at 4 times the preindustrial CO2 concentration. It is found that progressively from LGM to CTL and GHS, the SST variability pattern associated with ENSO is centered farther west, and the oscillation acquires a shorter dominant period. While there are no large changes in total SST variability, very strong events become less frequent, and El Niño events develop over a narrower period within the seasonal cycle. The westward ENSO pattern shift is concurrent with a similar shift in the climatological wind stress distribution and with increased convective activity over the west equatorial Pacific. The wind response to anomalous SSTs follows this shift and increases in strength. The thermocline feedback becomes stronger in the 4 × CO2 integration, but the largest SST anomalies are associated with surface processes. The role of surface flux damping for the decay of anomalous SSTs is reduced in LGM and increased in GHS. From the analysis, the principal changes in mean climate that appear to affect the evolution of ENSO-related SST anomalies in HadCM3 are thus the changes in zonal wind stress over the equator, the depth of the equatorial thermocline, and the sensitivity of atmospheric convection to equatorial SST anomalies.
A New Blocking Index and Its Application: Blocking Action in the Northern Hemisphere
Authors: Diao Yina , Li Jianping , Luo Dehai
Published: October 2006

In this paper, a new two-dimensional blocking index is proposed by defining a difference between the daily 500-hPa geopotenial heights at the reference latitude and its north side. The reference latitude is determined by a composite latitude-dependent 500-hPa geopotenial height of blocking events in different seasons and sectors. The new index can take account of the duration, intensity, propagation, and spatial structure of a blocking event. Using this index, the characteristics (frequency, duration, intensity, and preferred occurrence region) of the blocking action in the North Hemisphere (NH) are investigated using a 42-yr sample of blocking events from the NCEP–NCAR reanalyses.

It is found that blocking events in the NH are more frequent in the Atlantic–Europe sector than in the Pacific sector in winter and spring and autumn, but more persistent in the Atlantic–Europe sector than in the Pacific sector for all seasons. Blocking events in the Pacific sector tend to have larger amplitudes than the Atlantic counterparts. In addition, it is shown that in the NH independently occurring blocking events are most frequent, but simultaneously occurring blockings are rather rare, indicating that the blocking events in the NH should be a local phenomenon.

On the other hand, a comparison with the existing indices [e.g., Tibaldi and Molteni (TM) index] indicates that in summer and autumn the new index shows similar longitudinal dependency of NH blocking events as does the TM index, but it shows two distinct action centers of blocking events in the Atlantic sector in winter and spring (in which the most frequent one is situated more westward) and an eastward blocking action center in the Pacific sector in spring and autumn, compared to the TM index.

In addition, it is found that the new blocking index proposed here shows relatively low blocking frequency for all seasons compared to the TM index, especially in the Atlantic sector in spring and in the Pacific sector in winter and spring, which seems to be in agreement with the result obtained by Pelly and Hoskins using the PV–θ index.
Local Air–Sea Relationship in Observations and Model Simulations
Authors: Wu Renguang , Kirtman Ben P. , Pegion Kathy
Published: October 2006

The present study compares the local simultaneous correlation between rainfall–evaporation and sea surface temperature (SST)–SST tendency among observations, coupled general circulation model (CGCM) simulations, and stand-alone atmospheric general circulation model (AGCM) simulations. The purpose is to demonstrate to what extent the model simulations can reproduce the observed air–sea relationship. While the model-simulated correlation agrees with the observations in the tropical eastern Pacific, large discrepancies are found in the subtropics, midlatitudes, and tropical Indo-western Pacific Ocean regions. In tropical Indo-western Pacific Ocean regions and the midlatitudes where the atmosphere contributes to the observed SST changes, the specified SST simulations produce excessive SST forcing, whereas the CGCM captures the atmospheric feedback on the SST, but with somewhat of an overestimation. In the subtropics, both the AGCM and CGCM produce unrealistic positive rainfall–SST correlations. In the tropical western-central Pacific and the North Indian Ocean, the CGCM-simulated evaporation–SST correlation is opposite to that observed because of an excessive dependence of the sea–air humidity difference on the SST.
A New Perspective on the Climate Prediction of Asian Summer Monsoon Precipitation
Authors: Lim Young-Kwon , Kim Kwang-Yul
Published: October 2006

A new paradigm for climate (one month and longer) prediction is developed and is applied to the 5-day-averaged Asian summer monsoon (ASM) precipitation. The foundation of the method is to identify climate signals (deterministic components) that constitute the ASM system and predict the temporal fluctuations of the amplitudes (stochastic components) of the individual signals. Climate signals were identified via cyclostationary empirical orthogonal function (CSEOF) analysis of the Xie–Arkin pentad precipitation in this study and include the annual cycle, El Niño/La Niña, and the intraseasonal oscillations of the 40–50-day period band (the Madden–Julian oscillation). Prediction is much facilitated by forecasting the slowly undulating amplitude time series of each climate signal rather than the raw precipitation data directly. The new prediction method results in reasonable forecasts of the pentad precipitation for the test period of 1999–2001. Specifically, the propagation of the intraseasonal oscillations is predicted successfully 60 days in advance. The performance of the new method is significantly better than persistence and that of conventional prediction methods in which raw data is predicted directly.
Climate and Tropical Cyclone Activity: A New Model Downscaling Approach
Authors: Emanuel Kerry
Published: October 2006

While there is a pressing need to understand and predict the response of tropical cyclones to climate change, global climate models are at present too coarse to resolve tropical cyclones to the extent necessary to simulate their intensity, and their ability to simulate genesis is questionable. For these reasons, a “downscaling” approach to modeling the effect of climate change on tropical cyclones is desirable. Here a new approach to downscaling is introduced that consists of generating a large set of synthetic storm tracks whose statistics are consistent with the large-scale general circulation of the climate model, and then running a deterministic, coupled tropical cyclone model along each track, with atmospheric and upper-ocean thermodynamic conditions taken from the global climate model. As a first step in this direction, this paper explores the sensitivity of the intensity of a large sample of tropical cyclones to changes in potential intensity, shear, and ocean mixed layer depth, fixing other variables, including the space–time probability distribution of storm genesis. It is shown that a 10% increase in potential intensity leads to a 65% increase in the “power dissipation index,” a measure of the total amount of mechanical energy generated by tropical cyclones over their life spans. This is consistent with the observed increase of power dissipation over the past 50 yr. Storms are somewhat less influenced by equivalent fractional changes in environmental wind shear or ocean mixed layer depth.
Effects of Ekman Transport on the NAO Response to a Tropical Atlantic SST Anomaly
Authors: Peng Shiling , Robinson Walter A. , Li Shuanglin , Alexander Michael A.
Published: October 2006

A recent study showed that a tropical Atlantic sea surface temperature (SST) anomaly induces a significant coupled response in late winter [February–April (FMA)] in a coupled model, in which an atmospheric general circulation model is coupled to a slab mixed layer ocean model (AGCM_ML). The coupled response comprises a dipole in the geopotential height, like the North Atlantic Oscillation (NAO), and a North Atlantic tripole in the SST. The simulated NAO response developed 1 or 2 months later in the model than in observations. To determine the possible effects of Ekman heat transport on the development of the coupled response to the tropical forcing, an extended coupled model (AGCM_EML), including Ekman transport in the slab mixed layer ocean, is now used. Large ensembles of AGCM_EML experiments are performed, parallel to the previous AGCM_ML experiments, with the model forced by the same tropical Atlantic SST anomaly over the boreal winter months (September–April).

The inclusion of Ekman heat transport is found to result in an earlier development of the coupled NAO–SST tripole response in the AGCM_EML, compared to that in the AGCM_ML. The mutual reinforcement between the anomalous Ekman transport and the surface heat flux causes the tropical forcing to induce an extratropical SST response in November–January (NDJ) in the AGCM_EML that is twice as strong as that in the AGCM_ML. The feedback of this stronger extratropical SST response on the atmosphere in turn drives the development of the NAO response in NDJ. In FMA, the sign of the anomalous surface heat flux is reversed in the Gulf Stream region such that it opposes the anomalous Ekman transport. The resulting equilibrium NAO response in the AGCM_EML is similar to that in the AGCM_ML, but it is reached 1–2 months sooner in the AGCM_EML. Hence, the presence of Ekman transport causes a seasonal shift in the evolution of the coupled response. The faster development of the NAO response in the AGCM_EML suggests that tropical Atlantic SST anomalies should be able to influence the NAO, in nature, on the seasonal time scale, and that efficient interactions with the extratropical ocean play a significant role in determining the coupled response.
Characteristics of Satellite-Derived Clear-Sky Atmospheric Temperature Inversion Strength in the Arctic, 1980–96
Authors: Liu Yinghui , Key Jeffrey R. , Schweiger Axel , Francis Jennifer
Published: October 2006

The low-level atmospheric temperature inversion is a dominant feature of the Arctic atmosphere throughout most of the year. Meteorological stations that provide radiosonde data are sparsely distributed across the Arctic, and therefore provide little information on the spatial distribution of temperature inversions. Satellite-borne sensors provide an opportunity to fill the observational gap. In this study, a 17-yr time series, 1980–96, of clear-sky temperature inversion strength during the cold season is derived from High Resolution Infrared Radiation Sounder (HIRS) data using a two-channel statistical method. The satellite-derived clear-sky inversion strength monthly mean and trends agree well with radiosonde data. Both increasing and decreasing trends are found in the cold season for different areas. It is shown that there is a strong coupling between changes in surface temperature and changes in inversion strength, but that trends in some areas may be a result of advection aloft rather than warming or cooling at the surface.
Implicit Measurement of Attitudes, Stereotypes, and Self-Concepts in Organizations
Authors: Haines Elizabeth L. , Sumner Kenneth E.
Published: October 2006

Implicit measurement using latencies is proposed as a complement to conventional measurement to assess organizational constructs (e.g., job satisfaction), to assist in personnel decisions (e.g., selection), and to assess outcomes (e.g., diversity training). Latency-based measurements (i.e., the Implicit Association Test) use categorization tasks to measure attitudes, stereotypes, and self-concepts. Its routine inclusion in organizational research can address measurement limitations, enrich theoretical understanding of organizational phenomena, and inform practice by better predicting behavior.
Programs for Problems Created by Continuous Variable Distributions in Moderated Multiple Regression
Authors: O’Connor Brian P.
Published: October 2006

It is difficult to detect interactions between continuous variables in field research using moderated multiple regression (MMR). One reason is that multivariate normality, which occurs in field research but not experimental research, suppresses the residual variance of interaction terms. SPSS, SAS, and Matlab programs that expose the extent of this problem for any given data set are provided. Ironically, when significant interactions are found in field research using MMR, this is because the assumption of multivariate normality has been violated, thus rendering the significance tests potentially invalid. The programs presented in this article compute more trustworthy significance levels via data randomization.
The Presence of Equivalent Models in Strategic Management Research Using Structural Equation Modeling
Authors: Henley Amy B. , Shook Christopher L. , Peterson Mark
Published: October 2006

The use of structural-equation modeling (SEM) in strategic-management research has grown dramatically during recent years. Although this statistical technique offers researchers a valuable tool for testing hypothesized models, certain challenges accompany the use of SEM. The current article examines one of these challenges, equivalent models, and its prevalence in strategy research. An equivalent model is an alternative model that fits the data equally well, thus producing the same covariance or correlation matrix but often differing significantly in theoretical interpretation. We examined the application of SEM in 109 strategic-management studies and found that equivalent models are a cause for concern in most strategic-management studies. Using a published article, we also provide a statistical demonstration of the potential effect of equivalent models. This article highlights both the extent of potential equivalent models in strategy research and the possible effect of such models on strategic-management theory.
Ethnostatistics and Organizational Research Methodologies
Authors: Gephart Robert P.
Published: October 2006

Ethnostatistics is the empirical study of how professional scholars construct and use statistics and numerals in scholarly research. This article provides an overview of the objectives, contents, and contributions of the current theme issue. The nature and relevance of ethnostatistics to organizational issues are discussed. Three levels of ethnostatistics are identified and explained— constructing statistics, statistics at work, and the rhetoric of statistics. The contributions the theme issue provides to these three levels of ethnostatistics are discussed. Foundational perspectives that have shaped ethnostatistics are explored to highlight important assumptions of the field and to distinguish ethnostatistics from related fields. The theme issue broadens the field of ethnostatistics to address statistical practices used by business professionals for organizational purposes. The article concludes by arguing that the field of ethnostatistics needs to develop rapidly at this point in time to address the emerging centrality and importance that statistics hold for everyday organizational life.
Deconstructing Diffusion
Authors: Kilduff Martín , Oh Hongseok
Published: October 2006

Four published reanalyses of part of the celebrated medical innovation data focus on network effects on the diffusion of tetracycline. Each reanalysis rejects the findings of the previous analysis. This article shows that in the early 1950s, when the original data were collected, private practice physicians, swamped by demand, but facing threats to their autonomy from the federal government and from university medical centers, struggled to keep up with new therapies and relied on colleagues and friends within the profession for help and advice. This article examines the reanalyses' judgment calls concerning the use of a psychophysics power function, the employment of a time-sensitive model, the imputation and exclusion of data, and the addition of new variables. Given the radical undecidability of numerical evidence in the absence of context, the reanalysis of stand-alone data is likely to produce a continuing series of conflicting results.
(Mis)Using Numbers in the Enron Story
Authors: Boje David M. , Gardner Carolyn L. , Smith William L.
Published: October 2006

This article investigates the numeric construction, rhetorical moves, and metatheatre (defined as multiple stages for performing organization stories) pertaining to the widely publicized failure of Enron Corporation. The authors thus examine how statistics in financial reports and executive metatheatric presentations were used to persuade Wall Street experts to recommend Enron stock, when the writing was on the fourth wall. The authors' contribution to ethnostatistics is fourfold. First, they show that financial reports and discourse are a suitable and important topic for ethnostatistical analysis. Second, they extend ethnostatistics beyond how academic professionals tell stories with numbers, to how professional practitioners in organizations tell such stories. Third, they show the important role the rhetorical construction of financial performance measures played in the Enron failure. And fourth, they extend ethnostatistics by integrating ethnostatistics' third moment of rhetoric with theatrical theory to show the situated and staged nature of the rhetoric of quantification.
Ethnostatistics and Sensemaking
Authors: Mills Jean Helms , Weatherbee Terrance G. , Colwell Scott R.
Published: October 2006

This article combines ethnostatistics with Weick's sensemaking framework to explore how and why Canadian business schools and universities use comparative rankings and performance measures to signal to audiences about selected features and characteristics of their institutions. These quantitative performance-based strategies include seeking accreditation from the Association to Advance Collegiate Schools of Business and the use of data produced by Maclean's annual university rankings and other performance benchmarks—to position and validate themselves in their academic fields. Specifically, the authors deconstruct the production, meaning, and rhetoric used by business schools and universities when they draw on accreditation and rankings in the processes of socially constructing a sense of academic standing that is used to project a plausible image to both external and internal audiences.
Statistics as Fetishes
Authors: Carlon Donna M. , Downs Alexis A. , Wert-Gray Stacia
Published: October 2006

Research into compensation management continues to draw attention from scholars in many organizational disciplines ranging from accounting and finance to human resources and strategic management. Scholars search for empirical links between various compensation strategies and improved performance. A prime example is the institutionalization of executive compensation contracts that theoretically, at least, should reward executives on the basis of their firms' financial performance. Yet scholars are finding inconsistent evidence of any links. The authors suggest that an ethnostatistical analysis of these studies will yield one consistent finding: obsession with the value of rational data as the “truth” about organizational practices. This reliance on quantitative measures has become an organizational fetish. In this article, the authors explain how compensation strategies have become fetishes and then use semiotics and ethnostatistics to explore the fetish nature of compensation contracts that award annual salaries and bonuses based on various price and earnings measures of organizational performance.
XRate: a fast prototyping, training and annotation tool for phylo-grammars
Authors: Klosterman Peter S , Uzilov Andrew V , Bendaña Yuri R , Bradley Robert K , Chao Sharon , Kosiol Carolin , Goldman Nick , Holmes Ian
Published: October 2006

Background

Recent years have seen the emergence of genome annotation methods based on thephylo-grammar, a probabilistic model combining continuous-time Markov chains and stochastic grammars. Previously, phylo-grammars have required considerable effort to implement, limiting their adoption by computational biologists.

Results

We have developed an open source software tool, xrate, for working with reversible, irreversible or parametric substitution models combined with stochastic context-free grammars. xrate efficiently estimates maximum-likelihood parameters and phylogenetic trees using a novel "phylo-EM" algorithm that we describe. The grammar is specified in an external configuration file, allowing users to design new grammars, estimate rate parameters from training data and annotate multiple sequence alignments without the need to recompile code from source. We have used xrate to measure codon substitution rates and predict protein and RNA secondary structures.

Conclusion

Our results demonstrate that xrate estimates biologically meaningful rates and makes predictions whose accuracy is comparable to that of more specialized tools.
Construction of a multiple fluorescence labelling system for use in co-invasion studies of Listeria monocytogenes
Authors: Andersen Jens B , Roldgaard Bent B , Lindner Ariel B , Christensen Bjarke B , Licht Tine R
Published: October 2006

Background

Existing virulence models are often difficult to apply for quantitative comparison of invasion potentials of Listeria monocytogenes. Well-to-well variation between cell-line based in vitro assays is practically unavoidable, and variation between individual animals is the cause of large deviations in the observed capacity for infection when animal models are used.

One way to circumvent this problem is to carry out virulence studies as competition assays between 2 or more strains. This, however, requires invasion-neutral markers that enable easy discrimination between the different strains.

Results

A fluorescent marker system, allowing visualization and identification of single L. monocytogenes cells as well as colonies in a non-destructive manner, was developed. Five different fluorescent labels are available, and allowed simultaneous visual discrimination between three differently labelled strains at the single cell level by use of fluorescence microscopy. More than 90% of the L. monocytogenes host cells maintained the fluorescence tags for 40 generations.

The fluorescence tags did not alter the invasive capacity of the L. monocytogenes cells in a traditional Caco-2 cell invasion assay, and visual discrimination between invaded bacteria carrying different fluorescent labels inside the cells was possible.

Conclusion

The constructed fluorescent marker system is stable, easy to use, does not affect the virulence of L. monocytogenes in Caco-2 cell assays, and allows discrimination between differently labelled bacteria after internalization in these cells.
High-resolution analysis of HLA class I alterations in colorectal cancer
Authors: Dierssen Jan Willem F , de Miranda Noel FCC , Mulder Arend , van Puijenbroek Marjo , Verduyn Willem , Claas Frans HJ , van de Velde Cornelis JH , Jan Fleuren Gert , Cornelisse Cees J , Corver Willem E , Morreau Hans
Published: October 2006

Background

Previous studies indicate that alterations in Human Leukocyte Antigen (HLA) class I expression are frequent in colorectal tumors. This would suggest serious limitations for immunotherapy-based strategies involving T-cell recognition. Distinct patterns of HLA surface expression might conceal different immune escape mechanisms employed by the tumors and are worth further study.

Method

We applied four-color multiparameter flow cytometry (FCM), using a large panel of alloantigen-specific anti-HLA-A and -B monoclonal antibodies, to study membranous expression of individual HLA alleles in freshly isolated colorectal cancer cell suspensions from 21 patients.

Results

Alterations in HLA class I phenotype were observed in 8 (38%) of the 21 tumors and comprised loss of a single A or B alleles in 4 cases, and loss of all four A and B alleles in the other 4 cases. Seven of these 8 tumors were located on the right side of the colon, and those showing loss of both HLA-A and -B membranous expression were all of the MSI-H phenotype.

Conclusion

FCM allows the discrimination of complex phenotypes related to the expression of HLA class I. The different patterns of HLA class I expression might underlie different tumor behavior and influence the success rate of immunotherapy.