bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway
Authors: Dahlbäck Björn , Villoutreix Bruno O.
Published: April 2005

The protein C system provides important control of blood coagulation by regulating the activities of factor VIIIa (FVIIIa) and factor Va (FVa), cofactors in the activation of factor X and prothrombin, respectively. The system comprises membrane-bound and circulating proteins that assemble into multi-molecular complexes on cell surfaces. Vitamin K-dependent protein C, the key component of the system, circulates in blood as zymogen to an anticoagulant serine protease. It is efficiently activated on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial protein C receptor (EPCR) further stimulates the protein C activation. Activated protein C (APC) together with its cofactor protein S inhibits coagulation by degrading FVIIIa and FVa on the surface of negatively charged phospholipid membranes. Efficient FVIIIa degradation by APC requires not only protein S but also intact FV, which like thrombin is a Janus-faced protein with both procoagulant and anticoagulant potential. In addition to its anticoagulant properties, APC has antiinflammatory and antiapoptotic functions, which are exerted when APC binds to EPCR and proteolytic cleaves protease-activated receptor 1 (PAR-1). The protein C system is physiologically important, and genetic defects affecting the system are the most common risk factors of venous thrombosis. The proteins of the protein C system are composed of multiple domains and the 3-dimensional structures of several of the proteins are known. The molecular recognition of the protein C system is progressively being unraveled, giving us new insights into this fascinating and intricate molecular scenario at the atomic level.
Signal Transducer and Activator of Transcription 3α and Specificity Protein 1 Interact to Upregulate Intercellular Adhesion Molecule-1 in Ischemic–Reperfused Myocardium and Vascular Endothelium
Authors: Yang Xiao Ping , Irani Kaikobad , Mattagajasingh Subhendra , DiPaula Anthony , Khanday Firdous , Ozaki Michitaka , Fox-Talbot Karen , Baldwin William M. , Becker Lewis C.
Published: April 2005

Objective—

Intercellular adhesion molecule-1 (ICAM-1) is upregulated rapidly on endothelial cells during ischemia–reperfusion (I-R) and mediates tissue leukocyte accumulation. The ICAM-1 proximal promoter contains a signal transducer and activator of transcription (Stat) binding motif (gamma-interferon activation site [GAS] sequence), which flanks a specificity protein 1 (Sp1) binding site. We examined the roles of Stat and Sp1 in the regulation of ICAM-1 after myocardial I-R.

Methods and Results—

Open-chest anesthetized rats underwent coronary artery occlusion for 35 minutes and reperfusion for 0 to 240 minutes. Stat became activated within 15 minutes after reperfusion, primarily in vascular endothelial cells; the activated Stat protein was identified as Stat3 (α-isoform). After phosphorylation on serine 727 (p-S727), Stat3α was found in association with the transcriptional regulator Sp1, and the complex bound to an ICAM-1–GAS probe. ICAM-1 expression increased after I-R and lagged shortly behind Stat3α activation. In cultured human umbilical vein endothelial (HUVE) cells, activation of Stat3α after hypoxia–reoxygenation (H-R) was dependent on the small GTPase Rac1. Transfection of a dominant-negative Stat3 (Y705F) adenovirus or a GAS decoy oligonucleotide reduced ICAM-1 mRNA expression after H-R. Using a reporter gene transfected into HUVE cells, mutation of the GAS element in the ICAM-1 promoter resulted in reduced transcriptional activity after H-R. Sp1 coimmunoprecipitated with p-S727 Stat3 during H-R, and Sp1 or Stat3α interfering RNA markedly reduced ICAM-1 mRNA expression.

Conclusion—

The Sp1–Stat3 complex appears to play an important role in the upregulation of ICAM-1 transcription after reoxygenation or reperfusion.
Cardiac Overexpression of Melusin Protects From Dilated Cardiomyopathy Due to Long-Standing Pressure Overload
Authors: De Acetis Marika , Notte Antonella , Accornero Federica , Selvetella Giulio , Brancaccio Mara , Vecchione Carmine , Sbroggiò Mauro , Collino Federica , Pacchioni Beniamina , Lanfranchi Gerolamo , Aretini Alessandra , Ferretti Roberta , Maffei Angelo , Altruda Fiorella , Silengo Lorenzo , Tarone Guido , Lembo Giuseppe
Published: April 2005

We have previously shown that genetic ablation of melusin, a muscle specific β 1 integrin interacting protein, accelerates left ventricle (LV) dilation and heart failure in response to pressure overload. Here we show that melusin expression was increased during compensated cardiac hypertrophy in mice subjected to 1 week pressure overload, but returned to basal levels in LV that have undergone dilation after 12 weeks of pressure overload. To better understand the role of melusin in cardiac remodeling, we overexpressed melusin in heart of transgenic mice. Echocardiography analysis indicated that melusin over-expression induced a mild cardiac hypertrophy in basal conditions (30% increase in interventricular septum thickness) with no obvious structural and functional alterations. After prolonged pressure overload (12 weeks), melusin overexpressing hearts underwent further hypertrophy retaining concentric LV remodeling and full contractile function, whereas wild-type LV showed pronounced chamber dilation with an impaired contractility. Analysis of signaling pathways indicated that melusin overexpression induced increased basal phosphorylation of GSK3β and ERK1/2. Moreover, AKT, GSK3β and ERK1/2 were hyper-phosphorylated on pressure overload in melusin overexpressing compared with wild-type mice. In addition, after 12 weeks of pressure overload LV of melusin overexpressing mice showed a very low level of cardiomyocyte apoptosis and stromal tissue deposition, as well as increased capillary density compared with wild-type. These results demonstrate that melusin overexpression allows prolonged concentric compensatory hypertrophy and protects against the transition toward cardiac dilation and failure in response to long-standing pressure overload.
Angiotensin II Enhances Interleukin-18 Mediated Inflammatory Gene Expression in Vascular Smooth Muscle Cells
Authors: Sahar Saurabh , Dwarakanath Roopashree S. , Reddy Marpadga A. , Lanting Linda , Todorov Ivan , Natarajan Rama
Published: April 2005

Vascular smooth muscle cells (VSMCs) express functional interleukin-18 receptors (IL-18Rs), composed of α and β subunits. These subunits are elevated in VSMCs of atherosclerotic plaques and can be induced by inflammatory agents in cultured VSMC. Because both IL-18 and Angiotensin II (Ang II) are implicated in atherosclerosis, our objective was to analyze the role of IL-18 signaling and potential cross-talk with Ang II in VSMC. We observed that IL-18 activated Src kinase, protein kinase C, p38 and JNK MAPKs, Akt kinase, transcription factors NF-kB and AP-1, and induced expression of pro-inflammatory cytokines in VSMC. Pretreatment of VSMC with Ang II enhanced IL-18-induced NF-kB activation and cytokine gene expression. Interestingly, Ang II directly increased mRNA and cell surface protein levels of the IL-18Rα subunit. Functional relevance in an organ culture model was demonstrated by the observation that incubation of intact mouse aortas ex vivo with Ang II also significantly increased IL-18Rα expression. Furthermore, Ang II significantly stimulated transcription from a minimal IL-18Rα promoter containing putative binding sites for STAT and AP-1. Ang II also increased in vivo recruitment of STAT-3 on the IL-18Rα promoter. Finally, dominant negative STAT-3 mutant blocked Ang II-induced IL-18Rα promoter activation in CHO cells overexpressing AT1a receptor and IL-18Rα mRNA expression in HVSMC. Thus, Ang II enhances IL-18 induced inflammatory genes by increasing IL-18Rα expression. These results illustrate a novel mechanism wherein Ang II- mediated increases in inflammatory genes and proatherogenic effects in the vasculature are enhanced by a vicious loop and cross-talk with the IL-18 signaling pathway.
fMRI Evidence for the Role of Recollection in Suppressing Misattribution Errors: The Illusory Truth Effect
Authors: Mitchell Jason P. , Dodson Chad S. , Schacter Daniel L.
Published: April 2005

Misattribution refers to the act of attributing a memory or idea to an incorrect source, such as successfully remembering a bit of information but linking it to an inappropriate person or time [Jacoby, L. L., Kelley, C., Brown, J., & Jasechko, J. (1989). Becoming famous overnight: Limits on the ability to avoid unconscious influences of the past. Journal of Personality and Social Psychology, 56, 326–338; Schacter, D. L. (1999). The seven sins of memory: Insights from psychology and cognitive neuroscience. American Psychologist, 54, 182–203; Schacter, D. L. (2001). The seven sins of memory: How the mind forgets and remembers. Boston: Houghton Mifflin]. Cognitive studies have suggested that misattribution errors may occur in the absence of recollection for the details of an initial encounter with a stimulus, but little is known about the neural basis of this memory phenomenon. Here we used functional magnetic resonance imaging (fMRI) to examine the hypothesized role of recollection in counteracting the illusory truth effect, a misattribution error whereby perceivers systematically overrate the truth of previously presented information. Imaging was conducted during the encoding and subsequent judgment of unfamiliar statements that were presented as true or false. Event-related fMRI analyses were conditionalized as a function of subsequent performance. Results demonstrated that encoding activation in regions previously associated with successful recollection—including the hippocampus and the ventrolateral prefrontal cortex (PFC)—correlated with the successful avoidance of misattribution errors, providing initial neuroimaging support for earlier cognitive accounts of misattribution.
Hearing Two Things at Once: Neurophysiological Indices of Speech Segregation and Identification
Authors: Alain Claude , Reinke Karen , He Yu , Wang Chenghua , Lobaugh Nancy
Published: April 2005

The discrimination of concurrent sounds is paramount to speech perception. During social gatherings, listeners must extract information from a composite acoustic wave, which sums multiple individual voices that are simultaneously active. The observers' ability to identify two simultaneously presented vowels improves with increasing separation between the fundamental frequencies (f 0) of the two vowels. Event-related potentials to stimuli presented during attend and ignore conditions revealed activity between 130 and 170 msec after sound onset that reflected the f 0 differences between the two vowels. Another, more posterior and right-lateralized, negative wave maximal at 250 msec, and a central-parietal slow negativity were observed only during vowel identification and may index stimulus categorization. This sequence of neural events supports a multistage model of auditory scene analysis in which the spectral pattern of each vowel constituent is automatically extracted and then matched against representations of those vowels in working memory.
On-line Processing of “Pop-Out” Words in Spoken French Dialogues
Authors: Magne Cyrille , Astésano Corine , Lacheret-Dujour Anne , Morel Michel , Alter Kai , Besson Mireille
Published: April 2005

Highlighting relevant information in a discourse context is a major aim of spoken language communication. Prosodic cues such as focal prominences are used to fulfill this aim through the pragmatic function of prosody. To determine whether listeners make on-line use of focal prominences to build coherent representations of the informational structure of the utterances, we used the brain event-related potential (ERP) method. Short dialogues composed of a question and an answer were presented auditorily. The design of the experiment allowed us to examine precisely the time course of the processing of prosodic patterns of sentence-medial or -final words in the answer. These patterns were either congruous or incongruous with regard to the pragmatic context introduced by the question. Furthermore, the ERP effects were compared for words with or without focal prominences. Results showed that pragmatically congruous and incongruous prosodic patterns elicit clear differences in the ERPs, which were largely modulated in latency and polarity by their position within the answer. By showing that prosodic patterns are processed on-line by listeners in order to understand the informational structure of the message, the present results demonstrate the psychobiological validity of the pragmatic concept of focus, expressed via prosodic cues. Moreover, the functional significance of the positive-going effects found sentence medially and negative-going effects found sentence finally is discussed. Whereas the former may reflect the processing of surprising and task-relevant prosodic patterns, the latter may reflect the integration problems encountered in extracting the overall informational structure of the sentence.
The Inferior Temporal Lobe Mediates Distracter-Resistant Visual Search of Patients with Spatial Neglect
Authors: Ptak Radek , Valenza Nathalie
Published: April 2005

Although impaired visual search is a core deficit of patients with spatial neglect, current evidence is not conclusive about the mechanisms underlying this failure. We present evidence from 14 neglect patients searching for a target defined by two perceptual features that visual search is mediated by mechanisms of attentional competition. Participants were tested in three search conditions with constant target and distracter positions: Distracters did not share any feature with the target; distracters shared one feature with the target; two distracters shared one feature and one distracter shared the other feature with the target (mixed condition). Whereas search performance of healthy participants was comparable across conditions, neglect patients had a significant contralesional slowing in the mixed condition compared with the other two conditions. A detailed lesion analysis revealed that involvement of the parietal lobe did not predict the degree of distractibility in visual search. In contrast, neglect patients with high distractibility had more frequent damage to the inferior temporal lobe, suggesting a preliminary role of this region for competitive attentional processes involved in visual search of spatial neglect patients.
The Role of VMPC in Metamemorial Judgments of Content Retrievability
Authors: Schnyer David M. , Nicholls Lindsay , Verfaellie Mieke
Published: April 2005

Making judgments about the retrievability of information is a critical part of the metamemory processes engaged during remembering. A recent study of patients with frontal lesions suggests that ventral medial prefrontal cortex (VMPC) plays a critical role in such judgments [Schnyer, D. M., Verfaellie, M., Alexander, M. P., Lafleche, G., Nicholls, L., & Kaszniak, A. W. A role for right medial prefrontal cortex in accurate feeling of knowing judgments: Evidence from patients with lesions to frontal cortex. Neuropsychologia, 42, 957–966, 2004]. The observed impairment was thought to reflect an inability to determine the accessibility of memory contents. To further examine the neuroanatomical basis of content accessibility assessment, we used fMRI in an episodic feeling-of-knowing (FOK) paradigm. Participants were asked to make trial-by-trial predictions about the retrievability of the final word that completed studied sentences and then to select the correct completion from among alternatives. Results indicated that the VMPC is engaged during accurate FOK judgments and its activation is modulated by retrieval rating. Structural equations modeling supported the notion that VMPC, as part of a broader left hemisphere network involved in memory retrieval, monitors the output of the retrieval process. More generally, VMPC may participate in metacognitive processes that allow for the comparison of available data against an internal model.
Airborne Spectral Measurements of Ocean Directional Reflectance
Authors: Gatebe Charles K. , King Michael D. , Lyapustin Alexei I. , Arnold G. Thomas , Redemann Jens
Published: April 2005

The Cloud Absorption Radiometer (CAR) was flown aboard the University of Washington Convair 580 (CV-580) research aircraft during the Chesapeake Lighthouse and Aircraft Measurements for Satellites (CLAMS) field campaign and obtained measurements of bidirectional reflectance distribution function (BRDF) of the ocean in July and August 2001 under different illumination conditions with solar zenith angles ranging from 15° to 46°. The BRDF measurements were accompanied by concurrent measurements of atmospheric aerosol optical thickness and column water vapor above the airplane. The method of spherical harmonics with Cox–Munk wave-slope distribution is used in a new algorithm developed for this study to solve the atmosphere–ocean radiative transfer problem and to remove the effects of the atmosphere from airborne measurements. The algorithm retrieves simultaneously the wind speed and full ocean BRDF (sun’s glitter and water-leaving radiance) from CAR measurements and evaluates total albedo and equivalent albedo for the water-leaving radiance outside the glitter. Results show good overall agreement with other measurements and theoretical simulations, with the anisotropy of the water-leaving radiance clearly seen. However, the water-leaving radiance does not show a strong dependence on solar zenith angle as suggested by some theoretical studies. The spectral albedo was found to vary from 4.1%–5.1% at λ = 0.472 μm to 2.4%–3.5% for λ ≥ 0.682 μm. The equivalent water-leaving albedo ranges from 1.0%–2.4% at λ = 0.472 μm to 0.1%–0.6% for λ = 0.682 μm and 0.1%–0.3% for λ = 0.870 μm. Results of the validation of the Cox–Munk model under the conditions measured show that although the model reproduces the shape of sun’s glitter on average with an accuracy of better than 30%, it underestimates the center of the sun’s glitter reflectance by about 30% for low wind speeds (<2–3 m s−1). In cases of high wind speed, the model with Gram–Charlier expansion seems to provide the best fit.
MISR Calibration and Implications for Low-Light-Level Aerosol Retrieval over Dark Water
Authors: Kahn Ralph , Li Wen-Hao , Martonchik John V. , Bruegge Carol J. , Diner David J. , Gaitley Barbara J. , Abdou Wedad , Dubovik Oleg , Holben Brent , Smirnov Alexander , Jin Zhonghai , Clark Dennis
Published: April 2005

Studying aerosols over ocean is one goal of the Multiangle Imaging Spectroradiometer (MISR) and other spaceborne imaging systems. But top-of-atmosphere equivalent reflectance typically falls in the range of 0.03 to 0.12 at midvisible wavelengths and can be below 0.01 in the near-infrared, when an optically thin aerosol layer is viewed over a dark ocean surface. Special attention must be given to radiometric calibration if aerosol optical thickness, and any information about particle microphysical properties, are to be reliably retrieved from such observations. MISR low-light-level vicarious calibration is performed in the vicinity of remote islands hosting Aerosol Robotic Network (AERONET) sun- and sky-scanning radiometers, under low aerosol loading, low wind speed, relatively cloud free conditions. MISR equivalent reflectance is compared with values calculated from a radiative transfer model constrained by coincident, AERONET-retrieved aerosol spectral optical thickness, size distribution, and single scattering albedo, along with in situ wind measurements. Where the nadir view is not in sun glint, MISR equivalent reflectance is also compared with Moderate Resolution Imaging Spectroradiometer (MODIS) reflectance. The authors push the limits of the vicarious calibration method’s accuracy, aiming to assess absolute, camera-to-camera, and band-to-band radiometry. Patterns repeated over many well-constrained cases lend confidence to the results, at a few percent accuracy, as do additional vicarious calibration tests performed with multiplatform observations taken during the Chesapeake Lighthouse and Aircraft Measurements for Satellites (CLAMS) campaign. Conclusions are strongest in the red and green bands, but are too uncertain to accept for the near-infrared. MISR nadir-view and MODIS low-light-level absolute reflectances differ by about 4% in the blue and green bands, with MISR reporting higher values. In the red, MISR agrees with MODIS band 14 to better than 2%, whereas MODIS band 1 is significantly lower. Compared to the AERONET-constrained model, the MISR aft-viewing cameras report reflectances too high by several percent in the blue, green, and possibly the red. Better agreement is found in the nadir- and the forward-viewing cameras, especially in the blue and green. When implemented on a trial basis, calibration adjustments indicated by this work remove 40% of a 0.05 bias in retrieved midvisible aerosol optical depth over dark water scenes, produced by the early postlaunch MISR algorithm. A band-to-band correction has already been made to the MISR products, and the remaining calibration adjustments, totaling no more than a few percent, are planned.
Diagnosis of Meridional Ozone Transport Based on Mass-Weighted Isentropic Zonal Means
Authors: Miyazaki Kazuyuki , Iwasaki Toshiki
Published: April 2005

A transport equation based on mass-weighted isentropic zonal means applies to the diagnosis for the meridional ozone transport in the troposphere and stratosphere. The mean and eddy ozone fluxes are estimated from the global distributions of the temperature, wind, and ozone.

In comparison with the conventional Eulerian mean and transformed Eulerian mean (TEM), the present diagnosis has advantages for the expression of eddy transport terms. The adiabatic eddy flux is separated from the diabatic eddy flux, which is parallel to the isentropic surface. The analysis shows that the eddy flux is almost adiabatic except that it is significantly affected by diabatic effects near the lower troposphere. Another advantage lies in the mean meridional transport. Although it is almost similar to the TEM, significant differences can be found near the Antarctic polar vortex due to nongeostrophic effects. Furthermore, the isentropic diagnosis expresses a strong equatorward flux near the lower boundary, while the TEM hardly does this because of inadequate treatment of the lower-boundary conditions.

The life cycle of ozone can be understood through the exact estimation of the transport terms. Although the stratospheric meridional transport is mainly performed by the Brewer–Dobson circulation, the strong poleward eddy ozone flux is caused by planetary wave breaking, especially in the winter hemisphere. In the extratropics, the ozone subsides from the stratosphere to the troposphere by mean downward motions, mainly diffused to the lower latitudes probably due to strong baroclinic waves and effectively lost through chemical processes in the lower troposphere.
EOS Terra Aerosol and Radiative Flux Validation: An Overview of the Chesapeake Lighthouse and Aircraft Measurements for Satellites (CLAMS) Experiment
Authors: Smith W. L. , Charlock T. P. , Kahn R. , Martins J. V. , Remer L. A. , Hobbs P. V. , Redemann J. , Rutledge C. K.
Published: April 2005

NASA developed an Earth Observing System (EOS) to study global change and reduce uncertainties associated with aerosols and other key parameters controlling climate. The first EOS satellite, Terra, was launched in December 1999. The Chesapeake Lighthouse and Aircraft Measurements for Satellites (CLAMS) field campaign was conducted from 10 July to 2 August 2001 to validate several Terra data products, including aerosol properties and radiative flux profiles derived from three complementary Terra instruments: the Clouds and the Earth’s Radiant Energy System (CERES), the Multiangle Imaging Spectroradiometer (MISR), and the Moderate Resolution Imaging Spectroradiometer (MODIS). CERES, MISR, and MODIS are being used to investigate the critical role aerosols play in modulating the radiative heat budget of the earth–atmosphere system. CLAMS’ primary objectives are to improve understanding of atmospheric aerosols, to validate and improve the satellite data products, and to test new instruments and measurement concepts. A variety of in situ sampling devices and passive remote sensing instruments were flown on six aircraft to characterize the state of the atmosphere, the composition of atmospheric aerosols, and the associated surface and atmospheric radiation parameters over the U.S. eastern seaboard. Aerosol particulate matter was measured at two ground stations established at Wallops Island, Virginia, and the Chesapeake Lighthouse, the site of an ongoing CERES Ocean Validation Experiment (COVE) where well-calibrated radiative fluxes and Aerosol Robotic Network (AERONET) aerosol properties have been measured since 1999. Nine coordinated aircraft missions and numerous additional sorties were flown under a variety of atmospheric conditions and aerosol loadings. On one “golden day” (17 July 2001), under moderately polluted conditions with midvisible optical depths near 0.5, all six aircraft flew coordinated patterns vertically stacked between 100 and 65 000 ft over the COVE site as Terra flew overhead. This overview presents a description of CLAMS objectives, measurements, and sampling strategies. Key results, reported in greater detail in the collection of papers found in this special issue, are also summarized.
Characteristics of Landfalling Tropical Cyclones in the United States and Mexico: Climatology and Interannual Variability
Authors: Larson Joshua , Zhou Yaping , Higgins R. Wayne
Published: April 2005

The climatology and interannual variability of landfalling tropical cyclones and their impacts on precipitation in the continental United States and Mexico are examined. The analysis is based on National Hurricane Center 6-hourly tropical cyclone track data for the Atlantic and eastern Pacific basins and gridded daily U.S. precipitation data for the period August–October 1950–98. Geographic maps of total tropical cyclone strike days, and the mean and maximum percentage of precipitation due to tropical cyclones, are examined by month. To make the procedures objective, it is assumed that precipitation is symmetric about the storm’s center. While this introduces some uncertainty in the analysis, sensitivity tests show that this assumption is reasonable for precipitation within 5° of the circulation center.

The relationship between landfalling tropical cyclones and two leading patterns of interannual climate variability—El Niño–Southern Oscillation (ENSO) and the Arctic Oscillation (AO)—are then examined. Relationships between tropical cyclone frequency and intensity and composites of 200-hPa geopotential height and wind shear anomalies are also examined as a function of ENSO phase and AO phase using classifications devised at the Climate Prediction Center.

The data show that tropical cyclone activity in the Atlantic basin is modulated on both seasonal and intraseasonal time scales by the AO and ENSO and that impact of the two modes of climate variability is greater together than apart. This suggests that, during La Niña conditions, atmospheric circulation is more conducive to activity in the main development region during AO-positive conditions than during AO-negative ones and that, during El Niño conditions, atmospheric circulation appears even less conducive to tropical cyclone development during the negative phase of the AO than during the positive phase.
The Effect of Regional Climate Model Domain Choice on the Simulation of Tropical Cyclone–Like Vortices in the Southwestern Indian Ocean
Authors: Landman Willem A. , Seth Anji , Camargo Suzana J.
Published: April 2005

A regional climate model is tested for several domain configurations over the southwestern Indian Ocean to examine the ability of the model to reproduce observed cyclones and their landfalling tracks. The interaction between large-scale and local terrain forcing of tropical storms approaching and transiting the island landmass of Madagascar makes the southwestern Indian Ocean a unique and interesting study area. In addition, tropical cyclones across the southern Indian Ocean are likely to be significantly affected by the large-scale zonal flow. Therefore, the effects of model domain size and the positioning of its lateral boundaries on the simulation of tropical cyclone–like vortices and their tracks on a seasonal time scale are investigated. Four tropical cyclones, which occurred over the southwestern Indian Ocean in January of the years 1995–97, are studied, and four domains are tested. The regional climate model is driven by atmospheric lateral boundary conditions that are derived from large-scale meteorological analyses. The use of analyzed boundary forcing enables comparison with observed cyclones in these tests. Simulations are performed using a 60-km horizontal resolution and for an extended time integration of about 6 weeks. Results show that the positioning of the eastern boundary of the regional model domain is of major importance in the life cycle of simulated tropical cyclone–like vortices: a vortex entering through the eastern boundary of the regional model is generally well simulated. The size of the domain also has a bearing on the ability of the regional model to simulate vortices in the Mozambique Channel, and the island landmass of Madagascar additionally influences storm tracks. These results show that the regional model can produce cyclonelike vortices and their tracks (with some deficiencies) given analyzed lateral boundary forcing. Statistical analyses of GCM-driven nested model ensemble integrations are now required to further address predictive skill of cyclones in the southwestern Indian Ocean and to test if the model can realistically simulate tropical storm genesis as opposed to advecting existing tropical disturbances entering through the model boundaries.
A Method of Detecting Change in the Ice Conditions of the Central Greenland Sea by the Whelping Locations of Harp Seals
Authors: Wilkinson J. P. , Wadhams P.
Published: April 2005

Variations in the extent of sea ice within the Greenland Sea on daily, seasonal, or longer time scales are well documented, while changes in ice conditions are not. By combining historical information on the location and timing of the hunt for the whelping harp seal (Phoca groenlandica) with the ice conditions needed for the seals to give birth, details of the types, concentration, and extent of ice within the central Greenland Sea in winter have been determined for the mid- to late nineteenth century. These in turn have been compared to ice extent and concentration from the passive microwave era, as well as ice types from field work in the region. Results suggest that the ice conditions in the central Greenland Sea in the mid- to late nineteenth century were significantly different from those witnessed in recent decades. These differences manifest themselves not only in the extent of ice, but in ice types, concentration, and longevity of the ice cover. It is hypothesized that these changes could be due to an increase in both air temperature and wave energy, which is consistent with an increase in the strength and frequency of southerly and easterly winds during winter.
Mechanism of Interdecadal Thermohaline Circulation Variability in a Coupled Ocean–Atmosphere GCM
Authors: Dong Buwen , Sutton Rowan T.
Published: April 2005

Interdecadal variability of the Atlantic thermohaline circulation (THC) is studied in the third version of the Hadley Centre global coupled atmosphere–ocean sea-ice general circulation model (HadCM3). A diagnostic approach is used to elucidate the mechanism that governs the variability and its impacts on climate. An irregular and heavily damped THC oscillation with a period around 25 yr is identified. The oscillation appears to be forced by the atmosphere but the ocean is responsible for setting the time scale. Following a minimum in the THC, the mechanism for phase reversal involves the accumulation of cold water in the subpolar gyre, leading to an acceleration of the gyre circulation and the North Atlantic Current. This acceleration increases the transport of saline waters into the regions of active deep convection, raising the upper-ocean density and leading, after adjustment, to acceleration of the THC. The atmosphere stimulates this THC variability in two ways: 1) by forcing the subpolar gyre through (North Atlantic Oscillation) NAO-related wind stress curl and heat flux anomalies; and 2) by direct forcing of the region of active deep convection, also through wind stress curl and heat flux anomalies. The latter is not closely related to the NAO. The mechanism for phase reversal has many similarities to that found in a previous study with a much lower resolution coupled model, suggesting that this mechanism may be quite robust. However the time scale, and details of the atmospheric forcing, differ.

The THC variability in HadCM3 has significant impacts on the atmosphere not just in the Atlantic region but also more widely, throughout the global Tropics. The mechanism involves modulation by the THC of the cross-equator SST gradient in the tropical Atlantic. The SST anomalies induce a displacement of the ITCZ in the Atlantic basin with knock-on effects over the other ocean basins. These findings highlight the potential importance of the Atlantic THC as a cause of interdecadal climate variability on a global scale.
Regional Climate Simulations over North America: Interaction of Local Processes with Improved Large-Scale Flow
Authors: Miguez-Macho Gonzalo , Stenchikov Georgiy L. , Robock Alan
Published: April 2005

The reasons for biases in regional climate simulations were investigated in an attempt to discern whether they arise from deficiencies in the model parameterizations or are due to dynamical problems. Using the Regional Atmospheric Modeling System (RAMS) forced by the National Centers for Environmental Prediction–National Center for Atmospheric Research reanalysis, the detailed climate over North America at 50-km resolution for June 2000 was simulated. First, the RAMS equations were modified to make them applicable to a large region, and its turbulence parameterization was corrected. The initial simulations showed large biases in the location of precipitation patterns and surface air temperatures. By implementing higher-resolution soil data, soil moisture and soil temperature initialization, and corrections to the Kain–Fritch convective scheme, the temperature biases and precipitation amount errors could be removed, but the precipitation location errors remained. The precipitation location biases could only be improved by implementing spectral nudging of the large-scale (wavelength of 2500 km) dynamics in RAMS. This corrected for circulation errors produced by interactions and reflection of the internal domain dynamics with the lateral boundaries where the model was forced by the reanalysis.
The Ghost of Wittgenstein
Authors: Lynch William T.
Published: April 2005

In developing an “internal” sociology of science, the sociology of scientific knowledge drew on Wittgenstein’s later philosophy to reinterpret traditional epistemological topics in sociological terms. By construing scientific reasoning as rule following within a collective, sociologists David Bloor and Harry Collins effectively blocked outside criticism of a scientific field, whether scientific, philosophical, or political. Ethnomethodologist Michael Lynch developed an alternative, Wittgensteinian reading that similarly blocked philosophical or political critique, while also disallowing analytical appeals to historical or institutional contexts. I criticize these Wittgensteinian sociologies and argue for the historical and contemporary significance of methodological criticisms of scientific practice that conjoin epistemological and political categories. I consider two such cases briefly: the Baconian criticism of Scholastic science in the early Royal Society and the criticism of AIDS drug testing protocols by activists.
Book Review: On Interpretive Social Inquiry
Authors: Schatzki Theodore
Published: April 2005

This essay addresses various issues about interpretive social investigation that arise in recent books by Berel Lerner and by Mark Risjord. The general topics considered are the relation between interpretation and explanation, the explanation of action, and alternative rationalities. Part 1 centers on Risjord’s attempt to draw interpretation into the explanatory enterprise, among other things pointing out the limiting assumptions of his account and asking whether social investigation has epistemologically significant practical ends. Part 2 addresses the roles of normativity and rationality in explanations of action, taking up (1) a disagreement between Risjord and David Henderson on normativity, and (2) Lerner’s account of Winch’s appropriation of Wittgenstein’s idea of expressive action. Part 3, finally, endorses Lerner’s and Risjord’s version of the claim that rationality has multiple criteria while also suggesting that intelligibility, not rationality, lies at the heart of many debates on interpretive social science.
Rethinking Practices and Structures
Authors: Berard T. J.
Published: April 2005

Social theory remains puzzled by the relation between practices and structures, or the link between ‘micro’ and ‘macro’. Grand theorists including Giddens and Bourdieu have gained distinction for their writings on these questions, trying to marry insights and concerns of a ‘micro’ sociological nature with traditional ‘macro’ structural questions including inequality, power relations, and social reproduction. These theorists arguably fail, however, in their attempts to move social theory beyond traditional dualisms. Relevant but neglected contributions from ethnomethodology are introduced and compared to the work of Giddens and Bourdieu in an attempt to identify and outline an approach to practices and structures that more reliably avoids problems of dualism and reification, and at the same time offers an understanding of structures and their relations to practices that can be much more closely grounded in empirical studies.
How Much Decentralization?
Authors: Lonti Zsuzsanna
Published: April 2005

This article examines the extent of managerial autonomy middle managers in Canadian governments report in financial and human resources management areas. It analyzes whether during a period of intense government restructuring middle managers’ autonomy has increased or not and whether there are any environmental or structural factors that could explain the variation in the extent of managerial autonomy reported by them. Managers reported the most autonomy regarding quality and client consultation issues and relatively high levels of autonomy for performance management, training and development, and staffing decisions. The extent of perceived managerial autonomy was found to be statistically significantly related to being a manager of a work unit in the periphery, managing a small unit, leading a corporate unit, and having greater emphasis on results.
Factors Affecting State Government Information Technology Employee Turnover Intentions
Authors: Kim Soonhee
Published: April 2005

Electronic government expansion is creating the complex challenges of managing an effective information technology (IT) workforce in the public sector. Survey questionnaires were sent to IT employees working in the central IT departments of two state governments to analyze how job characteristics, work environment, and human resource management practices influence their turnover intentions. Results show that work exhaustion, an emphasis on participatory management, and opportunities for advancement were statistically significant variables affecting state government IT employee turnover intentions, and that salary satisfaction was not a statistically significant factor. Suggestions are offered for improving IT employee retention rates in government agencies.
Red Tape and Public Service Motivation
Authors: Scott Patrick G. , Pandey Sanjay K.
Published: April 2005

This article examines the relationship between red tape and public-service motivation. Using a recent national survey of public managers in various state health and human service organizations, the authors examine whether perceptions of red tape are determined by differences in the level of public-service motivation. Across a variety of dependent measures, the results showed a consistent linkage between managerial perceptions of red tape and public-service motivation. Managers reporting higher levels of public-service motivation were less likely to perceive high levels of red tape. Among the dimensions of public-service motivation, attraction to public policy making provided the greatest influence on perceptions of red tape.
MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients
Authors: Wood John C. , Enriquez Cathleen , Ghugre Nilesh , Tyzka J. Michael , Carson Susan , Nelson Marvin D. , Coates Thomas D.
Published: April 2005

Measurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2* (1/T2*) measured by magnetic resonance imaging (MRI) have different advantages for HIC estimation. This article compares noninvasive iron estimates using both optimized R2 and R2* methods in 102 patients with iron overload and 13 controls. In the iron-overloaded group, 22 patients had concurrent liver biopsy. R2 and R2* correlated closely with HIC (r2 ≥ .95) for HICs between 1.33 and 32.9 mg/g, but R2 had a curvilinear relationship to HIC. Of importance, the R2 calibration curve was similar to the curve generated by other researchers, despite significant differences in technique and instrumentation. Combined R2 and R2* measurements did not yield more accurate results than either alone. Both R2 and R2* can accurately measure hepatic iron concentration throughout the clinically relevant range of HIC with appropriate MRI acquisition techniques. (Blood. 2005;106:1460-1465)
Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells
Authors: Law Helen K. W. , Cheung Chung Yan , Ng Hoi Yee , Sia Sin Fun , Chan Yuk On , Luk Winsie , Nicholls John M. , Peiris J. S. Malik , Lau Yu Lung
Published: April 2005

Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV–infected DCs. The SARS-CoV–infected DCs showed low expression of antiviral cytokines (interferon α [IFN-α], IFN-β, IFN-γ, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor α [TNF-α] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1α [MIP-1α], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.
Infection of human CD34+ progenitor cells with Bartonella henselae results in intraerythrocytic presence of B henselae
Authors: Mändle Tanja , Einsele Hermann , Schaller Martin , Neumann Diana , Vogel Wichard , Autenrieth Ingo B. , Kempf Volkhard A. J.
Published: April 2005

Although there is evidence that endothelial cells are important targets for human pathogenic Bartonella species, the primary niche of infection is unknown. Here we elucidated whether human CD34+ hematopoietic progenitor cells (HPCs) internalize B henselae and may serve as a potential niche of the pathogen. We showed that B henselae does not adhere to or invade human erythrocytes. In contrast, B henselae invades and persists in HPCs as shown by gentamicin protection assays, confocal laser scanning microscopy (CLSM), and electron microscopy (EM). Fluorescence-activated cell sorting (FACS) analysis of glycophorin A expression revealed that erythroid differentiation of HPCs was unaffected following infection with B henselae. The number of intracellular B henselae continuously increased over a 13-day period. When HPCs were infected with B henselae immediately after isolation, intracellular bacteria were subsequently detectable in differentiated erythroid cells on day 9 and day 13 after infection, as shown by CLSM, EM, and FACS analysis. Our data provide, for the first time, evidence that a bacterial pathogen is able to infect and persist in differentiating HPCs, and suggest that HPCs might serve as a potential primary niche in Bartonella infections.
[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome
Authors: Haioun Corinne , Itti Emmanuel , Rahmouni Alain , Brice Pauline , Rain Jean-Didier , Belhadj Karim , Gaulard Philippe , Garderet Laurent , Lepage Eric , Reyes Felix , Meignan Michel
Published: April 2005

Assessment of early therapeutic response using metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma. Between January 2000 and January 2004, 90 patients with newly diagnosed aggressive lymphoma (median age 53 years, 94% diffuse large B-cell) were prospectively explored with [18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) prior to induction chemotherapy, after 2 cycles (“early PET”), and after induction completion. Therapeutic response was evaluated using conventional diagnostic methods at 4 cycles. Induction treatment with an anthracycline-containing regimen was administered to all patients, associated with rituximab in 41%. According to the International Prognostic Index (IPI), 37 patients and 53 patients belonged to the lower- and higher-risk groups, respectively. At midinduction, “early PET” was considered negative in 54 patients and positive in 36. After completion of induction, 83% of PET-negative patients achieved complete remission compared with only 58% of PET-positive patients. Outcome differed significantly between PET-negative and PET-positive groups; the 2-year estimates of event-free survival reached 82% and 43%, respectively (P < .001), and the 2-year estimates of overall survival reached 90% and 61%, respectively (P = .006). Predictive value of “early PET” was observed in both the lower-risk and higher-risk groups, indicating prognostic independence from the IPI. Therefore, FDG-PET should be an early guide to first-line strategies in aggressive lymphoma. (Blood. 2005;106:1376-1381)