bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adequacy of Observing Systems in Monitoring the Atlantic Meridional Overturning Circulation and North Atlantic Climate
Authors: Zhang S. , Rosati A. , Delworth T. 
Published: May 2010

Abstract
The Atlantic meridional overturning circulation (AMOC) has an important influence on climate, and yet adequate observations of this circulation are lacking. Here, the authors assess the adequacy of past and current widely deployed routine observing systems for monitoring the AMOC and associated North Atlantic climate. To do so, this study draws on two independent simulations of the twentieth century using an Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) coupled climate model. One simulation is treated as “truth” and is sampled according to the observing system being evaluated. The authors then assimilate these synthetic “observations” into the second simulation within a fully coupled system that instantaneously exchanges information among all coupled components and produces a nearly balanced and coherent estimate for global climate states including the North Atlantic climate system. The degree to which the assimilation recovers the truth is an assessment of the adequacy of the observing system being evaluated. As the coupled system responds to the constraint of the atmosphere or ocean, the assessment of the recovery for climate quantities such as Labrador Sea Water (LSW) and the North Atlantic Oscillation increases the understanding of the factors that determine AMOC variability. For example, the low-frequency sea surface forcings provided by the atmospheric and sea surface temperature observations are found to excite a LSW variation that governs the long-time-scale variability of the AMOC. When the most complete modern observing system, consisting of atmospheric winds and temperature, is used along with Argo ocean temperature and salinity down to 2000 m, a skill estimate of AMOC reconstruction is 90% (out of 100% maximum). Similarly encouraging results hold for other quantities, such as the LSW. The past XBT observing system, in which deep-ocean temperature and salinity were not available, has a lesser ability to recover the truth AMOC (the skill is reduced to 52%). While these results raise concerns about the ability to properly characterize past variations of the AMOC, they also hold promise for future monitoring of the AMOC and for initializing prediction models.
Dynamics of Downwelling in an Eddy-Resolving Convective Basin
Authors: Spall Michael A. 
Published: May 2010

Abstract
The mean downwelling in an eddy-resolving model of a convective basin is concentrated near the boundary where eddies are shed from the cyclonic boundary current into the interior. It is suggested that the buoyancy-forced downwelling in the Labrador Sea and the Lofoten Basin is similarly concentrated in analogous eddy formation regions along their eastern boundaries. Use of a transformed Eulerian mean depiction of the density transport reveals the central role eddy fluxes play in maintaining the adiabatic nature of the flow in a nonperiodic region where heat is lost from the boundary current. The vorticity balance in the downwelling region is primarily between stretching of planetary vorticity and eddy flux divergence of relative vorticity, although a narrow viscous boundary layer is ultimately important in closing the regional vorticity budget. This overall balance is similar in some ways to the diffusive–viscous balance represented in previous boundary layer theories, and suggests that the downwelling in convective basins may be properly represented in low-resolution climate models if eddy flux parameterizations are adiabatic, identify localized regions of eddy formations, and allow density to be transported far from the region of eddy formations.
An Inflated Ensemble Filter for Ocean Data Assimilation with a Biased Coupled GCM
Authors: Zhang S. , Rosati A. 
Published: May 2010

Abstract
A “biased twin” experiment using two coupled general circulation models (CGCMs) that are biased with respect to each other is used to study the impact of deep ocean bias on ensemble ocean data assimilation. The “observations” drawn from one CGCM based on the Argo network are assimilated into the other. Traditional ensemble filtering can successfully recover the upper-ocean temperature and salinity of the target model but it usually fails to converge in the deep ocean where the model bias is large compared to the ocean’s intrinsic variability. The inconsistency between the well-constrained upper ocean and poorly constrained deep ocean generates spurious assimilation currents. An adaptively inflated ensemble filter is designed to enhance the consistency of upper- and deep-ocean adjustments, based on “climatological” standard deviations being adaptively updated by observations. The new algorithm reduces deep-ocean errors greatly, in particular, reducing current errors up to 70% and vertical motion errors up to 50%. Specifically, the tropical circulation is greatly improved with a better representation of the undercurrent, upwelling, and Western Boundary Current systems. The structure of the subtropical gyre is also substantially improved. Consequently, the new algorithm leads to better estimates of important global hydrographic features such as global overturning and pycnocline depth. Based on these improved estimates, decadal trends of basin-scale heat content and salinity as well as the seasonal–interannual variability of the tropical ocean are constructed coherently. Interestingly, the Indian Ocean (especially the north Indian Ocean), which is associated with stronger atmospheric feedbacks, is the most sensitive basin to the covariance formulation used in the assimilation. Also, while reconstruction of the local thermohaline structure plays a leading-order role in estimating the decadal trend of the Atlantic meridional overturning circulation (AMOC), more accurate estimates of the AMOC variability require coupled assimilation to produce coherently improved external forcings as well as internal heat and salt transport.
Assessing Advances in the Assimilation of Radar Data and Other Mesoscale Observations within a Collaborative Forecasting–Research Environment
Authors: Kain John S. , Xue Ming , Coniglio Michael C. , Weiss Steven J. , Kong Fanyou , Jensen Tara L. , Brown Barbara G. , Gao Jidong , Brewster Keith , Thomas Kevin W. , Wang Yunheng , Schwartz Craig S. , Levit Jason J. 
Published: May 2010

Abstract
The impacts of assimilating radar data and other mesoscale observations in real-time, convection-allowing model forecasts were evaluated during the spring seasons of 2008 and 2009 as part of the Hazardous Weather Test Bed Spring Experiment activities. In tests of a prototype continental U.S.-scale forecast system, focusing primarily on regions with active deep convection at the initial time, assimilation of these observations had a positive impact. Daily interrogation of output by teams of modelers, forecasters, and verification experts provided additional insights into the value-added characteristics of the unique assimilation forecasts. This evaluation revealed that the positive effects of the assimilation were greatest during the first 3–6 h of each forecast, appeared to be most pronounced with larger convective systems, and may have been related to a phase lag that sometimes developed when the convective-scale information was not assimilated. These preliminary results are currently being evaluated further using advanced objective verification techniques.
Are Barriers to Physical Activity Similar for Adults With and Without Abnormal Glucose Metabolism?
Authors: Hume Clare , Dunstan David , Salmon Jo , Healy Genevieve , Andrianopoulos Nick , Owen Neville 
Published: May 2010

Purpose The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. Methods The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged ≥25 years. AGM was identified through an oral glucose tolerance test. The previous week’s physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Results Of the 7088 participants (47.5 ± 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P < .001). Key barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Conclusions Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.
The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche
Authors: Visigalli Ilaria , Ungari Silvia , Martino Sabata , Park Hyejung , Cesani Martina , Gentner Bernhard , Sergi Sergi Lucia , Orlacchio Aldo , Naldini Luigi , Biffi Alessandra 
Published: May 2010

Abstract
The balance between survival and death in many cell types is regulated by small changes in the intracellular content of bioactive sphingolipids. Enzymes that either produce or degrade these sphingolipids control this equilibrium. The findings here described indicate that the lysosomal galactocerebrosidase (GALC) enzyme, defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell (HSPC) niche by contributing to the control of the intracellular content of key sphingolipids. Indeed, we show that both insufficient and supraphysiologic GALC activity—by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model—induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect HSPC survival and function and the functionality of the stem cell niche. Therefore, GALC and, possibly, other enzymes for the maintenance of niche functionality and health tightly control the concentration of these sphingolipids within HSPCs.
GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice
Authors: Chang Jungshan , Patton John T. , Sarkar Arun , Ernst Beat , Magnani John L. , Frenette Paul S. 
Published: May 2010

Abstract
Leukocyte adhesion in the microvasculature influences blood rheology and plays a key role in vaso-occlusive manifestations of sickle cell disease. Notably, polymorphonuclear neutrophils (PMNs) can capture circulating sickle red blood cells (sRBCs) in inflamed venules, leading to critical reduction in blood flow and vaso-occlusion. Recent studies have suggested that E-selectin expression by endothelial cells plays a key role by sending activating signals that lead to the activation of Mac-1 at the leading edge of PMNs, thereby allowing RBC capture. Thus, the inhibition of E-selectin may represent a valuable target in this disease. Here, we have tested the biologic properties of a novel synthetic pan-selectin inhibitor, GMI-1070, with in vitro assays and in a humanized model of sickle cell vaso-occlusion analyzed by intravital microscopy. We have found that GMI-1070 predominantly inhibited E-selectin–mediated adhesion and dramatically inhibited sRBC-leukocyte interactions, leading to improved microcirculatory blood flow and improved survival. These results suggest that GMI-1070 may represent a valuable novel therapeutic intervention for acute sickle cell crises that should be further evaluated in a clinical trial.
Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study
Authors: Gratama Jan W. , Boeckh Michael , Nakamura Ryotaro , Cornelissen Jan J. , Brooimans Rik A. , Zaia John A. , Forman Stephen J. , Gaal Karl , Bray Kurtis R. , Gasior Gail H. , Boyce Christopher S. , Sullivan Linda A. , Southwick Paula C. 
Published: May 2010

Abstract
Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation. Major HLA types were included (A*0101, A*0201, B*0702, B*0801, B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8+ T cells by flow cytometry using a single-platform absolute counting method. Assay variability was 8% or less and results were available within 3 hours. Delayed recovery of CMV-specific T cells (< 7 cells/μL in all blood samples during the first 65 days after transplantation) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, P = .01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (P = .004). CMV tetramer–based immune monitoring, in conjunction with virologic monitoring, can be an important new tool to assess risk of CMV-related complications and to guide preemptive therapeutic choices.
Signal transduction mechanisms involved in S100A4-induced activation of the transcription factor NF-κB
Authors: Grotterød Ida , Mælandsmo Gunhild M , Boye Kjetil 
Published: May 2010

Abstract

Background
The metastasis-promoting protein S100A4 activates the transcription factor NF-κB through the classical NF-κB activation pathway. The upstream signal transduction mechanisms leading to increased NF-κB activity are, however, incompletely characterized.

Methods
The human osteosarcoma cell line II-11b was stimulated with recombinant S100A4 in the presence or absence of inhibitors of common signal transduction pathways, and NF-κB activity was examined using a luciferase-based reporter assay and phosphorylation of IκBα. mRNA expression was analyzed by real-time RT-PCR, protein expression was examined by Western blotting and IKK activity was measured using an in vitro kinase assay. The role of upstream kinases and the cell surface receptor RAGE was investigated by overexpression of dominant negative proteins and by siRNA transfection.

Results
The Ser/Thr kinase inhibitors H-7 and staurosporine inhibited S100A4-induced IκBα phosphorylation and subsequent NF-κB activation. The protein tyrosine kinase inhibitor genistein and the phospholipase C inhibitor compound 48/80 had a partial inhibitory effect on IκBα phosphorylation, whereas inhibitors of protein kinase C, G-protein coupled receptors and PI 3-kinases had no effect on the level of phosphorylation. Interestingly, S100A4 treatment induced activating phosphorylations of IKKα/β, but neither H-7 nor staurosporine was able to significantly inhibit IKK activation. Dominant negative MEKK1 or NIK did not inhibit S100A4-induced NF-κB activity, and S100A4 stimulation did not influence AKT phosphorylation. Furthermore, diminished expression of the putative S100 protein receptor RAGE did not affect the observed phosphorylation of IκBα.

Conclusions
S100A4 activates NF-κB by inducing phosphorylation of IKKα/β, leading to increased IκBα phosphorylation. The Ser/Thr kinase inhibitors H-7 and staurosporine attenuated S100A4-induced NF-κB activation and inhibited IKK-mediated phosphorylation of IκBα. S100A4-induced NF-κB activation was independent of the putative S100 protein receptor RAGE and the Ser/Thr kinases MEKK1, NIK and AKT. These findings lead to increased understanding of S100A4 signaling, which may contribute to the identification of novel targets for anti-metastatic therapy.
Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients
Authors: Raiko Irina , Sander Ingrid , Weber Daniel G , Raulf-Heimsoth Monika , Gillissen Adrian , Kollmeier Jens , Scherpereel Arnaud , Brüning Thomas , Johnen Georg 
Published: May 2010

Abstract

Background
Calretinin is one of the well-established immunohistochemical markers in the diagnostics of malignant mesothelioma (MM). Its utility as a diagnostic tool in human blood, however, is scarcely investigated. The aim of this study was to develop an enzyme-linked immunosorbent assay (ELISA) for human calretinin in blood and to assess its usefulness as a potential minimally invasive diagnostic marker for MM.

Methods
Initially, attempts were made to establish an assay using commercially available antibodies and to optimize it by including a biotin-streptavidin complex into the assay protocol. Subsequently, a novel ELISA based on polyclonal antibodies raised in rabbit immunized with human recombinant calretinin was developed. The assay performance in human serum and plasma (EDTA/heparin) and the influence of calcium concentrations on antibody recognition were studied. Stability of spiked-in calretinin in EDTA plasma under different storage conditions was also examined. In preliminary studies serum and plasma samples from 97 healthy volunteers, 35 asbestos-exposed workers, and 42 MM patients were analyzed.

Results
The mean detection range of the new ELISA was 0.12 to 8.97 ng/ml calretinin. The assay demonstrated markedly lower background and significantly higher sensitivity compared to the initially contrived assay that used commercial antibodies. Recovery rate experiments confirmed dependence of calretinin antibody recognition on calcium concentration. Calcium adjustment is necessary for calretinin measurement in EDTA plasma. Spiked-in calretinin revealed high stability in EDTA plasma when stored at room temperature, 4°C, or after repeated freeze/thaw cycles. Median calretinin values in healthy volunteers, asbestos workers, and MM patients were 0.20, 0.33, and 0.84 ng/ml, respectively (p < 0.0001 for healthy vs. MM, p = 0.0036 for healthy vs. asbestos-exposed, p < 0.0001 for asbestos-exposed vs. MM). Median values in patients with epithelioid and biphasic MM were similar. No influence of age, gender, smoking status, or type of medium (plasma/serum) on calretinin values was found.

Conclusions
The novel assay is highly sensitive and applicable to human serum and plasma. Calretinin appears to be a promising marker for the blood-based detection of MM and might complement other markers. However, further studies are required to prove its usefulness in the diagnosis of MM patients.
The Study of Environment on Aboriginal Resilience and Child Health (SEARCH): study protocol
Authors:   The SEARCH Investigators
Published: May 2010

Abstract

Background
Aboriginal Australians have a life expectancy more than ten years less than that of non-Aboriginal Australians, reflecting their disproportionate burden of both communicable and non-communicable disease throughout the lifespan. Little is known about the health and health trajectories of Aboriginal children and, although the majority of Aboriginal people live in urban areas, data are particularly sparse in relation to children living in urban areas.

Methods/Design
The Study of Environment on Aboriginal Resilience and Child Health (SEARCH) is a cohort study of Aboriginal children aged 0-17 years, from urban and large regional centers in New South Wales, Australia. SEARCH focuses on Aboriginal community identified health priorities of: injury; otitis media; vaccine-preventable conditions; mental health problems; developmental delay; obesity; and risk factors for chronic disease. Parents/caregivers and their children are invited to participate in SEARCH at the time of presentation to one of the four participating Aboriginal Community Controlled Health Organisations at Mount Druitt, Campbelltown, Wagga Wagga and Newcastle. Questionnaire data are obtained from parents/caregivers and children, along with signed permission for follow-up through repeat data collection and data linkage. All children have their height, weight, waist circumference and blood pressure measured and complete audiometry, otoscopy/pneumatic otoscopy and tympanometry. Children aged 1-7 years have speech and language assessed and their parents/caregivers complete the Parental Evaluation of Developmental Status. The Study aims to recruit 1700 children by the end of 2010 and to secure resources for long term follow up. From November 2008 to March 2010, 1010 children had joined the study. From those 446 children with complete data entry, participating children ranged in age from 2 weeks to 17 years old, with 144 aged 0-3, 147 aged 4-7, 75 aged 8-10 and 79 aged 11-17. 55% were male and 45% female.

Discussion
SEARCH is built on strong community partnerships, under Aboriginal leadership, and addresses community priorities relating to a number of under-researched areas. SEARCH will provide a unique long-term resource to investigate the causes and trajectories of health and illness in urban Aboriginal children and to identify potential targets for interventions to improve health.