bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of Simulated Boreal Fire Dynamics to Uncertainties in Climate Drivers
Authors: Rupp T. Scott , Chen Xi , Olson Mark , McGuire A. David 
Published: January 2007

Abstract
Projected climatic warming has direct implications for future disturbance regimes, particularly fire-dominated ecosystems at high latitudes, where climate warming is expected to be most dramatic. It is important to ascertain the potential range of climate change impacts on terrestrial ecosystems, which is relevant to making projections of the response of the Earth system and to decisions by policymakers and land managers. Computer simulation models that explicitly model climate–fire relationships represent an important research tool for understanding and projecting future relationships. Retrospective model analyses of ecological models are important for evaluating how to effectively couple ecological models of fire dynamics with climate system models. This paper uses a transient landscape-level model of vegetation dynamics, Alaskan Frame-based Ecosystem Code (ALFRESCO), to evaluate the influence of different driving datasets of climate on simulation results. Our analysis included the use of climate data based on first-order weather station observations from the Climate Research Unit (CRU), a statistical reanalysis from the NCEP–NCAR reanalysis project (NCEP), and the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5). Model simulations of annual area burned for Alaska and western Canada were compared to historical fire activity (1950–2000). ALFRESCO was only able to generate reasonable simulation results when driven by the CRU climate data. Simulations driven by the NCEP and MM5 climate data produced almost no annual area burned because of substantially colder and wetter growing seasons (May–September) in comparison with the CRU climate data. The results of this study identify the importance of conducting retrospective analyses prior to coupling ecological models of fire dynamics with climate system models. The authors’ suggestion is to develop coupling methodologies that involve the use of anomalies from future climate model simulations to alter the climate data of more trusted historical climate datasets.
Convective Forcing Fluctuations in a Cloud-Resolving Model: Relevance to the Stochastic Parameterization Problem
Authors: Shutts G. J. , Palmer T. N. 
Published: January 2007

Abstract
Idealized cloud-resolving model (CRM) simulations spanning a large part of the tropical atmosphere are used to evaluate the extent to which deterministic convective parameterizations fail to capture the statistical fluctuations in deep-convective forcing, and to provide probability distribution functions that may be used in stochastic parameterization schemes for global weather and climate models. A coarse-graining methodology is employed to deduce an effective convective warming rate appropriate to the grid scale of a forecast model, and a convective parameterization scheme is used to bin these computed tendencies into different ranges of convective forcing strength. The dependence of the probability distribution functions for the coarse-grained temperature tendency on parameterized tendency is then examined.
An aquaplanet simulation using a climate model, configured with similar horizontal resolution to that of the coarse-grained CRM fields, was used to compare temperature tendency variation (less the effect of advection and radiation) with that deduced as an effective forcing function from the CRM. The coarse-grained temperature tendency of the CRM is found to have a substantially broader probability distribution function than the equivalent quantity in the climate model.
The CRM-based probability distribution functions of precipitation rate and convective warming are related to the statistical mechanics theory of Craig and Cohen and the “stochastic physics” scheme of Buizza et al. It is found that the standard deviation of the coarse-grained effective convective warming is an approximately linear function of its mean, thereby providing some support for the Buizza et al. scheme, used operationally by ECMWF.
Effects of Land Surface–Vegetation on the Boreal Summer Surface Climate of a GCM
Authors: Alessandri Andrea , Gualdi Silvio , Polcher Jan , Navarra Antonio 
Published: January 2007

Abstract
A land surface model (LSM) has been included in the ECMWF Hamburg version 4 (ECHAM4) atmospheric general circulation model (AGCM). The LSM is an early version of the Organizing Carbon and Hydrology in Dynamic Ecosystems (ORCHIDEE) and it replaces the simple land surface scheme previously included in ECHAM4. The purpose of this paper is to document how a more exhaustive consideration of the land surface–vegetation processes affects the simulated boreal summer surface climate.
To investigate the impacts on the simulated climate, different sets of Atmospheric Model Intercomparison Project (AMIP)-type simulations have been performed with ECHAM4 alone and with the AGCM coupled with ORCHIDEE. Furthermore, to assess the effects of the increase in horizontal resolution the coupling of ECHAM4 with the LSM has been implemented at different horizontal resolutions.
The analysis reveals that the LSM has large effects on the simulated boreal summer surface climate of the atmospheric model. Considerable impacts are found in the surface energy balance due to changes in the surface latent heat fluxes over tropical and midlatitude areas covered with vegetation. Rainfall and atmospheric circulation are substantially affected by these changes. In particular, increased precipitation is found over evergreen and summergreen vegetated areas.
Because of the socioeconomical relevance, particular attention has been devoted to the Indian summer monsoon (ISM) region. The results of this study indicate that precipitation over the Indian subcontinent is better simulated with the coupled ECHAM4–ORCHIDEE model compared to the atmospheric model alone.
ENSO Amplitude Changes due to Climate Change Projections in Different Coupled Models
Authors: Yeh Sang-Wook , Kirtman Ben P. 
Published: January 2007

Abstract
Four climate system models are chosen here for an analysis of ENSO amplitude changes in 4 × CO2 climate change projections. Despite the large changes in the tropical Pacific mean state, the changes in ENSO amplitude are highly model dependant. To investigate why similar mean state changes lead to very different ENSO amplitude changes, the characteristics of sea surface temperature anomaly (SSTA) variability simulated in two coupled general circulation models (CGCMs) are analyzed: the Meteorological Research Institute (MRI) and Geophysical Fluid Dynamics Laboratory (GFDL) models. The skewed distribution of tropical Pacific SSTA simulated in the MRI model suggests the importance of nonlinearities in the ENSO physics, whereas the GFDL model lies in the linear regime. Consistent with these differences in ENSO regime, the GFDL model is insensitive to the mean state changes, whereas the MRI model is sensitive to the mean state changes associated with the 4 × CO2 scenario. Similarly, the low-frequency modulation of ENSO amplitude in the GFDL model is related to atmospheric stochastic forcing, but in the MRI model the amplitude modulation is insensitive to the noise forcing. These results suggest that the understanding of changes in ENSO statistics among various climate change projections is highly dependent on whether the model ENSO is in the linear or nonlinear regime.
Estimation of the Impact of Sampling Errors in the VOS Observations on Air–Sea Fluxes. Part II: Impact on Trends and Interannual Variability
Authors: Gulev Sergey , Jung Thomas , Ruprecht Eberhard 
Published: January 2007

Abstract
Using the same approach as in Part I, here it is shown how sampling problems in voluntary observing ship (VOS) data affect conclusions about interannual variations and secular changes of surface heat fluxes. The largest uncertainties in linear trend estimates are found in relatively poorly sampled regions like the high-latitude North Atlantic and North Pacific as well as the Southern Ocean, where trends can locally show opposite signs when computed from the regularly sampled and undersampled data. Spatial patterns of shorter-period interannual variability, quantified through the EOF analysis, also show remarkable differences between the regularly sampled and undersampled flux datasets in the Labrador Sea and northwest Pacific. In particular, it is shown that in the Labrador Sea region, in contrast to regularly sampled NCEP–NCAR reanalysis fluxes, VOS-like sampled NCEP–NCAR reanalysis fluxes neither show significant interannual variability nor significant trends. These regions, although quite localized covering small parts of the globe, play a crucial role for the coupled atmosphere–ocean system. In the Labrador Sea, for instance, interannual and decadal-scale changes of the surface net heat fluxes are known to affect oceanic convection and, thus, the meridional overturning circulation of the Atlantic Ocean. From a discussion of current atmospheric data assimilation systems it is argued that in poorly sampled regions reanalysis products are superior to VOS-based products for studying interannual and interdecadal variations of atmosphere–ocean interaction. In well-sampled regions, on the other hand, conclusions about surface heat flux variations are relatively insensitive to the choice of the flux products used (VOS versus reanalysis data). The results are confirmed for two different datasets, that is, ECMWF 40-yr Re-Analysis (ERA-40) data and seasonal integrations with a recent version of the ECMWF model in which no actual data were assimilated.
Modulation of DNA binding properties of CCAAT/enhancer binding protein epsilon by heterodimer formation and interactions with NFkappaB pathway
Authors: Chumakov Alexey M. , Silla Agnes , Williamson Elizabeth A. , Koeffler H. Phillip 
Published: January 2007

AbstractC/EBP epsilon is a transcription factor involved in myeloid cell differentiation. Along with C/EBP-α, -β, -γ, -δ, and -ζ, C/EBP-ϵ belongs to the family of CCAAT/enhancer binding proteins that are implicated in control of growth and differentiation of several cell lineages in inflammation and stress response. We have previously shown that C/EBP-ϵ preferentially binds DNA as a heterodimer with other C/EBP family members such as C/EBP-δ, CHOP (C/EBP-ζ), and the b-zip family protein ATF4. In this study, we define the consensus binding sites for C/EBP-ϵ dimers and C/EBP-ϵ–ATF4 heterodimers. We show that the activated NFkappaB pathway promotes interaction of the C/EBP-ϵ subunit with its cognate DNA binding site via interaction with RelA. RelA-C/EBP interaction is enhanced by phosphorylation of threonine at amino acid 75 and results in increased DNA binding compared with the wild-type nonphosphorylated C/EBP both in vitro and in vivo. We suggest that interaction of the activated NFkappaB pathway and C/EBP-ϵ may be important in selective activation of a subset of C/EBP-ϵ–responsive genes.
Inhibitory effect of tumor cell–derived lactic acid on human T cells
Authors: Fischer Karin , Hoffmann Petra , Voelkl Simon , Meidenbauer Norbert , Ammer Julia , Edinger Matthias , Gottfried Eva , Schwarz Sabine , Rothe Gregor , Hoves Sabine , Renner Kathrin , Timischl Birgit , Mackensen Andreas , Kunz-Schughart Leoni , Andreesen Reinhard , Krause Stefan W. , Kreutz Marina 
Published: January 2007

AbstractA characteristic feature of tumors is high production of lactic acid due to enhanced glycolysis. Here, we show a positive correlation between lactate serum levels and tumor burden in cancer patients and examine the influence of lactic acid on immune functions in vitro. Lactic acid suppressed the proliferation and cytokine production of human cytotoxic T lymphocytes (CTLs) up to 95% and led to a 50% decrease in cytotoxic activity. A 24-hour recovery period in lactic acid–free medium restored CTL function. CTLs infiltrating lactic acid–producing multicellular tumor spheroids showed a reduced cytokine production. Pretreatment of tumor spheroids with an inhibitor of lactic acid production prevented this effect. Activated T cells themselves use glycolysis and rely on the efficient secretion of lactic acid, as its intracellular accumulation disturbs their metabolism. Export by monocarboxylate transporter-1 (MCT-1) depends on a gradient between cytoplasmic and extracellular lactic acid concentrations and consequently, blockade of MCT-1 resulted in impaired CTL function. We conclude that high lactic acid concentrations in the tumor environment block lactic acid export in T cells, thereby disturbing their metabolism and function. These findings suggest that targeting this metabolic pathway in tumors is a promising strategy to enhance tumor immunogenicity.
Liver X receptors regulate dendritic cell phenotype and function through blocked induction of the actin-bundling protein fascin
Authors: Geyeregger René , Zeyda Maximilian , Bauer Wolfgang , Kriehuber Ernst , Säemann Marcus D. , Zlabinger Gerhard J. , Maurer Dieter , Stulnig Thomas M. 
Published: January 2007

AbstractLiver X receptors (LXRs) are nuclear receptors regulating lipid and cholesterol metabolism. Recent data revealed a cross talk between LXR and Toll-like receptor signaling in macrophages, indicating a role in immunity. Here, we show that LXRα is expressed in human myeloid dendritic cells (DCs) and induced during differentiation of monocyte-derived DCs, whereas LXRβ is expressed constitutively at a very low level. LXR activation by 2 different LXR agonists strongly interfered with lipopolysaccharide (LPS)–induced but not with CD40L-induced DC maturation by altering DC morphology and suppressing interleukin-12—but enhancing interleukin-10—secretion. LXR activation in DCs largely blocked their T-cell stimulatory ability despite essentially unaltered expression of various antigen-presenting and costimulatory molecules. Immunologic synapse formation was significantly inhibited by LXR activation along with a complete block in LPS- but not CD40L-induced expression of the actin-bundling protein fascin. Notably, overexpression of fascin in LXR agonist–treated DCs restored immunologic synapse formation and restored their ability to activate T cells. In conclusion, our data reveal LXR as a potent modulator of DC maturation and function mediated in part by blocking the expression of fascin. Due to the central position of DCs in immunity, LXRα could be a potential novel target for immunomodulation.
Cell-cycle–dependent oscillation of GATA2 expression in hematopoietic cells
Authors: Koga Shinichiro , Yamaguchi Nobuhiro , Abe Tomoko , Minegishi Masayoshi , Tsuchiya Shigeru , Yamamoto Masayuki , Minegishi Naoko 
Published: January 2007

AbstractIn vitro manipulation of hematopoietic stem cells (HSCs) is a key issue in both transplantation therapy and regenerative medicine, and thus new methods are required to achieve HSC expansion with self-renewal. GATA2 is a transcription factor controlling pool size of HSCs. Of interest, continuous overexpression of GATA2 does not induce HSC proliferation. In this report, we demonstrate that GATA2 expression, in leukemic and normal hematopoietic cells, oscillates during the cell cycle, such that expression is high in S phase but low in G1/S and M phase. GATA2 binding to target Bcl-X gene also oscillates in accordance with GATA2 expression. Using a green fluorescent protein (GFP)–GATA2 fusion protein, we demonstrate cell-cycle–specific activity of proteasome-dependent degradation of GATA2. Immunoprecipitation/immunoblotting analysis demonstrated phosphorylation of GATA2 at cyclin-dependent kinase (Cdk)–consensus motifs, S/T0P+1, and interaction of GATA2 with Cdk2/cyclin A2–, Cdk2/cyclin A2–, and Cdk4/cyclin D1–phosphorylated GATA2 in vitro. Mutants in phosphorylation motifs exhibited altered expression profiles of GFP-GATA2 domain fusion proteins. These results indicate that GATA2 phosphorylation by Cdk/cyclin systems is responsible for the cell-cycle–dependent regulation of GATA2 expression, and suggest the possibility that a cell-cycle–specific “on-off” response of GATA2 expression may control hematopoietic-cell proliferation and survival.
Macrophage glucocorticoid receptors regulate Toll-like receptor 4–mediated inflammatory responses by selective inhibition of p38 MAP kinase
Authors: Bhattacharyya Sandip , Brown Diane E. , Brewer Judson A. , Vogt Sherri K. , Muglia Louis J. 
Published: January 2007

AbstractTo explore the role of glucocorticoids in regulation of kinase pathways during innate immune responses, we generated mice with conditional deletion of glucocorticoid receptor (GR) in macrophages (MGRKO). Activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) caused greater mortality and cytokine production in MGRKO mice than in controls. Ex vivo, treatment with dexamethasone (Dex) markedly inhibited LPS-mediated induction of inflammatory genes in control but not GR-deficient macrophages. We show that Dex inhibits p38 MAPK, but not PI3K/Akt, ERK, or JNK, in control macrophages. Associated with p38 inhibition, Dex induced MAP kinase phosphatase-1 (MKP-1) in control, but not MGRKO, macrophages. Consistent with the ex vivo studies, treatment with a p38 MAPK–specific inhibitor resulted in rescue of MGRKO mice from LPS-induced lethality. Taken together, we identify p38 MAPK and its downstream targets as essential for GR-mediated immunosuppression in macrophages.
TCRζdimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues
Authors: Zhang Zhuoli , Gorman Claire L. , Vermi Anna-Chiara , Monaco Claudia , Foey Andrew , Owen Sally , Amjadi Parisa , Vallance Alena , McClinton Catherine , Marelli-Berg Federica , Isomäki Pia , Russell Andrew , Dazzi Francesco , Vyse Timothy J. , Brennan Fionula M. , Cope Andrew P. 
Published: January 2007

AbstractThe T-cell receptor ζ (TCRζ) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRζ expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRζ expression and effector function in T cells. We report here that TCRζdim lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRζbright counterparts, TCRζdim cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRζdim T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRζdim T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRζdim T cells make them promising cellular targets for the treatment of chronic inflammatory disease.
Scoring functions and enrichment: a case study on Hsp90
Authors: Konstantinou-Kirtay Chrysi , Mitchell John BO , Lumley James A 
Published: January 2007

Abstract

Background
The need for fast and accurate scoring functions has been driven by the increased use of in silico virtual screening twinned with high-throughput screening as a method to rapidly identify potential candidates in the early stages of drug development. We examine the ability of some the most common scoring functions (GOLD, ChemScore, DOCK, PMF, BLEEP and Consensus) to discriminate correctly and efficiently between active and non-active compounds among a library of ~3,600 diverse decoy compounds in a virtual screening experiment against heat shock protein 90 (Hsp90).

Results
Firstly, we investigated two ranking methodologies, GOLDrank and BestScorerank. GOLD
rank
is based on ranks generated using GOLD. The various scoring functions, GOLD, ChemScore, DOCK, PMF, BLEEP and Consensus, are applied to the pose ranked number one by GOLD for that ligand. BestScore
rank
uses multiple poses for each ligand and independently chooses the best ranked pose of the ligand according to each different scoring function. Secondly, we considered the effect of introducing the Thr184 hydrogen bond tether to guide the docking process towards a particular solution, and its effect on enrichment. Thirdly, we considered normalisation to account for the known bias of scoring functions to select larger molecules. All the scoring functions gave fairly similar enrichments, with the exception of PMF which was consistently the poorest performer. In most cases, GOLD was marginally the best performing individual function; the Consensus score usually performed similarly to the best single scoring function. Our best results were obtained using the Thr184 tether in combination with the BestScorerank protocol and normalisation for molecular weight. For that particular combination, DOCK was the best individual function; DOCK recovered 90% of the actives in the top 10% of the ranked list; Consensus similarly recovered 89% of the actives in its top 10%.

Conclusion
Overall, we demonstrate the validity of virtual screening as a method for identifying new leads from a pool of ligands with similar physicochemical properties and we believe that the outcome of this study provides useful insight into the setting up of a suitable docking and scoring protocol, resulting in enrichment of 'target active' compounds.
Detecting differential expression in microarray data: comparison of optimal procedures
Authors: Perelman Elena , Ploner Alexander , Calza Stefano , Pawitan Yudi 
Published: January 2007

AbstractBackgroundMany procedures for finding differentially expressed genes in microarray data are based on classical or modified t-statistics. Due to multiple testing considerations, the false discovery rate (FDR) is the key tool for assessing the significance of these test statistics. Two recent papers have generalized two aspects: Storey et al. (2005) have introduced a likelihood ratio test statistic for two-sample situations that has desirable theoretical properties (optimal discovery procedure, ODP), but uses standard FDR assessment; Ploner et al. (2006) have introduced a multivariate local FDR that allows incorporation of standard error information, but uses the standard t-statistic (fdr2d). The relationship and relative performance of these methods in two-sample comparisons is currently unknown.MethodsUsing simulated and real datasets, we compare the ODP and fdr2d procedures. We also introduce a new procedure called S2d that combines the ODP test statistic with the extended FDR assessment of fdr2d.ResultsFor both simulated and real datasets, fdr2d performs better than ODP. As expected, both methods perform better than a standard t-statistic with standard local FDR. The new procedure S2d performs as well as fdr2d on simulated data, but performs better on the real data sets.ConclusionThe ODP can be improved by including the standard error information as in fdr2d. This means that the optimality enjoyed in theory by ODP does not hold for the estimated version that has to be used in practice. The new procedure S2d has a slight advantage over fdr2d, which has to be balanced against a significantly higher computational effort and a less intuititive test statistic.