bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms for the Development of Locally Low-Dimensional Atmospheric Dynamics
Authors: Oczkowski Michael , Szunyogh Istvan , Patil D. J. 
Published: April 2005

Abstract
The complexity of atmospheric instabilities is investigated by a combination of numerical experiments and diagnostic tools that do not require the assumption of linear error dynamics. These tools include the well-established analysis of the local energetics of the atmospheric flow and the recently introduced ensemble dimension (E dimension). The E dimension is a local measure that varies in both space and time and quantifies the distribution of the variance between phase space directions for an ensemble of nonlinear model solutions over a geographically localized region. The E dimension is maximal, that is, equal to the number of ensemble members (k), when the variance is equally distributed between k phase space directions. The more unevenly distributed the variance, the lower the E dimension.
Numerical experiments with the state-of-the-art operational Global Forecast System (GFS) of the National Centers for Environmental Prediction (NCEP) at a reduced resolution are carried out to investigate the spatiotemporal evolution of the E dimension. This evolution is characterized by an initial transient phase in which coherent regions of low dimensionality develop through a rapid local decay of the E dimension. The typical duration of the transient is between 12 and 48 h depending on the flow; after the initial transient, the E dimension gradually increases with time.
The main goal of this study is to identify processes that contribute to transient local low-dimensional behavior. Case studies are presented to show that local baroclinic and barotropic instabilities, downstream development of upper-tropospheric wave packets, phase shifts of finite amplitude waves, anticyclonic wave breaking, and some combinations of these processes can all play crucial roles in lowering the E dimension.
The practical implication of the results is that a wide range of synoptic-scale weather events may exist whose prediction can be significantly improved in the short and early medium range by enhancing the prediction of only a few local phase space directions. This potential is demonstrated by a reexamination of the targeted weather observations missions from the 2000 Winter Storm Reconnaissance (WSR00) program.
Tropical Climate Regimes and Global Climate Sensitivity in a Simple Setting
Authors: Barsugli Joseph , Shin Sang-Ik , Sardeshmukh Prashant D. 
Published: April 2005

Abstract
Multiple tropical climate regimes are found in an atmospheric general circulation model (AGCM) coupled to a global slab ocean when the model is forced by different values of globally uniform insolation. Even in this simple setting, convection organizes into an intertropical convergence zone (ITCZ) solely due to the effect of planetary rotation, as was found in Kirtman and Schneider, for a single value of insolation. Here the response to a range of insolation values is explored, and surprisingly, multiple climate regimes characterized by radically different ITCZ structures are found. In order from the coldest to warmest climates, these are a symmetric double ITCZ, a near-symmetric equatorial ITCZ, a transient asymmetric ITCZ, and a stable, strongly asymmetric ITCZ.
The model exhibits hysteresis in the transition from the near-symmetric to the strongly asymmetric ITCZ regimes when insolation is increased and then decreased. The initial transition away from symmetry can occur in the absence of air–sea coupling; however, the coupling is essential for the establishment and maintenance of the strongly asymmetric ITCZ. Wind–evaporation–SST feedback as well as the longwave radiative effects of clouds and water vapor on SSTs appear to be important in maintaining the asymmetric regime. The existence of multiple regimes in a single AGCM, and the dependence of these regimes on SST feedbacks, may have a bearing on the ITCZ simulation errors of current coupled climate models.
The sensitivity of the global mean surface temperature generally decreases with increasing insolation, a consequence primarily of increasingly negative shortwave cloud forcing. Climate sensitivity measured across a regime transition can be much larger than the sensitivity within a single regime.
Modeling Diurnal and Intraseasonal Variability of the Ocean Mixed Layer
Authors: Bernie D. J. , Woolnough S. J. , Slingo J. M. , Guilyardi E. 
Published: April 2005

Abstract
The intraseasonal variability of SST associated with the passage of the Madden–Julian oscillation (MJO) is well documented; yet coupled model integrations generally underpredict the magnitude of this SST variability. Observations from the Improved Meteorological Instrument (IMET) mooring in the western Pacific during the intensive observing period (IOP) of the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE) showed a large diurnal signal in SST that is modulated by the passage of the MJO. In this study, observations from the IOP of the TOGA COARE and a one-dimensional (1D) ocean mixed layer model incorporating the K-Profile Parameterization (KPP) vertical mixing scheme have been used to investigate the rectification of the intraseasonal variability of SST by the diurnal cycle and the implied impact of the absence of a representation of this process on the modeled intraseasonal variability in coupled GCMs. Analysis of the SST observations has shown that the increase of the daily mean SST by the diurnal cycle of SST accounts for about one-third of the magnitude of intraseasonal variability of SST associated with the Madden–Julian oscillation in the western Pacific warm pool.
Experiments from the 1D model forced with fluxes at a range of temporal resolutions and with differing vertical resolution of the model have shown that to capture 90% of the diurnal variability of SST, and hence 95% of the intraseasonal variability of SST, requires a 3-h or better temporal resolution of the fluxes and a vertical grid with an upper-layer thickness of the order of 1 m. In addition to the impact of the representation of the diurnal cycle on the intraseasonal variability of SST, the strength of the mixing across the thermocline was found to be enhanced by the proper representation of the nighttime deep mixing in the ocean, implying a possible impact of the diurnal cycle onto the mean climate of the tropical ocean.
Changes toward Earlier Streamflow Timing across Western North America
Authors: Stewart Iris T. , Cayan Daniel R. , Dettinger Michael D. 
Published: April 2005

Abstract
The highly variable timing of streamflow in snowmelt-dominated basins across western North America is an important consequence, and indicator, of climate fluctuations. Changes in the timing of snowmelt-derived streamflow from 1948 to 2002 were investigated in a network of 302 western North America gauges by examining the center of mass for flow, spring pulse onset dates, and seasonal fractional flows through trend and principal component analyses. Statistical analysis of the streamflow timing measures with Pacific climate indicators identified local and key large-scale processes that govern the regionally coherent parts of the changes and their relative importance.
Widespread and regionally coherent trends toward earlier onsets of springtime snowmelt and streamflow have taken place across most of western North America, affecting an area that is much larger than previously recognized. These timing changes have resulted in increasing fractions of annual flow occurring earlier in the water year by 1–4 weeks. The immediate (or proximal) forcings for the spatially coherent parts of the year-to-year fluctuations and longer-term trends of streamflow timing have been higher winter and spring temperatures. Although these temperature changes are partly controlled by the decadal-scale Pacific climate mode [Pacific decadal oscillation (PDO)], a separate and significant part of the variance is associated with a springtime warming trend that spans the PDO phases.
Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1α
Authors: Nishio Mitsufumi , Endo Tomoyuki , Tsukada Nobuhiro , Ohata Junko , Kitada Shinichi , Reed John C. , Zvaifler Nathan J. , Kipps Thomas J. 
Published: April 2005

AbstractWe examined expression of B cell–activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic lymphocytic leukemia (CLL) B cells and nurselike cells (NLCs), which differentiate from CD14+ cells when cultured with CLL B cells. NLCs expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells cultured with NLCs was significantly reduced when CLL B cells were cultured with decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and APRIL, but not with BAFF receptor:Fc (BAFF-R:Fc), which binds only to BAFF. The effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and distinct from that of stromal cell–derived factor-1α (SDF-1α), which in contrast to BAFF or APRIL induced leukemia cell phosphorylation of p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase-1/2 [ERK1/2]) and AKT. Conversely, BAFF and APRIL, but not SDF-1α, induced CLL-cell activation of the nuclear factor–κB1 (NF-κB1) and enhanced CLL-cell expression of the antiapoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL-cell activation of NF-κB2. We conclude that BAFF and APRIL from NLCs can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1α, indicating that NLCs use multiple distinct pathways to support CLL-cell survival.
Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive lymphoblastic leukemia by increased expression of a novel ABC transporter homolog ATP11a
Authors: Zhang Bin , Groffen John , Heisterkamp Nora 
Published: April 2005

AbstractResistance to cytotoxic drugs frequently emerges during treatment of leukemia with conventional chemotherapy. New classes of anticancer drugs, such as the farnesyltransferase inhibitors (FTIs), show therapeutic promise, but whether cells will easily develop resistance against them is not known. Here, we grew breakpoint cluster region/Abelson murine leukemia (Bcr/Abl) P190 lymphoblasts on stroma and made them resistant to the FTI SCH66336/lonafarnib to model emerging drug resistance in a patient. These cells exhibited greatly increased (&gt; 100-fold) expression levels of a novel ATP (adenosine triphosphate)-binding cassette (ABC) transporter-homologous gene, ATP11A. We showed that overexpression of this gene provided protection against the effects of SCH66336, whereas knockdown of endogenous ATP11a using small interfering RNA (siRNA) made cells more sensitive to this drug. The lymphoblasts that were resistant to this FTI were also more resistant to FTI-276 and to GGTI-298, 2 other structurally similar inhibitors. Surprisingly, the cells were also able to survive higher concentrations of imatinib mesylate, the Bcr/Abl tyrosine kinase inhibitor. However, the cells remained sensitive to vincristine. Our results show that elevated levels of ATP11a can protect malignant lymphoblastic leukemia cells against several novel small molecule signal transduction inhibitors. A determination of the expression levels of this gene may have prognostic value when treatment with such classes of drugs is contemplated. (Blood. 2005;106: 1355-1361)
Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis
Authors: Han Song Yi , Lee Na Kyung , Kim Kyung Hee , Jang In Whan , Yim Mijung , Kim Jae Hong , Lee Won Jae , Lee Soo Young 
Published: April 2005

AbstractRegulation of osteoclast differentiation is key to understanding the pathogenesis and to developing treatments for bone diseases such as osteoporosis. To gain insight into the mechanism of the receptor activator of nuclear factor (NF)–κB ligand (RANKL)–specific induction of the osteoclast differentiation program, we took a suppression-subtractive hybridization screening approach to identify genes specifically induced via the RANKL-Rac1 signaling pathway. Among identified targets, we show that RANKL selectively induces cyclooxygenase (COX) 2 expression via Rac1 that results in turn in production of prostaglandin E2 (PGE2) in RAW 264.7 cells. By using transient transfection assays, we found that the –233/–206 region of the COX-2 promoter gene was critical for RANKL-induced promoter activity. This RANKL-responsive region contained an NF-κB site that, when mutated, completely abolished the induction of NF-κB DNA-binding activity by RANKL. Blockade of COX-2 by celecoxib inhibits differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) into tartrate-resistant acid phosphatase-positive (TRAP+) osteoclastic cells. This inhibition can be rescued by the addition of exogenous PGE2, suggesting that COX-2–dependent PGE2 induction by RANKL in osteoclast precursors is required for osteoclast differentiation.
Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development
Authors: Muntean Andrew G. , Crispino John D. 
Published: April 2005

AbstractGATA1 is mutated in patients with 2 different disorders. First, individuals with a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor Friend of GATA-1 (FOG-1) suffer from dyserythropoietic anemia and thrombocytopenia. Second, children with Down syndrome who develop acute megakaryoblastic leukemia harbor mutations in GATA1 that lead to the exclusive expression of a shorter isoform named GATA-1s. To determine the effect of these patient-specific mutations on GATA-1 function, we first compared the gene expression profile between wild-type and GATA-1–deficient megakaryocytes. Next, we introduced either GATA-1s or a FOG-binding mutant (V205G) into GATA-1–deficient megakaryocytes and assessed the effect on differentiation and gene expression. Whereas GATA-1–deficient megakaryocytes failed to undergo terminal differentiation and proliferated excessively in vitro, GATA-1s–expressing cells displayed proplatelet formation and other features of terminal maturation, but continued to proliferate aberrantly. In contrast, megakaryocytes that expressed V205G GATA-1 exhibited reduced proliferation, but failed to undergo maturation. Examination of the expression of megakaryocyte-specific genes in the various rescued cells correlated with the observed phenotypic differences. These studies show that GATA-1 is required for both normal regulation of proliferation and terminal maturation of megakaryocytes, and further, that these functions can be uncoupled by mutations in GATA1.
The Shwachman-Diamond SBDS protein localizes to the nucleolus
Authors: Austin Karyn M. , Leary Rebecca J. , Shimamura Akiko 
Published: April 2005

AbstractShwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The gene for this syndrome, SBDS, encodes a highly conserved novel protein. We characterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and intracellular localization in 7 patients with SDS and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. Patient DF277, who was homozygous for the IVS2 + 2 T&gt;C splice donor mutation, expressed scant levels of SBDS protein. Patient SD101 expressed low levels of SBDS protein harboring an R169C missense mutation. Patient DF269, who carried no detectable gene mutations, expressed wild-type levels of SBDS protein to add further support to the growing body of evidence for additional gene(s) that might contribute to the pathogenesis of the disease phenotype. The SBDS protein was detected in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell-cycle dependent, with nucleolar localization during G1 and G2 and diffuse nuclear localization during S phase. SBDS nucleolar localization was intact in SD101 and DF269. The intranucleolar localization of SBDS provides further supportive evidence for its postulated role in rRNA processing.
The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes
Authors: Steensma David P. , Dewald Gordon W. , Lasho Terra L. , Powell Heather L. , McClure Rebecca F. , Levine Ross L. , Gilliland D. Gary , Tefferi Ayalew 
Published: April 2005

AbstractA somatic mutation in the JH2 autoinhibitory domain of the Janus kinase 2 (JAK2) tyrosine kinase was recently described in polycythemia vera, essential thrombocythemia, and myelofibrosis with myeloid metaplasia. The prevalence of this mutation in either “atypical” myeloproliferative disorders (MPDs) or the myelodysplastic syndromes (MDSs) is unknown. Bone marrow–derived genomic DNA from 245 patients—119 with chronic myelomonocytic leukemia (CMML), 101 with MDS, 11 with hypereosinophilic syndrome (HES), 8 with systemic mastocytosis (SM), and 6 with chronic neutrophilic leukemia (CNL)—was screened for the JAK2 V617F mutation. A mutant allele was detected in 11 patients: 3 with CMML (3%), 5 with MDS (5%), 2 with SM, and 1 with CNL. Interestingly, one of the patients with SM and the patient with CNL with JAK2 V617F had a history of lymphoma, and this patient with SM also had associated myelofibrosis and CMML. The current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders.
Severity of obstructive airway disease and risk of osteoporotic fracture
Authors: de Vries F. , van Staa T. P. , Bracke M. S. G. M. , Cooper C. , Leufkens H. G. M. , Lammers J-W. J. 
Published: April 2005

The use of inhaled corticosteroids has been associated with a dose-related increased risk of fracture. This may be related to systemic absorption. However, several studies have found that patients with more severe reductions in pulmonary function had reduced bone mineral density, independent of inhaled corticosteroids. The objective of this study was to evaluate the relationship between disease severity and fracture risk.A large case–control study (108,754 cases) was conducted using data from the UK General Practice Research Database. It was found that higher doses of inhaled corticosteroids were associated with greater risks of fracture. The crude odds ratio of fracture among patients exposed to >1,600 μg beclomethasone equivalents per day was 1.95 (95% confidence interval (CI) 1.68–2.27). When adjustments were made for disease severity and use of bronchodilators, the initial dose–response relationship between inhaled corticosteroids and fracture risk disappeared (adjusted odds ratio of 1.19 (95% CI 1.01–1.41)).In conclusion, patients with severe obstructive airway disease are at risk of fracture. However, adequate adjustment for disease severity is essential when the association between the use of inhaled corticosteroids and risk of osteoporotic fracture is studied in observational research.
C-reactive protein as a marker of ventilator-associated pneumonia resolution: a pilot study
Authors: Póvoa P. , Coelho L. , Almeida E. , Fernandes A. , Mealha R. , Moreira P. , Sabino H. 
Published: April 2005

The aim of this study was to evaluate C-reactive protein (CRP) levels, body temperature and white cell count (WCC) after prescription of antibiotics in order to describe the clinical resolution of ventilator-associated pneumonia (VAP).A cohort of 47 VAP patients with microbiological confirmation of disease was assessed. CRP levels, body temperature and WCC were monitored daily.On day 4 of the antibiotic therapy, the CRP level of survivors was 0.62 times the initial value, whereas, in nonsurvivors, it was 0.98. Body temperature and WCC remained almost unchanged. By day 4, a CRP of >0.6 times the initial level was a marker of poor outcome (sensitivity 0.92; specificity 0.59). Patients were divided according to their CRP patterns of response to antibiotics: fast response, slow response, nonresponse, and biphasic response. All patients with fast and slow response patterns survived, whereas those showing nonresponse and a biphasic response pattern exhibited a mortality of 78 and 75%, respectively. The adequacy of the initial antibiotic therapy had a marked influence on the rate of CRP decrease, as well as on mortality.In conclusion, daily C-reactive protein measurements after antibiotic prescription were useful in the identification, as early as day 4, of ventilator-associated pneumonia patients with poor outcome. The identification of the pattern of C-reactive protein response to antibiotics was useful in the recognition of individual clinical course, improving or worsening, as well as of the rate of improvement.
Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics: Table. 1—
Authors: Shorr A. F. , Helman D. L. , Davies D. B. , Nathan S. D. 
Published: April 2005

Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little is known about the epidemiology of PH in sarcoidosis.The current authors reviewed the records of patients with sarcoidosis listed for lung transplantation in the USA between January 1995 and December 2002. PH was defined as a mean pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery pressure of ≥40 mmHg.The cohort included 363 patients of whom 73.8% had PH. Neither spirometric testing nor the need for corticosteroids was associated with PH. Subjects with PH required more supplemental oxygen (2.7±1.8 L·min−1versus1.6±1.4 L·min−1). The cardiac index was lower in individuals with PH, whereas the pulmonary capillary wedge pressure was higher. In multivariate analysis, supplemental oxygen remained an independent predictor of PH, whereas the relationship between cardiac index and PH was no longer significant. As a screening test, the need for oxygen had a sensitivity and specificity of 91.8% and 32.6%, respectively.Pulmonary hypertension is common in advanced sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.