bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Global Zonally Integrated Ocean Circulation, 1992–2006: Seasonal and Decadal Variability
Authors: Wunsch Carl , Heimbach Patrick 
Published: September 2008

Abstract
The zonally integrated meridional and vertical velocities as well as the enthalpy transports and fluxes in a least squares adjusted general circulation model are used to estimate the top-to-bottom oceanic meridional overturning circulation (MOC) and its variability from 1992 to 2006. A variety of simple theories all produce time scales suggesting that the mid- and high-latitude oceans should respond to atmospheric driving only over several decades. In practice, little change is seen in the MOC and associated heat transport except very close to the sea surface, at depth near the equator, and in parts of the Southern Ocean. Variability in meridional transports in both volume and enthalpy is dominated by the annual cycle and secondarily by the semiannual cycle, particularly in the Southern Ocean. On time scales longer than a year, the solution exhibits small trends with complicated global spatial patterns. Apart from a net uptake of heat from the atmosphere (forced by the NCEP–NCAR reanalysis, which produces net ocean heating), the origins of the meridional transport trends are not distinguishable and are likely a combination of model disequilibrium, shifts in the observing system, other trends (real or artificial) in the meteorological fields, and/or true oceanic secularities. None of the results, however, supports an inference of oceanic circulation shifts taking the system out of the range in which changes are more than small perturbations. That the oceanic observations do not conflict with an apparent excess heat uptake from the atmosphere implies a continued undersampling of the global ocean, even in the upper layers.
In Situ Data Biases and Recent Ocean Heat Content Variability*
Authors: Willis Josh K. , Lyman John M. , Johnson Gregory C. , Gilson John 
Published: September 2008

Abstract
Two significant instrument biases have been identified in the in situ profile data used to estimate globally integrated upper-ocean heat content. A large cold bias was discovered in a small fraction of Argo floats along with a smaller but more prevalent warm bias in expendable bathythermograph (XBT) data. These biases appear to have caused the bulk of the upper-ocean cooling signal reported by Lyman et al. between 2003 and 2005. These systematic data errors are significantly larger than sampling errors in recent years and are the dominant sources of error in recent estimates of globally integrated upper-ocean heat content variability. The bias in the XBT data is found to be consistent with errors in the fall-rate equations, suggesting a physical explanation for that bias. With biased profiles discarded, no significant warming or cooling is observed in upper-ocean heat content between 2003 and 2006.
An Objective Model for Identifying Secondary Eyewall Formation in Hurricanes
Authors: Kossin James P. , Sitkowski Matthew 
Published: September 2008

AbstractHurricanes, and particularly major hurricanes, will often organize a secondary eyewall at some distance around the primary eyewall. These events have been associated with marked changes in the intensity and structure of the inner core, such as large and rapid deviations of the maximum wind and significant broadening of the surface wind field. While the consequences of rapidly fluctuating peak wind speeds are of great importance, the broadening of the overall wind field also has particularly dangerous consequences in terms of increased storm surge and wind damage extent during landfall events. Despite the importance of secondary eyewall formation in hurricane forecasting, there is presently no objective guidance to diagnose or forecast these events. Here a new empirical model is introduced that will provide forecasters with a probability of imminent secondary eyewall formation. The model is based on environmental and geostationary satellite features applied to a naïve Bayes probabilistic model and classification scheme. In independent testing, the algorithm performs skillfully against a defined climatology.
Evaluation of Probabilistic Medium-Range Temperature Forecasts from the North American Ensemble Forecast System
Authors: McCollor Doug , Stull Roland 
Published: September 2008

Abstract
Ensemble temperature forecasts from the North American Ensemble Forecast System were assessed for quality against observations for 10 cities in western North America, for a 7-month period beginning in February 2007. Medium-range probabilistic temperature forecasts can provide information for those economic sectors exposed to temperature-related business risk, such as agriculture, energy, transportation, and retail sales.
The raw ensemble forecasts were postprocessed, incorporating a 14-day moving-average forecast–observation difference, for each ensemble member. This postprocessing reduced the mean error in the sample to 0.6°C or less. It is important to note that the North American Ensemble Forecast System available to the public provides bias-corrected maximum and minimum temperature forecasts.
Root-mean-square-error and Pearson correlation skill scores, applied to the ensemble average forecast, indicate positive, but diminishing, forecast skill (compared to climatology) from 1 to 9 days into the future. The probabilistic forecasts were evaluated using the continuous ranked probability skill score, the relative operating characteristics skill score, and a value assessment incorporating cost–loss determination. The full suite of ensemble members provided skillful forecasts 10–12 days into the future.
A rank histogram analysis was performed to test ensemble spread relative to the observations. Forecasts are underdispersive early in the forecast period, for forecast days 1 and 2. Dispersion improves rapidly but remains somewhat underdispersive through forecast day 6. The forecasts show little or no dispersion beyond forecast day 6. A new skill versus spread diagram is presented that shows the trade-off between higher skill but low spread early in the forecast period and lower skill but better spread later in the forecast period.
The Performance of MOS in the Digital Age
Authors: Ruth David P. , Glahn Bob , Dagostaro Valery , Gilbert Kathryn 
Published: September 2008

Abstract
Model output statistics (MOS) guidance forecasts have been produced for over three decades. Until recently, MOS guidance was prepared for observing stations and formatted in text bulletins while official National Weather Service (NWS) forecasts for stations and zones were prepared by forecasters typing text. The flagship product of today’s NWS is the National Digital Forecast Database (NDFD). In support of NDFD, MOS is now also produced on grids.
This paper compares MOS and gridded MOS (GMOS) to the forecaster-produced NDFD at approximately 1200 station locations in the conterminous United States. Results indicate that GMOS should provide good guidance for preparing the NDFD. In those areas of the country where station observations well represent the grid, GMOS features accuracy comparable to that of NDFD. In areas of complex terrain not well represented by station observations, GMOS appears similar to NDFD in its depiction. A new score is introduced to measure convergence from a long-range forecast to the final short-range forecast. This shows good GMOS forecast continuity when compared to station MOS and NDFD.
Visualizing Multiple Measures of Forecast Quality
Authors: Roebber Paul J. 
Published: September 2008

AbstractA method for visually representing multiple measures of dichotomous (yes–no) forecast quality (probability of detection, false alarm ratio, bias, and critical success index) in a single diagram is presented. Illustration of the method is provided using performance statistics from two previously published forecast verification studies (snowfall density and convective initiation) and a verification of several new forecast datasets: Storm Prediction Center forecasts of severe storms (nontornadic and tornadic), Hydrometeorological Prediction Center forecasts of heavy precipitation (greater than 12.5 mm in a 6-h period), National Weather Service Forecast Office terminal aviation forecasts (ceiling and visibility), and medium-range ensemble forecasts of 500-hPa height anomalies. The use of such verification metrics in concert with more detailed investigations to advance forecasting is briefly discussed.
The Risk of Acute Myocardial Infarction with Etodolac Is not Increased Compared to Naproxen: A Historical Cohort Analysis of a Generic COX-2 Selective Inhibitor
Authors: Warner John J. , Weideman Rick A. , Kelly Kevin C. , Brilakis Emmanouil S. , Banerjee Subhash , Cunningham Francesca , Harford William V. , Kazi Salahuddin , Little Bertis B. , Cryer Byron 
Published: September 2008

Background: This study compares the risk of acute myocardial infarction among patients exposed to etodolac, naproxen, celecoxib, and rofecoxib. Methods: A retrospective cohort study in 38 258 veteran patients (26 376 patient-years) measured the adjusted odds ratios of acute myocardial infarction during exposure to etodolac, naproxen, celecoxib, or rofecoxib. Results: Diagnosis of acute myocardial infarction was confirmed in 100 patients who were exposed to a study nonsteroidal anti-inflammatory drug. Compared to naproxen, the increased risk of acute myocardial infarction was not significant for etodolac (OR = 1.32, P = .27), whereas celecoxib (OR = 2.18, 95% CI 1.09-4.35, P = .03) and rofecoxib (OR = 2.16, 95 CI 1.04-4.46, P = .04) were significant. A post hoc analysis indicates that patients with a prior history of acute myocardial infarction had a significant, 4.26-fold risk for another acute myocardial infarction if taking celecoxib or rofecoxib. Conclusion: Etodolac is not associated with a statistically increased risk of acute myocardial infarction compared to naproxen.
Constitutive activation of the Wnt canonical pathway in mantle cell lymphoma
Authors: Gelebart Pascal , Anand Mona , Armanious Hanan , Peters Anthea C. , Dien Bard Jennifer , Amin Hesham M. , Lai Raymond 
Published: September 2008

AbstractAberrations of the Wnt canonical pathway (WCP) are known to contribute to the pathogenesis of various types of cancer. We hypothesize that these defects may exist in mantle cell lymphoma (MCL). Both the upstream and downstream aspects of WCP were examined in MCL cell lines and tumors. Using WCP-specific oligonucleotide arrays, we found that MCL highly and consistently expressed Wnt3 and Wnt10. β-catenin, a transcriptional factor that is a downstream target of WCP, is localized to the nucleus and transcriptionally active in all 3 MCL cell lines examined. By immunohistochemistry, 33 (52%) of 64 MCL tumors showed nuclear localization of β-catenin, which significantly correlated with the expression of the phosphorylated/inactive form of GSK3β (p-GSK3β; P = .011, Fisher). GSK3β inactivation is directly linked to WCP stimulation, since addition of recombinant sFRP proteins (a naturally occurring decoy for the Wnt receptors) resulted in a significant decrease in p-GSK3β. Down-regulation of DvL-2 (an upstream signaling protein in WCP) by siRNA or selective inhibition of β-catenin using quercetin significantly decreased cell growth in MCL cell lines. To conclude, WCP is constitutively activated in a subset of MCL and it appears to promote tumorigenesis in MCL.
Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression
Authors: Malleret Benoît , Manéglier Benjamin , Karlsson Ingrid , Lebon Pierre , Nascimbeni Michelina , Perié Leïla , Brochard Patricia , Delache Benoît , Calvo Julien , Andrieu Thibault , Spreux-Varoquaux Odile , Hosmalin Anne , Le Grand Roger , Vaslin Bruno 
Published: September 2008

AbstractPlasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)–producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immunodeficiency virus (SIV) infection in 18 macaques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in secondary lymphoid tissues. These changes correlated with the kinetic and intensity of viremia and were associated with a peak of plasma IFN-I. IFN-I and viremia were positively correlated with functional activity of the immune suppression associated enzyme indoleamine-2,3-dioxygenase (IDO) and FoxP3+CD8+ T cells, which both negatively correlated with SIV-specific T-cell proliferation and CD4+ T-cell activation. These data suggest that pDCs and IFN-I play a key role in shaping innate and adaptive immunity toward suppressive pathways during the acute phase of SIV/HIV primary infection.
Increasing the efficiency of bacterial transcription simulations: When to exclude the genome without loss of accuracy
Authors: Iafolla Marco AJ , Dong Guang Qiang , McMillen David R 
Published: September 2008

AbstractBackgroundSimulating the major molecular events inside anEscherichia colicell can lead to a very large number of reactions that compose its overall behaviour. Not only should the model be accurate, but it is imperative for the experimenter to create an efficient model to obtain the results in a timely fashion. Here, we show that for many parameter regimes, the effect of the host cell genome on the transcription of a gene from a plasmid-borne promoter is negligible, allowing one to simulate the system more efficiently by removing the computational load associated with representing the presence of the rest of the genome. The key parameter is the on-rate of RNAP binding to the promoter (k_on), and we compare the total number of transcripts produced from a plasmid vector generated as a function of this rate constant, for two versions of our gene expression model, one incorporating the host cell genome and one excluding it. By sweeping parameters, we identify the k_on range for which the difference between the genome and no-genome models drops below 5%, over a wide range of doubling times, mRNA degradation rates, plasmid copy numbers, and gene lengths.ResultsWe assess the effect of the simulating the presence of the genome over a four-dimensional parameter space, considering: 24 min <= bacterial doubling time <= 100 min; 10 <= plasmid copy number <= 1000; 2 min <= mRNA half-life <= 14 min; and 10 bp <= gene length <= 10000 bp. A simple MATLAB user interface generates an interpolated k_on threshold for any point in this range; this rate can be compared to the ones used in other transcription studies to assess the need for including the genome.ConclusionExclusion of the genome is shown to yield less than 5% difference in transcript numbers over wide ranges of values, and computational speed is improved by two to 24 times by excluding explicit representation of the genome.
Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145
Authors: Kucukzeybek Yuksel , Gul Mustafa K , Cengiz Ercument , Erten Cigdem , Karaca Burcak , Gorumlu Gurbuz , Atmaca Harika , Uzunoglu Selim , Karabulut Bulent , Sanli Ulus A , Uslu Ruchan 
Published: September 2008

AbstractBackgroundThe management of hormone-refractory prostate cancer (HRPC) still remains as an important challenge of daily oncology practice. Docetaxel has proved to be a first line treatment choice. All-trans retinoic acid (ATRA) could potently inhibit the growth of prostate cancer cellsin vitroand its combination with various anticancer agents results in increased cytotoxicity. Based on these data, our aim was to examine the synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and ATRA, in hormone- and drug refractory human DU-145 prostate cancer cells. Furthermore, we have searched for the underlying mechanisms of apoptosis by demonstrating apoptosis-related genes.MethodsXTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. For detecting the mechanism of apoptosis induced by docetaxel-ATRA combination, OligoGeArray®which consists of 112 apoptosis related genes was used.ResultsOur results revealed that docetaxel and ATRA were synergistically cytotoxic and apoptotic in DU-145 cells, in a dose- and time dependent manner. It was also shown by our studies that apoptosis was induced in DU-145 prostate carcinoma cells with significant cytotoxicity, no matter which agent applied first. We have found out that docetaxel-ATRA combination significantly downregulates survivin (BIRC5), myeloid cell leukemia-1 (MCL-1) and lymphotoxin β-receptor (LTβR) genes, which all three have pivotal roles in regulation of apoptosis and cell cycle progression.ConclusionIn conclusion, we strongly suggest that docetaxel and ATRA combination is a good candidate for this challenging era of daily oncologic practice. Also, the combination of docetaxel and ATRA might allow a reduction in docetaxel doses and by this way may diminish docetaxel adverse effects while maintaining the therapeutic effect in patients with HRPC.
Role of Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X Chromosome, Gene 1 in Protein Kinase A- and Protein Kinase C-Mediated Regulation of the Steroidogenic Acute Regulatory Protein Expression in Mouse Leydig Tumor Cells: Mechanism of Action
Authors: Manna Pulak R. , Dyson Matthew T. , Jo Youngah , Stocco Douglas M. 
Published: September 2008

Dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1 (DAX-1) is an orphan nuclear receptor that has been demonstrated to be instrumental to the expression of the steroidogenic acute regulatory (StAR) protein that regulates steroid biosynthesis in steroidogenic cells. However, its mechanism of action remains obscure. The present investigation was aimed at exploring the molecular involvement of DAX-1 in protein kinase A (PKA)- and protein kinase C (PKC)-mediated regulation of StAR expression and its concomitant impact on steroid synthesis using MA-10 mouse Leydig tumor cells. We demonstrate that activation of the PKA and PKC pathways, by a cAMP analog dibutyryl (Bu)2cAMP [(Bu)2cAMP] and phorbol 12-myristate 13-acetate (PMA), respectively, markedly decreased DAX-1 expression, an event that was inversely correlated with StAR protein, StAR mRNA, and progesterone levels. Notably, the suppression of DAX-1 requires de novo transcription and translation, suggesting that the effect of DAX-1 in regulating StAR expression is dynamic. Chromatin immunoprecipitation studies revealed the association of DAX-1 with the proximal but not the distal region of the StAR promoter, and both (Bu)2cAMP and PMA decreased in vivo DAX-1-DNA interactions. EMSA and reporter gene analyses demonstrated the functional integrity of this interaction by showing that DAX-1 binds to a DNA hairpin at position −44/−20 bp of the mouse StAR promoter and that the binding of DAX-1 to this region decreases progesterone synthesis by impairing transcription of the StAR gene. In support of this, targeted silencing of endogenous DAX-1 elevated basal, (Bu)2cAMP-, and PMA-stimulated StAR expression and progesterone synthesis. Transrepression of the StAR gene by DAX-1 was tightly associated with expression of the nuclear receptors Nur77 and steroidogenic factor-1, demonstrating these factors negatively modulate the steroidogenic response. These findings provide insight into the molecular events by which DAX-1 influences the PKA and PKC signaling pathways involved in the regulation of the StAR protein and steroidogenesis in mouse Leydig tumor cells.The characterization of protein kinase A- and protein kinase C-mediated steroidogenic acute regulatory (StAR) expression and steroidogenesis suggests that the orphan nuclear receptor DAX-1 is an important regulator of the steroidogenic response in Leydig cells.
Connexin40 Messenger Ribonucleic Acid Is Positively Regulated by Thyroid Hormone (TH) Acting in Cardiac Atria via the TH Receptor
Authors: Almeida Norma A. S. , Cordeiro Aline , Machado Danielle S. , Souza Luana L. , Ortiga-Carvalho Tânia M. , Campos-de-Carvalho Antonio C. , Wondisford Fredric E. , Pazos-Moura Carmen C. 
Published: September 2008

Thyroid hormone (TH) regulates many cardiac genes via nuclear thyroid receptors, and hyperthyroidism is frequently associated with atrial fibrillation. Electrical activity propagation in myocardium depends on the transfer of current at gap junctions, and connexins (Cxs) 40 and 43 are the predominant junction proteins. In mice, Cx40, the main Cx involved in atrial conduction, is restricted to the atria and fibers of the conduction system, which also express Cx43. We studied cardiac expression of Cx40 and Cx43 in conjunction with electrocardiogram studies in mice overexpressing the dominant negative mutant thyroid hormone receptor-β Δ337T exclusively in cardiomyocytes [myosin heavy chain (MHC-mutant)]. These mice develop the cardiac hypothyroid phenotype in the presence of normal serum TH. Expression was also examined in wild-type mice rendered hypothyroid or hyperthyroid by pharmacological treatment. Atrial Cx40 mRNA and protein levels were decreased (85 and 55%, respectively; P &lt; 0.001) in MHC-mt mice. Atrial and ventricular Cx43 mRNA levels were not significantly changed. Hypothyroid and hyperthyroid animals showed a 25% decrease and 40% increase, respectively, in Cx40 mRNA abundance. However, MHC-mt mice presented very low Cx40 mRNA expression regardless of whether they were made hypothyroid or hyperthyroid. Atrial depolarization velocity, as represented by P wave duration in electrocardiograms of unanesthetized mice, was extremely reduced in MHC-mt mice, and to a lesser extent also in hypothyroid mice (90 and 30% increase in P wave duration). In contrast, this measure was increased in hyperthyroid mice (19% decrease in P wave duration). Therefore, this study reveals for the first time that Cx40 mRNA is up-regulated by TH acting in cardiac atria via the TH receptor and that this may be one of the mechanisms contributing to atrial conduction alterations in thyroid dysfunctions.Cardiac-specific expression of a mutant thyroid hormone receptor unable to bind thyroid hormone profoundly reduces atrial connexin 40 expression in association with prolonged atrial conduction.