bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-Dimensional Structure and Dynamics of African Easterly Waves. Part I: Observations
Authors: Kiladis George N. , Thorncroft Chris D. , Hall Nicholas M. J. 
Published: September 2006

Abstract
The mean structure of African easterly waves (AEWs) over West Africa and the adjacent Atlantic is isolated by projecting dynamical fields from reanalysis and radiosonde data onto space–time-filtered satellite-derived outgoing longwave radiation. These results are compared with previous studies and an idealized modeling study in a companion paper, which provides evidence that the waves bear a close structural resemblance to the fastest-growing linear normal mode of the summertime basic-state flow over Africa. There is a significant evolution in the three-dimensional structure of AEWs as they propagate along 10°N across West Africa. At this latitude, convection occurs in northerly flow to the east of the Greenwich meridian, then shifts into the wave trough, and finally into southerly flow as the waves propagate offshore into the Atlantic ITCZ. In contrast, to the north of the African easterly jet along 15°N convection remains in southerly flow throughout the waves’ trajectory. Along 10°N over West Africa, the location of convection is consistent with the adiabatic dynamical forcing implied by the advection of perturbation vorticity by the mean thermal wind in the zonal direction, as in the companion paper. Offshore, and along 15°N, the relationship between the convection and dynamics is more complex, and not as easily explained in terms of dynamical forcing alone.
Tropical Cyclone Initialization and Prediction Based on Four-Dimensional Variational Data Assimilation
Authors: Wu Chun-Chieh , Chou Kun-Hsuan , Wang Yuqing , Kuo Ying-Hwa 
Published: September 2006

Abstract
Issues on the initialization and simulation of tropical cyclones (TCs) have been studied here based on four-dimensional variational data assimilation. In particular, experiments have been carried out to assess 1) what the most critical parameters for the so-called bogus data assimilation are and 2) how the current procedures for the bogus data assimilation can be further improved.
It is shown that the assimilation of wind fields is more successful than that of pressure fields in improving the initial structure and prediction of TCs. It is emphasized that the geostrophic adjustment favors the pressure field to adjust to the wind field because the TC vortex is much smaller than the radius of Rossby deformation. The results suggest that a better initial condition in the wind field is critical to the simulation of TCs.
Experiments from this study also show that inclusion of the initial TC movement in the data assimilation window can help improve the track prediction, particularly during the early integration period. This method is able to shed light on the improvement of TC simulation based on the bogus data assimilation.
In all, the results add a theoretical interpretation of the importance of the wind field to the sea level pressure field in terms of geostrophic adjustment, as well as a time dimension of the bogus data assimilation, by assimilating a movable vortex in the four-dimensional variational data assimilation.
Observed Boundary Layer Wind Structure and Balance in the Hurricane Core. Part I: Hurricane Georges
Authors: Kepert Jeffrey D. 
Published: September 2006

Abstract
The GPS dropsonde allows observations at unprecedentedly high horizontal and vertical resolution, and of very high accuracy, within the tropical cyclone boundary layer. These data are used to document the boundary layer wind field of the core of Hurricane Georges (1998) when it was close to its maximum intensity. The spatial variability of the boundary layer wind structure is found to agree very well with the theoretical predictions in the works of Kepert and Wang. In particular, the ratio of the near-surface wind speed to that above the boundary layer is found to increase inward toward the radius of maximum winds and to be larger to the left of the track than to the right, while the low-level wind maximum is both more marked and at lower altitude on the left of the storm track than on the right. However, the expected supergradient flow in the upper boundary layer is not found, with the winds being diagnosed as close to gradient balance.
The tropical cyclone boundary layer model of Kepert and Wang is used to simulate the boundary layer flow in Hurricane Georges. The simulated wind profiles are in good agreement with the observations, and the asymmetries are well captured. In addition, it is found that the modeled flow in the upper boundary layer at the eyewall is barely supergradient, in contrast to previously studied cases. It is argued that this lack of supergradient flow is a consequence of the particular radial structure in Georges, which had a comparatively slow decrease of wind speed with radius outside the eyewall. This radial profile leads to a relatively weak gradient of inertial stability near the eyewall and a strong gradient at larger radii, and hence the tropical cyclone boundary layer dynamics described by Kepert and Wang can produce only marginally supergradient flow near the radius of maximum winds. The lack of supergradient flow, diagnosed from the observational analysis, is thus attributed to the large-scale structure of this particular storm. A companion paper presents a similar analysis for Hurricane Mitch (1998), with contrasting results.
Three MCS Cases Occurring in Different Synoptic Environments in the Sub-Sahelian Wet Zone during the 2002 West African Monsoon
Authors: Schrage Jon M. , Fink Andreas H. , Ermert Volker , Ahlonsou Epiphane D. 
Published: September 2006

Abstract
Three mesoscale convective systems (MCSs) occurring in the sub-Sahelian wet zone of West Africa are examined using observations from the 2002 Integrated Approach to the Efficient Management of Scarce Water Resources in West Africa (IMPETUS) field campaign, the European Centre for Medium-Range Weather Forecasts (ECMWF) operational analyses, and Meteosat infrared imagery. These datasets enable the analysis of the synoptic-scale environment in which the MCSs were embedded, along with a high-resolution monitoring of surface parameters during the systems’ passages. The available data imply that cases I and II were of a squall-type nature. Case I propagated into a moderately sheared and rather moist lower and middle troposphere over the Upper Ouémé Valley (UOV). In contrast, case II was associated with a well-sheared and dry lower troposphere and a large, moist instability. In either case, behind the convective cluster a westward-propagating cyclonic vorticity maximum that was likely captured by the ECMWF analysis as a result of the special upper-air station at Parakou (Benin). In case I, the fast-moving vorticity signal slowed down over the Guinean Highlands where convection dissipated. Farther downstream, it might have played a role in the consolidation of an African easterly waves (AEW) trough over the West African coast and the eastern Atlantic. Case III proved to be a more stationary pattern of convection associated with a vortex in the monsoon flow. It also exhibited a moist and low shear environment.
The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors
Authors: Payne Shawn G. , Oskeritzian Carole A. , Griffiths Rachael , Subramanian Preeti , Barbour Suzanne E. , Chalfant Charles E. , Milstien Sheldon , Spiegel Sarah 
Published: September 2006

AbstractFTY720 is a potent immunomodulator drug that inhibits the egress of lymphocytes from secondary lymphoid tissues and thymus. FTY720 is phosphorylated in vivo by sphingosine kinase 2 to FTY720-phosphate, which acts as a potent sphingosine-1-phosphate (S1P) receptor agonist. However, in contrast to S1P, FTY720 has no effect on mast-cell degranulation, yet significantly reduces antigen-induced secretion of PGD2 and cysteinyl-leukotriene. Unexpectedly, this effect of FTY720 was independent of its phosphorylation and S1P receptor functions. The rate-limiting step in the biosynthesis of all eicosanoids is the phospholipase A2 (PLA2)–mediated release of arachidonic acid from glycerol phospholipids. Although FTY720 also reduced arachidonic acid release in response to antigen, it had no effect on translocation of cPLA2 or ERK1/2 activation, suggesting that it does not interfere with FcϵRI-mediated events leading to cPLA2 activation. Remarkably, however, FTY720 drastically inhibited recombinant cPLA2α activity, whereas FTY720-phosphate, sphingosine, or S1P had no effect. This study has uncovered a unique action of FTY720 as an inhibitor of cPLA2α and hence on production of all eicosanoids. Our results have important implications for the potential therapeutic mechanism of action of FTY720 in eicosanoid-driven inflammatory disorders such as asthma and multiple sclerosis.
Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function
Authors: Brogdon Jennifer L. , Xu Yongyao , Szabo Susanne J. , An Shaojian , Buxton Francis , Cohen Dalia , Huang Qian 
Published: September 2006

AbstractHistone deacetylases (HDACs) play a critical role in regulating gene expression and key biological processes. However, how HDACs are involved in innate immunity is little understood. Here, in this first systematic investigation of the role of HDACs in immunity, we show that HDAC inhibition by a small-molecule HDAC inhibitor (HDACi), LAQ824, alters Toll-like receptor 4 (TLR4)–dependent activation and function of macrophages and dendritic cells (DCs). Surprisingly, pan-HDAC inhibition modulates only a limited set of genes involved in distinct arms of immune responses. Specifically, it inhibited DC-controlled T helper 1 (Th1) effector but not Th2 effector cell activation and migration. It also inhibited macrophage- and DC-mediated monocyte but not neutrophil chemotaxis. These unexpected findings demonstrate the high specificity of HDAC inhibition in modulating innate and adaptive immune responses, and highlight the potential for HDACi to alter the Th1 and Th2 balance in therapeutic settings.
Annexin-1 modulates T-cell activation and differentiation
Authors: D'Acquisto Fulvio , Merghani Ahmed , Lecona Emilio , Rosignoli Guglielmo , Raza Karim , Buckley Christopher D. , Flower Roderick J. , Perretti Mauro 
Published: September 2006

AbstractAnnexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity; however, its potential actions in the modulation of adaptive immunity have never been explored. Although inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. This effect was paralleled by increased nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFATs), and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor (TCR)–induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells; in the collagen-induced arthritis model, treatment of mice with annexin-1 during the immunization phase exacerbated signs and symptoms at disease onset. Consistent with these findings, blood CD4+ cells from patients with rheumatoid arthritis showed a marked up-regulation of annexin-1 expression. Together these results demonstrate that annexin-1 is a molecular “tuner” of TCR signaling and suggest this protein might represent a new target for the development of drugs directed to pathologies where an unbalanced Th1/Th2 response or an aberrant activation of T cells is the major etiologic factor.
Glycoprotein Ibα forms disulfide bonds with 2 glycoprotein Ibβ subunits in the resting platelet
Authors: Luo Shi-Zhong , Mo Xi , Afshar-Kharghan Vahid , Srinivasan Sankaranarayanan , López José A. , Li Renhao 
Published: September 2006

AbstractIt is widely accepted that glycoprotein (GP) Ib contains one Ibα and one Ibβ subunit that are connected by a disulfide bond. It is unclear which Cys residue in Ibα, C484 or C485, forms the disulfide bond with Ibβ. Using mutagenesis studies in transfected Chinese hamster ovary (CHO) cells, we found that both C484 and C485 formed a disulfide bond with C122 in Ibβ. In the context of isolated peptides containing the Ibα or Ibβ transmembrane domain and nearby Cys residue, C484 and C485 in the Ibα peptide were both capable of forming a disulfide bond with the Ibβ peptide. Furthermore, coimmunoprecipitation of epitope-tagged subunits showed that at least 2 Ibβ subunits but only 1 Ibα and 1 IX subunit were present in the GP Ib-IX complex. Finally, the size difference between GP Ib from transfected CHO cells and human platelets was attributed to a combination of sequence polymorphism and glycosylation difference in Ibα, not the number of Ibβ subunits therein. Overall, these results demonstrate that Ibα is covalently connected to 2 Ibβ subunits in the resting platelet, necessitating revision of the subunit stoichiometry of the GP Ib-IX-V complex. The αβ2 composition in GP Ib may provide the basis for possible disulfide rearrangement in the receptor complex.
Dynamic posttranscriptional regulation of ϵ-globin gene expression in vivo
Authors: He Zhenning , Russell J. Eric 
Published: September 2006

AbstractFunctional studies of embryonic ϵ-globin indicate that individuals with β thalassemia or sickle cell disease are likely to benefit from therapeutic, transcriptional derepression of its encoding gene. The success of ϵ-globin gene-reactivation strategies, however, will be tempered by the stability that ϵ-globin mRNA exhibits in developmental stage-discordant definitive erythroid progenitors. Using cell culture and transgenic mouse model systems, we demonstrate that ϵ-globin mRNA is modestly unstable in immature, transcriptionally active erythroid cells, but that this characteristic has relatively little impact on the accumulation of ϵ-globin mRNA at subsequent stages of terminal differentiation. Importantly, the constitutive stability of ϵ-globin mRNA increases in transgenic mouse models of β thalassemia, suggesting that ϵ- and β-globin mRNAs are coregulated through a shared posttranscriptional mechanism. As anticipated, relevant cis-acting determinants of ϵ-globin mRNA stability map to its 3′ UTR, consistent with the positioning of functionally related elements in other globin mRNAs. These studies demonstrate that posttranscriptional processes do not pose a significant practical barrier to ϵ-globin gene reactivation and, moreover, indicate that related therapeutic strategies may be particularly effective in individuals carrying β-thalassemic gene defects.
Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia
Authors: Kay Neil E. , Geyer Susan M. , Call Timothy G. , Shanafelt Tait D. , Zent Clive S. , Jelinek Diane F. , Tschumper Renee , Bone Nancy D. , Dewald Gordon W. , Lin Thomas S. , Heerema Nyla A. , Smith Lisa , Grever Michael R. , Byrd John C. 
Published: September 2006

AbstractBuilding on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.
Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension
Authors: Hoeper M. M. , Leuchte H. , Halank M. , Wilkens H. , Meyer F. J. , Seyfarth H. J. , Wensel R. , Ripken F. , Bremer H. , Kluge S. , Hoeffken G. , Behr J. 
Published: September 2006

Addition of inhaled iloprost to bosentan may have beneficial effects in patients with idiopathic pulmonary arterial hypertension (IPAH). A multicentre, open, randomised, controlled trial was performed to assess the safety and efficacy of inhaled iloprost in patients with IPAH who had already been treated with bosentan.The trial was terminated early after a futility analysis predicted failure with respect to the predetermined sample size. At that time, 40 patients were randomised to receive either bosentan alone (control group) or bosentan plus inhaled iloprost (combination group) for a 12-week period.The primary end-point, change in 6-min walking distance, was not met (mean changes +1 m and -9 m in the control and combination group, respectively). These results may have been skewed by three outliers in the iloprost group who presented with severe clinical worsening. None of the secondary end-points including functional class, peak oxygen uptake, and time to clinical worsening differed significantly between groups.The current study failed to show a positive effect of adding inhaled iloprost to bosentan in idiopathic pulmonary arterial hypertension patients. Further studies involving larger sample sizes and long-term follow-up are needed to determine the efficacy of adding inhaled iloprost to bosentan in patients with idiopathic pulmonary arterial hypertension.
Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air: a SOMA study
Authors: Haahtela T. , Tamminen K. , Malmberg L. P. , Zetterström O. , Karjalainen J. , Ylä-Outinen H. , Svahn T. , Ekström T. , Selroos O. 
Published: September 2006

Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned.The current study compared as-needed use of a rapid-acting β2-agonist with as-needed use of a β2-agonist and corticosteroid combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled β2-agonist as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) ≥20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis® Turbuhaler®) 4.5 μg as needed (n = 47) or budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5 μg as needed (n = 45) in a double-blind, parallel-group 24-week study.The primary variable of efficacy was change inFeNO. BaselineFeNOwas 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions inFeNOin the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5–23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% CI -4.7– -0.7). In the budesonide/formoterol group, use of ≥4 inhalations·day-1of study medication was seen on 21 treatment days compared with 74 in the formoterol group.In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a β2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown.
The validity and responsiveness of three quality of life measures in the assessment of psoriasis patients: results of a phase II study
Authors: Shikiar Richard , Willian Mary Kaye , Okun Martin M , Thompson Christine S , Revicki Dennis A 
Published: September 2006

Abstract

Background
Patient-reported outcome (PROs) measures are being used more frequently in investigational studies of treatments for moderate to severe plaque psoriasis. The objective of this study was to examine the relationships among the Dermatology Life Quality Index (DLQI), the Short Form 36 (SF-36), and the EuroQOL 5D (EQ-5D) and to assess their validity, responsiveness, and estimates of minimum important differences.

Methods
A Phase II, randomized, double-blind, parallel group, placebo-controlled, multi-center clinical trial assessed the clinical efficacy and safety of two doses of subcutaneously administered adalimumab vs. placebo for 12 weeks in the treatment of 147 patients with moderate to severe plaque psoriasis. This study provided the opportunity to evaluate the validity and responsiveness to change in clinical status of PROs instruments. Patients completed the DLQI, SF-36, and EQ-5D questionnaires at baseline and at 12 weeks. Blinded investigators assessed the Psoriasis Area and Severity Index (PASI) scores and the Physician's Global Assessment (PGA) scores of enrolled patients. The responsiveness of the measures to changes in the clinical endpoints from baseline to Week 12 was assessed. Estimates of minimum important differences (MID) were derived. All analyses were performed with blinded data; findings and conclusions were not biased based on treatment condition.

Results
The dermatology-specific DLQI was highly correlated to clinical endpoints at baseline and at Week 12, and was the most responsive PRO to changes in endpoints. Compared with the SF-36, the EQ-5D index score and VAS scores were generally more highly correlated with clinical endpoints, but displayed about the same degree of responsiveness. The most responsive SF-36 scales were the Bodily Pain and Social Functioning scales. Estimates of the MID for the DLQI ranged from 2.3–5.7 and for the SF-36 Physical Component Summary (PCS) score ranged from 2.5–3.9.

Conclusion
This study provides support for the continued use of the DLQI and SF-36 PCS in the assessment of treatments for psoriasis. On the basis of the results from this trial, the EQ-5D should be considered as a general PRO measure in future clinical trials of patients with moderate to severe plaque psoriasis.