bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a CCSM3 Simulation with a Finite Volume Dynamical Core for the Atmosphere at 1° Latitude × 1.25° Longitude Resolution
Authors: Bala G. , Rood R. B. , Mirin A. , McClean J. , Achutarao Krishna , Bader D. , Gleckler P. , Neale R. , Rasch P. 
Published: April 2008

Abstract
A simulation of the present-day climate by the Community Climate System Model version 3 (CCSM3) that uses a Finite Volume (FV) numerical method for solving the equations governing the atmospheric dynamics is presented. The simulation is compared to observations and to the well-documented simulation by the standard CCSM3, which uses the Eulerian spectral method for the atmospheric dynamics. The atmospheric component in the simulation herein uses a 1° latitude × 1.25° longitude grid, which is a slightly finer resolution than the T85-grid used in the spectral transform. As in the T85 simulation, the ocean and ice models use a nominal 1-degree grid. Although the physical parameterizations are the same and the resolution is comparable to the standard model, substantial testing and slight retuning were required to obtain an acceptable control simulation. There are significant improvements in the simulation of the surface wind stress and sea surface temperature. Improvements are also seen in the simulations of the total variance in the tropical Pacific, the spatial pattern of ice thickness distribution in the Arctic, and the vertically integrated ocean circulation in the Antarctic Circumpolar Current. The results herein demonstrate that the FV version of the CCSM coupled model is a state-of-the-art climate model whose simulation capabilities are in the class of those used for Intergovernmental Panel on Climate Change (IPCC) assessments. The simulated climate is very similar to that of the T85 version in terms of its biases, and more like the T85 model than the other IPCC models.
NKG2D-dependent effector function of bronchial epithelium-activated alloreactive T-cells
Authors: Kraetzel K. , Stoelcker B. , Eissner G. , Multhoff G. , Pfeifer M. , Holler E. , Schulz C. 
Published: April 2008

Allogeneic haematopoietic stem cell transplantation (SCT) has emerged as a curative therapeutic option. However, the role of graft-versus-host disease in lung injury after SCT has yet to be determined.In the present study, primary bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used to investigate immune responses of allogeneic CD8+ T-cells directed against respiratory epithelial cells.Following stimulation with irradiated bronchial epithelial cells, CD8+ T-cells produced significant amounts of interferon-γ, upregulated alloantigen activation markers and proliferated highly compared with T-cells stimulated with interleukin-2 alone. Furthermore, cytotoxicity assays demonstrated that bronchial epithelial cell-specific and granzyme B-mediated cytolytic activity was induced in CD8+ T-cells. Generation of natural killer (NK) T-cells, NK-like T-cells, cytokine-induced killer cells or lymphokine-activated killer cells could be excluded by phenotyping, culture conditions and neglectable lytic activity following stimulation with interleukin-2 alone. Inhibition experiments showed that lysis of bronchial epithelial cells was not major histocompatibility complex-I restricted, but depended on NK group 2 member D signalling; a stimulatory receptor initially shown to be expressed on NK cells.The present data imply that the respiratory epithelium has an antigen presenting function and directly alloactivates cytotoxic CD8+ T-cells that show nonclassical effector function.
The incidence of respiratory symptoms and sensitisation in baker apprentices
Authors: Skjold T. , Dahl R. , Juhl B. , Sigsgaard T. 
Published: April 2008

The aim of the current study was to describe the incidence of respiratory symptoms and allergic sensitisation and the sequence of events leading to respiratory symptoms among Danish baker apprentices (BA). A total of 114 BA were surveyed over a 20-month period. Questionnaires were completed along with spirometric analysis and skin-prick tests to common and work-related allergens. Bronchial hyperresponsiveness (BHR) was determined at baseline and at the end of the follow-up period.The incidences of work-related rhinitis and asthma-like symptoms were 22.1 and 10.0 cases·100 person-yrs−1, respectively. At 20 months the cumulative incidence proportion was 40.2 and 20.5% for rhinitis and asthma-like symptoms, respectively. The cumulative incidence of occupational sensitisation was 6.1%.An increased risk of asthma-like symptoms was found in both atopic subjects and in females. In the BA with new onset respiratory symptoms, an increase in BHR from baseline was observed. Forced expiratory volume in one second and forced vital capacity did not change during the follow-up period. No relationship was observed between new sensitisation and new symptoms.In conclusion rhinitis- and asthma-like symptoms were found to develop commonly in Danish baker apprentices. The mechanism by which symptoms arose was perceived to reflect the development of an inflammation rather than the production of a specific immunoglobulin E pathway, as sensitisation to occupational allergens was rarely observed. Hence, respiratory symptoms and allergy may develop through separate pathways.
Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13
Authors: Williams A. S. , Nath P. , Leung S-Y. , Khorasani N. , McKenzie A. N. J. , Adcock I. M. , Chung K. F. 
Published: April 2008

The present study aimed to determine whether the T-helper cell type 2-derived cytokines, interleukin (IL)-4 and -13, can modulate the lung response to ozone exposure.IL-13-/-, IL-4/13-/-and IL-13-overexpressing transgenic (Tg) mice were exposed to ozone (3 ppm; 3 h) or air. Wild-type (Wt) Balb/c mice and transgenic-negative littermates (IL-13Wt) were used as controls for gene-deficient and IL-13Tg mice, respectively.IL-4/13-/-and IL-13-/-mice developed a lesser degree of ozone-induced airway hyperresponsiveness (AHR) while IL-13Tg mice developed a greater degree of AHR compared with ozone-exposed wild-type or IL-13Wt mice, respectively. Ozone caused a time-dependent increase of bronchoalveolar lavage (BAL) neutrophils and macrophages in wild-type mice, maximal at 20–24 h, which was attenuated in the IL-13-/-and IL-4/13-/-mice. In IL-13Tg mice, there was a greater increase in BAL neutrophils after ozone exposure compared with IL-13Wt mice. Using quantitative real-time PCR, ozone-induced mRNA expression for IL-6 and keratinocyte chemokine was further enhanced in IL-13-/-and IL-4/13-/-mice, and was inhibited in IL-13Tg mice. Macrophage inflammatory protein (MIP)-3α/CCL20 expression was enhanced after ozone exposure in wild-type mice, inhibited in IL-13-/-and IL-4/13-/-mice, while in IL-13Tg mice it was enhanced. A similar pattern of expression was observed with lipopolysaccharide-induced cytokine (LIX/CXCL5/ENA-78) expression.In conclusion, interleukin-13 augments ozone-induced airway hyperresponsiveness and neutrophilic inflammation, possibly through modulation of certain cytokines induced by ozone exposure.
Higher pulmonary artery pressure in children than in adults upon fast ascent to high altitude
Authors: Kriemler S. , Jansen C. , Linka A. , Kessel-Schaefer A. , Zehnder M. , Schürmann T. , Kohler M. , Bloch K. , Brunner-La Rocca H. P. 
Published: April 2008

The response of pulmonary artery pressure to high altitude has not been studied in children. It is also not known whether the individual response is hereditary. Therefore, the response of pulmonary artery pressure to high altitude was measured in pre-pubertal children in comparison to that in their biological fathers.Echocardiography was performed at 450 m and over 3 days at 3,450 m. Systolic pulmonary artery pressure was estimated from the pressure gradient of tricuspid regurgitation.The increase in pulmonary artery pressure in children was greater than that in adults at day 1 of high altitude (15.5±9.1versus7.9±6.4 mmHg), but returned to adult levels on day 2. The increase in pulmonary artery pressure from low to high altitude of each child correlated with that in the father.Pre-pubertal children transiently develop greater pulmonary hypertension than their fathers when exposed to high altitude. The individual response of pulmonary pressure to high altitude seems to be at least partly hereditary.
Novel thin bronchoscope with a 1.7-mm working channel for peripheral pulmonary lesions
Authors: Oki M. , Saka H. , Kitagawa C. , Tanaka S. , Shimokata T. , Mori K. , Kajikawa S. 
Published: April 2008

In the present study, the authors evaluated the diagnostic utility of a novel thin bronchoscope with a 1.7-mm working channel for peripheral pulmonary lesions.A total of 118 patients were included in this prospective study. Bronchoscopic examination was performed using a 5.9-mm standard bronchoscope. If no visible endobronchial lesion was found, transbronchial biopsies were performed with 1.5-mm biopsy forceps under fluoroscopic guidance and the bronchus were washed with 10–20 mL of saline solution, using a prototype 3.5-mm thin bronchoscope with a 1.7-mm working channel.Endobronchial lesion was visualised with the standard bronchoscope in 16 patients, and the other 102 patients underwent biopsies with the thin bronchoscope. The mean bronchus levels reached with the standard bronchoscope and the thin bronchoscope were 2.3 and 4.3 generations, respectively. Endobronchial abnormality was revealed with the thin bronchoscope in a further 14 patients. Diagnostic material was obtained in 50 of 68 (74%) patients with malignant disease and 18 of 30 (60%) patients with benign disease. Four patients did not return to follow-up. The diagnostic yield was 57%, even in lesions <20 mm. There were no major complications.In conclusion, bronchoscopy using a 3.5-mm thin bronchoscope with a 1.7-mm working channel is useful and safe for the diagnosis of peripheral pulmonary lesions.
Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study
Authors: Ward Heather , Chapelais Gaelle , Kuhnle Gunter GC , Luben Robert , Khaw Kay-Tee , Bingham Sheila 
Published: April 2008

Abstract
Introduction
Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. Their potential effects may alter the risk of breast cancer, but only a limited range of phytoestrogens has been examined in prospective cohort studies.

Methods
Serum and urine samples from 237 incident breast cancer cases and 952 control individuals (aged 45 to 75 years) in the European Prospective into Cancer-Norfolk cohort were analysed for seven phytoestrogens (daidzein, enterodiol, enterolactone, genistein, glycitein, o-desmethylangolensin, and equol) using liquid chromatography/mass spectrometry. Data on participants' diet, demographics, anthropometrics, and medical history were collected upon recruitment. All models were adjusted for weight, fat and energy intake, family history of breast cancer, social class, analytical batch, and factors related to oestrogen exposure.

Results
Urinary or serum phytoestrogens were not associated with protection from breast cancer in the European Prospective into Cancer-Norfolk cohort. Breast cancer risk was marginally increased with higher levels of total urinary isoflavones (odds ratio = 1.08 (95% confidence interval = 1.00 to 1.16), P = 0.055); among those with oestrogen receptor-positive tumours, the risk of breast cancer was increased with higher levels of urinary equol (odds ratio = 1.07 (95% confidence interval = 1.01 to 1.12), P = 0.013).

Conclusion
There was limited evidence of an association between phytoestrogen biomarkers and breast cancer risk in the present study. There was no indication of decreased likelihood of breast cancer with higher levels of phytoestrogen biomarkers, but the observation that some phytoestrogen biomarkers may be associated with greater risk of breast cancer warrants further study with greater statistical power.
Erect wing regulates synaptic growth in Drosophilaby integration of multiple signaling pathways
Authors: Haussmann Irmgard U , White Kalpana , Soller Matthias 
Published: April 2008

Abstract
Background
Formation of synaptic connections is a dynamic and highly regulated process. Little is known about the gene networks that regulate synaptic growth and how they balance stimulatory and restrictive signals.

Results
Here we show that the neuronally expressed transcription factor gene erect wing (ewg) is a major target of the RNA binding protein ELAV and that EWG restricts synaptic growth at neuromuscular junctions. Using a functional genomics approach we demonstrate that EWG acts primarily through increasing mRNA levels of genes involved in transcriptional and post-transcriptional regulation of gene expression, while genes at the end of the regulatory expression hierarchy (effector genes) represent only a minor portion, indicating an extensive regulatory network. Among EWG-regulated genes are components of Wingless and Notch signaling pathways. In a clonal analysis we demonstrate that EWG genetically interacts with Wingless and Notch, and also with TGF-β and AP-1 pathways in the regulation of synaptic growth.

Conclusion
Our results show that EWG restricts synaptic growth by integrating multiple cellular signaling pathways into an extensive regulatory gene expression network.
Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer
Authors: Piccart-Gebhart Martine J. , Burzykowski Tomasz , Buyse Marc , Sledge George , Carmichael James , Lück Hans-Joachim , Mackey John R. , Nabholtz Jean-Marc , Paridaens Robert , Biganzoli Laura , Jassem Jacek , Bontenbal Marijke , Bonneterre Jacques , Chan Stephen , Basaran Gul Atalay , Therasse Patrick 
Published: April 2008

Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. Patients and Methods Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. Results Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. Conclusion Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.
Asparaginase May Influence Dexamethasone Pharmacokinetics in Acute Lymphoblastic Leukemia
Authors: Yang Lei , Panetta John C. , Cai Xiangjun , Yang Wenjian , Pei Deqing , Cheng Cheng , Kornegay Nancy , Pui Ching-Hon , Relling Mary V. 
Published: April 2008

PurposeDexamethasone is used widely in oncology, but pharmacokinetic studies are lacking. We evaluated dexamethasone pharmacokinetics in children with acute lymphoblastic leukemia.Patients and MethodsWe assessed 214 children with acute lymphoblastic leukemia who received 418 courses of oral dexamethasone (8 mg/m2/d) on days 1 and 8 of reinduction. Extensive asparaginase use preceded reinduction in the 101 children in the standard/high-risk treatment arm but not in the 113 children in the low-risk treatment arm. A one-compartment model with first-order absorption and disposition was fit to dexamethasone plasma concentrations by using maximum a posteriori probability estimation; we evaluated covariates by using linear mixed models.ResultsInterpatient and intrapatient variabilities in apparent clearance were substantial; they were 46% and 53%, respectively. Variability was explained by the serum albumin concentration (P < .0001), concomitant use of fentanyl (P = .008) and ketoconazole (P = .03), and age (P = .006). Apparent clearance was higher in the low-risk arm (P < .001) and was related to a greater serum albumin concentration (P < .001) and to a lower exposure to asparaginase than in the standard/high-risk arm. Hypoalbuminemia, a biomarker of asparaginase activity, was associated with a lower dexamethasone apparent clearance (P = .04) in patients in the standard/high-risk arm that was more pronounced in those not allergic to asparaginase. Ethnicity or gender did not explain apparent clearance variability.ConclusionDexamethasone pharmacokinetics are highly variable and are related to the concurrent use of particular drugs, age, and treatment intensity. Patients allergic to asparaginase may be doubly disadvantaged: they not only suffer from diminished exposure to asparaginase but also, by maintaining high clearance of dexamethasone, may experience fewer antileukemic effects of dexamethasone.
Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer
Authors: Cassidy Jim , Clarke Stephen , Díaz-Rubio Eduardo , Scheithauer Werner , Figer Arie , Wong Ralph , Koski Sheryl , Lichinitser Mikhail , Yang Tsai-Shen , Rivera Fernando , Couture Felix , Sirzén Florin , Saltz Leonard 
Published: April 2008

Purpose To evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC). Patients and Methods The initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival. Results The intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4. Conclusion XELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.
Response of a new zealand mayfly (Deleatidium spp.) to acid mine drainage: Implications for mine remediation
Authors: O'Halloran Kathryn , Cavanagh Jo-Anne , Harding Jon S 
Published: April 2008

Abstract
Investigating the toxicity of acid mine drainage (AMD) on benthic communities in receiving waters can be highly challenging because of the difficulty in unraveling the effects of acidity, dissolved metals, and precipitates. Furthermore, the survival of different species may vary depending on any natural adaptation they may have acquired to low pH, metals, or sedimentation. We investigated the effect of different pHs and AMD on the survival of a common New Zealand leptophlebiid mayfly (Deleatidium spp.) in 96-h laboratory trials. Our results indicate that the primary driver of toxicity in AMD was pH, although some mortality could be attributable to the presence of dissolved heavy metals at low pH (≤3.6). Mayflies sourced from three naturally acidic streams (pH ≈︁ 5.7-6.5) had a distinctly higher tolerance to AMD and low pH (3.5-4.0) compared to mayflies sourced from three circumneutral streams (pH ≈︁ 7.0-7.4). This indicates that the chemistry of the natal stream strongly influences the sensitivity of mayflies to AMD, which, in turn, could have consequences for the successful remediation of a given AMD-impacted stream. Furthermore, the water chemistry of unimpacted streams that could be sources of potential recolonists might provide ecologically relevant water-quality targets for remediation of AMD-damaged streams. Understanding the variable tolerances of common lotic benthic taxa can provide ecologically relevant water-quality criteria for mine remediation.
Evaluating the trophic transfer of cadmium, polonium, and methylmercury in an estuarine food chain
Authors: Mathews Teresa , Fisher Nicholas S 
Published: April 2008

Abstract
We examined the transfer of Cd, methylmercury (MeHg), and Po in an estuarine food chain (from phytoplankton to zooplankton [Daphnia pulex] to killifish [Fundulus heteroclitus] and, finally, to juvenile striped bass [Morone saxatilis]) to better understand both the extent to which these elements may biomagnify and the underlying mechanisms governing this biomagnification. Among the phytoplankton examined (Cyclotella meneghiniana and Chlamdomonas reinhardtii), metal uptake was rapid, and volume concentration factors for all metals reached values between 104 and 105. The resulting assimilation efficiencies (AEs) of ingested metals in all animals were highest for MeHg, with values greater than 76%. The AEs of Cd were 21 to 33% in D. pulex, 1 to 16% in F. heteroclitus, and 38 to 56% in M. saxatilis. Polonium AEs were 69 to 87% in D. pulex, 25 to 41% in F. heteroclitus, and 9 to 21% in M. saxatilis. Loss rate constants (ke) of metals in D. pulex ranged from 0.04/d for MeHg to 0.39/d for Po; metal ke values for F. heteroclitus ranged from 0.01 to 0.02/d. Using a kinetic model, we showed that the trophic transfer factor, defined as the ratio of metal concentration in predatory animals to metal concentration in prey organisms, was greater than unity for all three metals in D. pulex feeding on phytoplankton, suggesting that these metals may be biomagnified at this trophic step. In killifish feeding on D. pulex, the trophic transfer factor was consistently greater than one for MeHg, consistently less than one for Cd, and from 0.1 to 1.4 for Po, suggesting that both MeHg and Po have the potential to biomagnify at this trophic step.