bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCL and associated proteins distinguish active from repressive GATA transcription factor complexes
Authors: Tripic Tamara , Deng Wulan , Cheng Yong , Zhang Ying , Vakoc Christopher R. , Gregory Gregory D. , Hardison Ross C. , Blobel Gerd A. 
Published: November 2008

AbstractGATA-1 controls hematopoietic development by activating and repressing gene transcription, yet the in vivo mechanisms that specify these opposite activities are unknown. By examining the composition of GATA-1–associated protein complexes in a conditional erythroid rescue system as well as through the use of tiling arrays we detected the SCL/TAL1, LMO2, Ldb1, E2A complex at all positively acting GATA-1–bound elements examined. Similarly, the SCL complex is present at all activating GATA elements in megakaryocytes and mast cells. In striking contrast, at sites where GATA-1 functions as a repressor, the SCL complex is depleted. A DNA-binding defective form of SCL maintains association with a subset of active GATA elements indicating that GATA-1 is a key determinant for SCL recruitment. Knockdown of LMO2 selectively impairs activation but not repression by GATA-1. ETO-2, an SCL-associated protein with the potential for transcription repression, is also absent from GATA-1–repressed genes but, unlike SCL, fails to accumulate at GATA-1–activated genes. Together, these studies identify the SCL complex as a critical and consistent determinant of positive GATA-1 activity in multiple GATA-1–regulated hematopoietic cell lineages.
Amifostine reduces lung vascular permeabilityviasuppression of inflammatory signalling
Authors: Fu P. , Birukova A. A. , Xing J. , Sammani S. , Murley J. S. , Garcia J. G. N. , Grdina D. J. , Birukov K. G. 
Published: November 2008

Despite an encouraging outcome of antioxidant therapy in animal models of acute lung injury, effective antioxidant agents for clinical application remain to be developed. The present study investigated the effect of pre-treatment with amifostine, a thiol antioxidant compound, on lung endothelial barrier dysfunction induced by Gram-negative bacteria wall-lipopolysaccharide (LPS).Endothelial permeability was monitored by changes in transendothelial electrical resistance. Cytoskeletal remodelling and reactive oxygen species (ROS) production was examined by immunofluorescence. Cell signalling was assessed by Western blot. Measurements of Evans blue extravasation, cell count and protein content in bronchoalveolar lavage fluid were used asin vivoparameters of lung vascular permeability.Hydrogen peroxide, LPS and interleukin-6 caused cytoskeletal reorganisation and increased permeability in the pulmonary endothelial cells, reflecting endothelial barrier dysfunction. These disruptive effects were inhibited by pre-treatment with amifostine and linked to the amifostine-mediated abrogation of ROS production and redox-sensitive signalling cascades, including p38, extracellular signal regulated kinase 1/2, mitogen-activated protein kinases and the nuclear factor-κB pathway.In vivo, concurrent amifostine administration inhibited LPS-induced oxidative stress and p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and neutrophil recruitment to the lungs.The present study demonstrates, for the first time, protective effects of amifostine against lipopolysaccharide-induced lung vascular leakin vitroand in animal models of lipopolysaccharide-induced acute lung injury.
Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion
Authors: Mühlfeld C. , Schaefer I-M. , Becker L. , Bussinger C. , Vollroth M. , Bosch A. , Nagib R. , Madershahian N. , Richter J. , Wahlers T. , Wittwer T. , Ochs M. 
Published: November 2008

The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model.Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4°C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included “worst case” without Perfadex and surfactant (5), “no injury” without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood–air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (Ppa) were determined during reperfusion in groups 1 to 4.Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood–air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4.Ppadid not differ between the groups.In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood–air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.
High-sensitive C-reactive protein is associated with reduced lung function in young adults
Authors: Rasmussen F. , Mikkelsen D. , Hancox R. J. , Lambrechtsen J. , Nybo M. , Hansen H. S. , Siersted H. C. 
Published: November 2008

Systemic inflammation has been associated with reduced lung function. However, data on the interrelationships between lung function and inflammation are sparse, and it is not clear if low-grade inflammation leads to reduced lung function.Associations between high-sensitive C-reactive protein (CRP) and spirometric lung function were assessed in a population-based cohort of ∼1,000 Danes aged 20 yrs.In males, the average decline in forced expiratory volume in one second (FEV1) in the highest CRP quintile was 23 mL·yr−1versus1.6 mL·yr−1in the lowest quintile. In females, the average decline was 6.2 mL·yr−1in the highest CRP quintileversusan increase of 1.8 mL·yr−1in the lowest CRP quintile. In a multiple regression analysis adjusted for sex, body mass index, cardiorespiratory fitness, smoking, asthma, airway hyperresponsiveness and serum eosinophil cationic protein, higher levels of CRP at age 20 yrs were associated with a greater reduction in both FEV1and forced vital capacity between ages 20 and 29 yrs.The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation.
Acquisition and eradication ofP. aeruginosain young children with cystic fibrosis
Authors: Douglas T. A. , Brennan S. , Gard S. , Berry L. , Gangell C. , Stick S. M. , Clements B. S. , Sly P. D. 
Published: November 2008

When do infants and young children with cystic fibrosis acquire infection withPseudomonas aeruginosa? Can this be eradicated when first detected?Children <6 yrs of age participated in an annual bronchoalveolar lavage (BAL)-based microbiological surveillance programme in Perth, Australia. WhenP. aeruginosawas detected, an eradication programme using combination treatment withi.v., oral and nebulised antibiotics was undertaken. Repeat BAL was performed 3 months following treatment, to assess eradication success.P. aeruginosawas detected in 33 (28.4%) children; median (range) age at detection was 30.5 (3.3–71.4) months.P. aeruginosawas mucoid at detection in six (18.2%) out of 33 patients and associated with respiratory symptoms in 16 (48.5%) out of 33 children. In total, 26 children underwent eradication therapy, withP. aeruginosaeradicated in 20 (77%) out of 26 following one eradication cycle and in three (total 88%) additional children following a second cycle. Eradication was associated with a significant decrease in neutrophil elastase and interleukin-1β in BAL fluid 12 months post eradication.Eradication ofPseudomonas aeruginosainfection is achievable in young children with cystic fibrosis for up to 5 yrs using combinationi.v., oral and nebulised antibiotic therapy and is associated with reduced pulmonary inflammation 12 months post eradication.
Progression of snoring and obstructive sleep apnoea: the role of increasing weight and time
Authors: Berger G. , Berger R. , Oksenberg A. 
Published: November 2008

The aim of the present study was to examine the natural evolution of primary snoring and obstructive sleep apnoea (OSA) in adult male patients.Retrospective analysis was performed on 160 untreated patients with primary snoring and mild, moderate and severe OSA who had two polysomnographic recordings. The mean time between recordings (TBR) was 5.1±3 yrs.The mean apnoea/hypopnoea index (AHI), body mass index (BMI), and lowest arterial oxygen saturation level during rapid eye movement (REM) and non-REM sleep showed a significant worsening effect. The change in AHI differed among the groups showing a similar significant increase in AHI for primary snoring, mild and moderate OSA and an insignificant decrease for severe OSA patients. Stepwise linear regression showed that only ΔBMI and time were significant predictors for AHI change. A model for the mean AHI change showed that ΔAHI  =  (4.33×ΔBMI) + (0.66×TBR). After adjusting for confounders, multiple regression analysis indicated that age and high BMI, but not AHI, were significant risk factors for developing hypertension and/or cardiovascular disease.Patients with primary snoring and mild and moderate obstructive sleep apnoea had a similar increase in the apnoea/hypopnoea index over time, which depended mainly on weight gain and, to a lesser extent, on time.
Evolution of microRNA expression during human bronchial squamous carcinogenesis
Authors: Mascaux C. , Laes J. F. , Anthoine G. , Haller A. , Ninane V. , Burny A. , Sculier J. P. 
Published: November 2008

MicroRNAs, negative post-transcriptional regulators of gene expression, are involved in cancer.Their role in early bronchial carcinogenesis was analysed in 60 biopsies obtained by fluorescence bronchoscopy (six per stage: normal tissue of nonsmokers, normal normofluorescent and hypofluorescent bronchial tissue of smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia,in situcarcinoma and invasive squamous cell carcinoma (SQCC)).In total, 69 microRNAs were found to be differentially expressed in the course of bronchial carcinogenesis. Among them, some microRNAs showed a linear evolution of their expression level, such as miR-32 and miR-34c, whose expression progressively decreased from normal bronchial tissues of nonsmokers to SQCC. Others behaved differently at successive stages, such as miR-142-3p or miR-9, or are only altered from a specific stage, such as miR-199a or miR-139. MicroRNAs globally followed a two-step evolution, first decreasing (a reverse of their increase during embryogenesis) during the earliest morphological modifications of bronchial epithelium, and thereafter increasing at later stages of lung carcinogenesis. Moreover, microRNA expression was very efficient for the prediction of the histological classification between low- and high-grade lesions and betweenin situand invasive carcinoma.The present data show, for the first time, that microRNAs are involved in bronchial carcinogenesis from the very early steps of this process and, thus, could provide tools for early detection of lung cancer.
Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers
Authors: Regueiro V. , Campos M. A. , Morey P. , Sauleda J. , Agustí A.G.N. , Garmendia J. , Bengoechea J. A. 
Published: November 2008

Lipopolysaccharide-binding protein (LBP) and CD14 contribute to the recognition of pathogens by cells, which triggers the activation of defence responses. Smoking is a risk factor for the development of chronic obstructive pulmonary disease (COPD) and respiratory infections. The current authors theorised that levels of LBP and CD14 in the lungs of smokers would be higher than those in the lungs of never-smokers. These elevated levels could affect host responses upon infection.LBP, soluble CD14 (sCD14) and interleukin (IL)-8 were detected by ELISA. Nuclear factor (NF)-κB, p38 and the inhibitor IκBα were studied by immunoassays. Gene expression was assessed by RT-PCR.Bronchoalveolar lavage levels of LBP and CD14 were significantly higher in smokers and COPD patients than in never-smokers, whereas levels of both proteins were not significantly different between smokers and COPD patients. IL-6, IL-1β and cigarette smoke condensate induced the expression of LBP and CD14 by airway epithelial cells. LBP and sCD14 inhibited the nontypeableHaemophilus influenzae(NTHi)-dependent secretion of IL-8 and the activation of NF-κB and p38 mitogen-activated protein kinase signalling pathways but they increased the internalisation of NTHi by airway epithelial cells.Thus, in the inflamed airways of smokers both proteins could contribute to inhibit bacteria-dependent cellular activation without compromising the internalisation of pathogens by airway cells.
Clinical signs and symptoms of oropharyngeal aspiration and dysphagia in children
Authors: Weir K. , McMahon S. , Barry L. , Masters I. B. , Chang A. B. 
Published: November 2008

The diagnostic value of various signs and symptoms (clinical markers) in predicting oropharyngeal aspiration (OPA) or swallowing dysfunction has not been established in children. The present retrospective study was undertaken to: 1) identify specific clinical markers associated with radiographic evidence of OPA, isolated laryngeal penetration (ILP) and post-swallow residue (PSR); 2) determine the sensitivity and specificity of clinical markers associated with OPA; and 3) determine the influence of age and neurological impairment on clinical markers of OPA.In total, 11 clinical markers of dysphagia were compared with the videofluoroscopic swallow study (VFSS) results (OPA, ILP and PSR) in 150 children on diets of thin fluid and purée consistencies. Chi-squared and logistic regression were used to analyse the association between clinical markers and VFSS-identified swallowing dysfunction.In children with OPA, wet voice (odds ratio (OR) 8.90, 95% confidence interval (CI) 2.87–27.62), wet breathing (OR 3.35, 95% CI 1.09–10.28) and cough (OR 3.30, 95% CI 1.17–9.27) were significantly associated with thin fluid OPA. Predictive values included: wet voice (sensitivity 0.67; specificity 0.92); wet breathing (sensitivity 0.33; specificity 0.83); and cough (sensitivity 0.67; specificity 0.53). No clinical markers were significantly associated with OPA, ILP or PSR on the purée consistency. Cough was significantly associated with PSR on thin fluids (OR 3.59, 95% CI 1.22–10.55). Differences were found for age.Wet voice, wet breathing and cough were good clinical markers for children with oropharyngeal aspiration on thin fluid but not on purée. Age and neurological status influenced the significance of these clinical markers.
Three Times Weekly Tacrolimus Ointment Reduces Relapse in Stabilized Atopic Dermatitis: A New Paradigm for Use
Authors: Paller Amy S. , Eichenfield Lawrence F. , Kirsner Robert S. , Shull Toni , Jaracz Eileen , Simpson Eric L. ,   for the US Tacrolimus Ointment Study Group
Published: November 2008

OBJECTIVE. Long-term, safe and effective therapeutic options for managing the chronic relapsing nature of atopic dermatitis are essential for improving patient quality of life. To minimize the risks of continued topical corticosteroid usage and potentially reduce the incidence of flares, we tested the efficacy and safety of a rotational paradigm of initial brief application of topical corticosteroid followed by long-term intermittent application of non-steroidal tacrolimus ointment to previously inflamed sites of dermatitis.METHODS. In this 2-phase study, patients who were 2 to 15 years of age and had moderate to severe atopic dermatitis were randomly assigned to 4 days of twice-daily double-blind therapy with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (Phase I acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (Phase I short-term). Patients whose disease stabilized underwent new randomization to double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week to clinically normal-appearing skin for up to 40 weeks (Phase II). Corticosteroid use was prohibited.RESULTS. Of 206 randomly assigned patients, 152 completed Phase I; 105 of 152 were randomly assigned into Phase II (68 tacrolimus ointment and 37 vehicle). There were no differences in adverse events between alclometasone and tacrolimus (Phase I) or between tacrolimus and vehicle (Phase II). In the acute period, alclometasone-treated patients showed greater improvement in atopic dermatitis signs and symptoms; thereafter, when all patients applied tacrolimus ointment (short-term), there were no differences. In Phase II, tacrolimus-treated patients had significantly more disease-free days compared with vehicle, significantly longer time to first relapse, and significantly fewer disease relapse days.CONCLUSIONS. For patients with stabilized moderate to severe atopic dermatitis, long-term intermittent application of tacrolimus ointment to normal-appearing but previously affected skin was significantly more effective than vehicle at maintaining disease stabilization, with a safety profile similar to vehicle.
History Matching for Determination of Fracture Permeability and Capillary Pressure
Authors: Gang Tao , Kelkar Mohan 
Published: November 2008

Summary
For naturally fractured reservoirs, it is very difficult to quantify future prediction without proper fracture properties, including such factors as fracture permeability, fracture orientation, and fracture length, and capillary pressure. Capillary pressure and fracture permeability can interact in a way that can produce nonunique results. Evaluation of core data may provide us with some information about imbibition capillary pressure curves; however, quantification of fracture permeability is determined largely by matching production data.
This paper presents an integrated approach to history matching naturally fractured reservoirs by adjusting the fracture permeability of individual fractures and water/oil capillary pressure curves. This paper is focused mainly on history-matching procedure and not on geological-model construction. By minimizing an objective function to history matching production data, we generate estimates of fracture permeability of individual fractures and water/oil capillary pressure curves. All implementations were incorporated into a commercial simulator and iterated in the automatic-history-matching scheme. The adjoint method and an efficient direct solver were used to reduce CPU time for calculating the sensitivity-coefficient matrix. A 2D synthetic case was used, with the fracture distribution from a Middle East reservoir, to validate this method.
Designing Hydraulic Fractures in Russian Oil and Gas Fields To Accommodate Non-Darcy and Multiphase Flow
Authors: Dedurin Andrey V. , Majar Vadim A. , Voronkov Andrey A. , Zagurenko Alexey G. , Zakharov Alexander Y. , Palisch Terry , Vincent M. C. 
Published: November 2008

Summary
Non-Darcy and multiphase flow effects in hydraulic fractures have been well documented in the last several years. The pressure losses caused by these phenomena are accepted widely to be of great significance in most gas-well completions in the United States and elsewhere (Palisch et al. 2007; Forchheimer 1901; Milton-Tayler 1993a; Penny and Jin 1995; Flowers et al. 2003; Miskimins et al. 2005; Handren et al. 2001; Lolon et al. 2004; Vincent 2004; Olson et al. 2004). Although the importance in gas wells is evident, the authors pose the question of whether non-Darcy and multiphase flow effects are of concern in typical oil wells in Russia.
For the analysis, the authors evaluate three primary categories of Russian production wells: gas wells, oil wells producing above the bubblepoint, and oil wells producing below the bubblepoint. For each category, the authors describe the significance of non-Darcy and multiphase flow effects by use of the fracture-flow theory and state-of-the-art fracture-production models. This paper will illustrate that non-Darcy and multiphase flow effects can substantially decrease the production potential of gas wells and the many oil wells found in Russia that are producing below the bubblepoint.
Historically, Russian oil wells have been operated intentionally above the bubblepoint. However, more-aggressive well designs have recently been shown to increase production more than threefold. The authors explore the economics of producing these wells below the bubblepoint and show that for these more aggressive strategies, the effects of non-Darcy and multiphase flow can be significant and should be accommodated during fracture design.
The authors propose solutions for mitigating these effects with various modifications to the fracture design, including the impact of proppant selection on performance. Several operators within Russia have already successfully accounted for these phenomena in their fracture designs, and new field examples are explored, analyzed, and presented in the paper. Recent field results are presented for Gazpromneft's Achimovskoya formation BV8 in the Tomsk region (western Siberia) and BP-TNK's field near Buzuluk in the Orenburg region (Volga-Urals). The results found here are compared to published results from the Achimovskoya sandstone in the Kalchinskoye oil field, the BP12 formation of the Vyngayakhinskoe oil field, the Priobskoye and Sugmutskoe oil fields, and Gazprom's Yamburgskoe gas-condensate development.
A New Rate-Allocation-Optimization Framework
Authors: Güyagüler B. , Byer T. 
Published: November 2008

Summary
Determination of the operating conditions of a field under a set of physical system constraints (e.g., compressor limits) and engineering preferences (e.g., voidage replacement) is a primary concern for petroleum engineers. Rule-based systems have been proposed for this, but the process is most suitably defined as an optimization problem. An optimization procedure that uses mixed-integer linear programming (MILP) is discussed in this study. Well rates that honor system and engineering constraints are handled simultaneously while the maximum for an objective is calculated (e.g., field oil rate or cash revenue). Optimal rates for the current conditions of the field are determined. Note that this results in instantaneous optimization and, thus, cannot account for recurrent events such as water breakthrough. Nevertheless, an efficient and robust instantaneous optimizer is useful within a grander optimization scheme, short forecast periods and, also, in real-time allocation situations. The approach is able to efficiently handle the nonlin-earities in the system by way of piecewise linear functions. Also, as a result of the formulation, the exact optimal solution of the problem is guaranteed. Another property of the approach is that, in cases in which it is not possible to honor all the targets and limits of the system simultaneously, a scheme is introduced that enables the engineer to prioritize the constraints. This prioritization scheme proves to be of great practical significance because most real cases have conflicting targets and limits that result in optimization systems with no feasible solutions. Also, a heuristic is used that ensures realistic results by elimination of mathematical artifacts (rate oscillations in time) that often arise when the reservoir contains wells with similar properties [e.g., water/oil ratio (WOR) and gas/ oil ratio (GOR)]. The optimization system is applied to synthetic cases and two real-field cases. The real-field cases pose problems that cannot be handled by conventional rule-based systems.