bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Impact of Convective Entrainment on the Tropical Tropopause
Authors: Robinson F. J. , Sherwood S. C. 
Published: April 2006

Abstract
Simulations with the Weather Research and Forecasting (WRF) cloud-resolving model of deep moist convective events reveal net cooling near the tropopause (∼15–18 km above ground), caused by a combination of large-scale ascent and small-scale cooling by the irreversible mixing of turbulent eddies overshooting their level of neutral buoyancy. The turbulent cooling occurred at all CAPE values investigated (local peak values ranging from 1900 to 3500 J kg−1) and was robust to grid resolution, subgrid-scale turbulence parameterization, horizontal domain size, model dimension, and treatment of ice microphysics. The ratio of the maximum downward heat flux in the tropopause to the maximum tropospheric upward heat flux was close to 0.1. This value was independent of CAPE but was affected by changes in microphysics or subgrid-scale turbulence parameterization.
The convective cooling peaked roughly 1 km above the cold point in the background input sounding and the mean cloud- and (turbulent kinetic energy) TKE-top heights, which were all near 16.5 km above ground. It was associated with turbulent entrainment of stratospheric air from as high as 18.25 km into the troposphere. Typical cooling in the experiments was of order 1 K during convective events that produced order 10 mm of precipitation, which implied a significant contribution to the tropopause energy budget. Given the sharp concentration gradients and long residence times near the cold point, even such a small entrainment rate is likely consequential for the transport and ambient distribution of trace gases such as water vapor and ozone, and probably helps to explain the gradual increase of ozone typically observed below the tropical tropopause.
IL-4 induced MUC4 enhancement in respiratory epithelial cells in vitro is mediated through JAK-3 selective signaling
Authors: Damera Gautam , Xia Baoyun , Sachdev Goverdhan P 
Published: April 2006

AbstractBackgroundRecent studies have identified MUC4 mucin as a ligand for activation of ErbB2, a receptor tyrosine kinase that modulates epithelial cell proliferation following epithelial damage in airways of asthmatics. In this study, we investigated the potential role of IL-4, one of the Th2 inflammatory cytokines persistent in asthmatic airways, in regulating MUC4 expression using a cell line NCI-H650.MethodsReal time PCR analysis was performed to determine concentration and time dependent effects of IL-4 uponMUC4expression. Nuclear run on experiments were carried out to explore potential transcriptional modulation. Western blotting experiments using a monoclonal antibody specific to ASGP-2 domain of MUC4 were performed to analyze MUC4 glycoprotein levels in plasma membrane fractions. To analyze potential signal transduction cascades, IL-4 treated confluent cultures were co-incubated, separately with a pan-JAK inhibitor, a JAK-3 selective inhibitor or a MEK-1, 2 (MAPK) inhibitor at various concentrations beforeMUC4transcript analysis. Corresponding transcription factor activation was tested by western blotting using a monoclonal p-STAT-6 antibody.ResultsMUC4levels increased in a concentration and time specific fashion reaching peak expression at 2.5 ng/ml and 8 h. Nuclear run on experiments revealed transcriptional enhancement. Corresponding increases in MUC4 glycoprotein levels were observed in plasma membrane fractions. Pan-JAK inhibitor revealed marked reduction in IL-4 stimulatedMUC4levels and JAK3 selective inhibitor down-regulated MUC4 mRNA expression in a concentration-dependent fashion. In accordance with the above observations, STAT-6 activation was detected within 5 minutes of IL-4 stimulus. No effect inMUC4levels was observed on using a MAPK inhibitor.ConclusionThese observations signify a potential role for IL-4 in MUC4 up-regulation in airway epithelia.
Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression
Authors: Schaub Bianca , Campo Monica , He Hongzhen , Perkins David , Gillman Matthew W , Gold Diane R , Weiss Scott , Lieberman Ellice , Finn Patricia W 
Published: April 2006

AbstractBackgroundMaternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2), may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy.MethodsWe analyzed immune responses of cord blood mononuclear cells (CBMC) from 50 healthy neonates (31 non-atopic and 19 atopic mothers). Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg) or the allergen house dust mite Dermatophagoides farinae (Derf1), and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR), and the cytotoxic lymphocyte antigen 4 (CTLA4). Lymphocyte proliferation was measured by3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR.ResultsPpg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07). Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049). IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001), GITR (r = 0.47, p = 0.004) and CTLA4 (r = 0.49, p = 0.003), independent of maternal atopy.ConclusionTLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to respond to microbial stimuli.
The Directly Observed Therapy Short-Course (DOTS) strategy in Samara Oblast, Russian Federation
Authors: Balabanova Y , Drobniewski F , Fedorin I , Zakharova S , Nikolayevskyy V , Atun R , Coker R 
Published: April 2006

Abstract

Background
The World Health Organisation (WHO) defines Russia as one of the 22 highest-burden countries for tuberculosis (TB). The WHO Directly Observed Treatment Short Course (DOTS) strategy employing a standardised treatment for 6 months produces the highest cure rates for drug sensitive TB. The Russian TB service traditionally employed individualised treatment.
The purpose of this study was to implement a DOTS programme in the civilian and prison sectors of Samara Region of Russia, describe the clinical features and outcomes of recruited patients, determine the proportion of individuals in the cohorts who were infected with drug resistant TB, the degree to which resistance was attributed to the Beijing TB strain family and establish risk factors for drug resistance.

Methods
prospective study

Results
2,099 patients were recruited overall. Treatment outcomes were analysed for patients recruited up to the third quarter of 2003 (n = 920). 75.3% of patients were successfully treated. Unsuccessful outcomes occurred in 7.3% of cases; 3.6% of patients died during treatment, with a significantly higher proportion of smear-positive cases dying compared to smear-negative cases. 14.0% were lost and transferred out. A high proportion of new cases (948 sequential culture-proven TB cases) had tuberculosis that was resistant to first-line drugs; (24.9% isoniazid resistant; 20.3% rifampicin resistant; 17.3% multidrug resistant tuberculosis). Molecular epidemiological analysis demonstrated that half of all isolated strains (50.7%; 375/740) belonged to the Beijing family. Drug resistance including MDR TB was strongly associated with infection with the Beijing strain (for MDR TB, 35.2% in Beijing strains versus 9.5% in non-Beijing strains, OR-5.2. Risk factors for multidrug resistant tuberculosis were: being a prisoner (OR 4.4), having a relapse of tuberculosis (OR 3.5), being infected with a Beijing family TB strain (OR 6.5) and having an unsuccessful outcome from treatment (OR 5.0).

Conclusion
The implementation of DOTS in Samara, Russia, was feasible and successful. Drug resistant tuberculosis rates in new cases were high and challenge successful outcomes from a conventional DOTS programme alone.
Can HRCT be used as a marker of airway remodelling in children with difficult asthma?
Authors: Saglani S , Papaioannou G , Khoo L , Ujita M , Jeffery PK , Owens C , Hansell DM , Payne DN , Bush A 
Published: April 2006

Abstract

Background
Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA.

Methods
27 children (median age 10.5 [range 4.1–16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0–4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter – airway lumen diameter]/airway outer diameter ×100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated.

Results
Median RBM thickness in endobronchial biopsies was 6.7(range 4.6 – 10.0) μm. Median qualitative score for BWT of the right lower lobe was 1(range 0 – 1.5) and quantitative score was 54.3 (range 48.2 – 65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness.

Conclusion
Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with DA.
Prenatal and postnatal tobacco smoke exposure and respiratory health in Russian children
Authors: Jaakkola Jouni JK , Kosheleva Anna A , Katsnelson Boris A , Kuzmin Sergey V , Privalova Larissa I , Spengler John D 
Published: April 2006

Abstract

Background
Only few studies have assessed the relative impact of prenatal and postnatal exposure to tobacco smoke on the child's later asthma or chronic respiratory symptoms and to our knowledge no studies have elaborated respiratory infections and allergies in this context.

Objective
To assess the effects of prenatal and postnatal exposure to tobacco smoke on respiratory health of Russian school children.

Methods
We studied a population of 5951 children (8 to12 years old) from 9 Russian cities, whose parents answered a questionnaire on their children's respiratory health, home environment, and housing characteristics. The main health outcomes were asthma, allergies, chronic respiratory symptoms, chronic bronchitis, and upper respiratory infections. We used adjusted odds ratios (ORs) from logistic regression analyses as measures of effect.

Results
Prenatal exposure due to maternal smoking had the strongest effects on asthma (adjusted OR 2.46, 95% CI 1.19–5.08), chronic bronchitis (adjusted OR 1.45, 95% CI 1.08–1.96) and respiratory symptoms, such as wheezing (adjusted OR 1.30, 95% CI 0.90–1.89). The associations were weaker for exposure during early-life (adjusted ORs 1.38/1.27/1.15 respectively) and after 2 years of age (adjusted ORs 1.45/1.34/1.18) compared to prenatal exposure and the weakest or non-existent for current exposure (adjusted ORs 1.05/1.09/1.06). Upper respiratory infections were associated more strongly with early-life exposure (adjusted OR 1.25, 95% CI 1.09–1.42) than with prenatal (adjusted OR 0.74, 95% CI 0.54–1.01) or current exposure (adjusted OR1.05, 95% CI 0.92–1.20). The risk of allergies was also related to early life exposure to tobacco smoke (adjusted OR 1.26, 95% CI 1.13–1.42).

Conclusion
Adverse effects of tobacco smoke on asthma, chronic bronchitis, and chronic respiratory symptoms are strongest when smoking takes place during pregnancy. The relations are weaker for exposure during early-life and after 2 years of age and weakest or non-existent for current exposure.
Tissue fibrocytes in patients with mild asthma: A possible link to thickness of reticular basement membrane?
Authors: Nihlberg Kristian , Larsen Kristoffer , Hultgårdh-Nilsson Anna , Malmström Anders , Bjermer Leif , Westergren-Thorsson Gunilla 
Published: April 2006

Abstract

Background
Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveolar lavage fluid (BALF) in steroid-naive patients with mild asthma and controls.

Methods
Patients with mild asthma (n = 9) were recruited and divided into two categories based on whether or not fibroblast-like cells could be established from BALF. Non-asthmatic healthy subjects (n = 5) were used as controls. Colocalization of the fibrocyte markers CD34, CD45RO, procollagen I, and α-smooth muscle actin (α-SMA) were identified in bronchial biopsies from patients and controls by confocal microscopy. Kruskall-Wallis method was used to calculate statistical significance and Spearman coefficient of rank correlation was used to assess the degree of association.

Results
In patients with BALF fibroblasts, a 14-fold increase of tissue cells expressing CD34/CD45RO/α-SMA and a 16-fold increase of tissue cells expressing CD34/procollagen I was observed when compared to controls (p < 0.05). In contrast, patients without BALF fibroblasts displayed a 2-fold increase when compared to controls (p < 0.05). Fibrocytes were localized close to the basement membrane which was significantly thicker in patients with BALF fibroblasts when compared to the other two groups of subjects. Furthermore, basement membrane thickness could be correlated to the number of fibrocytes in tissue (r = 0.711). Fibroblasts-like cells were cultured from BALF where 17.6% of these cells expressed CD34, CD45RO and α-SMA.

Conclusion
These findings indicate a correlation between recruited fibrocytes in tissue and thickness of basement membrane. Fibroblast progenitor cells may therefore be important in airway remodeling in steroid-naive patients with mild asthma.
EAAC1 is expressed in rat and human prostate epithelial cells; functions as a high-affinity L-aspartate transporter; and is regulated by prolactin and testosterone
Authors: Franklin Renty B , Zou Jing , Yu Ziqiang , Costello Les C 
Published: April 2006

Abstract

Background
Prostate epithelial cells accumulate a high level of aspartate that is utilized as a substrate for their unique function of production and secretion of enormously high levels of citrate. In most mammalian cells aspartate is synthesized; and, therefore is a non-essential amino acid. In contrast, in citrate-producing prostate cells, aspartate is an essential amino acid that must be derived from circulation. The prostate intracellular/extracellular conditions present a 40:1 concentration gradient. Therefore, these cells must possess a plasma membrane-associated aspartate uptake transport process to achieve their functional activity. In earlier kinetic studies we identified the existence of a unique Na+-dependent high-affinity L-aspartate transport process in rat prostate secretory epithelial cells. The present report is concerned with the identification of this putative L-aspartate transporter in rat and human prostate cells.

Results
The studies show for the first time that EAAC1 is expressed in normal rat prostate epithelial cells, in normal and hyperplastic human prostate glands, and in human malignant prostate cell lines. EAAC1 expression and high-affinity L-aspartate transport are correspondingly down-regulated by EAAC1 siRNA knock down. Exposure of prostate cells to physiological levels of prolactin or testosterone results in an up-regulation of EAAC1 expression and a corresponding increase in the high-affinity transport of L-aspartate into the cells.

Conclusion
This study shows that EAAC1 functions as the high-affinity L-aspartate transporter that is responsible for the uptake and accumulation of aspartate in prostate cells. In other cells (predominantly excitable tissue cells), EAAC1 has been reported to function as a glutamate transporter rather than as an aspartate transporter. The regulation of EAAC1 expression and L-aspartate transport by testosterone and prolactin is consistent with their regulation of citrate production in prostate cells. The identification of EAAC1 as the high-affinity L-aspartate transporter now permits studies to elucidate the mechanism of hormonal regulation of EAAC1 gene expression, and to investigate the mechanism by which the cellular environment effects the functioning of EAAC1 as an aspartate transporter or as a glutamate transporter.
Choosing the best heuristic for seeded alignment of DNA sequences
Authors: Sun Yanni , Buhler Jeremy 
Published: April 2006

Abstract
Background
Seeded alignment is an important component of algorithms for fast, large-scale DNA similarity search. A good seed matching heuristic can reduce the execution time of genomic-scale sequence comparison without degrading sensitivity. Recently, many types of seed have been proposed to improve on the performance of traditional contiguous seeds as used in, e.g., NCBI BLASTN. Choosing among these seed types, particularly those that use information besides the presence or absence of matching residue pairs, requires practical guidance based on a rigorous comparison, including assessment of sensitivity, specificity, and computational efficiency. This work performs such a comparison, focusing on alignments in DNA outside widely studied coding regions.

Results
We compare seeds of several types, including those allowing transition mutations rather than matches at fixed positions, those allowing transitions at arbitrary positions ("BLASTZ" seeds), and those using a more general scoring matrix. For each seed type, we use an extended version of our Mandala seed design software to choose seeds with optimized sensitivity for various levels of specificity. Our results show that, on a test set biased toward alignments of noncoding DNA, transition information significantly improves seed performance, while finer distinctions between different types of mismatches do not. BLASTZ seeds perform especially well. These results depend on properties of our test set that are not shared by EST-based test sets with a strong bias toward coding DNA.

Conclusion
Practical seed design requires careful attention to the properties of the alignments being sought. For noncoding DNA sequences, seeds that use transition information, especially BLASTZ-style seeds, are particularly useful. The Mandala seed design software can be found at http://www.cse.wustl.edu/~yanni/mandala/.
Identification and evolutionary analysis of novel exons and alternative splicing events using cross-species EST-to-genome comparisons in human, mouse and rat
Authors: Chen Feng-Chi , Chen Chuang-Jong , Ho Jar-Yi , Chuang Trees-Juen 
Published: April 2006

Abstract

Background
Alternative splicing (AS) is important for evolution and major biological functions in complex organisms. However, the extent of AS in mammals other than human and mouse is largely unknown, making it difficult to study AS evolution in mammals and its biomedical implications.

Results
Here we describe a cross-species EST-to-genome comparison algorithm (ENACE) that can identify novel exons for EST-scanty species and distinguish conserved and lineage-specific exons. The identified exons represent not only novel exons but also evolutionarily meaningful AS events that are not previously annotated. A genome-wide AS analysis in human, mouse and rat using ENACE reveals a total of 758 novel cassette-on exons and 167 novel retained introns that have no EST evidence from the same species. RT-PCR-sequencing experiments validated ~50 ~80% of the tested exons, indicating high presence of exons predicted by ENACE. ENACE is particularly powerful when applied to closely related species. In addition, our analysis shows that the ENACE-identified AS exons tend not to pass the nonsynonymous-to-synonymous substitution ratio test and not to contain protein domain, implying that such exons may be under positive selection or relaxed negative selection. These AS exons may contribute to considerable inter-species functional divergence. Our analysis further indicates that a large number of exons may have been gained or lost during mammalian evolution. Moreover, a functional analysis shows that inter-species divergence of AS events may be substantial in protein carriers and receptor proteins in mammals. These exons may be of interest to studies of AS evolution. The ENACE programs and sequences of the ENACE-identified AS events are available for download.

Conclusion
ENACE can identify potential novel cassette exons and retained introns between closely related species using a comparative approach. It can also provide information regarding lineage- or species-specificity in transcript isoforms, which are important for evolutionary and functional studies.
A joint model for nonparametric functional mapping of longitudinal trajectory and time-to-event
Authors: Lin Min , Wu Rongling 
Published: April 2006

AbstractBackgroundThe characterization of the relationship between a longitudinal response process and a time-to-event has been a pressing challenge in biostatistical research. This has emerged as an important issue in genetic studies when one attempts to detect the common genes or quantitative trait loci (QTL) that govern both a longitudinal trajectory and developmental event.ResultsWe present a joint statistical model for functional mapping of dynamic traits in which the event times and longitudinal traits are taken to depend on a common set of genetic mechanisms. By fitting the Legendre polynomial of orthogonal properties for the time-dependent mean vector, our model does not rely on any curve, which is different from earlier parametric models of functional mapping. This newly developed nonparametric model is demonstrated and validated by an example for a forest tree in which stemwood growth and the time to first flower are jointly modelled.ConclusionOur model allows for the detection of specific QTL that govern both longitudinal traits and developmental processes through either pleiotropic effects or close linkage, or both. This model will have great implications for integrating longitudinal and event data to gain better insights into comprehensive biology and biomedicine.