bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isotopic constraints on crustal architecture and Permo‐Triassic tectonics in New Guinea: possible links with eastern Australia
Authors: Crowhurst P. V. , Maas R. , Hill K. C. , Foster D. A. , Fanning C. M. 
Published: March 2004

New U–Pb zircon ages and Sr–Nd isotopic data for Triassic igneous and metamorphic rocks from northern New Guinea help constrain models of the evolution of Australia's northern and eastern margin. These data provide further evidence for an Early to Late Triassic volcanic arc in northern New Guinea, interpreted to have been part of a continuous magmatic belt along the Gondwana margin, through South America, Antarctica, New Zealand, the New England Fold Belt, New Guinea and into southeast Asia. The Early to Late Triassic volcanic arc in northern New Guinea intrudes high‐grade metamorphic rocks probably resulting from Late Permian to Early Triassic (ca 260–240 Ma) orogenesis, as recorded in the New England Fold Belt. Late Triassic magmatism in New Guinea (ca 220 Ma) is related to coeval extension and rifting as a precursor to Jurassic breakup of the Gondwana margin. In general, mantle‐like Sr–Nd isotopic compositions of mafic Palaeozoic to Tertiary granitoids appear to rule out the presence of a North Australian‐type Proterozoic basement under the New Guinea Mobile Belt. Parts of northern New Guinea may have a continental or transitional basement whereas adjacent areas are underlain by oceanic crust. It is proposed that the post‐breakup margin comprised promontories of extended Proterozoic–Palaeozoic continental crust separated by embayments of oceanic crust, analogous to Australia's North West Shelf. Inferred movement to the south of an accretionary prism through the Triassic is consistent with subduction to the south‐southwest beneath northeast Australia generating arc‐related magmatism in New Guinea and the New England Fold Belt.
Soldiers Cap Group iron‐formations, Mt Isa Inlier, Australia, as windows into the hydrothermal evolution of a base‐metal‐bearing Proterozoic rift basin
Authors: Hatton O. J. , Davidson G. J. 
Published: March 2004

The Proterozoic Soldiers Cap Group, a product of two major magmatic rift phases separated by clastic sediment deposition, hosts mineralised (e.g. Pegmont Broken Hill‐type deposit) and barren iron oxide‐rich units at three main stratigraphic levels. Evaluation of detailed geological and geochemical features was carried out for one lens of an apatite–garnet‐rich, laterally extensive (1.9 km) example, the Weatherly Creek iron‐formation, and it was placed in the context of reconnaissance studies of other similar units in the area. Chemical similarities with iron‐formations associated with Broken Hill‐type Pb–Zn deposit iron‐formations are demonstrated here. Concordant contact relationships, mineralogy, geochemical patterns and pre‐deformational alteration all indicate that the Soldiers Cap Group iron‐formations are mainly hydrothermal chemical sediments. Chondrite normalised REE patterns display positive Eu and negative Ce anomalisms, consistent with components of both high‐temperature, reduced, hydrothermal fluid (≥250°C) and cool oxidised seawater. Major element data suggest a largely mafic provenance for montmorillonitic clays and other detritus during chemical sedimentation, consistent with westward erosion of Cover Sequence 2 volcanic rocks, rather than local mafic sources. Ni enrichment is most consistent with hydrogenous uptake by Mn‐oxides or carbonates. Temperatures inferred from REE data indicate that although they are not strongly enriched, base metals such as Pb and Zn are likely to have been transported and deposited prior to or following iron‐formation deposition. Most chemical sedimentation pre‐dated emplacement of the major mafic igneous sill complexes present in the upper part of the basin. Heating of deep basinal brines in a regional‐scale aquifer by deep‐seated mafic magma chambers is inferred to have driven development of hydrothermal fluids. Three major episodes of extension exhausted this aquifer, but were succeeded by a final climactic extensional phase, which produced widespread voluminous mafic volcanism. The lateral extent of the iron‐formations requires a depositional setting such as a sea‐floor metalliferous sediment blanket or series of brine pools, with iron‐formation deposition likely confined to much smaller fault‐fed areas surrounded by Fe–Mn–P‐anomalous sediments. These relationships indicate that in such settings, major sulfide deposits and their associated chemical sediment marker horizons need not overlie major igneous sequences. Rather, the timing of expulsion of hydrothermal fluid reflects the interplay between deep‐seated heating, extension and magmatism.
Classroom research or w(h)ither development: gender, complexity and diversity in the UK, the USA and Australia
Authors: Rhedding‐jones Jeanette 
Published: March 2004

Starting school—young children learning cultures L. BrookerEmbracing identities in early childhood education: diversity and possibilities S. Grieshaber & G. Cannella, G. (Eds)Caring classrooms/intelligent schools: the social emotional education of young children J. Cohen (Ed.)
CisML: an XML-based format for sequence motif detection software
Authors: Haverty Peter M. , Weng Zhiping 
Published: March 2004

Abstract
Summary: CisML is an XML-based format for sequence motif detection software. This proposed standard is applicable to many types of sequence motif detection programs. It is intended to facilitate the integration of data and the comparison of results from different software packages, and to simplify the development of downstream tools. XSL stylesheets are provided for easy generation of text, html and graphical reports from CisML-formatted data.
Availability: http://zlab.bu.edu/CisML/
Supplementary information: Example CisML-formatted data and XSL stylesheets for report generation are available along with the sample output.
Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs
Authors: Kashtan N. , Itzkovitz S. , Milo R. , Alon U. 
Published: March 2004

Abstract
Summary: Biological and engineered networks have recently been shown to display network motifs: a small set of characteristic patterns that occur much more frequently than in randomized networks with the same degree sequence. Network motifs were demonstrated to play key information processing roles in biological regulation networks. Existing algorithms for detecting network motifs act by exhaustively enumerating all subgraphs with a given number of nodes in the network. The runtime of such algorithms increases strongly with network size. Here, we present a novel algorithm that allows estimation of subgraph concentrations and detection of network motifs at a runtime that is asymptotically independent of the network size. This algorithm is based on random sampling of subgraphs. Network motifs are detected with a surprisingly small number of samples in a wide variety of networks. Our method can be applied to estimate the concentrations of larger subgraphs in larger networks than was previously possible with exhaustive enumeration algorithms. We present results for high-order motifs in several biological networks and discuss their possible functions.
Availability: A software tool for estimating subgraph concentrations and detecting network motifs (mfinder 1.1) and further information is available at http://www.weizmann.ac.il/mcb/UriAlon/
A Web-based design center for vector-based siRNA and siRNA cassette
Authors: Wang Luquan , Mu Forest Y. 
Published: March 2004

Abstract
Summary: To facilitate the designing process for vector-based siRNA and siRNA cassette, a tool set has been developed consisting of a siRNA target finder, a siRNA construct builder and a siRNA sequence scrambler. The siRNA target finder is used to identify candidate siRNA target sites. The program automates homology filtering, minimizes non-specific cross-reaction, filters target sites based on RNA duplex internal stability and siRNA sense/anti-sense strand secondary structure. The siRNA construct builder is used to create a siRNA hairpin construct as a vector insert or a cassette insert. The siRNA sequence scrambler is used to generate a negative control sequence for siRNA experiments. Together, these programs provide a comprehensive utility set to address the specific bioinformatics need of DNA-based siRNA design.
Availability: The Web-based design tools are available at GenScript Website (siRNA design center). http://www.genscript.com or http://www.genscript.com/rnai.html#design or http://www.genscript.com/sirna_ca.html#design
Comparison of the pharmacokinetic profiles of two locally administered doxycycline gels in crevicular fluid and saliva
Authors: Kim Ti‐Sun , Klimpel Homa , Fiehn Walter , Eickholz Peter 
Published: March 2004

AbstractBackground:  Controlled‐release delivery systems enable the clinician to extend the half‐life period of locally administered antibiotics in gingival crevicular fluid (GCF) significantly. The aim of this split‐mouth study was to compare the pharmacokinetic profile of two different doxycycline gels (DOXY and ATRI) for topical subgingival application. Pharmacokinetics of both doxycycline gels were analyzed in GCF and saliva.Methods:  In 10 patients suffering from severe periodontitis, 10 pairs of contralateral defects (pocket depth 5 mm/bleeding on probing or 6 mm) were randomly assigned either to the first application of DOXY or ATRI. Fourteen days after the topical application of the first antibiotic gel, the application of the second gel in the contralateral defect took place. Clinical examinations at baseline showed no significant differences between sites treated with DOXY and ATRI. Samples of GCF and saliva were drawn baseline, 2, 5 and 24 h after application, 2, 3, 4, 7, 9 and 11 days after application. Separation and quantitative measurement of both doxycycline‐gels was performed with HPLC‐ and UV‐detection at λ=260 nm.Results:  In saliva specimens, time‐dependent changes of mean doxycycline concentration were almost identical for both doxycycline‐gels and declined from a maximum 2 h after application (ATRI: 6653.90±3096.14 μg/ml; DOXY: 5386.60±1542.02 μg/ml [arithmetic mean±SEM]) to zero values 9 days after application. In crevicular fluid specimens, sites treated with ATRI exhibited a faster decrease of mean doxycycline concentration (1085.30, 264.00, 273.94, and 258.00 μg/ml measured 2, 5, 24, and 48 h after application) than sites treated with DOXY (1388.38, 1300.40, 803.73, and 235.10 μg/ml). The faster decrease of ATRI compared with DOXY could not be proved to be statistically significantly different.Conclusions:  Both doxycycline gels showed pharmacokinetics of controlled‐release delivery systems.
Changing Strategies and Tactics for New Product Development
Authors: Ettlie John E. , Subramaniam Mohan 
Published: March 2004

There has been a considerable amount of effort and writing devoted to improving the new product development process during the last two decades. Although there have been some surprises in this literature and in reports from the field on how to manage this complex business process, we now have a good view of the state‐of‐the‐art practices that work and do not work to accelerate commercial success of new ventures. We know much less about how firms change their strategies for new product development.In this article, we report on a study to investigate how companies change the way they originate and develop new products in manufacturing. We made no prior assumptions about what best practices might be for changing the direction of the new product development process, but we reasonably were sure there would be trends in how companies were attempting to create this strategic change. Even though one size does not fit all, there were significant trends in our findings.We studied eight manufacturing firms using in‐depth, open‐ended interviews and were surprised to find that most of these companies are beginning to develop products that are new to the firm, industry, and the world (nearly half, or 10 of 21 new product projects), where they had not been eager for radical change in the past. These newer products likely are to be driven by a combination of market and technology forces, with general requirements being directed by internal forces: middle and top management. Results also indicate significantly that being able to marshal resources and capabilities is easier if change is less demanding and less radical, but when middle managers are driving the conversion of general requirements into specifications, resource issues have yet to be resolved. Implications of these findings are discussed for companies aspiring to change the entire process of new product development in their firms based on these significant results.
Increased expression of allergen‐induced in vitro interleukin‐10 and interleukin‐18 mRNA in peripheral blood mononuclear cells of allergic rhinitis patients after specific immunotherapy
Authors: Savolainen J. , Laaksonen K. , Rantio‐Lehtimäki A. , Terho E.O. 
Published: March 2004

SummaryBackground
During specific pollen immunotherapy (SIT) there is a local mucosal shift from Th2‐ to Th1‐ type cytokine predominance, with IL‐12 having a major role in this shift. IL‐10‐induced tolerance is supposed to be a key phenomenon in venom immunotherapy (VIT). However, the role of Th1‐promoting cytokines, on the one hand, and the role of regulatory cytokines, on the other hand, have not been studied in parallel during SIT.Objective
This study was undertaken to analyse the allergen‐induced in vitro mRNA expression of Th1‐type effector cytokine IL‐18 and regulatory cytokines IL‐10 and TGF‐β during SIT in peripheral blood mononuclear cells (PBMC) of allergic rhinitis (AR) patients.Methods
Thirty patients with AR undergoing pollen SIT and 10 patients with AR who were not treated with SIT were included in the study. The symptoms and medications were registered post‐seasonally before the beginning of SIT and after 1 year of therapy. PBMC samples were collected and stimulated with pollen allergen extract prior to the treatment, at the maintenance phase in 12 patients and after 1 year of the treatment. The cytokine mRNA expression was assessed using kinetic real‐time RT‐PCR (TaqMan®).Results
There was a clear increase in the treated AR patients, in comparison with untreated AR patients, in the expression of both IL‐10 (mean change from baseline (SEM): 3.1 (0.8) vs. −0.3 (0.3), P<0.002, Mann–Whitney U‐test) and IL‐18 (2.7 (0.9) vs. −0.2 (0.6), P<0.03) mRNA after 1 year. The clearest increase in IL‐10 mRNA expression was seen in patients who did not benefit at all (6.0 (2.3), P<0.001 vs. untreated) and the least increase in patients that had the greatest reduction of symptoms (0.8 (0.6), n.s. vs. untreated) at 1 year. The clearest increase in IL‐18 mRNA expression was seen in patients with moderate outcome (3.4 (1.6), P<0.04 vs. untreated). In intermediate samples, taken when the maintenance dose was reached, the peak expression of allergen‐induced IL‐10 mRNA was associated with the most favourable outcome of SIT (P=0.01, Fisher exact test). A similar trend was seen in IL‐18 mRNA expression.Conclusions
The results suggest that an early and transient increase in allergen‐specific IL‐10 and IL‐18 mRNA expression in PBMC is essential for the therapeutic outcome after 1 year of SIT.
Glucocorticoids up‐regulate constitutive interleukin‐10 production by human monocytes
Authors: Mozo L. , Suárez A. , Gutiérrez C. 
Published: March 2004

SummaryBackground
IL‐10 plays an immunosuppressive role in inflammatory responses. Increased plasma levels of IL‐10 have been detected in patients under glucocorticoid (GC) therapy, indicating that steroids may exert their suppressive effect, in part, by increasing IL‐10 production.Objectives
The aim was to define possible mechanisms by which steroids up‐regulate IL‐10 production. To this end, we have analysed ex vivo the effect of GCs on the constitutive production of IL‐10 by lymphocytes and cells of myeloid origin.Methods
Monocytes and T cells were isolated by a Percoll gradient and B cells were purified by rosetting. Protein and mRNA IL‐10 levels were determined by ELISA and by Northern blot, respectively.Results
Monocytes, but not T or B cells, up‐regulated the constitutive production of IL‐10 following pre‐treatment for at least 12 h with physiological doses of dexamethasone (Dex). Up‐regulation of IL‐10 occurred at both protein and mRNA levels, probably indicating that the effect of Dex was by incrementing gene transcription. Other steroids had similar outcomes, their effects being dose‐related, proportional to the steroid potency and totally reversed by the steroid antagonist RU486. Thus, transcript levels of IL‐10 were up‐regulated by GCs probably through binding of the GC receptor to its specific glucocorticoid response element sequence in the IL‐10 promoter. In contrast to monocytes, differentiated immature macrophages and dendritic cells did not vary their constitutive IL‐10 production after pre‐treatment with Dex.Conclusion
Our results support the fact that steroids up‐regulate constitutive IL‐10 production by selectively triggering activation signals on monocytes.
Association between polymorphisms in serine protease inhibitor, kazal type 5 and asthma phenotypes in a large German population sample
Authors: Kabesch M. , Carr D. , Weiland S. K. , Von Mutius E. 
Published: March 2004

SummaryBackground
Atopic diseases are characterized by immunoglobulin E (IgE)‐mediated immune responses towards common allergens, many of which are proteases. Recently it has been suggested that a proteinase inhibitor gene, SPINK5, which is located on chromosome 5q31, may play a role in the pathogenesis of atopic diseases.Objective
We investigated the association between the polymorphism G1258A leading to a putative amino acid change (Glu420Lys) in serine protease inhibitor, kazal type 5 (SPINK5) and phenotypes of atopic diseases in a large general population sample of German children.Methods
Parental questionnaires were used and children underwent skin prick testing, pulmonary function testing and bronchial challenge. Blood was collected for serum IgE measurements and DNA extraction. In total, 1161 children were genotyped for the SPINK5 Glu420Lys polymorphism and association studies were performed.Results
A significant association between SPINK5 420Lys and the development of asthma was observed (OR 1.77; 95%CI: 1.02–3.06, P=0.041 for 420Lys homocygotes). Atopic carriers of SPINK5 420Lys showed an increased risk for asthma and asthma symptoms (OR 2.06; 95%CI: 1.01–4.20, P=0.047). When children with a combination of asthma and atopic dermatitis were compared with normal controls, the SPINK5 420Lys genotype was more prevalent in the disease group (OR 4.56; 95%CI: 1.370–15.12, P=0.007). No association between SPINK5 420Lys genotypes and total serum IgE levels, skin prick test (SPT) reactivity or atopic dermatitis was observed.Conclusion
These results suggest that SPINK5 Glu420Lys polymorphism may be associated with certain asthma phenotypes characterized by the concomitant expression of asthma and atopic dermatitis or SPT reactivity.
Bacillus Calmette–Guérin‐induced interleukin‐12 did not additionally improve clinical and immunologic parameters in asthmatic children treated with sublingual immunotherapy
Authors: Arikan C. , Bahceciler N. N. , Deniz G. , Akdis M. , Akkoc T. , Akdis C. A. , Barlan I. B. 
Published: March 2004

SummaryObjective
To evaluate the effect of bacillus Calmette–Guérin (BCG) as an adjuvant to specific sublingual immunotherapy (SLIT) on the cytokine profile of peripheral blood mononuclear cells (PBMCs) and clinical outcome.Methods
Thirty‐two children with asthma and rhinitis allergic to house dust mite (HDM) with negative purified protein derivative (PPD) skin test response were enrolled. After a run‐in period of 8 weeks, patients were randomized to receive either SLIT only (n=16) or one dose of BCG immunization before initiation of SLIT (n=16) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus)+D. farinea 50/50 extract. PPD‐negative asthmatics (n=5) allergic to HDM receiving inhaled therapy only were included for comparison of cytokine levels in PBMC cultures. Efficacy was assessed both at the end of run‐in and 6 months of treatment periods with criteria including symptom, medication and quality‐of‐life (QoL) scores, IgE levels, lung function, provocation concentration (PC20), eosinophil count and skin prick tests. IL‐4, IL‐5, IL‐10, IL‐12, IL‐13 and IFN‐γ levels were determined in antigen specifically and polyclonally stimulated PBMC cultures.Results
Both treatment groups showed significant improvement at the end of 6 months for asthma and rhinitis scores and QoL, number of asthma attacks, amount of β2‐agonists, inhaled and intranasal steroids, blood eosinophil counts and PC20. Interestingly, phytohaemagglutinin (PHA)‐stimulated IL‐12 and D. pteronyssinus‐stimulated IFN‐γ in PBMC were significantly higher in the treatment groups than controls. In addition, IL‐12 levels in response to D. pteronyssinus and PHA stimulation were significantly higher in the SLIT+BCG group than the SLIT alone group and controls.Conclusion
The present study demonstrates that successful SLIT is parallel to increased IFN‐γ production by PBMC. Although simultaneous BCG vaccination enhanced IL‐12 production, it did not additionally improve the clinical outcome.
Determinants of endotoxin levels in living environments of farmers' children and their peers from rural areas
Authors: Waser M. , Schierl R. , Von mutius E. , Maisch S. , Carr D. , Riedler J. , Eder W. , Schreuer M. , Nowak D. , Braun‐fahrländer C. ,   the ALEX Study Team
Published: March 2004

SummaryBackground
Lower frequencies of asthma and hayfever have been observed in children with contact to livestock. At school age, the amount of endotoxin measured in the dust of children's mattresses is inversely related to the occurrence of atopic asthma, hayfever and atopic sensitization both in children from farming and non‐farming households.Objective
The aim of the present study was to investigate which home and lifestyle characteristics of farm and non‐farm families contribute to endotoxin levels measured in different indoor home environments.Methods
In the framework of the Allergy and Endotoxin (ALEX) Study, endotoxin was measured in dust samples from the living room floor and the child's mattress of 319 farmers' families and 493 non‐farming families, and in settled dust from stables. Endotoxin content of all dust samples was determined by a kinetic Limulus assay (Limulus‐Amebocyte‐Lysate test). Information about the child's activities on farms, home characteristics and cleaning behaviours was obtained from parental questionnaires.Results
Endotoxin levels in stables did not predict the amount of endotoxin measured in floors or mattresses. However, a dose‐dependent association between the child's activity on the farm and indoor home endotoxin levels was observed, both in farm and non‐farm children. In non‐farm children pet keeping and the frequency of floor cleaning were additionally associated with endotoxin levels, whereas in farm children parental farm activities, study area, time since last cleaning, the mattress type as well as younger age of the children contributed to increased microbial exposure.Conclusion
These results demonstrate that regular contact to farm animals increases indoor home endotoxin concentrations, both in farm and non‐farm children, and might thus explain the protective effect of contact to livestock on atopic outcomes. To assess children's individual exposure to a microbial environment, measures of mattress dust exposure are needed as stable endotoxin concentrations were not associated with indoor home levels.