bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the Polarity Protein Par6 by TGFß Receptors Controls Epithelial Cell Plasticity
Authors: Ozdamar Barish , Bose Rohit , Barrios-Rodiles Miriam , Wang Hong-Rui , Zhang Yue , Wrana Jeffrey L.
Published: March 2005

The transition of cells from an epithelial to a mesenchymal phenotype is a critical event during morphogenesis in multicellular organisms and underlies the pathology of many diseases, including the invasive phenotype associated with metastatic carcinomas. Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms that control the dissolution of tight junctions, an early event in EMT, remain elusive. We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFβ receptors and is a substrate of the type II receptor, TβRII. Phosphorylation of Par6 is required for TGFβ-dependent EMT in mammary gland epithelial cells and controls the interaction of Par6 with the E3 ubiquitin ligase Smurf1. Smurf1, in turn, targets the guanosine triphosphatase RhoA for degradation, thereby leading to a loss of tight junctions. These studies define how an extracellular cue signals to the polarity machinery to control epithelial cell morphology.
Complement Factor H Polymorphism and Age-Related Macular Degeneration
Authors: Edwards Albert O. , Ritter Robert , Abel Kenneth J. , Manning Alisa , Panhuysen Carolien , Farrer Lindsay A.
Published: March 2005

Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the
ARMD1
locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (
P
= 4.95 × 10
-10
) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.
FT Raman Spectroscopy as a Tool for Characterization of Derivatized Silica Gel Sorbents
Authors: Tománková Zuzana , Matějka Pavel , Volka Karel , Král Vladimír
Published: March 2005

The potential of Fourier-transform (FT) Raman spectroscopy for verification of individual steps of synthesis of new chromatographic stationary phases was studied. 3-Aminopropylated silica gel was modified with two different optically active compounds ((+)-cloprostenol, (+)-(R)-2,2'-dihydroxy-1,1'-binaphthalene-3-carboxylic acid) via amide bonds. In the next step, free silanol groups were protected with trimethylsilyl groups. The FT Raman spectroscopic results compared with the data obtained by elemental analysis enable not only qualitative verification of synthetic steps, but also a semiquantitative determination of covering of the silica gel surface by derivatization agent.
Chemical changes to leaf litter from trees grown under elevated CO2and the implications for microbial utilization in a stream ecosystem
Authors: Rier Steven T , Tuchman Nancy C , Wetzel Robert G
Published: March 2005

Chemical alterations to leaf litter associated with growth under elevated CO2may impact aquatic ecosystems that rely on terrestrial leaf litter as a carbon source. This study examined how elevated CO2altered the chemistry and subsequent response of stream microorganisms growing on the leaf litter of three riparian tree species. Quaking aspen (Populus tremuloides), white willow (Salix alba), and sugar maple (Acer saccharum) were grown under ambient (360 parts per million) and elevated (720 parts per million) CO2for an entire growing season and senesced leaf litter was incubated in a stream for 80 days. Elevated-CO2effects on the chemistry of senesced litter were species-specific. Aspen leaves contained higher concentrations of lignin, maple leaves contained higher concentrations of soluble phenolic compounds, and willow leaves contained higher concentrations of carbohydrate-bound condensed tannins. Initially higher concentrations of soluble phenolic compounds in maple leaves were rapidly leached in stream water. However, higher concentrations of carbohydrate-bound tannins in elevated-CO2-grown willow leaves persisted and were correlated with reduced phenol oxidase activities of attached microbiota. Overall, altered leaf chemistry associated with growth under elevated CO2did not strongly suppress microbial activity during stream incubation. In cases where there was evidence of suppression, it was largely species-specific.
Slope failure in underconsolidated soft soils during the development of a port in Tianjin, China. Part 2: Analytical study
Authors: Li S , Yue Z Q , Tham L G , Lee C F , Yan S W
Published: March 2005

This paper presents the analytical study of a major landslide that occurred in a newly dredged slope during port development in the city of Tianjin, northern China. The slope comprised mainly underconsolidated and submerged soft soils. The landslide consisted of a number of individual slides that occurred sequentially and extended retrogressively and laterally into the reclaimed land. The paper proposes a slope stability assessment methodology for the examination of such slope failures, with retrogressive and lateral extension into reclaimed land. Both the total and the effective stress approaches are adopted in the slope stability assessment. Eight different sets of soil shear strength parameters are used in the assessment. They were determined by using different methods in the laboratory and in the field or by back analysis. The assessment results indicate that the total stress approach, together with undrained vane strength values, gives the best result in the stability assessment of the original dredged slope and the subsequent failed slopes. The paper further examines the factors that might have caused or triggered the occurrence of the landslide. Backfilling of a thick general soil layer and a sand cushion for vacuum preloading of the hydraulic fill in the reclaimed land might have rendered the entire slope marginally stable. Lowering of the tidal level might also have had an effect in triggering the landslide. The engineering approach and results presented in this study could be useful in the design and construction of dredged slopes in underconsolidated soft soils.Key words: land reclamation, dredge excavation, slope stability assessment, landslide investigation, marine mud, case studies.
Effects of aspen (Populus tremuloides) sucker removal on postfire conifer regeneration in central Alaska
Authors: Johnstone Jill F
Published: March 2005

This experiment tests the effects of early canopy development by asexually regenerating aspen (Populus tremuloides Michx.) on conifer recruitment after fire in central Alaska. The establishment and growth of three conifer species were observed in response to aboveground removal of aspen suckers for three seasons after burning by wildfire. Of the three species, Pinus contorta Dougl. ex Loud. had the most widespread seed germination and showed the strongest negative response to the presence of the aspen canopy. Picea mariana (Mill.) BSP and Picea glauca (Moench) Voss had low germination and weak or neutral responses to aspen removal. Seedlings of all species accumulated more biomass in the removal treatment. Results from the experiment suggest that competition by aspen early after disturbance can significantly reduce conifer recruitment and growth, an effect that may reinforce the long-term dominance of aspen in asexually regenerating stands.
Pollination and cone morphology affect cone and seed production in lodgepole pine seed orchards
Authors: Owens John N , Bennett Jordan , L'Hirondelle Sylvia
Published: March 2005

We describe the phenology and mechanisms of pollen-cone and seed-cone development in lodgepole pine in the interior of British Columbia and the methods for monitoring cone phenology, pollination, seed production, and causes of seed and cone losses in seed orchards over the 15-month reproductive cycle. Pollination lasted about 2 weeks, between mid-May and mid-June. Pollen shedding and female receptivity showed homogamy, protandry, or protogyny depending on weather, site, and year. Morphological and developmental features explain why pollination as early as stage 3 was most successful and why self-pollination led to a seriously reduced production of filled seed. Early pollination increased the seed potential per cone and consequently the filled seed per cone. Cone drop occurred when less than 80% of ovules were pollinated per cone and was higher in trees from Prince George than those in the Okanagan Valley. Misting of trees and mechanical blowing of pollen in the orchards did not increase filled seed per cone. Clonal effect was the most important factor in all trials and has implications for orchard management.
Losses of nitrate from gaps of different sizes in a managed beech (Fagus sylvatica) forest
Authors: Ritter E , Starr M , Vesterdal L
Published: March 2005

In the ongoing discussion about sustainable forestry, gap regeneration is suggested to reduce nitrate (NO3) losses from forest ecosystems. The effect of gap formation and gap size on soil moisture and NO3 leaching was studied in two managed beech (Fagus sylvatica L.) stands in Denmark for about 2 years after formation of four gaps (approx. 20 and 30 m in diameter). Soil moisture content, soil solution NO3-N concentrations, and nitrogen (N) concentrations in throughfall and precipitation were measured along transects from the gaps into the surrounding forests. Losses of NO3-N were estimated using the water balance model WATBAL. Soil moisture content in gaps remained close to field capacity throughout the year, while it decreased to 50%70% of field capacity under the closed canopy during the growing season. Drainage water fluxes, soil solution NO3-N concentrations, and NO3-N losses were increased in the gaps as compared to under the canopy. For the whole study period, losses of NO3-N were 3- to 13-fold higher in the gaps than in the surrounding forests. However, a significant effect of gap size was not found within the range of the investigated gap diameters and canopy heights. Presumably, not only the aboveground canopy gaps, but also the belowground root gaps affected soil moisture and thus drainage water fluxes and NO3- losses.
SYNCHRONIZATION OF MODIFIED CHEN SYSTEM
Authors: ELABBASY E. M. , AGIZA H. N. , EL-DESSOKY M. M.
Published: March 2005

This paper addresses the synchronization problem of two modified Chen systems in the presence of unknown system parameters. One-way coupling and active control laws are applied to achieve the state synchronization of two identical modified Chen systems. Based on Lyapunov stability theory, active control laws are derived such that the two modified Chen systems are to be synchronized. Numerical simulations results are used to demonstrate the effectiveness of the proposed control methods.
Inhibition of shivering in hypothermic seals during diving
Authors: Kvadsheim Petter H. , Folkow Lars P. , Blix Arnoldus Schytte
Published: March 2005

The mammalian response to hypothermia is increased metabolic heat production, usually by way of muscular activity, such as shivering. Seals, however, have been reported to respond to diving with hypothermia, which in other mammals under other circumstances would have elicited vigorous shivering. In the diving situation, shivering could be counterproductive, because it obviously would increase oxygen consumption and therefore reduce diving capacity. We have measured the electromyographic (EMG) activity of three different muscles and the rectal and brain temperature of hooded seals ( Cystophora cristata) while they were exposed to low ambient temperatures in a climatic chamber and while they performed a series of experimental dives in cold water. In air, the seals had a normal mammalian shivering response to cold. Muscles were recruited in a sequential manner until body temperature stopped dropping. Shivering was initiated when rectal temperature fell below 35.3 ± 0.6°C ( n = 6). In the hypothermic diving seal, however, the EMG activity in all of the muscles that had been shivering vigorously before submergence was much reduced, or stopped altogether, whereas it increased again upon emergence but was again reduced if diving was repeated. We conclude that shivering is inhibited during diving to allow a decrease in body temperature whereby oxygen consumption is decreased and diving capacity is extended.
Acromegaly and Serum Insulin-Like Growth Factor I
Authors: Thorner Michael O.
Published: March 2005

Random levels of growth hormone (GH) are usually not helpful in diagnosing either GH deficiency or GH hypersecretion because GH is secreted in a pulsatile fashion. Insulin-like growth factor I (IGF-I), however, is a good indicator of GH secretion and action, particularly at the level of the liver. There is a good correlation between IGF-I and several clinical indices of acromegaly. Measurements of both IGF-I and GH are cornerstones of biochemical diagnosis and follow-up of acromegaly, although in patients treated with pegvisomant, IGF-I levels should be followed rather than GH levels. IGF-I immunoassays differ in assay design, label, intra- and inter-assay precision, and calibrator or standard used, so IGF-I assays may be difficult to compare with one another. Hence, it is essential that the assays used in the laboratory are well validated and adequate normal ranges are available for the levels to be interpreted in a robust manner.
Exercise and Circulating Insulin-Like Growth Factor I
Authors: Berg Ulrika , Bang Peter
Published: March 2005

Determinations of serum concentrations of total insulin-like growth factor I (tIGF-I) are important in the diagnosis, monitoring of treatment and safety evaluation of patients with growth disorders and/or metabolic disease. It is well established that tIGF-I status varies over time. Changes in tIGF-I levels in relation to an acute bout of exercise or repeated bouts, known as training, are likely to contribute to this variation. Serum tIGF-I has also been found to be of predictive value in growth prediction models employed before the start of growth hormone (GH) treatment. Furthermore, IGF-I generation tests have been suggested to be of value in the assessment of the growth response to GH administration in patients suspected of GH deficiency with or without some degree of GH insensitivity. This is discussed elsewhere in this issue. Recent progress in our understanding of growth hormone-dependent and -independent expression of the IGF1 gene in skeletal muscle and the role of sufficient energy intake during training for muscle and liver generation of IGF-I raises important questions regarding their relative contribution to the circulating pool of IGF-I. The present review is focused on circulating levels of tIGF-I in relation to a single bout of exercise or to a period of training. In addition, the expression of IGF-I locally in muscle in response to these stimuli will be discussed.
Laboratory Diagnosis in Ulcerative Keratitis
Authors: Khanal B. , Deb M. , Panda A. , Sethi Harinder Singh
Published: March 2005

Aims: To identify the common bacterial and fungal isolates from corneal ulcers and to determine the antimicrobial susceptibility patterns of bacterial isolates to commonly used antibiotics at B.P. Koirala Institute of Health Sciences (BPKIHS), eastern Nepal. Culture and direct microscopic correlation and reliability were also compared. Methods: All patients with suspected corneal ulceration presenting to the Ophthalmology Department of BPKIHS from 1st August 1998 to 31st July 2001 were evaluated. Corneal scraping was performed and processed for direct microscopy and culture for bacterial and fungal isolates. Bacterial isolates were subjected to antimicrobial susceptibility testing. Results: Of 447 specimens examined direct microscopy was positive in 216 (48%) specimens. Culture positivity could be correlated with direct microscopy in 179 (83%) of specimens. Growth of etiologic agents was found in 303 (67.8%) samples. Of these 145 (47.8%) had pure fungal growth, 103 (34%) had pure bacterial growth and 55 (18.2%) had mixed fungal and bacterial infection. The commonest fungal pathogen was Aspergillus spp.in 78 (38.4%) followed by Fusarium spp. in 45 (22%). Aureobasidium sp. was isolated in 25 (12.3%) samples. Staphylococcus aureus (93, 56.7%) dominated the scene as the commonest bacterial agent. Streptococcus pneumoniae (33, 20%) was second in the list. Most of the bacterial isolates were sensitive to commonly used antibiotics. Conclusion: This study emphasizes the importance and need of the continued surveillance of the agents and their antimicrobial susceptibility for the prevention and management of corneal ulcers and their complications.
Effect of Glucagon-Like Peptide-1(7–36) and Exendin-4 on the Vascular Reactivity in Streptozotocin/Nicotinamide-Induced Diabetic Rats
Authors: Özyazgan Sibel , Kutluata Nilüfer , Afşar Selim , Özdaş Şule Beyhan , Akkan Ahmet Gökhan
Published: March 2005

We investigated the vascular effects of glucagon-like peptide-1 (GLP-1) and Exendin-4 in type 2 diabetic rat aortae. Studies were performed in a normal control group (NC) (0.2 ml i.p. saline, n = 10), streptozotocin (STZ)/nicotinamide diabetic control group (DC) (a single dose of 80 mg/kg STZ i.p. injection 15 min after administration of 230 mg/kg nicotinamide i.p.), GLP-1 (GLPC) control group (1 µg/kg twice daily i.p. for 1 month, n = 10), Exendin-4 control group (EXC) (0.1 µg/kg twice daily i.p. for 1 month, n = 10), GLP-1-treated diabetic group (GLPT) (1 µg/kg twice daily i.p. for 1 month, n = 10), and Exendin-4-treated diabetic group (EXT) (0.1 µg/kg twice daily i.p. for 1 month, n = 10). One month of GLP-1 and Exendin-4 treatment significantly decreased the blood glucose levels of diabetic rats (113 ± 2 mg/dl, p < 0.001, and 117 ± 1 mg/dl, p < 0.001, respectively versus 181 ± 9 mg/dl in the DC group). Sensitivity (pD2) and maximum response (% Max. Relax) of acetylcholine-stimulated relaxations in the DC group (pD2: 6.73 ± 0.12 and 55 ± 6, respectively) were decreased compared with the non-diabetic NC group (pD2: 7.41 ± 0.25, p < 0.05, and 87 ± 4, p < 0.01). Treating diabetic rats with GLP-1, pD2 values and with Exendin-4, Max. Relax %values of aortic strips to acetylcholine returned to near non-diabetic NC values (pD2: 7.47 ± 0.15, p < 0.05, and 87 ± 3, p < 0.01, respectively). Maximal contractile responses (Emax) to noradrenaline in aortic strips from the diabetic DC group (341 ± 27 mg tension/mg wet weight) were significantly decreased compared with the non-diabetic NC (540 ± 66 mg tension/mg wet weight, p < 0.001) and the GLPT group (490 ± 25 mg tension/mg wet weight, p < 0.05). There were no significant differences in pD2 values of aortic strips to noradrenaline from all groups. Emax to KCl in aortic strips from the DC group (247 ± 10 mg tension/mg wet weight, p < 0.01) was significantly decreased compared with non-diabetic NC group (327 ± 26 mg tension/mg wet weight). Treating diabetic rats with GLP-1 (GLPT), Emax values of aortic strips to KCl returned to near non-diabetic NC values (271 ± 12 mg tension/mg wet weight). GLP-1 and (partially) Exendin-4 treatment could improve the increased blood glucose level and normalize the altered vascular tone in type 2 diabetic rats.
The Evolution of Cerebrotypes in Birds
Authors: Iwaniuk Andrew N. , Hurd Peter L.
Published: March 2005

Multivariate analyses of brain composition in mammals, amphibians and fish have revealed the evolution of ‘cerebrotypes’ that reflect specific niches and/or clades. Here, we present the first demonstration of similar cerebrotypes in birds. Using principal component analysis and hierarchical clustering methods to analyze a data set of 67 species, we demonstrate that five main cerebrotypes can be recognized. One type is dominated by galliforms and pigeons, among other species, that all share relatively large brainstems, but can be further differentiated by the proportional size of the cerebellum and telencephalic regions. The second cerebrotype contains a range of species that all share relatively large cerebellar and small nidopallial volumes. A third type is composed of two species, the tawny frogmouth (Podargus strigoides) and an owl, both of which share extremely large Wulst volumes. Parrots and passerines, the principal members of the fourth group, possess much larger nidopallial, mesopallial and striatopallidal proportions than the other groups. The fifth cerebrotype contains species such as raptors and waterfowl that are not found at the extremes for any of the brain regions and could therefore be classified as ‘generalist’ brains. Overall, the clustering of species does not directly reflect the phylogenetic relationships among species, but there is a tendency for species within an order to clump together. There may also be a weak relationship between cerebrotype and developmental differences, but two of the main clusters contained species with both altricial and precocial developmental patterns. As a whole, the groupings do agree with behavioral and ecological similarities among species. Most notably, species that share similarities in locomotor behavior, mode of prey capture or cognitive ability are clustered together. The relationship between cerebrotype and behavior/ecology in birds suggests that future comparative studies of brain-behavior relationships will benefit from adopting a multivariate approach.
Rosuvastatin Reduces Platelet Activation in Heart Failure
Authors: Schäfer Andreas , Fraccarollo Daniela , Eigenthaler Martin , Tas Piet , Firnschild Andreas , Frantz Stefan , Ertl Georg , Bauersachs Johann
Published: March 2005

Objectives—

Endothelial dysfunction and platelet activation are part of the cardiovascular phenotype in congestive heart failure (CHF). We investigated whether 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibition would beneficially modulate vascular NO bioavailability and platelet activation in experimental CHF.

Methods and Results—

Chronic myocardial infarction was induced by coronary ligation in male Wistar rats. Animals were either treated with placebo or the HMG-CoA reductase inhibitor rosuvastatin. After 10 weeks, hemodynamic assessment was performed and endothelial function was determined in organ bath studies. NO bioavailability was assessed by in vivo platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Markers of platelet degranulation (surface expression of P-selectin and glycoprotein 53) were determined as well as the amount of circulating platelet–leukocyte aggregates. Endothelium-dependent, acetylcholine-induced vasorelaxation was significantly impaired in aortic rings from CHF rats and improved by rosuvastatin. In parallel, in vivo VASP phosphorylation reflecting NO bioavailability was significantly attenuated in platelets from CHF rats and normalized by rosuvastatin. Platelet activation, which was increased in CHF, was reduced by treatment with rosuvastatin.

Conclusion—

HMG-CoA reductase inhibition improved endothelial function, increased systemic NO bioavailability and inhibited exaggerated platelet activation in CHF rats. These mechanisms may contribute to the beneficial effects of statin treatment in CHF.
Analyzing the Reliability of Multidimensional Measures: An Example from Intelligence Research
Authors: Brunner Martin , SÜβ Heinz-Martin
Published: March 2005

Two aspects of the reliability of multidimensional measures can be distinguished: the amount of scale score variance that is accounted for by all underlying factors (composite reliability) and the degree to which the scale score reflects one particular factor (construct reliability). Confidence intervals for composite and construct reliabilities can be estimated by bootstrap methods. The authors demonstrate the application of these methods by analyzing the reliability of an eight-factor, nested-factor model that represents the structure of 45 tasks in an intelligence test ( N= 1,233). Composite reliabilities ranged between .78 and .93, whereas construct reliabilities ranged between .17 and .68 when the scale indicators were equally weighted to compute the scale scores and between .52 and .90 with weights based on pattern coefficients. The results indicate the importance of distinguishing diagnostic from research applications when judging whether the reliability values of multidimensional measures are substantial.
Village-State Cooperation
Authors: VanderVen Elizabeth
Published: March 2005

This article draws on archival sources from Haicheng county, Fengtian province, to examine how rural communities responded to early-twentieth-century state orders to establish modern primary schools adhering to a set of uniform standards. Past scholarship has denied China’s rural communities an important role in early-twentieth-century modernization, arguing either that the mandate to establish primary schools at the local level engendered hostile relations between state and society or that the introduction of modern schools led to community dissolution. This article highlights the contribution in Haicheng county of rural communities, mostly villages, to China’s early-twentieth-century modernization. It argues that villages were willing participants in state-guided educational reform, pursuing creative and cooperative strategies that enabled them to set up hundreds of modern primary schools and simultaneously mark their identification with both the nation-state and their own local communities.
Smart Growth and Urban Development Pattern: A Comparative Study
Authors: Song Yan
Published: March 2005

This article evaluates the efficacy of smart growth instruments in bringing forth compact urban development and neotraditional neighborhood design. The article first sets forth a set of quantitative measures that operationalize five dimensions of compact urban development and neotraditional neighborhood design: street network connectivity, density, land use mix, accessibility, and pedestrian walkability. Using these measures, three study areas are evaluated to determine how well their urban development patterns meet smart growth principles. These study areas are Portland, Oregon; Orange County, Florida; and Montgomery County, Maryland. Findings indicate that all three areas have quite similar development patterns. Findings also suggest that smart growth instruments have altered subdivision design, which is a traditional aspect of physical urban planning. However, smart growth plans have not branched out into non-traditional aspects of planning to encourage mixed land uses and to improve regional accessibility.
Immunohistochemistry accurately predicts FGFR3 aberrant expression and t(4;14) in multiple myeloma
Authors: Chang Hong , Stewart A. Keith , Qi Xiao Ying , Li Zhi Hua , Yi Qi Long , Trudel Suzanne
Published: March 2005

The t(4;14) translocation detected by fluorescence in situ hybridization (FISH) is an independent prognostic factor for an adverse outcome of multiple myeloma (MM). Because t(4;14) uniquely results in fibroblast growth factor receptor 3 (FGFR3) expression, decalcified, paraffin-embedded bone marrow biopsies were immunostained for FGFR3, and its expression was correlated with the t(4;14) status. FISH detected t(4;14) in 16 (19%) of 85 MM patient specimens, and immunocytochemistry detected aberrant FGFR3 expression in 13 (15%). Twelve (75%) t(4;14)-positive cases expressed FGFR3, and 12 (92%) FGFR3-positive cases harbored a t(4;14). FGFR3 expression and t(4;14) were strongly correlated (P < .001). FGFR3 expression by immunohistochemistry was associated with the immunoglobulin A (IgA) isotype (P < .001), a shorter progression-free survival (median, 11.5 versus 25.8 months; P < .001), and a shorter overall survival (median, 19.2 versus 46.3 months; P < .001).
Unbiased descriptor and parameter selection confirms the potential of proteochemometric modelling
Authors: Freyhult Eva , Prusis Peteris , Lapinsh Maris , Wikberg Jarl ES , Moulton Vincent , Gustafsson Mats G
Published: March 2005

Background

Proteochemometrics is a new methodology that allows prediction of protein function directly from real interaction measurement data without the need of 3D structure information. Several reported proteochemometric models of ligand-receptor interactions have already yielded significant insights into various forms of bio-molecular interactions. The proteochemometric models are multivariate regression models that predict binding affinity for a particular combination of features of the ligand and protein. Although proteochemometric models have already offered interesting results in various studies, no detailed statistical evaluation of their average predictive power has been performed. In particular, variable subset selection performed to date has always relied on using all available examples, a situation also encountered in microarray gene expression data analysis.

Results

A methodology for an unbiased evaluation of the predictive power of proteochemometric models was implemented and results from applying it to two of the largest proteochemometric data sets yet reported are presented. A double cross-validation loop procedure is used to estimate the expected performance of a given design method. The unbiased performance estimates (P2) obtained for the data sets that we consider confirm that properly designed single proteochemometric models have useful predictive power, but that a standard design based on cross validation may yield models with quite limited performance. The results also show that different commercial software packages employed for the design of proteochemometric models may yield very different and therefore misleading performance estimates. In addition, the differences in the models obtained in the double CV loop indicate that detailed chemical interpretation of a single proteochemometric model is uncertain when data sets are small.

Conclusion

The double CV loop employed offer unbiased performance estimates about a given proteochemometric modelling procedure, making it possible to identify cases where the proteochemometric design does not result in useful predictive models. Chemical interpretations of single proteochemometric models are uncertain and should instead be based on all the models selected in the double CV loop employed here.
Marine Genomics: A clearing-house for genomic and transcriptomic data of marine organisms
Authors: McKillen David J , Chen Yian A , Chen Chuming , Jenny Matthew J , Trent Harold F , Robalino Javier , McLean David C , Gross Paul S , Chapman Robert W , Warr Gregory W , Almeida Jonas S
Published: March 2005

Background

The Marine Genomics project is a functional genomics initiative developed to provide a pipeline for the curation of Expressed Sequence Tags (ESTs) and gene expression microarray data for marine organisms. It provides a unique clearing-house for marine specific EST and microarray data and is currently available at http://www.marinegenomics.org.

Description

The Marine Genomics pipeline automates the processing, maintenance, storage and analysis of EST and microarray data for an increasing number of marine species. It currently contains 19 species databases (over 46,000 EST sequences) that are maintained by registered users from local and remote locations in Europe and South America in addition to the USA. A collection of analysis tools are implemented. These include a pipeline upload tool for EST FASTA file, sequence trace file and microarray data, an annotative text search, automated sequence trimming, sequence quality control (QA/QC) editing, sequence BLAST capabilities and a tool for interactive submission to GenBank. Another feature of this resource is the integration with a scientific computing analysis environment implemented by MATLAB.

Conclusion

The conglomeration of multiple marine organisms with integrated analysis tools enables users to focus on the comprehensive descriptions of transcriptomic responses to typical marine stresses. This cross species data comparison and integration enables users to contain their research within a marine-oriented data management and analysis environment.
Silhouette scores for assessment of SNP genotype clusters
Authors: Lovmar Lovisa , Ahlford Annika , Jonsson Mats , Syvänen Ann-Christine
Published: March 2005

Background

High-throughput genotyping of single nucleotide polymorphisms (SNPs) generates large amounts of data. In many SNP genotyping assays, the genotype assignment is based on scatter plots of signals corresponding to the two SNP alleles. In a robust assay the three clusters that define the genotypes are well separated and the distances between the data points within a cluster are short. "Silhouettes" is a graphical aid for interpretation and validation of data clusters that provides a measure of how well a data point was classified when it was assigned to a cluster. Thus "Silhouettes" can potentially be used as a quality measure for SNP genotyping results and for objective comparison of the performance of SNP assays at different circumstances.

Results

We created a program (ClusterA) for calculating "Silhouette scores", and applied it to assess the quality of SNP genotype clusters obtained by single nucleotide primer extension ("minisequencing") in the Tag-microarray format. A Silhouette score condenses the quality of the genotype assignment for each SNP assay into a single numeric value, which ranges from 1.0, when the genotype assignment is unequivocal, down to -1.0, when the genotype assignment has been arbitrary. In the present study we applied Silhouette scores to compare the performance of four DNA polymerases in our minisequencing system by analyzing 26 SNPs in both DNA polarities in 16 DNA samples. We found Silhouettes to provide a relevant measure for the quality of SNP assays at different reaction conditions, illustrated by the four DNA polymerases here. According to our result, the genotypes can be unequivocally assigned without manual inspection when the Silhouette score for a SNP assay is > 0.65. All four DNA polymerases performed satisfactorily in our Tag-array minisequencing system.

Conclusion

"Silhouette scores" for assessing the quality of SNP genotyping clusters is convenient for evaluating the quality of SNP genotype assignment, and provides an objective, numeric measure for comparing the performance of SNP assays. The program we created for calculating Silhouette scores is freely available, and can be used for quality assessment of the results from all genotyping systems, where the genotypes are assigned by cluster analysis using scatter plots.
Assessment of the paraspinal muscles of subjects presenting an idiopathic scoliosis: an EMG pilot study
Authors: Gaudreault Nathaly , Arsenault A Bertrand , Larivière Christian , DeSerres Sophie J , Rivard Charles-Hilaire
Published: March 2005

Background

It is known that the back muscles of scoliotic subjects present abnormalities in their fiber type composition. Some researchers have hypothesized that abnormal fiber composition can lead to paraspinal muscle dysfunction such as poor neuromuscular efficiency and muscle fatigue. EMG parameters were used to evaluate these impairments. The purpose of the present study was to examine the clinical potential of different EMG parameters such as amplitude (RMS) and median frequency (MF) of the power spectrum in order to assess the back muscles of patients presenting idiopathic scoliosis in terms of their neuromuscular efficiency and their muscular fatigue.

Methods

L5/S1 moments during isometric efforts in extension were measured in six subjects with idiopathic scoliosis and ten healthy controls. The subjects performed three 7 s ramp contractions ranging from 0 to 100% maximum voluntary contraction (MVC) and one 30 s sustained contraction at 75% MVC. Surface EMG activity was recorded bilaterally from the paraspinal muscles at L5, L3, L1 and T10. The slope of the EMG RMS/force (neuromuscular efficiency) and MF/force (muscle composition) relationships were computed during the ramp contractions while the slope of the EMG RMS/time and MF/time relationships (muscle fatigue) were computed during the sustained contraction. Comparisons were performed between the two groups and between the left and right sides for the EMG parameters.

Results

No significant group or side differences between the slopes of the different measures used were found at the level of the apex (around T10) of the major curve of the spine. However, a significant side difference was seen at a lower level (L3, p = 0.01) for the MF/time parameter.

Conclusion

The EMG parameters used in this study could not discriminate between the back muscles of scoliotic subjects and those of control subject regarding fiber type composition, neuromuscular efficiency and muscle fatigue at the level of the apex. The results of this pilot study indicate that compensatory strategies are potentially seen at lower level of the spine with these EMG parameters.
High-Temperature unfolding of a trp-Cage mini-protein: a molecular dynamics simulation study
Authors: Seshasayee Aswin Sai Narain
Published: March 2005

Background

Trp cage is a recently-constructed fast-folding miniprotein. It consists of a short helix, a 3,10 helix and a C-terminal poly-proline that packs against a Trp in the alpha helix. It is known to fold within 4 ns.

Results

High-temperature unfolding molecular dynamics simulations of the Trp cage miniprotein have been carried out in explicit water using the OPLS-AA force-field incorporated in the program GROMACS. The radius of gyration (Rg) and Root Mean Square Deviation (RMSD) have been used as order parameters to follow the unfolding process. Distributions of Rg were used to identify ensembles.

Conclusion

Three ensembles could be identified. While the native-state ensemble shows an Rg distribution that is slightly skewed, the second ensemble, which is presumably the Transition State Ensemble (TSE), shows an excellent fit. The denatured ensemble shows large fluctuations, but a Gaussian curve could be fitted. This means that the unfolding process is two-state. Representative structures from each of these ensembles are presented here.
Evidence against the Hypothesis that Endothelial Endothelin B Receptor Expression Is Regulated by Relaxin and Pregnancy
Authors: Kerchner Laurie J. , Novak Jacqueline , Hanley-Yanez Karen , Doty Ketah D. , Danielson Lee A. , Conrad Kirk P.
Published: March 2005

The endothelial endothelin B (ETB) receptor subtype is critical for renal vasodilation induced by relaxin in nonpregnant rats and during pregnancy (the latter via endogenous circulating relaxin). Here we tested whether expression of vascular ETB receptor protein is regulated by relaxin. Small renal arteries were harvested from virgin and midterm pregnant rats as well as nonpregnant rats that were administered recombinant human relaxin (rhRLX) at 4 μg/h or vehicle for 5 d or 4–6 h. Small renal arteries dissected from additional virgin rats were incubated in vitro with rhRLX or vehicle for 3 h at 37 C. ETB expression was also evaluated in cultured human endothelial cells: aortic, coronary, umbilical vein, and dermal microvascular endothelial cells. Cells were incubated for 4, 8, or 24 h with rhRLX (5, 1, or 0.1 ng/ml) or vehicle. ETB protein expression in arteries and cells was evaluated by Western analysis. No regulation of ETB expression was observed in small renal arteries in any of the experimental protocols, nor was there an increase in the vasorelaxation response to ET-3 in small renal arteries incubated in vitro with rhRLX. rhRLX only sporadically altered ETB expression in human coronary artery endothelial cells and human umbilical vein endothelial cells at certain time points or doses, and no regulation was observed in human aortic endothelial cells or human dermal microvascular endothelial cells. These results suggest that regulation of ETB receptor protein has little or no role in relaxin stimulation of the endothelial ETB/nitric oxide vasodilatory pathway.
On a deposition process on the circle with disorder
Authors: Huillet Thierry
Published: March 2005

Thrownpoints sequentially and at random onto a unit circle and append a clockwise arc (or rod) of lengthsto each such point. The resulting random set (the free gas of rods) is a union of a random number of clusters with random sizes modelling a free deposition process on a one-dimensional substrate. A variant of this model is investigated in order to take into account the role of the disorder,θ> 0; this involves Dirichlet(θ) distributions. For such free deposition processes with disorderθ, we shall be interested in the occurrence times and probabilities, asngrows, of two specific types of configurations: those avoiding overlapping rods (the hard-rod gas) and those for which the largest gap is smaller than the rod lengths(the packing gas). Special attention is paid to the thermodynamic limit whenns=ρfor some finite densityρof points. The occurrence of parking configurations, those for which hard-rod and packing constraints are both fulfilled, is then studied. Finally, some aspects of these problems are investigated in the low-disorder limitθ↓ 0 asn↑ ∞ whilenθ=γ> 0. Here, Poisson-Dirichlet(γ) partitions play some role.
Improving the performance of third-generation wireless communication systems
Authors: van der Hofstad Remco , Klok Marten J.
Published: March 2005

The third-generation (3G) mobile communication system uses a technique called code division multiple access (CDMA), in which multiple users use the same frequency and time domain. The data signals of the users are distinguished using codes. When there are many users, interference deteriorates the quality of the system. For more efficient use of resources, we wish to allow more users to transmit simultaneously, by using algorithms that utilize the structure of the CDMA system more effectively than the simple matched filter (MF) system used in the proposed 3G systems. In this paper, we investigate an advanced algorithm called hard-decision parallel interference cancellation (HD-PIC), in which estimates of the interfering signals are used to improve the quality of the signal of the desired user. We compare HD-PIC with MF in a simple case, where the only two parameters are the number of users and the length of the coding sequences. We focus on the exponential rate for the probability of a bit-error, explain the relevance of this parameter, and investigate how it scales when the number of users grows large. We also review extensions of our results, proved elsewhere, showing that in HD-PIC, more users can transmit without errors than in the MF system.
Overshoots over curved boundaries. II
Authors: Doney R. A. , Griffin P. S.
Published: March 2005

We continue the study of the asymptotic behaviour of a random walk when it exits from a symmetric region of the form {(x, n): |x| ≤ rnb} as r → ∞ which was begun in Part I of this work. In contrast to that paper, we are interested in the case where the probability of exiting at the upper boundary tends to 1. In this scenario we treat the case where the power b lies in the interval [0, 1), and we establish necessary and sufficient conditions for the overshoot to be relatively stable in probability (except for the case ), and for the pth moment of the overshoot to be O(rq) as r → ∞.
Solving the Fisher-Wright and coalescence problems with a discrete Markov chain analysis
Authors: Buss Samuel R. , Clote Peter
Published: March 2005

We develop a new, self-contained proof that the expected number of generations required for gene allele fixation or extinction in a population of sizenisO(n) under general assumptions. The proof relies on a discrete Markov chain analysis. We further develop an algorithm to compute expected fixation or extinction time to any desired precision. Our proofs establishO(nH(p)) as the expected time for gene allele fixation or extinction for the Fisher-Wright problem, where the gene occurs with initial frequencypandH(p) is the entropy function. Under a weaker hypothesis on the variance, the expected time isO(n(p(1-p))1/2) for fixation or extinction. Thus, the expected-time bound ofO(n) for fixation or extinction holds in a wide range of situations. In the multi-allele case, the expected time for allele fixation or extinction in a population of sizenwithndistinct alleles is shown to beO(n). From this, a new proof is given of a coalescence theorem about the mean time to the most recent common ancestor (MRCA), which applies to a broad range of reproduction models satisfying our mean and weak variation conditions.
Linear dynamics for the state vector of Markov chain functions
Authors: Ledoux James
Published: March 2005

Let (φ(Xn))n be a function of a finite-state Markov chain (Xn)n. In this article, we investigate the conditions under which the random variables φ(n) have the same distribution as Yn (for every n), where (Yn)n is a Markov chain with fixed transition probability matrix. In other words, for a deterministic function φ, we investigate the conditions under which (Xn)n is weakly lumpable for the state vector. We show that the set of all probability distributions of X0, such that (Xn)n is weakly lumpable for the state vector, can be finitely generated. The connections between our definition of lumpability and the usual one (i.e. as the proportional dynamics property) are discussed.
Filters and parameter estimation for a partially observable system subject to random failure with continuous-range observations
Authors: Lin Daming , Makis Viliam
Published: March 2005

We consider a failure-prone system operating in continuous time. Condition monitoring is conducted at discrete time epochs. The state of the system is assumed to evolve as a continuous-time Markov process with a finite state space. The observation process with continuous-range values is stochastically related to the state process, which, except for the failure state, is unobservable. Combining the failure information and the condition monitoring information, we derive a general recursive filter, and, as special cases, we obtain recursive formulae for the state estimation and other quantities of interest. Updated parameter estimates are obtained using the expectation-maximization (EM) algorithm. Some practical prediction problems are discussed and finally an illustrative example is given using a real dataset.
Super‐Efficient Exciton Funneling in Layer‐by‐Layer Semiconductor Nanocrystal Structures
Authors: Klar T. A. , Franzl T. , Rogach A. L. , Feldmann J.
Published: March 2005

In semiconductor nanocrystals the electronic energy gap is determined not only by the material but also by the size of the nanocrystals. This allows the construction of an energy‐gap gradient normal to multiple layers of nanocrystals where the diameters of the nanocrystals are monotonically increasing or decreasing in subsequent layers. In such devices we observe a highly efficient funneling of excitation energy from layers comprising smaller nanocrystals towards the layer with the largest nanocrystals in the center of the funnel. Most importantly, not only are excitons in radiative states transferred, but also excitons from trapped states, usually lost for luminescence, can be effectively recycled, hence increasing the overall luminescence yield.