bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerosol Characterization and Direct Radiative Forcing Assessment over the Ocean. Part II: Application to Test Cases and Validation
Authors: Costa Maria João , Levizzani Vincenzo , Silva Ana Maria
Published: January 2005

A method based on the synergistic use of low earth orbit and geostationary earth orbit satellite data for aerosol-type characterization and aerosol optical thickness (AOT: τa) retrieval and monitoring over the ocean is presented in Part I of this paper. The method is now applied to a strong dust outbreak over the Atlantic Ocean in June 1997 and to two other relevant transport events of biomass burning and desert dust aerosol that occurred in 2000 over the Atlantic and Indian Oceans, respectively. The retrievals of the aerosol optical properties are checked against retrievals from sun and sky radiance measurements from the ground-based Aerosol Robotic Network (AERONET). The single-scattering albedo values obtained from AERONET are always within the error bars presented for Global Ozone Monitoring Experiment (GOME) retrievals, resulting in differences lower than 0.041. The retrieved AOT values are compared with the independent space–time-collocated measurements from the AERONET, as well as to the satellite aerosol official products of the Polarization and Directionality of the Earth Reflectances (POLDER) and the Moderate Resolution Imaging Spectroradiometer (MODIS). A first estimate of the AOT accuracy derived from comparisons with AERONET data leads to ±0.02 ± 0.22τa when all AOT values are retained or to ±0.02 ± 0.16τa for aerosol transport events (AOT > 0.4). The upwelling flux at the top of the atmosphere (TOA) was computed with radiative transfer calculations and used to estimate the TOA direct shortwave aerosol radiative forcing; a comparison with space–time-collocated measurements from the Clouds and the Earth's Radiant Energy System (CERES) TOA flux product was also done. It was found that more than 90% of the values differ from CERES fluxes by less than ±15%.
Water Vapor Exchange between Soil and Atmosphere over a Gobi Surface near an Oasis in the Summer
Authors: Zhang Qiang , Huang Ronghui
Published: January 2005

Using data observed at Dunhuang, in the Gansu, in the arid region of northwest China in the summer, the characteristics of the soil water content, temperature, and atmospheric humidity were analyzed. It was found that the depth of the active soil temperature layer is about 5 cm, which is much thinner than that of typical soils. In addition, not only is the atmospheric humidity gradient in the surface layer often inverted, but so too is the soil water content gradient in the shallow layer. The diurnal variation of soil water content can be divided into four stages, including wet, water loss, dry, and water gain. It is shown that in soil water content profiles the depth of the active soil layer is about 10 cm, and soil water content inversion is the primary feature in the shallow layer during the “wet” stage. The presence of soil water content inversion indicates that soil in the shallow layer can absorb water from the air through condensation in the nighttime and emit water vapor to the air through evaporation in the daytime. The formation of a soil water content inversion is mainly related to the state of the soil surface temperature.
Precipitation Estimation from Remotely Sensed Imagery Using an Artificial Neural Network Cloud Classification System
Authors: Hong Yang , Hsu Kuo-Lin , Sorooshian Soroosh , Gao Xiaogang
Published: January 2005

A satellite-based rainfall estimation algorithm, Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN) Cloud Classification System (CCS), is described. This algorithm extracts local and regional cloud features from infrared (10.7 μm) geostationary satellite imagery in estimating finescale (0.04° × 0.04° every 30 min) rainfall distribution. This algorithm processes satellite cloud images into pixel rain rates by 1) separating cloud images into distinctive cloud patches; 2) extracting cloud features, including coldness, geometry, and texture; 3) clustering cloud patches into well-organized subgroups; and 4) calibrating cloud-top temperature and rainfall (Tb–R) relationships for the classified cloud groups using gauge-corrected radar hourly rainfall data. Several cloud-patch categories with unique cloud-patch features and Tb–R curves were identified and explained. Radar and gauge rainfall measurements were both used to evaluate the PERSIANN CCS rainfall estimates at a range of temporal (hourly and daily) and spatial (0.04°, 0.12°, and 0.25°) scales. Hourly evaluation shows that the correlation coefficient (CC) is 0.45 (0.59) at a 0.04° (0.25°) grid scale. The averaged CC of daily rainfall is 0.57 (0.63) for the winter (summer) season.
Background Error Correlation between Surface Skin and Air Temperatures: Estimation and Impact on the Assimilation of Infrared Window Radiances
Authors: Garand Louis , Buehner Mark , Wagneur Nicolas
Published: January 2005

This paper makes use of ensemble forecasts to infer the correlation between surface skin temperature Ts and air temperature Ta model errors. The impact of this correlation in data assimilation is then investigated. In the process of assimilating radiances that are sensitive to the surface skin temperature, the Ts–Ta error correlation becomes important because it allows statistically optimal corrections to the background temperature profile in the boundary layer. In converse, through this correlation, surface air temperature data can substantially influence the analysis of skin temperature. One difficulty is that the Ts–Ta correlation depends on the local static stability conditions that link the two variables. Therefore, a correlation estimate based on spatial or temporal averages is not appropriate. Ensembles of forecasts valid at the analysis time provide a novel means to infer the correlation dynamically at each model grid point. Geostationary Operational Environmental Satellite (GOES)-8 and -10 surface-sensitive imager radiances are assimilated with and without the inferred correlations in a 3D variational analysis system. The impact of the correlation on analyses is assessed using independent radiosonde data. The impact on 6-h forecasts is also evaluated using surface synoptic reports. The influence of the correlation extends from the surface to about 1.5 km. Temperature differences in the resulting analyses on the order of 0.3–0.6 K are typical in the boundary layer and may extend over broad regions. These difference patterns persist beyond 6 h into the forecasts.
Remote Cloud Ceiling Assessment Using Data-Mining Methods
Authors: Bankert Richard L. , Hadjimichael Michael , Kuciauskas Arunas P. , Thompson William T. , Richardson Kim
Published: January 2005

Data-mining methods are applied to numerical weather prediction (NWP) output and satellite data to develop automated algorithms for the diagnosis of cloud ceiling height in regions where no local observations are available at analysis time. A database of hourly records that include Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) output, satellite data, and ground truth observations [aviation routine weather reports (METAR)] has been created. Data were collected over a 2.5-yr period for specific locations in California. Data-mining techniques have been applied to the database to determine relationships in the collected physical parameters that best estimate cloud ceiling conditions, with an emphasis on low ceiling heights. Algorithm development resulted in a three-step approach: 1) determine if a cloud ceiling exists, 2) if a cloud ceiling is determined to exist, determine if the ceiling is high or low (below 1 000 m), and 3) if the cloud ceiling is determined to be low, compute ceiling height. A sample of the performance evaluation indicates an average absolute height error of 120.6 m with a 0.76 correlation and a root-mean-square error of 168.0 m for the low-cloud-ceiling testing set. These results are a significant improvement over the ceiling-height estimations generated by an operational translation algorithm applied to COAMPS output.
Dynamical Response of the Oceanic Eddy Field to the North Atlantic Oscillation: A Model–Data Comparison
Authors: Penduff Thierry , Barnier Bernard , Dewar W. K. , O'Brien James J.
Published: January 2005

Observational studies have shown that in many regions of the World Ocean the eddy kinetic energy (EKE) significantly varies on interannual time scales. Comparing altimeter-derived EKE maps for 1993 and 1996, Stammer and Wunsch have mentioned a significant meridional redistribution of EKE in the North Atlantic Ocean and suggested the possible influence of the North Atlantic Oscillation (NAO) cycle. This hypothesis is examined using 7 yr of Ocean Topography Experiment (TOPEX)/Poseidon altimeter data and three ⅙°-resolution Atlantic Ocean model simulations performed over the period 1979–2000 during the French “CLIPPER” experiment. The subpolar–subtropical meridional contrast of EKE in the real ocean appears to vary on interannual time scales, and the model reproduces it realistically. The NAO cycle forces the meridional contrast of energy input by the wind. The analysis in this paper suggests that after 1993 the large amplitude of the NAO cycle induces changes in the transport of the baroclinically unstable large-scale circulation (Gulf Stream/North Atlantic Current) and, thus, changes in the EKE distribution. Model results suggest that NAO-like fluctuations were not followed by EKE redistributions before 1994, probably because NAO oscillations were weaker. Strong NAO events after 1994 were followed by gyre-scale EKE fluctuations with a 4–12-month lag, suggesting that complex, nonlinear adjustment processes are involved in this oceanic adjustment.
Forcing of a Two-Layered Water Column over a Sloping Seafloor
Authors: Nilsen F.
Published: January 2005

The response of a time-dependent atmospheric function close to a slope region is studied. A forced two-layered model over a sloping topography is examined with focus on the particular solution and interaction between the constructed barotropic and baroclinic mode. The water column responds with long periodic waves along the sloping bottom, and the solution includes a time-dependent Ekman transport in the upper layer. Despite its relative simplicity, the model produces a resonant response in the barotropic mode to a northward-propagating plane-wave wind stress field. The particular solution shows that a state close to resonance in the barotropic mode is given by a 1/λy line for the barotropic coefficient when plotted as a function of the forcing wave period and wavelength λy. From the Norwegian Meteorological Institute (NMI) Hindcast database, the calculated time series of the wind stress curl reveals a high energy level in the forcing period interval between 48 and 185 h. The Vøring Plateau slope has a natural oscillation period around 100 h for topographically trapped waves, and the model shows that an along-slope wavelength of 76 km will produce a resonant response in the water column for this wave period. Hence, when the forcing function is constructed as a sum of (infinitely) many Fourier components, topographic waves will be triggered along the Vøring Plateau slope for a northward-moving atmospheric pressure system.
Isopycnal Averaging at Constant Height. Part II: Relating to the Residual Streamfunction in Eulerian Space
Authors: Nurser A. J. George , Lee Mei-Man
Published: January 2005

In Part I, the “vertical” transport streamfunction was defined as resulting from isopycnic averaging at constant height in the same way that the meridional streamfunction results from averaging at constant latitude. Part II here discusses the relationship between these two isopycnic streamfunctions and the Eulerian residual streamfunction that arises from the transformed Eulerian mean (TEM). It is known that the meridional isopycnic streamfunction can be approximated by a Taylor expansion to give an Eulerian residual streamfunction involving the horizontal eddy flux. This Taylor expansion approximation works well in the interior, removing the spurious mixing associated with the simple Eulerian-averaged streamfunction. However, it fails near the surface where isopycnals outcrop to the surface. It can be shown in a similar way that the vertical isopycnic streamfunction can formally be approximated by a residual streamfunction involving the vertical eddy flux. However, if horizontal isopycnal displacements are large, this approximation fails even in the ocean interior. Inspired by the two different residual streamfunctions, a more general form of TEM formulation is explored. It is shown that the different TEM residual streamfunctions arise from decomposing the eddy flux into a component along isopycnals, which leads to advective flow, and a remaining diffusive component, which is oriented either vertically or horizontally. In theory the diffusive flux can be oriented in any direction, although in practice the orientation should be such that neither the advective flow nor the diffusive flux cross any boundary (surface, sidewalls, and bottom). However, it is not clear how to merge the continuously changing orientation in a physically meaningful way. A variety of approaches are discussed.
Simulation of the Transformation of Internal Solitary Waves on Oceanic Shelves
Authors: Grimshaw Roger , Pelinovsky Efim , Talipova Tatiana , Kurkin Audrey
Published: January 2005

Internal solitary waves transform as they propagate shoreward over the continental shelf into the coastal zone, from a combination of the horizontal variability of the oceanic hydrology (density and current stratification) and the variable depth. If this background environment varies sufficiently slowly in comparison with an individual solitary wave, then that wave possesses a soliton-like form with varying amplitude and phase. This stage is studied in detail in the framework of the variable-coefficient extended Korteweg–de Vries equation where the variation of the solitary wave parameters can be described analytically through an asymptotic description as a slowly varying solitary wave. Direct numerical simulation of the variable-coefficient extended Korteweg–de Vries equation is performed for several oceanic shelves (North West shelf of Australia, Malin shelf edge, and Arctic shelf) to demonstrate the applicability of the asymptotic theory. It is shown that the solitary wave may maintain its soliton-like form for large distances (up to 100 km), and this fact helps to explain why internal solitons are widely observed in the world's oceans. In some cases the background stratification contains critical points (where the coefficients of the nonlinear terms in the extended Korteweg–de Vries equation change sign), or does not vary sufficiently slowly; in such cases the solitary wave deforms into a group of secondary waves. This stage is studied numerically.
Dependence of Sea Ice Yield-Curve Shape on Ice Thickness
Authors: Wilchinsky Alexander V. , Feltham Daniel L.
Published: January 2005

In this note, the authors discuss the contribution that frictional sliding of ice floes (or floe aggregates) past each other and pressure ridging make to the plastic yield curve of sea ice. Using results from a previous study that explicitly modeled the amount of sliding and ridging that occurs for a given global strain rate, it is noted that the relative contribution of sliding and ridging to ice stress depends upon ice thickness. The implication is that the shape and size of the plastic yield curve is dependent upon ice thickness. The yield-curve shape dependence is in addition to plastic hardening/weakening that relates the size of the yield curve to ice thickness. In most sea ice dynamics models the yield-curve shape is taken to be independent of ice thickness. The authors show that the change of the yield curve due to a change in the ice thickness can be taken into account by a weighted sum of two thickness-independent rheologies describing ridging and sliding effects separately. It would be straightforward to implement the thickness-dependent yield-curve shape described here into sea ice models used for global or regional ice prediction.
The Labeling Game
Authors: Denegri-Knott Janice , Taylor Jacqui
Published: January 2005

This article draws on sociological and psychological theory to explore the meaning application of deviance to behaviors observed on the Internet. First, definitions of deviancein online and offline contexts are discussed. Observations of the Internet as a so-called yet-to-be-normalized environment present a conflicting scenario for labeling emergent behaviors as deviant. The question stands as to whether devianceis an appropriate term to apply to some behavior observed on the Internet. The second section examines deviance on the Internet at a macro, cybercultural level and at a micro, communicational level using two key examples to illustrate some of the issues raised earlier in defining deviance. The sharing of mp3 files is used as an example to illustrate problems in definition at a macro level and at a microlevel; psychological approximations to normative and antinormative communication on the Net are discussed, using flaming as an example.
Inhibition of c-Jun NH2-terminal kinase or extracellular signal-regulated kinase improves lung injury
Authors: Lee Hui Su , Kim Hee Jae , Moon Chang Sook , Chong Young Hae , Kang Jihee Lee
Published: January 2005

Background

Although in vitro studies have determined that the activation of mitogen-activated protein (MAP) kinases is crucial to the activation of transcription factors and regulation of the production of proinflammatory mediators, the roles of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in acute lung injury have not been elucidated.

Methods

Saline or lipopolysaccharide (LPS, 6 mg/kg of body weight) was administered intratracheally with a 1-hour pretreatment with SP600125 (a JNK inhibitor; 30 mg/kg, IO), or PD98059 (an MEK/ERK inhibitor; 30 mg/kg, IO). Rats were sacrificed 4 hours after LPS treatment.

Results

SP600125 or PD98059 inhibited LPS-induced phosphorylation of JNK and ERK, total protein and LDH activity in BAL fluid, and neutrophil influx into the lungs. In addition, these MAP kinase inhibitors substantially reduced LPS-induced production of inflammatory mediators, such as CINC, MMP-9, and nitric oxide. Inhibition of JNK correlated with suppression of NF-κB activation through downregulation of phosphorylation and degradation of IκB-α, while ERK inhibition only slightly influenced the NF-κB pathway.

Conclusion

JNK and ERK play pivotal roles in LPS-induced acute lung injury. Therefore, inhibition of JNK or ERK activity has potential as an effective therapeutic strategy in interventions of inflammatory cascade-associated lung injury.
Value of supplemental interventions to enhance the effectiveness of physical exercise during respiratory rehabilitation in COPD patients. A Systematic Review
Authors: Puhan Milo A , Schünemann Holger J , Frey Martin , Bachmann Lucas M
Published: January 2005

Background

There is a controversy about the additional benefit of various supplemental interventions used in clinical practice to further enhance the effectiveness of respiratory rehabilitation in patients with Chronic obstructive pulmonary disease (COPD). The aim of this research was to assess randomised controlled trials (RCTs) testing the additional benefit of supplemental interventions during respiratory rehabilitation in COPD patients.

Methods

Systematic review with literature searches in six electronic databases, extensive hand-searching and contacting of authors. Two reviewers selected independently eligible RCTs, rated the methodological quality and extracted the data, which were analyzed considering the minimal important difference of patient-important outcomes where possible.

Findings

We identified 20 RCTs whereof 18 provided sufficient data for analysis. The methodological quality was low and sample sizes were too small for most trials to produce meaningful results (median total sample size = 28). Data from five trials showed that supplemental oxygen during exercise did not have clinically meaningful effects on health-related quality of life while improvements of exercise capacity may be even larger for patients exercising on room air. RCTs of adding assisted ventilation, nutritional supplements or a number of anabolically acting drugs do not provide sufficient evidence for or against the use any of these supplemental interventions.

Interpretation

There is insufficient evidence for most supplemental interventions during respiratory rehabilitation to estimate their additional value, partly due to methodological shortcomings of included RCTs. Current data do not suggest benefit from supplemental oxygen during exercise, although the methodological quality of included trials limits conclusions. To appropriately assess any of the various supplemental interventions used in clinical practice, pragmatic trials on respiratory rehabilitation of COPD patients need to consider methodological aspects as well as appropriate sample sizes.
Application of microarray technology in pulmonary diseases
Authors: Tzouvelekis Argyris , Patlakas George , Bouros Demosthenes
Published: January 2005

Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives.
Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts
Authors: Carlisle Diane L , Hopkins Toni M , Gaither-Davis Autumn , Silhanek Michele J , Luketich James D , Christie Neil A , Siegfried Jill M
Published: January 2005

Background

Non-neuronal cells, including those derived from lung, are reported to express nicotinic acetylcholine receptors (nAChR). We examined nAChR subunit expression in short-term cultures of human airway cells derived from a series of never smokers, ex-smokers, and active smokers.

Methods and Results

At the mRNA level, human bronchial epithelial (HBE) cells and airway fibroblasts expressed a range of nAChR subunits. In multiple cultures of both cell types, mRNA was detected for subunits that constitute functional muscle-type and neuronal-type pentomeric receptors. Two immortalized cell lines derived from HBE cells also expressed muscle-type and neuronal-type nAChR subunits. Airway fibroblasts expressed mRNA for three muscle-type subunits (α1, δ, and ε) significantly more often than HBE cells. Immunoblotting of HBE cell and airway fibroblast extracts confirmed that mRNA for many nAChR subunits is translated into detectable levels of protein, and evidence of glycosylation of nAChRs was observed. Some minor differences in nAChR expression were found based on smoking status in fibroblasts or HBE cells. Nicotine triggered calcium influx in the immortalized HBE cell line BEAS2B, which was blocked by α-bungarotoxin and to a lesser extent by hexamethonium. Activation of PKC and MAPK p38, but not MAPK p42/44, was observed in BEAS2B cells exposed to nicotine. In contrast, nicotine could activate p42/44 in airway fibroblasts within five minutes of exposure.

Conclusions

These results suggest that muscle-type and neuronal-type nAChRs are functional in airway fibroblasts and HBE cells, that prior tobacco exposure does not appear to be an important variable in nAChR expression, and that distinct signaling pathways are observed in response to nicotine.
Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer
Authors: Bollivar David W , Clauson Cheryl , Lighthall Rachel , Forbes Siiri , Kokona Bashkim , Fairman Robert , Kundrat Lenka , Jaffe Eileen K
Published: January 2005

Background

The enzyme porphobilinogen synthase (PBGS), which is central to the biosynthesis of heme, chlorophyll and cobalamins, has long been known to use a variety of metal ions and has recently been shown able to exist in two very different quaternary forms that are related to metal ion usage. This paper reports new information on the metal ion independence and quaternary structure of PBGS from the photosynthetic bacterium Rhodobacter capsulatus.

Results

The gene for R. capsulatus PBGS was amplified from genomic DNA and sequencing revealed errors in the sequence database. R. capsulatus PBGS was heterologously expressed in E. coli and purified to homogeneity. Analysis of an unusual phylogenetic variation in metal ion usage by PBGS enzymes predicts that R. capsulatus PBGS does not utilize metal ions such as Zn2+, or Mg2+, which have been shown to act in other PBGS at either catalytic or allosteric sites. Studies with these ions and chelators confirm the predictions. A broad pH optimum was determined to be independent of monovalent cations, approximately 8.5, and the Km value shows an acidic pKa of ~6. Because the metal ions of other PBGS affect the quaternary structure, gel permeation chromatography and analytical ultracentrifugation experiments were performed to examine the quaternary structure of metal ion independent R. capsulatus PBGS. The enzyme was found to be predominantly hexameric, in contrast with most other PBGS, which are octameric. A protein concentration dependence to the specific activity suggests that the hexameric R. capsulatus PBGS is very active and can dissociate to smaller, less active, species. A homology model of hexameric R. capsulatus PBGS is presented and discussed.

Conclusion

The evidence presented in this paper supports the unusual position of the R. capsulatus PBGS as not requiring any metal ions for function. Unlike other wild-type PBGS, the R. capsulatus protein is a hexamer with an unusually high specific activity when compared to other octameric PBGS proteins.
Discriminative topological features reveal biological network mechanisms
Authors: Middendorf Manuel , Ziv Etay , Adams Carter , Hom Jen , Koytcheff Robin , Levovitz Chaya , Woods Gregory , Chen Linda , Wiggins Chris
Published: January 2005

Background

Recent genomic and bioinformatic advances have motivated the development of numerous network models intending to describe graphs of biological, technological, and sociological origin. In most cases the success of a model has been evaluated by how well it reproduces a few key features of the real-world data, such as degree distributions, mean geodesic lengths, and clustering coefficients. Often pairs of models can reproduce these features with indistinguishable fidelity despite being generated by vastly different mechanisms. In such cases, these few target features are insufficient to distinguish which of the different models best describes real world networks of interest; moreover, it is not clear a priori that any of the presently-existing algorithms for network generation offers a predictive description of the networks inspiring them.

Results

We present a method to assess systematically which of a set of proposed network generation algorithms gives the most accurate description of a given biological network. To derive discriminative classifiers, we construct a mapping from the set of all graphs to a high-dimensional (in principle infinite-dimensional) "word space". This map defines an input space for classification schemes which allow us to state unambiguously which models are most descriptive of a given network of interest. Our training sets include networks generated from 17 models either drawn from the literature or introduced in this work. We show that different duplication-mutation schemes best describe the E. coli genetic network, the S. cerevisiae protein interaction network, and the C. elegans neuronal network, out of a set of network models including a linear preferential attachment model and a small-world model.

Conclusions

Our method is a first step towards systematizing network models and assessing their predictability, and we anticipate its usefulness for a number of communities.
Protein family comparison using statistical models and predicted structural information
Authors: Chung Richard , Yona Golan
Published: January 2005

Background

This paper presents a simple method to increase the sensitivity of protein family comparisons by incorporating secondary structure (SS) information. We build upon the effective information theory approach towards profile-profile comparison described in [Yona & Levitt 2002]. Our method augments profile columns using PSIPRED secondary structure predictions and assesses statistical similarity using information theoretical principles.

Results

Our tests show that this tool detects more similarities between protein families of distant homology than the previous primary sequence-based method. A very significant improvement in performance is observed when the real secondary structure is used.

Conclusions

Integration of primary and secondary structure information can substantially improve detection of relationships between remotely related protein families.
Integrating partonomic hierarchies in anatomy ontologies
Authors: Burger Albert , Davidson Duncan , Yang Yiya , Baldock Richard
Published: January 2005

Background

Anatomy ontologies play an increasingly important role in developing integrated bioinformatics applications. One of the primary relationships between anatomical tissues represented in such ontologies is part-of. As there are a number of ways to divide up the anatomical structure of an organism, each may be represented by more than one valid partonomic (part-of) hierarchy. This raises the issue of how to represent and integrate multiple such hierarchies.

Results

In this paper we describe a solution that is based on our work on an anatomy ontology for mouse embryo development, which is part of the Edinburgh Mouse Atlas Project (EMAP). The paper describes the basic conceptual aspects of our approach and discusses strengths and limitations of the proposed solution. A prototype was implemented in Prolog for evaluation purposes.

Conclusion

With the proposed name set approach, rather than having to standardise hierarchies, it is sufficient to agree on a suitable set of basic tissue terms and their meaning in order to facilitate the integration of multiple partonomic hierarchies.
Noise filtering and nonparametric analysis of microarray data underscores discriminating markers of oral, prostate, lung, ovarian and breast cancer
Authors: Aris Virginie M , Cody Michael J , Cheng Jeff , Dermody James J , Soteropoulos Patricia , Recce Michael , Tolias Peter P
Published: January 2005

Background

A major goal of cancer research is to identify discrete biomarkers that specifically characterize a given malignancy. These markers are useful in diagnosis, may identify potential targets for drug development, and can aid in evaluating treatment efficacy and predicting patient outcome. Microarray technology has enabled marker discovery from human cells by permitting measurement of steady-state mRNA levels derived from thousands of genes. However many challenging and unresolved issues regarding the acquisition and analysis of microarray data remain, such as accounting for both experimental and biological noise, transcripts whose expression profiles are not normally distributed, guidelines for statistical assessment of false positive/negative rates and comparing data derived from different research groups. This study addresses these issues using Affymetrix HG-U95A and HG-U133 GeneChip data derived from different research groups.

Results

We present here a simple non parametric approach coupled with noise filtering to identify sets of genes differentially expressed between the normal and cancer states in oral, breast, lung, prostate and ovarian tumors. An important feature of this study is the ability to integrate data from different laboratories, improving the analytical power of the individual results. One of the most interesting findings is the down regulation of genes involved in tissue differentiation.

Conclusions

This study presents the development and application of a noise model that suppresses noise, limits false positives in the results, and allows integration of results from individual studies derived from different research groups.
Haplotype frequency estimation error analysis in the presence of missing genotype data
Authors: Kelly Enda D , Sievers Fabian , McManus Ross
Published: January 2005

Background

Increasingly researchers are turning to the use of haplotype analysis as a tool in population studies, the investigation of linkage disequilibrium, and candidate gene analysis. When the phase of the data is unknown, computational methods, in particular those employing the Expectation-Maximisation (EM) algorithm, are frequently used for estimating the phase and frequency of the underlying haplotypes. These methods have proved very successful, predicting the phase-known frequencies from data for which the phase is unknown with a high degree of accuracy. Recently there has been much speculation as to the effect of unknown, or missing allelic data – a common phenomenon even with modern automated DNA analysis techniques – on the performance of EM-based methods. To this end an EM-based program, modified to accommodate missing data, has been developed, incorporating non-parametric bootstrapping for the calculation of accurate confidence intervals.

Results

Here we present the results of the analyses of various data sets in which randomly selected known alleles have been relabelled as missing. Remarkably, we find that the absence of up to 30% of the data in both biallelic and multiallelic data sets with moderate to strong levels of linkage disequilibrium can be tolerated. Additionally, the frequencies of haplotypes which predominate in the complete data analysis remain essentially the same after the addition of the random noise caused by missing data.

Conclusions

These findings have important implications for the area of data gathering. It may be concluded that small levels of drop out in the data do not affect the overall accuracy of haplotype analysis perceptibly, and that, given recent findings on the effect of inaccurate data, ambiguous data points are best treated as unknown.
DEDB: a database of Drosophila melanogaster exons in splicing graph form
Authors: Lee Bernett TK , Tan Tin Wee , Ranganathan Shoba
Published: January 2005

Background

A wealth of quality genomic and mRNA/EST sequences in recent years has provided the data required for large-scale genome-wide analysis of alternative splicing. We have capitalized on this by constructing a database that contains alternative splicing information organized as splicing graphs, where all transcripts arising from a single gene are collected, organized and classified. The splicing graph then serves as the basis for the classification of the various types of alternative splicing events.

Description

DEDB http://proline.bic.nus.edu.sg/dedb/index.html is a database of Drosophila melanogaster exons obtained from FlyBase arranged in a splicing graph form that permits the creation of simple rules allowing for the classification of alternative splicing events. Pfam domains were also mapped onto the protein sequences allowing users to access the impact of alternative splicing events on domain organization.

Conclusions

DEDB's catalogue of splicing graphs facilitates genome-wide classification of alternative splicing events for genome analysis. The splicing graph viewer brings together genome, transcript, protein and domain information to facilitate biologists in understanding the implications of alternative splicing.
Optimal cDNA microarray design using expressed sequence tags for organisms with limited genomic information
Authors: Chen Yian A , Mckillen David J , Wu Shuyuan , Jenny Matthew J , Chapman Robert , Gross Paul S , Warr Gregory W , Almeida Jonas S
Published: January 2005

Background

Expression microarrays are increasingly used to characterize environmental responses and host-parasite interactions for many different organisms. Probe selection for cDNA microarrays using expressed sequence tags (ESTs) is challenging due to high sequence redundancy and potential cross-hybridization between paralogous genes. In organisms with limited genomic information, like marine organisms, this challenge is even greater due to annotation uncertainty. No general tool is available for cDNA microarray probe selection for these organisms. Therefore, the goal of the design procedure described here is to select a subset of ESTs that will minimize sequence redundancy and characterize potential cross-hybridization while providing functionally representative probes.

Results

Sequence similarity between ESTs, quantified by the E-value of pair-wise alignment, was used as a surrogate for expected hybridization between corresponding sequences. Using this value as a measure of dissimilarity, sequence redundancy reduction was performed by hierarchical cluster analyses. The choice of how many microarray probes to retain was made based on an index developed for this research: a sequence diversity index (SDI) within a sequence diversity plot (SDP). This index tracked the decreasing within-cluster sequence diversity as the number of clusters increased. For a given stage in the agglomeration procedure, the EST having the highest similarity to all the other sequences within each cluster, the centroid EST, was selected as a microarray probe. A small dataset of ESTs from Atlantic white shrimp (Litopenaeus setiferus) was used to test this algorithm so that the detailed results could be examined. The functional representative level of the selected probes was quantified using Gene Ontology (GO) annotations.

Conclusions

For organisms with limited genomic information, combining hierarchical clustering methods to analyze ESTs can yield an optimal cDNA microarray design. If biomarker discovery is the goal of the microarray experiments, the average linkage method is more effective, while single linkage is more suitable if identification of physiological mechanisms is more of interest. This general design procedure is not limited to designing single-species cDNA microarrays for marine organisms, and it can equally be applied to multiple-species microarrays of any organisms with limited genomic information.
Comparing functional annotation analyses with Catmap
Authors: Breslin Thomas , Edén Patrik , Krogh Morten
Published: January 2005

Background

Ranked gene lists from microarray experiments are usually analysed by assigning significance to predefined gene categories, e.g., based on functional annotations. Tools performing such analyses are often restricted to a category score based on a cutoff in the ranked list and a significance calculation based on random gene permutations as null hypothesis.

Results

We analysed three publicly available data sets, in each of which samples were divided in two classes and genes ranked according to their correlation to class labels. We developed a program, Catmap (available for download at http://bioinfo.thep.lu.se/Catmap), to compare different scores and null hypotheses in gene category analysis, using Gene Ontology annotations for category definition. When a cutoff-based score was used, results depended strongly on the choice of cutoff, introducing an arbitrariness in the analysis. Comparing results using random gene permutations and random sample permutations, respectively, we found that the assigned significance of a category depended strongly on the choice of null hypothesis. Compared to sample label permutations, gene permutations gave much smaller p-values for large categories with many coexpressed genes.

Conclusions

In gene category analyses of ranked gene lists, a cutoff independent score is preferable. The choice of null hypothesis is very important; random gene permutations does not work well as an approximation to sample label permutations.
GECKO: a complete large-scale gene expression analysis platform
Authors: Theilhaber Joachim , Ulyanov Anatoly , Malanthara Anish , Cole Jack , Xu Dapeng , Nahf Robert , Heuer Michael , Brockel Christoph , Bushnell Steven
Published: January 2005

Background

Gecko (Gene Expression: Computation and Knowledge Organization) is a complete, high-capacity centralized gene expression analysis system, developed in response to the needs of a distributed user community.

Results

Based on a client-server architecture, with a centralized repository of typically many tens of thousands of Affymetrix scans, Gecko includes automatic processing pipelines for uploading data from remote sites, a data base, a computational engine implementing ~ 50 different analysis tools, and a client application. Among available analysis tools are clustering methods, principal component analysis, supervised classification including feature selection and cross-validation, multi-factorial ANOVA, statistical contrast calculations, and various post-processing tools for extracting data at given error rates or significance levels. On account of its open architecture, Gecko also allows for the integration of new algorithms. The Gecko framework is very general: non-Affymetrix and non-gene expression data can be analyzed as well. A unique feature of the Gecko architecture is the concept of the Analysis Tree (actually, a directed acyclic graph), in which all successive results in ongoing analyses are saved. This approach has proven invaluable in allowing a large (~ 100 users) and distributed community to share results, and to repeatedly return over a span of years to older and potentially very complex analyses of gene expression data.

Conclusions

The Gecko system is being made publicly available as free software http://sourceforge.net/projects/geckoe. In totality or in parts, the Gecko framework should prove useful to users and system developers with a broad range of analysis needs.
SCOPmap: Automated assignment of protein structures to evolutionary superfamilies
Authors: Cheek Sara , Qi Yuan , Krishna S Sri , Kinch Lisa N , Grishin Nick V
Published: January 2005

Background

Inference of remote homology between proteins is very challenging and remains a prerogative of an expert. Thus a significant drawback to the use of evolutionary-based protein structure classifications is the difficulty in assigning new proteins to unique positions in the classification scheme with automatic methods. To address this issue, we have developed an algorithm to map protein domains to an existing structural classification scheme and have applied it to the SCOP database.

Results

The general strategy employed by this algorithm is to combine the results of several existing sequence and structure comparison tools applied to a query protein of known structure in order to find the homologs already classified in SCOP database and thus determine classification assignments. The algorithm is able to map domains within newly solved structures to the appropriate SCOP superfamily level with ~95% accuracy. Examples of correctly mapped remote homologs are discussed. The algorithm is also capable of identifying potential evolutionary relationships not specified in the SCOP database, thus helping to make it better. The strategy of the mapping algorithm is not limited to SCOP and can be applied to any other evolutionary-based classification scheme as well. SCOPmap is available for download.

Conclusion

The SCOPmap program is useful for assigning domains in newly solved structures to appropriate superfamilies and for identifying evolutionary links between different superfamilies.
GenomeViz: visualizing microbial genomes
Authors: Ghai Rohit , Hain Torsten , Chakraborty Trinad
Published: January 2005

Background

An increasing number of microbial genomes are being sequenced and deposited in public databases. In addition, several closely related strains are also being sequenced in order to understand the genetic basis of diversity and mechanisms that lead to the acquisition of new genetic traits. These exercises have necessitated the requirement for visualizing microbial genomes and performing genome comparisons on a finer scale. We have developed GenomeViz to enable rapid visualization and subsequent comparisons of several microbial genomes in an interactive environment.

Results

Here we describe a program that allows visualization of both qualitative and quantitative information from complete and partially sequenced microbial genomes. Using GenomeViz, data deriving from studies on genomic islands, gene/protein classifications, GC content, GC skew, whole genome alignments, microarrays and proteomics may be plotted. Several genomes can be visualized interactively at the same time from a comparative genomic perspective and publication quality circular genome plots can be created.

Conclusions

GenomeViz should allow researchers to perform visualization and comparative analysis of up to eight different microbial genomes simultaneously.
The architecture of chicken chromosome territories changes during differentiation
Authors: Stadler Sonja , Schnapp Verena , Mayer Robert , Stein Stefan , Cremer Christoph , Bonifer Constanze , Cremer Thomas , Dietzel Steffen
Published: January 2005

Background

Between cell divisions the chromatin fiber of each chromosome is restricted to a subvolume of the interphase cell nucleus called chromosome territory. The internal organization of these chromosome territories is still largely unknown.

Results

We compared the large-scale chromatin structure of chromosome territories between several hematopoietic chicken cell types at various differentiation stages. Chromosome territories were labeled by fluorescence in situ hybridization in structurally preserved nuclei, recorded by confocal microscopy and evaluated visually and by quantitative image analysis. Chromosome territories in multipotent myeloid precursor cells appeared homogeneously stained and compact. The inactive lysozyme gene as well as the centromere of the lysozyme gene harboring chromosome located to the interior of the chromosome territory. In further differentiated cell types such as myeloblasts, macrophages and erythroblasts chromosome territories appeared increasingly diffuse, disaggregating to separable substructures. The lysozyme gene, which is gradually activated during the differentiation to activated macrophages, as well as the centromere were relocated increasingly to more external positions.

Conclusions

Our results reveal a cell type specific constitution of chromosome territories. The data suggest that a repositioning of chromosomal loci during differentiation may be a consequence of general changes in chromosome territory morphology, not necessarily related to transcriptional changes.