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Computational analysis of flow-cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification.

Precursor B-acute lymphoblastic leukemia (pB-ALL) is a heterogeneous disease and multiparameter flow cytometry, molecular genetics, and cytogenetic studies have all contributed to classification of subgroups with prognostic significance. Recently, gene expression microarray technology has been used to investigate lymphoblastic leukemias, demonstrating that known and novel pB-ALL subclasses can be separated on the basis of gene expression profiles. The strength of microarray technique lays in part in the multivariate nature of the expression data. We propose a parallel multiparametric approach based on immunophenotypic flow-cytometry expression data for the analysis of leukemia patients. Specifically, we tested the potential of this approach on a data set of 145 samples of pediatric pB-ALL that included 46 samples positive for mixed lineage leukemia (MLL) translocations (MLL+) and 99 control pB-ALLs, negative for this translocation (MLL-). The expression levels of 16 marker proteins have been monitored by four-color flow cytometry using a standardized diagnostic panel of antibodies. The protein expression database has been then analyzed using those univariate and multivariate computational techniques normally applied to mine and model large microarray data sets. Marker protein expression profiling not only allowed separating pB-ALL cases with an MLL rearrangement from other ALLs, but also demonstrates that MLL+ leukemias constitute a heterogeneous group in which MLL/AF4 leukemias represent a homogenous subclass described by a specific expression fingerprint.

Adolescent↗

Occupational diseases in South African mines--a neglected epidemic?

A major difficulty in assessing incidence and prevalence of occupational diseases among the workforce employed on South African mines is the lack of epidemiological data. Published and unpublished data were collated and analysed for the period 1915-1988 in order to provide insights into occupational disease trends. Using proxies for incidence rates, it was demonstrated that the rates of silicosis and tuberculosis were likely to be high. In the case of silicosis among black miners, disease was contracted in a relatively short period on average. The stabilisation of the black workforce on the mines, which started in 1975 and continues, is an important factor likely to lead to an increase in occupational disease rates. Recommendations for improved data reporting and research are made, in particular the need to identify occupational groups at high risk and the calculation of prevalences.

Adult↗

Seq2Saccharide: Discovering Oligosaccharides and Aminoglycosides Natural Products by Integrating Computational Mass Spectrometry and Genome Mining.

Natural oligosaccharides and aminoglycosides are important sources of new drug candidates, especially in the development of antibiotics. In the past, discovering novel saccharides has been time-consuming and costly. However, the rapid expansion of high-throughput data, including genomic and mass spectrometry data sets, has greatly increased opportunities for natural saccharide discovery. Yet, due to the complex biosynthesis pathways of saccharides, no existing method can predict their structures with high precision. To address this, we introduce Seq2Saccharide, a tool designed to automate saccharide natural product discovery by integrating both genomic and mass spectrometry data. To enhance accuracy, Seq2Saccharide predicts hundreds or thousands of putative structures for each gene cluster. The correct structure is then identified from these predictions using a mass spectral search. Benchmarks against saccharides in the MiBIG database show that Seq2Saccharide outperforms existing methods in predicting the structure of saccharides. Furthermore, mass spectrometry analysis indicates that the variable search module can correct mispredictions from genome mining. By searching genomic and mass spectrometry data of microbial strains, Seq2Saccharide correctly identified the biosynthetic gene cluster for the polysaccharide oligosaccharide trestatin B.

Aminoglycosides↗

Respiratory abnormalities in employees of the hard rock mining industry.

Respiratory symptoms, forced vital capacity, and the single breath N2 test were assessed in male employees (25 to 54 yr of age) who had been employed for more than 5 yr in the mining industry in Manitoba. The results were compared with those in a similar group of men selected from the general population. The prevalence of cough and/or phlegm in both nonsmoking and smoking mining employees was significantly greater than that in the sample of the general population (p less than 0.05). In both nonsmokers and ex-smokers amongst the mining employees, the parameters derived from the single breath N2 test tended to be lower and maximal expiratory flow rates tended to be higher than in comparable groups in the general population sample. In smokers, FVC, FEV1, FEV1/FVC, maximal expiratory flow rates, RV/TLC, and the slope of phase III were significantly worse in smelter workers than in underground workers. Alterations in lung function in those who worked underground, but not in those who worked in the smelter, was related to the duration of employment in the industry. The data suggest that exposure to mining irritants may result in disorders of lung function, and that this effect is greater in cigarette smokers.

Adult↗

Informatics and quantitative analysis in biological imaging.

Biological imaging is now a quantitative technique for probing cellular structure and dynamics and is increasingly used for cell-based screens. However, the bioinformatics tools required for hypothesis-driven analysis of digital images are still immature. We are developing the Open Microscopy Environment (OME) as an informatics solution for the storage and analysis of optical microscope image data. OME aims to automate image analysis, modeling, and mining of large sets of images and specifies a flexible data model, a relational database, and an XML-encoded file standard that is usable by potentially any software tool. With this design, OME provides a first step toward biological image informatics.

Algorithms↗

Text mining of full-text journal articles combined with gene expression analysis reveals a relationship between sphingosine-1-phosphate and invasiveness of a glioblastoma cell line.

BACKGROUND: Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in various cellular processes such as migration, proliferation, and survival. To date, the impact of S1P on human glioblastoma is not fully understood. Particularly, the concerted role played by matrix metalloproteinases (MMP) and S1P in aggressive tumor behavior and angiogenesis remains to be elucidated. RESULTS: To gain new insights in the effect of S1P on angiogenesis and invasion of this type of malignant tumor, we used microarrays to investigate the gene expression in glioblastoma as a response to S1P administration in vitro. We compared the expression profiles for the same cell lines under the influence of epidermal growth factor (EGF), an important growth factor. We found a set of 72 genes that are significantly differentially expressed as a unique response to S1P. Based on the result of mining full-text articles from 20 scientific journals in the field of cancer research published over a period of five years, we inferred gene-gene interaction networks for these 72 differentially expressed genes. Among the generated networks, we identified a particularly interesting one. It describes a cascading event, triggered by S1P, leading to the transactivation of MMP-9 via neuregulin-1 (NRG-1), vascular endothelial growth factor (VEGF), and the urokinase-type plasminogen activator (uPA). This interaction network has the potential to shed new light on our understanding of the role played by MMP-9 in invasive glioblastomas. CONCLUSION: Automated extraction of information from biological literature promises to play an increasingly important role in biological knowledge discovery. This is particularly true for high-throughput approaches, such as microarrays, and for combining and integrating data from different sources. Text mining may hold the key to unraveling previously unknown relationships between biological entities and could develop into an indispensable instrument in the process of formulating novel and potentially promising hypotheses.

Cell Line, Tumor↗

Resource exploitation and cross-region growth trajectories: nonparametric estimates for Chile.

As a sector of primary concern for national development strategies, mining keeps stimulating an intensive debate in Chile, regarding its role for long-term growth. Partly drawn on theoretical contributions to growth and mineral resource accounting, this analysis assesses patterns of economic growth across Chilean regions. The theoretical and methodological rationale for focusing on weak sustainability, by testing convergence across regions in a distribution dynamics perspective, is first discussed. This is followed by a brief review of policy issues and previous empirical findings of concern to Chile's mining and regional growth. Panel data over the period 1960-2001 are analysed, with growth measured in terms of both income per capita as such, and sustainable measures of this variable. Kernel density and quantile regression estimates indicate persistent bimodal (if not possibly trimodal) distribution of nationally standardised regional incomes per capita, whereby conditions for cross-region convergence are matched only within the inner range of this distribution.

Chile↗

Mining for single nucleotide polymorphisms and insertions/deletions in maize expressed sequence tag data.

We have developed a computer based method to identify candidate single nucleotide polymorphisms (SNPs) and small insertions/deletions from expressed sequence tag data. Using a redundancy-based approach, valid SNPs are distinguished from erroneous sequence by their representation multiple times in an alignment of sequence reads. A second measure of validity was also calculated based on the cosegregation of the SNP pattern between multiple SNP loci in an alignment. The utility of this method was demonstrated by applying it to 102,551 maize (Zea mays) expressed sequence tag sequences. A total of 14,832 candidate polymorphisms were identified with an SNP redundancy score of two or greater. Segregation of these SNPs with haplotype indicates that candidate SNPs with high redundancy and cosegregation confidence scores are likely to represent true SNPs. This was confirmed by validation of 264 candidate SNPs from 27 loci, with a range of redundancy and cosegregation scores, in four inbred maize lines. The SNP transition/transversion ratio and insertion/deletion size frequencies correspond to those observed by direct sequencing methods of SNP discovery and suggest that the majority of predicted SNPs and insertion/deletions identified using this approach represent true genetic variation in maize.

Base Sequence↗

ParPEST: a pipeline for EST data analysis based on parallel computing.

BACKGROUND: Expressed Sequence Tags (ESTs) are short and error-prone DNA sequences generated from the 5' and 3' ends of randomly selected cDNA clones. They provide an important resource for comparative and functional genomic studies and, moreover, represent a reliable information for the annotation of genomic sequences. Because of the advances in biotechnologies, ESTs are daily determined in the form of large datasets. Therefore, suitable and efficient bioinformatic approaches are necessary to organize data related information content for further investigations. RESULTS: We implemented ParPEST (Parallel Processing of ESTs), a pipeline based on parallel computing for EST analysis. The results are organized in a suitable data warehouse to provide a starting point to mine expressed sequence datasets. The collected information is useful for investigations on data quality and on data information content, enriched also by a preliminary functional annotation. CONCLUSION: The pipeline presented here has been developed to perform an exhaustive and reliable analysis on EST data and to provide a curated set of information based on a relational database. Moreover, it is designed to reduce execution time of the specific steps required for a complete analysis using distributed processes and parallelized software. It is conceived to run on low requiring hardware components, to fulfill increasing demand, typical of the data used, and scalability at affordable costs.

Algorithms↗

Mining for putative regulatory elements in the yeast genome using gene expression data.

We have developed a set of methods and tools for automatic discovery of putative regulatory signals in genome sequences. The analysis pipeline consists of gene expression data clustering, sequence pattern discovery from upstream sequences of genes, a control experiment for pattern significance threshold limit detection, selection of interesting patterns, grouping of these patterns, representing the pattern groups in a concise form and evaluating the discovered putative signals against existing databases of regulatory signals. The pattern discovery is computationally the most expensive and crucial step. Our tool performs a rapid exhaustive search for a priori unknown statistically significant sequence patterns of unrestricted length. The statistical significance is determined for a set of sequences in each cluster with respect to a set of background sequences allowing the detection of subtle regulatory signals specific for each cluster. The potentially large number of significant patterns is reduced to a small number of groups by clustering them by mutual similarity. Automatically derived consensus patterns of these groups represent the results in a comprehensive way for a human investigator. We have performed a systematic analysis for the yeast Saccharomyces cerevisiae. We created a large number of independent clusterings of expression data simultaneously assessing the "goodness" of each cluster. For each of the over 52,000 clusters acquired in this way we discovered significant patterns in the upstream sequences of respective genes. We selected nearly 1,500 significant patterns by formal criteria and matched them against the experimentally mapped transcription factor binding sites in the SCPD database. We clustered the 1,500 patterns to 62 groups for which we derived automatically alignments and consensus patterns. Of these 62 groups 48 had patterns that have matching sites in SCPD database.

Gene Expression Profiling↗

Epidemiology of occupational noise-induced hearing loss in Poland throughout 1971--1979.

In Poland a uniform system for registering occupational diseases is mandatory. Special individual statistical cards of diagnosed cases are delivered from all over the country to the Institute of Occupational Medicine in Lodź, where the incidence of diseases is analysed using electronic data processing system; such procedure is aimed, among others, at specification of prophylactic needs. Due to this, epidemiological studies could be carried out of the prevalence of occupational noise -- induced hearing loss in the total national economy throughout 1971--1979. Of the 35 mln Polish population, approx. 5 mln. 240 thous. persons are employed in industry, in this about 600 000 workers exposed to noise levels posing a risk of the hearing impairment of (Leq greater than or equal to 90 dB-A). It was found that occupational noise -- induced hearing loss was most frequent among all occupational diseases and its incidence rate exceeded 16 new cases annually per 100 000 employees. The highest incidence rate concerned transport means industry, coal mining and textile industry. The data analysis, by age and exposure duration, showed that the disease mostly affects those aged 40 -- 49 and 50 -- 59, as well as those exposed to excessive noise levels for over 20 years. In addition, the distribution of occupational noise -- induced hearing loss in specific areas throughout the country, considering the degree of industrialization, was analysed. The highest incidence rate was found in the Southern and Western areas of Poland. The above information seems to be essential for setting up more efficient hearing conservation program in industry.

Adult↗

Absolute bioavailability of lead acetate and mining waste lead in rats.

The primary purpose of this study was to generate data that could be used to determine the absolute bioavailability of lead using data from a previous study in which soil containing lead from mining waste was mixed with feed. Young male and female Sprague-Dawley rats (7-8 weeks of age, five/sex/group) were given either soluble lead acetate mixed in a purified diet (AIN-76) at three different dose levels (1, 25, and 250 ppm Pb for 30 consecutive days) or intravenously at doses of 0.02, 0.20, and 2.0 mg Pb/kg BW for 29 days. A control group (purified diet only) was also included. The intravenous groups were used to provide maximal absorption (lead presumed to be 100% bioavailable) and accumulation data for lead in blood, bone, and liver. The lead acetate groups were used to evaluate the comparability of the present study with a previous study that compared bioavailable lead from ingested soil and lead acetate. Group mean whole blood, bone and liver lead concentration values increased with increasing dose levels for all treatment groups. A linear relationship was observed between blood lead concentration and dose following intravenous administration of lead and this provided empirical support for using blood lead concentrations at supposed steady state (approximately 30 days) to compute the bioavailability of lead administered by different routes and from different sources. The absolute bioavailability values of mining waste lead in soil were low based on the results for all tissue types. Absolute bioavailability values for lead acetate in dosed feed for blood, bone, and liver were approximately 6-, 19-, and 20-fold greater, respectively, than mining waste lead. Based on the current design and test system used, the absolute bioavailability of mining waste lead in soil administered in feed was approximately 3% based on blood data and less than 1% based on bone and liver data. These data are consistent with the low solubility of the constituent lead mineral phases in Butte soils.

Administration, Oral↗

[Current problems of treatment of mine explosion wounds].

On the basis of their many-years experiences in the clinic of field surgery with wounded having mine explosion pathology during the Afghan war and military operations in the North Caucasus the authors discuss the specificity of terminology, diagnosis and surgical treatment of mine-explosion wounds and traumas. The article presents statistical data concerned with the results of treatment of patients with mine-explosion wounds and explosion traumas in the North Caucasus (1994-1996), where the mine-explosion pathology made up 15% in the structure of military surgical traumas, frequency of complications was 70%, total lethality--5.2%.

Afghanistan↗

Modeling metal removal onto natural particles formed during mixing of acid rock drainage with ambient surface water.

Studies have examined partitioning of trace metals onto natural particles to better understand the fate and transport of trace metals in the environment, but few studies have compared model predictions with field results. We evaluate the application of an empirical modeling approach, using surface complexation parameters available in the literature, to complex natural systems. In this work, the equilibrium speciation computer program PHREEQC was used along with the diffuse double-layer surface complexation model to simulate metal removal onto natural oxide particles formed during the mixing of acid rock drainage with ambient surface water. End-member solutions sampled in the Coeur d'Alene (CdA) Mining District in September 1999 from the Bunker Hill Mine and the South Fork Coeur d'Alene (SFCdA) River were filtered and mixed in several ratios. Solution chemistry was determined for end-members and mixed solutions, and X-ray diffraction (XRD) was used to determine the mineralogy of precipitate phases. Predicted amounts of Fe precipitates were in good agreement with measured values for particulate Fe. Surface area and reactive site characteristics were used along with surface complexation constants for ferrihydrite (Dzombak, D. A.; Morel, F. M. M. Surface Complexation Modeling: Hydrous Ferric Oxide; John Wiley & Sons: New York, 1990) to predict ion sorption as a function of mixing fraction. Comparisons of model predictions with field results indicate that Pb and Cu sorption are predicted well by the model, while As, Mo, and Sb sorption are less well-predicted. Additional comparisons with particulate metal and Fe data collected from the CdA Mining District in 1996 and 1997 suggest that sorption on particulate Fe, including amorphous iron oxides and schwertmannite, may be described using universal model parameters.

Adsorption↗

Contamination of houses by workers occupationally exposed in a lead-zinc-copper mine and impact on blood lead concentrations in the families.

OBJECTIVE: To evaluate the pathway of leaded dust from a lead-zinc-copper mine to houses of employees, and the impact on blood lead concentrations (PbB) of children. METHODS: High precision lead isotope and lead concentration data were obtained on venous blood and environmental samples (vacuum cleaner dust, interior dustfall accumulation, water, paint) for eight children of six employees (and the employees) from a lead-zinc-copper mine. These data were compared with results for 11 children from occupationally unexposed control families living in the same city. RESULTS: The median (range) concentrations of lead in vacuum cleaner dust was 470 (21-1300) ppm. In the houses of the mine employees, vacuum cleaner dust contained varying higher proportions of mine lead than did airborne particulate matter measured as dustfall accumulated over a three month period. The median (range) concentrations of lead in soil were 30 (5-407) ppm and these showed no evidence of any mine lead. Lead in blood of the mine employees varied from 7 to 25 micrograms/dl and was generally dominated by mine lead (> 60%). The mean (SD) PbB in the children of the mine employees was 5.7 (1.7) micrograms/dl compared with 4.1 (1.4) micrograms/dl for the control children (P = 0.02). The PbB of all children was always < 10 micrograms/dl, the Australian National Health and Medical Research Council goal for all Australians. Some of the control children had higher PbB than the children of mine employees, probably from exposure to leaded paint as six of the eight houses of the control children were > 50 years old. In five of the eight children of mine employees > 20% of PbB was from the lead mine. However, in the other three cases of children of mine employees, their PbB was from sources other than mine lead (paint, petrol, background sources). CONCLUSIONS: Houses of employees from a lead mine can be contaminated by mine lead even if they are not situated in the same place as the mine. Delineation of the mine to house pathway indicates that lead is probably transported into the houses on the clothes, shoes, hair, skin, and in some cases, motor vehicles of the workers. In one case, dust shaken from clothes of a mine employee contained 3000 ppm lead which was 100% mine lead. The variable contamination of the houses was not expected given the precautions taken by mine employees to minimise transportation of lead into their houses. Although five out of the eight children of mine employees had > 20% mine lead in their blood, in no case did the PbB of a child exceed the Australian National Health and Medical Research Council goal of 10 micrograms/dl. In fact, some children in the control families had higher PbB than children of mine employees. In two cases, this was attributed to a pica habit for paint. The PbB in the children of mine employees and controls was independent of the source of lead. The low PbB in the children of mine employees may reflect the relatively low solubility (bioavailability) of the mine dust in 0.1 M hydrochloric acid (< 40 %), behaviour--for example, limited mouthing activity--or diet.

Adult↗

UTAB: a computer database on residues of xenobiotic organic chemicals and heavy metals in plants.

The UTAB Database contains information concerned with the uptake/accumulation, translocation, adhesion, and biotransformation of both xenobiotic organic chemicals and heavy metals by vascular plants. UTAB can be used to estimate the accumulation of chemicals in vegetation and their subsequent movement through the food chain. The database contains actual data from papers in the published literature dating from 1926 for organic chemicals and from 1976 for heavy metals. At present the database is comprised of more than 37,000 records pertaining to 900 different organic chemicals, 21 heavy metals, and over 350 plant species. Each record contains information on a single combination of species, chemical, and dose. Other information includes the application and destination sites, amount accumulated, rates of uptake or translocation, products and sites of biotransformation, experimental condition parameters, and the source paper. Thus, the database can be used to quickly obtain specific data pertaining to a chemical, plant species, mine spoil, etc. or it can be used for the comparative analysis of a set of data pertaining to groups of chemicals and plants.

Databases, Bibliographic↗

[Evaluation of the effectiveness of medical prevention of pneumoconiosis based on studies of its incidence in selected coal mines].

In a group of 3,938 persons--pit miners of 3 coal mines--employed over 8 years, full-size X-ray pictures of the chest have been taken and through a special questionnaire information has been collected on the length of employment, workstation, risk of dustiness, exposure to fibrogenic dusts outside the mine. Basing on the studies, the mean annual incidence of pneumoconiosis in particular mines has been calculated. The data has been compared with the mean annual incidence rate of pneumoconiosis calculated for 10 years prior to epidemiological studies and based on the primary selection by means of small-size pictures. This comparison indicated that the full-size pictures revealed 3-7 times more pneumoconioses as compared to the hitherto applied system. The comparison of full-size and small-size X-ray pictures demonstrated that the lesions visible in full-size pictures have not been registered in small-size pictures in as many as half of the cases. The obtained results indicate that the effectiveness of the hitherto applied system of medical prevention of pneumoconiosis is insufficient. A change in this system is indispensable; miniature roentgenography should be replaced by full-size X-ray pictures.

Adult↗

Sampling results of the improved SKC diesel particulate matter cassette.

Diesel particulate matter (DPM) samples from underground metal/nonmetal mines are collected on quartz fiber filters and measured for carbon content using National Institute for Occupational Safety and Health Method 5040. If size-selective samplers are not used to collect DPM in the presence of carbonaceous ore dust, both the ore dust and DPM will collect on the quartz filters, causing the carbon attributed to DPM to be artificially high. Because the DPM particle size is much smaller than that of mechanically generated mine dust aerosols, it can be separated from the larger mine dust aerosol by a single-stage impactor. The SKC DPM cassette is a single-stage impactor designed to collect only DPM aerosols in the presence of carbonaceous mine ore aerosols, which are commonly found in underground nonmetal mines. However, there is limited data on how efficiently the SKC DPM cassette can collect DPM in the presence of ore dust. In this study we investigated the ability of the SKC DPM cassette to collect DPM while segregating ore dust from the sample. We found that the SKC DPM cassette accurately collected DPM. In the presence of carbon-based ore aerosols having an average concentration of 8 mg/m3, no ore dust was detected on SKC DPM cassette filters. We did discover a problem: the surface areas of the DPM deposits on SKC DPM cassettes, manufactured prior to August 2002 were inconsistent. To correct this problem, SKC modified the cassette. The new cassette produced, with 99% confidence, a range of DPM deposit areas between 8.05 and 8.28 cm2, a difference of less than 3%.

Air Pollution, Indoor↗