Turbulent channel flow near maximum drag reduction: simulations, experiments and mechanisms

It is well known that the drag in a turbulent flow of a polymer solution is significantly reduced compared to Newtonian flow. Here we consider this phenomenon by means of a direct numerical simulation of a turbulent channel flow. The polymers are modelled as elastic dumbbells using the FENE-P model. In the computations the polymer model is solved simultaneously with the flow equations, i.e. the polymers are deformed by the flow and in their turn influence the flow structures by exerting a polymer stress. We have studied the results of varying the polymer parameters, such as the maximum extension, the elasticity and the concentration. For the case of highly extensible polymers the results of our simulations are very close to the maximum drag reduction or Virk (1975) asymptote. Our simulation results show that at approximately maximum drag reduction the slope of the mean velocity profile is increased compared to the standard logarithmic profile in turbulent wall flows. For the r.m.s. of the streamwise velocity fluctuations we find initially an increase in magnitude which near maximum drag reduction changes to a decrease. For the velocity fluctuations in the spanwise and wall-normal directions we find a continuous decrease as a function of drag reduction. The Reynolds shear stress is strongly reduced, especially near the wall, and this is compensated by a polymer stress, which at maximum drag reduction amounts to about 40% of the total stress. These results have been compared with LDV experiments of Ptasinski et al. (2001) and the agreement, both qualitatively and quantitatively, is in most cases very good. In addition we have performed an analysis of the turbulent kinetic energy budgets. The main result is a reduction of energy transfer from the streamwise direction, where the production of turbulent kinetic energy takes place, to the other directions. A substantial part of the energy production by the mean flow is transferred directly into elastic energy of the polymers. The turbulent velocity fluctuations also contribute energy to the polymers. The elastic energy of the polymers is subsequently dissipated by polymer relaxation. We have also computed the various contributions to the pressure fluctuations and identified how these change as a function of drag reduction. Finally, we discuss some cross-correlations and various length scales. These simulation results are explained here by two mechanisms. First, as suggested by Lumley (1969) the polymers damp the cross-stream or wall-normal velocity fluctuations and suppress the bursting in the buffer layer. Secondly, the ‘shear sheltering’ mechanism acts to amplify the streamwise fluctuations in the thickened buffer layer, while reducing and decoupling the motions within and above this layer. The expression for the substantial reduction in the wall drag derived by considering the long time scales of the nonlinear fluctuations of this damped shear layer, is shown to be consistent with the experimental data of Virk et al. (1967) and Virk (1975)

Benchmarking ortholog identification methods using functional genomics data

BACKGROUND: The transfer of functional annotations from model organism proteins to human proteins is one of the main applications of comparative genomics. Various methods are used to analyze cross-species orthologous relationships according to an operational definition of orthology. Often the definition of orthology is incorrectly interpreted as a prediction of proteins that are functionally equivalent across species, while in fact it only defines the existence of a common ancestor for a gene in different species. However, it has been demonstrated that orthologs often reveal significant functional similarity. Therefore, the quality of the orthology prediction is an important factor in the transfer of functional annotations (and other related information). To identify protein pairs with the highest possible functional similarity, it is important to qualify ortholog identification methods. RESULTS: To measure the similarity in function of proteins from different species we used functional genomics data, such as expression data and protein interaction data. We tested several of the most popular ortholog identification methods. In general, we observed a sensitivity/selectivity trade-off: the functional similarity scores per orthologous pair of sequences become higher when the number of proteins included in the ortholog groups decreases. CONCLUSION: By combining the sensitivity and the selectivity into an overall score, we show that the InParanoid program is the best ortholog identification method in terms of identifying functionally equivalent proteins

PhyloPat: phylogenetic pattern analysis of eukaryotic genes

BACKGROUND: Phylogenetic patterns show the presence or absence of certain genes or proteins in a set of species. They can also be used to determine sets of genes or proteins that occur only in certain evolutionary branches. Phylogenetic patterns analysis has routinely been applied to protein databases such as COG and OrthoMCL, but not upon gene databases. Here we present a tool named PhyloPat which allows the complete Ensembl gene database to be queried using phylogenetic patterns. DESCRIPTION: PhyloPat is an easy-to-use webserver, which can be used to query the orthologies of all complete genomes within the EnsMart database using phylogenetic patterns. This enables the determination of sets of genes that occur only in certain evolutionary branches or even single species. We found in total 446,825 genes and 3,164,088 orthologous relationships within the EnsMart v40 database. We used a single linkage clustering algorithm to create 147,922 phylogenetic lineages, using every one of the orthologies provided by Ensembl. PhyloPat provides the possibility of querying with either binary phylogenetic patterns (created by checkboxes) or regular expressions. Specific branches of a phylogenetic tree of the 21 included species can be selected to create a branch-specific phylogenetic pattern. Users can also input a list of Ensembl or EMBL IDs to check which phylogenetic lineage any gene belongs to. The output can be saved in HTML, Excel or plain text format for further analysis. A link to the FatiGO web interface has been incorporated in the HTML output, creating easy access to functional information. Finally, lists of omnipresent, polypresent and oligopresent genes have been included. CONCLUSION: PhyloPat is the first tool to combine complete genome information with phylogenetic pattern querying. Since we used the orthologies generated by the accurate pipeline of Ensembl, the obtained phylogenetic lineages are reliable. The completeness and reliability of these phylogenetic lineages will further increase with the addition of newly found orthologous relationships within each new Ensembl release

Testing statistical significance scores of sequence comparison methods with structure similarity

BACKGROUND: In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. RESULTS: All experiments are performed on the ASTRAL SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST and FASTA algorithms are used as reference. We find that two out of three Smith-Waterman implementations with e-value are better at predicting structural similarities between proteins than the Smith-Waterman implementation with Z-score. SSEARCH especially has very high scores. CONCLUSION: The compute intensive Z-score does not have a clear advantage over the e-value. The Smith-Waterman implementations give generally better results than their heuristic counterparts. We recommend using the SSEARCH algorithm combined with e-values for pairwise sequence comparisons

Integrated Epigenome Profiling of Repressive Histone Modifications, DNA Methylation and Gene Expression in Normal and Malignant Urothelial Cells

Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20–30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5–10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer

Mastitis diagnostics and performance monitoring: a practical approach

In this paper a review is given of frequently used mastitis diagnostic methods in modern dairy practice. Methods used at the quarter, cow, herd and regional or national level are discussed, including their usability for performance monitoring in udder health. Future developments, such as systems in which milk-derived parameters are combined with modern analytical techniques, are discussed. It is concluded that, although much knowledge is available and science is still developing and much knowledge is available, it is not always fully exploited in practice

Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration

Malignant mesothelioma is an asbestos induced cancer that is difficult to diagnose. Several studies have combined biomarkers to improve mesothelioma diagnosis, but with moderate success, and there is a need for new mesothelioma biomarkers. The tumour is often resistant to treatment and most patients will survive less than a year. An indicator of patient survival is the tumours growth pattern, which in turn is influenced by expressed proteoglycans. In this thesis work, we aim to improve the possibilities to diagnose malignant mesothelioma by combining biomarkers and by identifying new ones. We also investigate tumour driving mechanisms with focus on one of these suggested biomarkers, the cell-bound proteoglycan syndecan-1. We were able to construct a diagnostic two-step model based on biomarkers in patient material. By implementing a cut-off level and thereafter focusing on unresolved patients we combined hyaluronan and N-ERC/mesothelin (paper I), which significantly increased the diagnostic accuracy for malignant mesothelioma. To further improve diagnosis, we used mass spectrometry to find new biomarkers. We identified and validated galectin-1, which was excellent in discriminating mesotheliomas from adenocarcinomas (paper II). In the same study, we were also the first to describe aldo-keto reductase 1B10 as a novel prognostic mesothelioma biomarker. Syndecan-1 has been indicated as a marker for carcinomas. In paper I we describe how higher levels of syndecan-1 indicate the presence of a carcinoma over a mesothelioma. This was verified in paper II when syndecan-1 was identified as downregulated in fluids from mesothelioma patients compared to lung cancer patients. Paper III and paper IV focus on this proteoglycan. Malignant cell lines transfected with syndecan-1 and various truncated forms of syndecan-1 affected adhesion and migration, which are key features of cancer invasion (paper III). The results showed a domain- and cell type specific effect on the cells’ motility. Regulating syndecan-1 levels and analysing the global gene expression of mesothelioma cells made it evident that this proteoglycan has a strong influence on transforming growth factor β signalling and several growth factor pathways (paper IV). Links to cell migration and proliferation were furthermore identified, along with glycosaminoglycan modifying enzymes. These results can shed light on the complex role of syndecan-1 in invasion and growth of malignant mesenchymal cells. Taken together, this thesis work describes a complement to conventional mesothelioma diagnosis and identifies novel biomarkers. Furthermore, the potential biomarker syndecan-1 was shown to have an effect on cell motility and proliferation. These results increase our understanding of this aggressive malignancy

The human phylome

The human phylome, which includes evolutionary relationships of all human proteins and their homologs among thirty-nine fully sequenced eukaryotes, is reconstructed

Mitochondrial genome deletions and minicircles are common in lice (Insecta: Phthiraptera)

Background The gene composition, gene order and structure of the mitochondrial genome are remarkably stable across bilaterian animals. Lice (Insecta: Phthiraptera) are a major exception to this genomic stability in that the canonical single chromosome with 37 genes found in almost all other bilaterians has been lost in multiple lineages in favour of multiple, minicircular chromosomes with less than 37 genes on each chromosome. Results Minicircular mt genomes are found in six of the ten louse species examined to date and three types of minicircles were identified: heteroplasmic minicircles which coexist with full sized mt genomes (type 1); multigene chromosomes with short, simple control regions, we infer that the genome consists of several such chromosomes (type 2); and multiple, single to three gene chromosomes with large, complex control regions (type 3). Mapping minicircle types onto a phylogenetic tree of lice fails to show a pattern of their occurrence consistent with an evolutionary series of minicircle types. Analysis of the nuclear-encoded, mitochondrially-targetted genes inferred from the body louse, Pediculus, suggests that the loss of mitochondrial single-stranded binding protein (mtSSB) may be responsible for the presence of minicircles in at least species with the most derived type 3 minicircles (Pediculus, Damalinia). Conclusions Minicircular mt genomes are common in lice and appear to have arisen multiple times within the group. Life history adaptive explanations which attribute minicircular mt genomes in lice to the adoption of blood-feeding in the Anoplura are not supported by this expanded data set as minicircles are found in multiple non-blood feeding louse groups but are not found in the blood-feeding genus Heterodoxus. In contrast, a mechanist explanation based on the loss of mtSSB suggests that minicircles may be selectively favoured due to the incapacity of the mt replisome to synthesize long replicative products without mtSSB and thus the loss of this gene lead to the formation of minicircles in lice