Bioinformatic-driven search for metabolic biomarkers in disease

The search and validation of novel disease biomarkers requires the complementary power of professional study planning and execution, modern profiling technologies and related bioinformatics tools for data analysis and interpretation. Biomarkers have considerable impact on the care of patients and are urgently needed for advancing diagnostics, prognostics and treatment of disease. This survey article highlights emerging bioinformatics methods for biomarker discovery in clinical metabolomics, focusing on the problem of data preprocessing and consolidation, the data-driven search, verification, prioritization and biological interpretation of putative metabolic candidate biomarkers in disease. In particular, data mining tools suitable for the application to omic data gathered from most frequently-used type of experimental designs, such as case-control or longitudinal biomarker cohort studies, are reviewed and case examples of selected discovery steps are delineated in more detail. This review demonstrates that clinical bioinformatics has evolved into an essential element of biomarker discovery, translating new innovations and successes in profiling technologies and bioinformatics to clinical application

Effects of Pooling Samples on the Performance of Classification Algorithms: A Comparative Study

A pooling design can be used as a powerful strategy to compensate for limited amounts of samples or high biological variation. In this paper, we perform a comparative study to model and quantify the effects of virtual pooling on the performance of the widely applied classifiers, support vector machines (SVMs), random forest (RF), k-nearest neighbors (k-NN), penalized logistic regression (PLR), and prediction analysis for microarrays (PAMs). We evaluate a variety of experimental designs using mock omics datasets with varying levels of pool sizes and considering effects from feature selection. Our results show that feature selection significantly improves classifier performance for non-pooled and pooled data. All investigated classifiers yield lower misclassification rates with smaller pool sizes. RF mainly outperforms other investigated algorithms, while accuracy levels are comparable among all the remaining ones. Guidelines are derived to identify an optimal pooling scheme for obtaining adequate predictive power and, hence, to motivate a study design that meets best experimental objectives and budgetary conditions, including time constraints

Functional Integration of Subcomponents for Hybridization of Fused Filament Fabrication

One of the main advantages of additive manufacturing by Fused Filament Fabrication is its wide variety of materials and cost-effective production systems. However, the resolution and tightness of the produced structures are limited. The following article describes a novel approach of the functional integration of stereolithographic produced subcomponents into the Fused Filament Fabrication process and the challenges during integration in terms of adhesion, taking into account different surface pretreatments. Furthermore, it is investigated how conductive polymer composites could be used successfully for conducting mechatronic subcomponents automatically. With the help of these investigations it is aimed to extend the field of application of additive manufactured plastic components

Canal blocking optimization in restoration of drained peatlands

Drained peatlands are one of the main sources of carbon dioxide (CO2) emissions globally. Emission reduction and, more generally, ecosystem restoration can be enhanced by raising the water table using canal or drain blocks. When restoring large areas, the number of blocks becomes limited by the available resources, which raises the following question: in which exact positions should a given number of blocks be placed in order to maximize the water table rise throughout the area? There is neither a simple nor an analytic answer. The water table response is a complex phenomenon that depends on several factors, such as the topology of the canal network, site topography, peat hydraulic properties, vegetation characteristics and meteorological conditions. We developed a new method to position the canal blocks based on the combination of a hydrological model and heuristic optimization algorithms. We simulated 3 d dry downs from a water saturated initial state for different block positions using the Boussinesq equation, and the block configurations maximizing water table rise were searched for by means of genetic algorithm and simulated annealing. We applied this approach to a large drained peatland area (931 km(2)) in Sumatra, Indonesia. Our solution consistently outperformed traditional block locating methods, indicating that drained peatland restoration can be made more effective at the same cost by selecting the positions of the blocks using the presented scheme.Peer reviewe

Updating quasar bolometric luminosity corrections. II. Infrared bolometric corrections

We present infrared bolometric luminosity corrections derived from the detailed spectral energy distributions of 62 bright quasars of low- to moderate-redshift (z=0.03-1.4). At 1.5, 2, 3, 7, 12, 15, and 24 microns we provide bolometric corrections of the mathematical forms L_iso=\zeta \lambda L_\lambda and log(L_iso)=A+B log(\lambda L_\lambda). Bolometric corrections for radio-loud and radio-quiet objects are consistent within 95% confidence intervals, so we do not separate them. Bolometric luminosities estimated using these corrections are typically smaller than those derived from some commonly used in the literature. We investigate the possibility of a luminosity dependent bolometric correction and find that, while the data are consistent with such a correction, the dispersion is too large and the luminosity range too small to warrant such a detailed interpretation. Bolometric corrections at 1.5 $\mu$m are appropriate for objects with properties that fall in the range log(L_bol)=45.4-47.3 and bolometric corrections at all other wavelengths are appropriate for objects with properties that fall in the range log(L_bol)=45.1-47.0.Comment: 13 pages, 4 tables, 8 figures, accepted to MNRA

Quasar bolometric corrections: theoretical considerations

Bolometric corrections based on the optical-to-ultraviolet continuum spectrum of quasars are widely used to quantify their radiative output, although such estimates are affected by a myriad of uncertainties, such as the generally unknown line-of-sight angle to the central engine. In order to shed light on these issues, we investigate the state-of-the-art models of Hubeny et al. that describe the continuum spectrum of thin accretion discs and include relativistic effects. We explore the bolometric corrections as a function of mass accretion rates, black hole masses and viewing angles, restricted to the parameter space expected for type-1 quasars. We find that a nonlinear relationship log L_bol=A + B log(lambda L_lambda) with B<=0.9 is favoured by the models and becomes tighter as the wavelength decreases. We calculate from the model the bolometric corrections corresponding to the wavelengths lambda = 1450A, 3000A and 5100A. In particular, for lambda=3000A we find A=9.24 +- 0.77 and B=0.81 +- 0.02. We demonstrate that the often-made assumption that quasars emit isotropically may lead to severe systematic errors in the determination of L_bol, when using the method of integrating the "big blue bump" spectrum. For a typical viewing angle of ~30 degrees to the quasar central engine, we obtain that the value of L_bol resulting from the isotropy assumption has a systematic error of ~30% high compared to the value of L_bol which incorporates the anisotropic emission of the accretion disc. These results are of direct relevance to observational determinations of the bolometric luminosities of quasars, and may be used to improve such estimates.Comment: 9 pages, 11 figures, accepted for publication in MNRA