EDISA: extracting biclusters from multiple time-series of gene expression profiles

<p>Abstract</p> <p>Background</p> <p>Cells dynamically adapt their gene expression patterns in response to various stimuli. This response is orchestrated into a number of gene expression modules consisting of co-regulated genes. A growing pool of publicly available microarray datasets allows the identification of modules by monitoring expression changes over time. These time-series datasets can be searched for gene expression modules by one of the many clustering methods published to date. For an integrative analysis, several time-series datasets can be joined into a three-dimensional <it>gene-condition-time </it>dataset, to which standard clustering or biclustering methods are, however, not applicable. We thus devise a probabilistic clustering algorithm for <it>gene-condition-time </it>datasets.</p> <p>Results</p> <p>In this work, we present the EDISA (Extended Dimension Iterative Signature Algorithm), a novel probabilistic clustering approach for 3D <it>gene-condition-time </it>datasets. Based on mathematical definitions of gene expression modules, the EDISA samples initial modules from the dataset which are then refined by removing genes and conditions until they comply with the module definition. A subsequent extension step ensures gene and condition maximality. We applied the algorithm to a synthetic dataset and were able to successfully recover the implanted modules over a range of background noise intensities. Analysis of microarray datasets has lead us to define three biologically relevant module types: 1) We found modules with independent response profiles to be the most prevalent ones. These modules comprise genes which are co-regulated under several conditions, yet with a different response pattern under each condition. 2) Coherent modules with similar responses under all conditions occurred frequently, too, and were often contained within these modules. 3) A third module type, which covers a response specific to a single condition was also detected, but rarely. All of these modules are essentially different types of biclusters.</p> <p>Conclusion</p> <p>We successfully applied the EDISA to different 3D datasets. While previous studies were mostly aimed at detecting coherent modules only, our results show that coherent responses are often part of a more general module type with independent response profiles under different conditions. Our approach thus allows for a more comprehensive view of the gene expression response. After subsequent analysis of the resulting modules, the EDISA helped to shed light on the global organization of transcriptional control. An implementation of the algorithm is available at http://www-ra.informatik.uni-tuebingen.de/software/IAGEN/.</p

Integrated nutrient transport modelling with respect to the implementation of the European WFD: The Weiße Elster Case Study, Germany

The goal of the European Water Framework Directive (WFD) is to protect and enhance the status of aquatic and terrestrial ecosystems. To reach this objective an integrated methodology for the implementation of the WFD is essential. The methodology presented was developed within an interdisciplinary research project on the highly polluted 4th order Weiße Elster River basin, a large subcatchment of the Saale basin (Germany), which is part of the UNESCO-IHP HELP program. The project focuses on nutrient management in order to achieve a good ecological status of surface waters. The paper focuses on an integrated modelling of nitrogen transport and comprises combined terrestrial and in-stream transport processes. The mitigation of diffuse and point sources pollution is thereby essential to meet the environmental objectives. Land-use scenarios on both organic farming systems and best management practices were analysed and compared with different strategies to reduce point source. The results show that the possible reduction of nitrogen inputs from point sources is much lower compared to the reduction of diffuse inputs from agricultural land use. The results on in-stream nitrogen transformation show that different morphological factors influence the nitrogen retention considerably. The potential of management measures to reduce nitrogen loads by river restoration measures seems to be limited. This is caused by infrastructural facilities that restrict attaining a natural state of river morphology.Keywords: river basin management, nutrient transport, river restoration, SWAT, WAS

Room-temperature deformation of single crystals of the sigma-phase compound FeCr with the tetragonal D8b structure investigated by micropillar compression

The deformation behavior of single crystals of the sigma-phase compound FeCr with the tetragonal D8b structure has been investigated by micropillar compression at room temperature as a function of crystal orientation and specimen size. In spite of the repeatedly reported brittleness, plastic flow is observed at room temperature for all loading axis orientations tested. Three slip systems, {100}[001], {100} and {111} are newly identified to be operative at room temperature depending on the loading axis, in addition to {110}[001] slip we previously identified. The CRSS values for all the identified slip systems are very high exceeding 1.3 GPa and decrease with increasing specimen size, following an inverse power-law relationship with a very small power-law exponent. Similarly to {110}[001] slip, {100}[001] slip is confirmed to be carried by the motion of [001] zonal dislocations through atomic-resolution scanning transmission electron microscopy imaging of their core structures. dislocations gliding on {100} are confirmed to dissociate into two collinear partial dislocations, while dislocations gliding on {111} to dissociate into three collinear partial dislocations. The fracture toughness values estimated by micro-cantilever bend tests of chevron-notched micro beam specimens are indeed very low, 1.6∼1.8 MPa·m1/2 (notch plane // (001) and (100)), indicating significant brittleness of sigma FeCr

Atomic-scale grain boundary engineering to overcome hot-cracking in additively-manufactured superalloys

There are still debates regarding the mechanisms that lead to hot cracking in parts build by additive manufacturing (AM) of non-weldable Ni-based superalloys. This lack of in-depth understanding of the root causes of hot cracking is an impediment to designing engineering parts for safety-critical applications. Here, we deploy a near-atomic-scale approach to investigate the details of the compositional decoration of grain boundaries in the coarse-grained, columnar microstructure in parts built from a non-weldable Ni-based superalloy by selective electron-beam melting. The progressive enrichment in Cr, Mo and B at grain boundaries over the course of the AM-typical successive solidification and remelting events, accompanied by solid-state diffusion, causes grain boundary segregation induced liquation. This observation is consistent with thermodynamic calculations. We demonstrate that by adjusting build parameters to obtain a fine-grained equiaxed or a columnar microstructure with grain width smaller than 100 $\mu$m enables to avoid cracking, despite strong grain boundary segregation. We find that the spread of critical solutes to a higher total interfacial area, combined with lower thermal stresses, helps to suppress interfacial liquation.Comment: Accepted version at Acta Materiali

Palladium-Based Bimetallic Nanocrystal Catalysts for the Direct Synthesis of Hydrogen Peroxide

The direct synthesis of H$_{2}$O$_{2}$ from H$_{2}$ and O$_{2}$ is a strongly desired reaction for green processes and a promising alternative to the commercialized anthraquinone process. The design of efficient catalysts with high activity and H$_{2}$O$_{2}$ selectivity is highly desirable and yet challenging. Metal dopants enhance the performance of the active phase by increasing reaction rates, stability, and/or selectivity. The identification of efficient dopants relies mostly on catalysts prepared with a random and non‐uniform deposition of active and promoter phases. To study the promotional effects of metal doping on Pd catalysts, we employ colloidal, bimetallic nanocrystals (NCs) to produce catalysts in which the active and doping metals are colocalized to a fine extent. In the absence of any acid and halide promotors, PdSn and PdGa NCs supported on acid‐pretreated TiO$_{2}$ (PdSn/s‐TiO$_{2}$, PdGa/s‐TiO$_{2}$) were highly efficient and outperformed the monometallic Pd catalyst (Pd/s‐TiO$_{2}$), whereas in the presence of an acid promotor, the overall H$_{2}$O$_{2}$ productivity was also further enhanced for the Ni‐, Ga‐, In‐, and Sn‐doped catalysts with respect to Pd/s‐TiO$_{2}$