Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.     

The social bookmark and publication management system bibsonomy

Social resource sharing systems are central elements of the Web 2.0 and use the same kind of lightweight knowledge representation, called folksonomy. Their large user communities and ever-growing networks of user-generated content have made them an attractive object of investigation for researchers from different disciplines like Social Network Analysis, Data Mining, Information Retrieval or Knowledge Discovery. In this paper, we summarize and extend our work on different aspects of this branch of Web 2.0 research, demonstrated and evaluated within our own social bookmark and publication sharing system BibSonomy, which is currently among the three most popular systems of its kind. We structure this presentation along the different interaction phases of a user with our system, coupling the relevant research questions of each phase with the corresponding implementation issues. This approach reveals in a systematic fashion important aspects and results of the broad bandwidth of folksonomy research like capturing of emergent semantics, spam detection, ranking algorithms, analogies to search engine log data, personalized tag recommendations and information extraction techniques. We conclude that when integrating a real-life application like BibSonomy into research, certain constraints have to be considered; but in general, the tight interplay between our scientific work and the running system has made BibSonomy a valuable platform for demonstrating and evaluating Web 2.0 research.     

Affinity chromatography of tryptases: design, synthesis and characterization of a novel matrix-bound bivalent inhibitor

beta-Tryptases are mast cell-derived serine proteases that are enzymatically active in the form of an oligomer consisting of four subunits each with trypsin-like activity. The active-site clefts, which are directed toward the central pore of the tetramer, form spatial arrays of four negatively charged S1 binding pockets. Therefore, dibasic inhibitors of appropriate geometry can bind in a bivalent fashion to neighboring subunits. We have recently identified a potent bivalent inhibitor (K(i)=18 nM), based on the bifunctional scaffold cyclo-(-D-Asp-L-Asp-) and the arginine mimetic dl-3-aminomethyl-phenylalanine methyl ester as a ligand for S1 pockets that takes advantage of the this unique tetrameric geometry. To generate an affinity matrix, the bivalent ligand was modified and immobilized on a Sepharose matrix by use of the PEG derivative Jeffamine ED 900 as spacer. This matrix selectively recognizes and binds beta-tryptase from crude protein mixtures and thus is useful as a geometry-driven means of isolating and purifying human mast cell tryptases.     

Multilevel surrogate modeling of an amine scrubbing process for CO2capture

Surrogate models provide a powerful method for simplifying calculations within complex simulations. While surrogate models are broadly applied within chemical engineering, little research exists investigating the level of surrogacy's impact on a simplified process model. In this work, artificial neural networks (ANN) and Kriging models are used as surrogate models at the process, process unit, and thermodynamic levels for a CO₂ amine scrubbing process. The surrogated models are evaluated against an Aspen Plus simulation for accuracy, convergence behavior, computational cost, and ability to extrapolate. The thermodynamic and process unit models can better handle discontinuous, non-smooth behavior, and convergence issues in the surrogated truth model, but poor conditioning in the final system of equations results in a lower accuracy and convergence rate than the process level surrogate. Beyond model accuracy, availability of diverse data, intended re-usability, and the desired outputs must be considered when selecting a level of abstraction.     

Functional group distributions on mesoporous silica

Most applications of mesoporous silica require some degree of functionalization. The surface of porous materials can be divided into external and internal (pore) surfaces, and in many cases, a selective functionalization of these surface subsections is desired. This short review outlines our recent work in this field and focuses on the postsynthetic functionalization of mesoporous silica with aminopropylalkoxysilanes and on the analysis of the respective functional group distributions by confocal laser scanning microscopy. Methods to obtain an amino-functionalized external surface and functional group gradients on the pore surface are reported. Arrays of silica nanochannels (ASNCs) serve as a model system for mesoporous silica.     

Time-resolved photoelectron spectroscopy to probe ultrafast charge transfer and electron dynamics in solid surface systems and at metal-molecule interfaces

Photoelectron spectroscopy (PES) is a versatile tool, which provides insight into electronic structure and dynamics in condensed matter, surfaces, interfaces and molecules. The history of PES is briefly outlined and illustrated by current developments in the field of time-resolved PES. Our group's research is mostly aimed at studying ultrafast processes and associated lifetimes related to electronic excitation at solid surfaces.     

Effect of lanthanum-modified magnesium silicate on isotactic polypropylene crystallization in composite materials during shear flow

The activity of isotactic polypropylene (iPP) nucleating additives during shear flow of composite materials is still not entirely explained. In current work the sol-gel method was employed to synthesize MgO·SiO₂ filler, surface-modified with trivalent lanthanum. The crystallization of commercial iPP in the presence of 0.5% by weight La³⁺ modified or unmodified silicates was analyzed. The wide angle X-ray scattering analysis proved that the presence of even small amount of filler influences significantly on supermolecular structure of iPP. The results of microscope observations confirmed that the lanthanum-modified filler shows the nucleating ability for iPP. In that case a significant reduction of crystallization induction time was noticed. The investigation of iPP crystallization in composites after shear treatment confirmed that the increase of shear rate reduces the nucleating ability of additives. Moreover, the flow of filler particles during shearing may impede the shear-induced crystallization phenomenon.     

Low-pressure,thermo-compressive lamination

Lamination of green ceramic tapes is one of the most important technological processes in multilayer ceramic technology. Lamination affects the quality of all 3D structures (e.g., channels, chambers, membranes, etc.). Novel chemical methods of lamination reduce the deformation of 3D structures. However, these methods are useless in the fabrication of thin membranes and structures with thick-film electronic components or electric vias. Therefore, thermo-compressive lamination is still the best solution for the lamination of green ceramic tapes. Low-pressure thermo-compressive lamination with an insert material is presented in this paper. The influence of pressure and Low Temperature Cofired Ceramics (LTCC) material on the compressibility and shrinkage of LTCC, as well as the influence of the insert material on deflection and distortion of the membranes are presented and discussed in this paper.