Task-based parser output combination : workflow and infrastructure

This dissertation introduces the method of task-based parser output combination as a device to enhance the reliability of automatically generated syntactic information for further processing tasks. Parsers, i.e. tools generating syntactic analyses, are usually based on reference data. Typically these are modern news texts. However, the data relevant for applications or tasks beyond parsing often differs from this standard domain, or only specific phenomena from the syntactic analysis are actually relevant for further processing. In these cases, the reliability of the parsing output might deviate essentially from the expected outcome on standard news text. Studies for several levels of analysis in natural language processing have shown that combining systems from the same analysis level outperforms the best involved single system. This is due to different error distributions of the involved systems which can be exploited, e.g. in a majority voting approach. In other words: for an effective combination, the involved systems have to be sufficiently different. In these combination studies, usually the complete analyses are combined and evaluated. However, to be able to combine the analyses completely, a full mapping of their structures and tagsets has to be found. The need for a full mapping either restricts the degree to which the participating systems are allowed to differ or it results in information loss. Moreover, the evaluation of the combined complete analyses does not reflect the reliability achieved in the analysis of the specific aspects needed to resolve a given task. This work presents an abstract workflow which can be instantiated based on the respective task and the available parsers. The approach focusses on the task-relevant aspects and aims at increasing the reliability of their analysis. Moreover, this focus allows a combination of more diverging systems, since no full mapping of the structures and tagsets from the single systems is needed. The usability of this method is also increased by focussing on the output of the parsers: It is not necessary for the users to reengineer the tools. Instead, off-the-shelf parsers and parsers for which no configuration options or sources are available to the users can be included. Based on this, the method is applicable to a broad range of applications. For instance, it can be applied to tasks from the growing field of Digital Humanities, where the focus is often on tasks different from syntactic analysis

A stable backbone for the fungi

Fungi are abundant in the biosphere. They have fascinated mankind as far as written history goes and have considerably influenced our culture. In biotechnology, cell biology, genetics, and life sciences in general fungi constitute relevant model organisms. Once the phylogenetic relationships of fungi are stably resolved individual results from fungal research can be combined into a holistic picture of biology. However, and despite recent progress, the backbone of the fungal phylogeny is not yet fully resolved. Especially the early evolutionary history of fungi and the order or below-order relationships within the ascomycetes remain uncertain. Here we present the first phylogenomic study for a eukaryotic kingdom that merges all publicly available fungal genomes and expressed sequence tags (EST) to build a data set comprising 128 genes and 146 taxa. The resulting tree provides a stable phylogenetic backbone for the fungi. Moreover, we present the first formal supertree based on 161 fungal taxa and 128 gene trees. The combined evidences from the trees support the deep-level stability of the fungal groups towards a comprehensive natural system of the fungi. They indicate that the classification of the fungi, especially their alliance with the Microsporidia, requires careful revision. Our analysis is also an inventory of present day sequence information for the fungi. It provides insights into which phylogenenetic conclusions can and which cannot be drawn from the current data and may serve as a guide to direct further sequencing initiatives. Together with a comprehensive animal phylogeny, we provide the second of three pillars to understand the evolution of the multicellular eukaryotic kingdoms, fungi, metazoa, and plants, in the past 1.6 billion years

Biological characterization of Poly-L-lactic acid (PLLA)/Hydroxyapatite (HA)/Bioglass (BG) composite scaffolds made by Thermally Induced Phase Separation (TIPS) hosting human Mesenchymal Stem Cells

In the last few years, Tissue Engineering has focused on the favourable effects that composite scaffolds have on cell adhesion, growth and differentiation. In fact, composite scaffolds, usually composed of a synthetic polymer supplemented with naturally occurring components, display superior mechanical properties and bioconductivity than scaffolds consisting of a single component. Hydroxyapatite (HA) is the major inorganic component of bones. Bioglass (BG) is known to exert stimulatory effects on cells by ion release and hence, could be also advantageous for Bone Tissue Engineering. Poly-L-lactic acid (PLLA) is a versatile synthetic polymer combinable with HA and BG. The aim of this work was to assess the effectiveness of PLLA/HA and PLLA/HA/BG 1393 composite scaffolds as suitable artificial Extracellular Matrix (ECM) for human Mesenchymal Stromal Cells (h-MSCs). In order to check if composite scaffolds are actually superior, a comparison was made between the scaffolds above mentioned and PLLA and PLLA/BG scaffolds. All four types of scaffolds (PLLA, PLLA/HA, PLLA/BG and PLLA/HA/BG) were manufactured in Palermo, at the University of Palermo, using the Thermally Induced Phase Separation (TIPS) technique, for which a PLLA/1,4-dioxane/water ternary solution was chosen. In composite scaffolds, HA and BG 1393 were added in the solution as powder phase. The temperature selected for promoting the phase separation was 30 °C and the residence time in the thermostatic bath was set to 80 minutes. The samples were then placed in a cooling bath at -20 °C for 15 minutes, in order to freeze the porous structure thus formed. With these process conditions, scaffolds with a porosity higher than 90% and a mean pore size of 100 μm were obtained. After subsequent washing and drying steps, the as-obtained cylindrical structures were cut in disk-shaped specimens with a diameter of 6 mm and a thickness of 1.5 mm. Before the seeding stage, scaffolds were sterilized in 70% ethanol solution, stored in Phosphate Buffered Saline (PBS) and finally soaked in h-MSCs culture medium. The seeding of h-MSCs occurred in a 96-well plate and monitoring analyses were carried out at time points of 48 hours and 8 days. Before used for seeding experiments, undifferentiated MSCs were characterized for a set of markers (CD34, CD44, CD45, CD90, CD105, Vimentin) to show their typical expression pattern before seeding. Multilineage differentiation potential was proven by adipogenic, osteogenic and chondrogenic differentiation. Life/dead assays, Haematoxylin/Eosin, Alcian blue and Alizarin red stainings were employed to verify cells viability, ECM synthesis, adhesion to the polymeric structure and migration into the scaffold. Cell proliferation was calculated from DNA content using CyQuant assay. h-MSCs expressed the typical markers, they were able to spread evenly on both upper and lower surfaces of all types of scaffold. The majority of the adhering cells survived on the scaffolds over the whole observation period. Scaffolds supplemented with HA revealed a higher seeded area compared with PLLA and BG alone. Furthermore, h-MSCs penetrated in mean 260 µm into the porous polymeric structure of all scaffolds. The next step will involve long time experiments with h-MSCs under osteogenic and non-osteogenic conditions in the same types of scaffolds. Successful osteogenic differentiation will be tested by monitoring osteogenic marker expression, e.g. type X collagen

Highly porous novel chondro-instructive bioactive glass scaffolds tailored for cartilage tissue engineering.

Abstract Cartilage injuries remain challenging since the regenerative capacity of cartilage is extremely low. The aim was to design a novel type of bioactive glass (BG) scaffold with suitable topology that allows the formation of cartilage-specific extracellular matrix (ECM) after colonization with chondrogenic cells for cartilage repair. Highly porous scaffolds with interconnecting pores consisting of 100 % BG were manufactured using a melting, milling, sintering and leaching technique. Scaffolds were colonized with porcine articular chondrocytes (pAC) and undifferentiated human mesenchymal stromal cells (hMSC) for up to 35 days. Scaffolds displayed high cytocompatibility with no major pH shift. Scanning electron microscopy revealed the intimate pAC-scaffold interaction with typical cell morphology. After 14 days MSCs formed cell clusters but still expressed cartilage markers. Both cell types showed aggrecan, SOX9 gene and protein expression, cartilage proteoglycan and sulfated glycosaminoglycan synthesis for the whole culture time. Despite type II collagen gene expression could not anymore be detected at day 35, protein synthesis was visualized for both cell types during the whole culturing period, increasing in pAC and declining after day 14 in hMSC cultures. The novel BG scaffold was stable, cytocompatible and cartilage-specific protein synthesis indicated maintenance of pAC's differentiated phenotype and chondro-instructive effects on hMSCs

Recent Initiatives towards New Standards for Language Resources

International audienceno abstrac

Quantitative and time-resolved miRNA pattern of early human T cell activation

T cells are central to the immune response against various pathogens and cancer cells. Complex networks of transcriptional and post-transcriptional regulators, including microRNAs (miRNAs), coordinate the T cell activation process. Available miRNA datasets, however, do not sufficiently dissolve the dynamic changes of miRNA controlled networks upon T cell activation. Here, we established a quantitative and time-resolved expression pattern for the entire miRNome over a period of 24 h upon human Tcell activation. Based on our time-resolved datasets, we identified central miRNAs and specified common miRNA expression profiles. We found the most prominent quantitative expression changes for miR155-5p with a range from initially 40 molecules/cell to 1600 molecules/cell upon T-cell activation. We established a comprehensive dynamic regulatory network of both the up- and downstream regulation of miR155. Upstream, we highlight IRF4 and its complexes with SPI1 and BATF as central for the transcriptional regulation of miR-155. Downstream of miR-155-5p, we verified 17 of its target genes by the time-resolved data recorded after T cell activation. Our data provide comprehensive insights into the range of stimulus induced miRNA abundance changes and lay the ground to identify efficient points of intervention for modifying the T cell response

GeneTrail 3: advanced high-throughput enrichment analysis

We present GeneTrail 3, a major extension of our web service GeneTrail that offers rich functionality for the identification, analysis, and visualization of deregulated biological processes. Our web service provides a comprehensive collection of biological processes and signaling pathways for 12 model organisms that can be analyzed with a powerful framework for enrichment and network analysis of transcriptomic, miRNomic, proteomic, and genomic data sets. Moreover, GeneTrail offers novel workflows for the analysis of epigenetic marks, time series experiments, and single cell data. We demonstrate the capabilities of our web service in two case-studies, which highlight that GeneTrail is well equipped for uncovering complex molecular mechanisms. GeneTrail is freely accessible at: http://genetrail.bioinf.uni-sb.de

ClinOmicsTrailbc: a visual analytics tool for breast cancer treatment stratification

Motivation: Breast cancer is the second leading cause of cancer death among women. Tumors, even of the same histopathological subtype, exhibit a high genotypic diversity that impedes therapy stratification and that hence must be accounted for in the treatment decision-making process. Results: Here, we present ClinOmicsTrailbc, a comprehensive visual analytics tool for breast cancer decision support that provides a holistic assessment of standard-of-care targeted drugs, candidates for drug repositioning and immunotherapeutic approaches. To this end, our tool analyzes and visualizes clinical markers and (epi-)genomics and transcriptomics datasets to identify and evaluate the tumor’s main driver mutations, the tumor mutational burden, activity patterns of core cancerrelevant pathways, drug-specific biomarkers, the status of molecular drug targets and pharmacogenomic influences. In order to demonstrate ClinOmicsTrailbc’s rich functionality, we present three case studies highlighting various ways in which ClinOmicsTrailbc can support breast cancer precision medicine. ClinOmicsTrailbc is a powerful integrated visual analytics tool for breast cancer research in general and for therapy stratification in particular, assisting oncologists to find the best possible treatment options for their breast cancer patients based on actionable, evidence-based results. Availability and implementation: ClinOmicsTrailbc can be freely accessed at https://clinomicstrail. bioinf.uni-sb.de

The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma—a pooled trials analysis

Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma and commonly used induction immunochemotherapies include the anti-CD20 antibody rituximab. However, efficacy data for rituximab regarding overall survival (OS) in first line MCL therapy remain conflicting. We report long-term outcomes of a pooled trials analysis comparing Cyclophosphamide, Doxorubicine, Vincristine, Prednisone (CHOP) to R-CHOP in MCL to confirm efficacy on failure free survival (FFS) and OS in relevant subgroups. Untreated, adult MCL patients of two prospective trials assigned to CHOP or R-CHOP were included. Primary endpoints were FFS and OS, secondary endpoints included duration of response (DOR), secondary malignancies and OS after relapse. Between 1996 and 2003, 385 MCL patients were assigned to CHOP (201) or R-CHOP (184). After a median follow-up of 13.4 years, the addition of Rituximab significantly improved FFS (1.36 vs. 2.07 years, HR 0.62 (0.50–0.77)), OS (4.84 vs. 5.81 years, HR 0.78 (0.61–0.99)) and DOR (1.48 vs. 2.08 years, HR 0.67 (0.53–0.86)). Furthermore, Rituximab improved survival across different MCL risk groups. In a post-hoc analysis of OS after relapse comparing patients receiving chemotherapy with / without rituximab, rituximab maintained efficacy with a median OS of 3.10 vs. 2.11 years (HR 0.70, 0.54–0.91). The rate of secondary malignancies was 0.5 and 3.9% for hematological and 7 and 8% for non-hematological malignancies for CHOP and R-CHOP patients, respectively. We present mature results of a pooled MCL cohort, demonstrating prolonged FFS, OS and DOR for the combined immuno-chemotherapy, confirming the standard of care in first line treatment