BLLDB : bibliography of linguistic literature database

Am 15.11.2006 gehaltener Vortrag zum Thema "Benutzung der Datenbank BLLDB : bibliography of linguistic literature database

Lin|gu|is|tik: building the linguist's pathway to bibliographies, libraries, language resources and linked open data

This paper introduces a novel research tool for the field of linguistics: The Lin|gu|is|tik web portal provides a virtual library which offers scientific information on every linguistic subject. It comprises selected internet sources and databases as well as catalogues for linguistic literature, and addresses an interdisciplinary audience. The virtual library is the most recent outcome of the Special Subject Collection Linguistics of the German Research Foundation (DFG), and also integrates the knowledge accumulated in the Bibliography of Linguistic Literature. In addition to the portal, we describe long-term goals and prospects with a special focus on ongoing efforts regarding an extension towards integrating language resources and Linguistic Linked Open Data

Interoperability of language-related information: mapping the BLL Thesaurus to Lexvo and Glottolog

Since 2013, the thesaurus of the Bibliography of Linguistic Literature (BLL Thesaurus) has been applied in the context of the Linguistik portal, a hub for linguistically relevant information. Several consecutive projects focus on the modeling of the BLL Thesaurus as ontology and its linking to terminological repositories in the Linguistic Linked Open Data (LLOD) cloud. Those mappings facilitate the connection between the Linguistik portal and the cloud. In the paper, we describe the current efforts to establish interoperability between the language-related index terms and repositories providing language identifiers for the web of Linked Data. After an introduction of Lexvo and Glottolog, we outline the scope, the structure, and the peculiarities of the BLL Thesaurus. We discuss the challenges for the design of scientifically plausible language classification and the linking between divergent classifications. We describe the prototype of the linking model and propose pragmatic solutions for structural or conceptual conflicts. Additionally, we depict the benefits from the envisaged interoperability - for the Linguistik portal, and the Linked Open Data Community in general

Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours

Background Certain paediatric nervous system malignancies have dismal prognoses. Retinoic acid (RA) is used in neuroblastoma treatment, and preclinical data indicate potential benefit in selected paediatric brain tumour entities. However, limited single-agent efficacy necessitates combination treatment approaches. Methods We performed drug sensitivity profiling of 76 clinically relevant drugs in combination with RA in 16 models (including patient-derived tumouroids) of the most common paediatric nervous system tumours. Drug responses were assessed by viability assays, high-content imaging, and apoptosis assays and RA relevant pathways by RNAseq from treated models and patient samples obtained through the precision oncology programme INFORM (n = 2288). Immunoprecipitation detected BCL-2 family interactions, and zebrafish embryo xenografts were used for in vivo efficacy testing. Results Group 3 medulloblastoma (MBG3) and neuroblastoma models were highly sensitive to RA treatment. RA induced differentiation and regulated apoptotic genes. RNAseq analysis revealed high expression of BCL2L1 in MBG3 and BCL2 in neuroblastomas. Co-treatments with RA and BCL-2/XL inhibitor navitoclax synergistically decreased viability at clinically achievable concentrations. The combination of RA with navitoclax disrupted the binding of BIM to BCL-XL in MBG3 and to BCL-2 in neuroblastoma, inducing apoptosis in vitro and in vivo. Conclusions RA treatment primes MBG3 and NB cells for apoptosis, triggered by navitoclax cotreatment

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs

Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours

Background: Certain paediatric nervous system malignancies have dismal prognoses. Retinoic acid (RA) is used in neuroblastoma treatment, and preclinical data indicate potential benefit in selected paediatric brain tumour entities. However, limited single-agent efficacy necessitates combination treatment approaches. Methods: We performed drug sensitivity profiling of 76 clinically relevant drugs in combination with RA in 16 models (including patient-derived tumouroids) of the most common paediatric nervous system tumours. Drug responses were assessed by viability assays, high-content imaging, and apoptosis assays and RA relevant pathways by RNAseq from treated models and patient samples obtained through the precision oncology programme INFORM (n = 2288). Immunoprecipitation detected BCL-2 family interactions, and zebrafish embryo xenografts were used for in vivo efficacy testing. Results: Group 3 medulloblastoma (MBG3) and neuroblastoma models were highly sensitive to RA treatment. RA induced differentiation and regulated apoptotic genes. RNAseq analysis revealed high expression of BCL2L1 in MBG3 and BCL2 in neuroblastomas. Co-treatments with RA and BCL-2/XL inhibitor navitoclax synergistically decreased viability at clinically achievable concentrations. The combination of RA with navitoclax disrupted the binding of BIM to BCL-XL in MBG3 and to BCL-2 in neuroblastoma, inducing apoptosis in vitro and in vivo. Conclusions: RA treatment primes MBG3 and NB cells for apoptosis, triggered by navitoclax cotreatment

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs