Isabelle/DOF: Design and Implementation

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record17th International Conference, SEFM 2019 Oslo, Norway, September 18–20, 2019DOF is a novel framework for defining ontologies and enforcing them during document development and evolution. A major goal of DOF is the integrated development of formal certification documents (e. g., for Common Criteria or CENELEC 50128) that require consistency across both formal and informal arguments. To support a consistent development of formal and informal parts of a document, we provide Isabelle/DOF, an implementation of DOF on top of the formal methods framework Isabelle/HOL. A particular emphasis is put on a deep integration into Isabelleâs IDE, which allows for smooth ontology development as well as immediate ontological feedback during the editing of a document. In this paper, we give an in-depth presentation of the design concepts of DOFâs Ontology Definition Language (ODL) and key aspects of the technology of its implementation. Isabelle/DOF is the first ontology language supporting machine-checked links between the formal and informal parts in an LCF-style interactive theorem proving environment. Sufficiently annotated, large documents can easily be developed collabo- ratively, while ensuring their consistency, and the impact of changes (in the formal and the semi-formal content) is tracked automatically.IRT SystemX, Paris-Saclay, Franc

A novel EGFR inhibitor acts as potent tool for hypoxia-activated prodrug systems and exerts strong synergistic activity with VEGFR inhibition in vitro and in vivo

Small-molecule EGFR inhibitors have distinctly improved the overall survival especially in EGFR-mutated lung cancer. However, their use is often limited by severe adverse effects and rapid resistance development. To overcome these limitations, a hypoxia-activatable Co(III)-based prodrug (KP2334) was recently synthesized releasing the new EGFR inhibitor KP2187 in a highly tumor-specific manner only in hypoxic areas of the tumor. However, the chemical modifications in KP2187 necessary for cobalt chelation could potentially interfere with its EGFR-binding ability. Consequently, in this study, the biological activity and EGFR inhibition potential of KP2187 was compared to clinically approved EGFR inhibitors. In general, the activity as well as EGFR binding (shown in docking studies) was very similar to erlotinib and gefitinib (while other EGFR-inhibitory drugs behaved different) indicating no interference of the chelating moiety with the EGFR binding. Moreover, KP2187 significantly inhibited cancer cell proliferation as well as EGFR pathway activation in vitro and in vivo. Finally, KP2187 proved to be highly synergistic with VEGFR inhibitors such as sunitinib. This indicates that KP2187releasing hypoxia-activated prodrug systems are promising candidates to overcome the clinically observed enhanced toxicity of EGFR-VEGFR inhibitor combination therapies

Espon-Interstrat. Espon in Integrated Territorial Strategies.

The INTERSTRAT project’s overall aim is “to encourage and facilitate the use of ESPON 2013 Programme findings in the creation and monitoring of Integrated Territorial Development Strategies (ITDS) and to support transnational learning about the actual and potential contribution of ESPON to integrated policy-making.” We defined integrated territorial development as ‘the process of shaping economic, social and environmental change through spatially sensitive policies and programmes’

Transposable elements are associated with the variable response to influenza infection

インフルエンザ重症度に関連する転移因子を特定: マルチオミクス解析で見えた「動く遺伝子」の新たな役割. 京都大学プレスリリース. 2023-05-11.A multiomics approach provides insights into flu severity. 京都大学プレスリリース. 2023-05-11.Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Here, we wanted to explore the potential contribution of transposable elements (TEs) to the variable human immune response. Transcriptome profiling in monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation in viral load post-infection. Using transposase-accessible chromatin using sequencing (ATAC-seq), we identified a set of TE families with either enhanced or reduced accessibility upon infection. Of the enhanced families, 15 showed high variability between individuals and had distinct epigenetic profiles. Motif analysis showed an association with known immune regulators (e.g., BATFs, FOSs/JUNs, IRFs, STATs, NFkBs, NFYs, and RELs) in stably enriched families and with other factors in variable families, including KRAB-ZNFs. We showed that TEs and host factors regulating TEs were predictive of viral load post-infection. Our findings shed light on the role TEs and KRAB-ZNFs may play in inter-individual variation in immunity

Липоксигеназное окисление жирных кислот в растениях.

Lipid peroxidation is common to all biological systems, both appearing in developmentally and environmentally regulated processes of plants. The hydroperoxy polyunsaturated fatty acids, synthesized by the action of various highly specialized forms of lipoxygenases, are substrates of at least seven different enzymе families. Signaling compounds such as jasmonates, antimicrobial and antifungal compounds such as leaf aldehydes or divinyl ethers, and a plant-specific blend of volatiles including leaf alcohols are among the numerous productsПерекисное окисление является общим процессом для всех биологических систем, причем в растениях онo происходит под влиянием как природных механизмов развития, так и стимулов окружающей среды. Гидропероксиды полиненасыщенных жирных кислот, биосинтезируемые под действием различных специфичных изоформ липоксигеназ, представляют собой субстраты по меньшей мере для семи различных семейств ферментов. Среди множества продуктов ферментативных реакций ключевую роль играют сигнальные соединения растений, такие как жасмонаты, альдегиды, спирты и дивиниловые эфиры полиненасыщенных жирных кислот из листьев (антимикробные и антигрибковые соединения)

The Bone Dysplasia Ontology: integrating genotype and phenotype information in the skeletal dysplasia domain

<p>Abstract</p> <p>Background</p> <p>Skeletal dysplasias are a rare and heterogeneous group of genetic disorders affecting skeletal development. Patients with skeletal dysplasias suffer from many complex medical issues including degenerative joint disease and neurological complications. Because the data and expertise associated with this field is both sparse and disparate, significant benefits will potentially accrue from the availability of an ontology that provides a shared conceptualisation of the domain knowledge and enables data integration, cross-referencing and advanced reasoning across the relevant but distributed data sources.</p> <p>Results</p> <p>We introduce the design considerations and implementation details of the Bone Dysplasia Ontology. We also describe the different components of the ontology, including a comprehensive and formal representation of the skeletal dysplasia domain as well as the related genotypes and phenotypes. We then briefly describe SKELETOME, a community-driven knowledge curation platform that is underpinned by the Bone Dysplasia Ontology. SKELETOME enables domain experts to use, refine and extend and apply the ontology without any prior ontology engineering experience--to advance the body of knowledge in the skeletal dysplasia field.</p> <p>Conclusions</p> <p>The Bone Dysplasia Ontology represents the most comprehensive structured knowledge source for the skeletal dysplasias domain. It provides the means for integrating and annotating clinical and research data, not only at the generic domain knowledge level, but also at the level of individual patient case studies. It enables links between individual cases and publicly available genotype and phenotype resources based on a community-driven curation process that ensures a shared conceptualisation of the domain knowledge and its continuous incremental evolution.</p