An architecture for establishing legal semantic workflows in the context of integrated law enforcement

A previous version of this paper was presented at the Third Workshop on Legal Knowledge and the Semantic Web (LK&SW-2016), EKAW-2016, November 19th, Bologna, ItalyTraditionally the integration of data from multiple sources is done on an ad-hoc basis for each to "silos" that prevent sharing data across different agencies or tasks, and is unable to cope with the modern environment, where workflows, tasks, and priorities frequently change. Operating within the Data to Decision Cooperative Research Centre (D2D CRC), the authors are currently involved in the Integrated Law Enforcement Project, which has the goal of developing a federated data platform that will enable the execution of integrated analytics on data accessed from different external and internal sources, thereby providing effective support to an investigator or analyst working to evaluate evidence and manage lines of inquiries in the investigation. Technical solutions should also operate ethically, in compliance with the law, and subject to good governance principles

Immunological resilience and biodiversity for prevention of allergic diseases and asthma

Increase of allergic conditions has occurred at the same pace with the Great Acceleration, which stands for the rapid growth rate of human activities upon earth from 1950s. Changes of environment and lifestyle along with escalating urbanization are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors, and biological medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: Risk factors increase the risk, while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008-2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fast urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.Peer reviewe

An outlook for the acquisition of marine sedimentary ancient DNA (sedaDNA) from North Atlantic Ocean archive material

Studies incorporating sedimentary ancient DNA (sedaDNA) analyses to investigate paleo-environments have increased considerably over the last few years, and the possibility of utilizing archived sediment cores from previous field campaigns could unlock an immense resource of sampling material for such paleo-investigations. However, sedaDNA research is at a high risk of contamination by modern environmental DNA, as sub-optimal sediment storage conditions may allow for contaminants (e.g., fungi) to grow and become dominant over preserved sedaDNA in the sample. Here, we test the feasibility of sedaDNA analysis applied to archive sediment material from five sites in the North Atlantic, collected between 1994 and 2013. We analyzed two samples (one younger and one older) per site using a metagenomic shotgun approach and were able to recover eukaryotic sedaDNA from all samples. We characterized the authenticity of each sample through sedaDNA fragment size and damage analyses, which allowed us to disentangle sedaDNA and contaminant DNA. Although we determined that contaminant sequences originated mainly from Ascomycota (fungi), most samples were dominated by Emiliania huxleyi, a haptophyte species that commonly blooms in the study region. We attribute the presence of contaminants to non-ideal sampling and sample storage conditions of the investigated samples. Therefore, while we demonstrate that sedaDNA analysis of archival North Atlantic seafloor sediment samples are generally achievable, we stress the importance of best-practice ship-board sampling techniques and storage conditions to minimize contamination. We highly recommend the application of robust bioinformatic tools that help distinguish ancient genetic signals from modern contaminants, especially when working with archive material.</p

A Novel Mechanism for Activation of GLI1 by Nuclear SMO That Escapes Anti-SMO Inhibitors.

Small-molecule inhibitors of the Hedgehog (HH) pathway receptor Smoothened (SMO) have been effective in treating some patients with basal cell carcinoma (BCC), where the HH pathway is often activated, but many patients respond poorly. In this study, we report the results of investigations on PTCH1 signaling in the HH pathway that suggest why most patients with BCC respond poorly to SMO inhibitors. In immortalized human keratinocytes, PTCH1 silencing led to the generation of a compact, holoclone-like morphology with increased expression of SMO and the downstream HH pathway transcription factor GLI1. Notably, although siRNA silencing of SMO in PTCH1-silenced cells was sufficient to suppress GLI1 activity, this effect was not phenocopied by pharmacologic inhibition of SMO, suggesting the presence of a second undefined pathway through which SMO can induce GLI1. Consistent with this possibility, we observed increased nuclear localization of SMO in PTCH1-silenced cells as mediated by a putative SMO nuclear/nucleolar localization signal [N(o)LS]. Mutational inactivation of the N(o)LS ablated this increase and suppressed GLI1 induction. Immunohistologic analysis of human and mouse BCC confirmed evidence of nuclear SMO, although the pattern was heterogeneous between tumors. In PTCH1-silenced cells, >80% of the genes found to be differentially expressed were unaffected by SMO inhibitors, including the putative BCC driver gene CXCL11. Our results demonstrate how PTCH1 loss results in aberrant regulation of SMO-independent mechanisms important for BCC biology and highlights a novel nuclear mechanism of SMO-GLI1 signaling that is unresponsive to SMO inhibitors.Significance: This study describes novel noncanonical Hedgehog signaling, where SMO enters the nucleus to activate GLI1, a mode that is unaffected by SMO inhibitors, thus prompting re-evaluation of current BCC treatment as well as new potential therapies targeting nuclear SMO. Cancer Res; 78(10); 2577-88. ©2018 AACR.The authors gratefully acknowledge the funding from the British Skin Foundation. The authors also thank Anna Saran (ENEA, Rome, Italy) for providing mouse BCC tissue for immunohistochemistry and Dr. Monika Cichon for the shRNA control sequences. The authors also thank the Dr. Hadwen Trust (DHT) for Humane Research for additional funding to develop human models for human disease and confirm that no funding from the DHT was used for any animal research in this article

Displaced cratonic mantle concentrates deep carbon during continental rifting

International audienceContinental rifts are important sources of mantle carbon dioxide (CO 2) emission into Earth's atmosphere 1-3. Because deep carbon is stored for long periods in the lithospheric mantle 4-6 , rift CO 2 flux depends on lithospheric processes that control melt and volatile transport 1,3,7. The influence of compositional and thickness differences between Archaean and Proterozoic lithosphere on deep-carbon fluxes remains untested. Here we propose that displacement of carbon-enriched Tanzanian cratonic mantle concentrates deep carbon below parts of the East African Rift System. Sources and fluxes of CO 2 and helium are examined over a 350-kilometre-long transect crossing the boundary between orogenic (Natron and Magadi basins) and cratonic (Balangida and Manyara basins) lithosphere from north to south. Areas of diffuse CO 2 degassing exhibit increasing mantle CO 2 flux and 3 He/ 4 He ratios as the rift transitions from Archaean (cratonic) to Proterozoic (orogenic) lithosphere. Active carbonatite magmatism also occurs near the craton edge. These data indicate that advection of the root of thick Archaean lithosphere laterally to the base of the much thinner adjacent Proterozoic lithosphere creates a zone of highly concentrated deep carbon. This mode of deep-carbon extraction may increase CO 2 fluxes in some continental rifts, helping to control the production and location of carbonate-rich magmas