Proceedings of the ECCS 2005 satellite workshop: embracing complexity in design - Paris 17 November 2005

Embracing complexity in design is one of the critical issues and challenges of the 21st century. As the realization grows that design activities and artefacts display properties associated with complex adaptive systems, so grows the need to use complexity concepts and methods to understand these properties and inform the design of better artifacts. It is a great challenge because complexity science represents an epistemological and methodological swift that promises a holistic approach in the understanding and operational support of design. But design is also a major contributor in complexity research. Design science is concerned with problems that are fundamental in the sciences in general and complexity sciences in particular. For instance, design has been perceived and studied as a ubiquitous activity inherent in every human activity, as the art of generating hypotheses, as a type of experiment, or as a creative co-evolutionary process. Design science and its established approaches and practices can be a great source for advancement and innovation in complexity science. These proceedings are the result of a workshop organized as part of the activities of a UK government AHRB/EPSRC funded research cluster called Embracing Complexity in Design (www.complexityanddesign.net) and the European Conference in Complex Systems (complexsystems.lri.fr). Embracing complexity in design is one of the critical issues and challenges of the 21st century. As the realization grows that design activities and artefacts display properties associated with complex adaptive systems, so grows the need to use complexity concepts and methods to understand these properties and inform the design of better artifacts. It is a great challenge because complexity science represents an epistemological and methodological swift that promises a holistic approach in the understanding and operational support of design. But design is also a major contributor in complexity research. Design science is concerned with problems that are fundamental in the sciences in general and complexity sciences in particular. For instance, design has been perceived and studied as a ubiquitous activity inherent in every human activity, as the art of generating hypotheses, as a type of experiment, or as a creative co-evolutionary process. Design science and its established approaches and practices can be a great source for advancement and innovation in complexity science. These proceedings are the result of a workshop organized as part of the activities of a UK government AHRB/EPSRC funded research cluster called Embracing Complexity in Design (www.complexityanddesign.net) and the European Conference in Complex Systems (complexsystems.lri.fr)

Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

Introduction: Neurofilament light chain protein (NfL) is a fluid biomarker of neural injury measurable in cerebrospinal fluid and blood. Patients with different neurodegenerative disorders and mild traumatic brain injury display elevated levels of NfL. However, so far, elevated levels of NfL have not been demonstrated in persons with psychiatric disorders. To our knowledge, the occurrence of NfL in the blood has not previously been studied in persons undergoing forensic psychiatric assessment or persons treated in forensic mental health services. Supposedly, these persons suffer from experiences and conditions with a higher risk of neural injury than other psychiatric patients. Methods: In this pilot study, we investigated plasma levels of NfL in 20 persons undergoing forensic psychiatric assessment and 20 patients at a forensic psychiatric hospital. NfL values were compared with control groups of healthy individuals matched for age and sex. Results: The prevalence of increased NfL in both forensic groups was low and did not differ compared with the controls. However, some persons undergoing forensic psychiatric assessment showed slightly elevated values. Discussion: The slightly elevated values were observed in the group investigated closer in time to the index crime, when elevated NfL levels could be expected to be more prevalent due to acute conditions from the time of the offense. This gives reason to look further into this group

Modern therapies in atopic dermatitis: biologics and small molecule drugs

Atopic dermatitis (AD) is a frequent, chronic remittent skin disease. The pathophysiology of AD has been increasingly understood within the last years, which may help to identify different endotypes suitable for defined therapies in the future. A patient-oriented therapy considers phenotypical features in addition to genetic and biological markers. The most recent developments in biologics and small-molecule drugs for AD treatment are presented in this article. These molecules, if approved, could change the perspectives for future therapies. Dupilumab is the first approved biologic for the treatment of moderate to severe atopic dermatitis in adolescence and adulthood and has led to a significant improvement in the treatment of this chronic disease. In the present article we present real-life data on the efficacy of dupilumab in adult dermatitis patients. We also discuss other data relevant to the use of dupilumab, and address open questions important for the standard care of atopic dermatitis patients

Development and validation of anti-human Alpha synuclein DNA aptamer using computer modelling techniques—an in silico study

Biomarker detection strategies have, in recent years, been moving towards nucleic acid-based detection systems in the form of aptamers, short oligonucleotide sequences which have shown promise in pre-clinical and research settings. One such aptamer is M5-15, a DNA aptamer raised against human alpha synuclein (α-syn) the causative agent in Lewy body and Parkinson’s disease (PD) associated dementia. While this aptamer has shown promise, in silico methodologies have demonstrated a capacity to produce aptamers that have higher affinities for their targets than in vitro generated sequences. A Python script random generated library of DNA sequences were screened based on their thermodynamic stability with the use of DINAMelt server-QuickFold web server. The selected sequences were examined with MFold in order to generate secondary structure data that were used to produce 3D data with the use of RNA composer software. Further on, the structure was corrected and RNA was replaced with DNA and the virtual screening for α-syn aptamer took place with a series of molecular docking experiments with the use of CSD-Discovery-GOLD software. Herein we propose an alternative in silico generated aptamer we call TMG-79 which demonstrates greater affinity for the target compared to M5-15 (M5-15 = –15.9 kcal/mol, TMG-79 = –17.77 kcal/mol) as well as better ChemPLP fitness scoring between the top poses (M5-15 = 32.33, TMG-79 = 53.32). Structural analysis suggests that while there are similarities, the greater potential flexibility of TMG-79 could be promoting greater affinity for the α-syn compared to M5-15. In silico methods of aptamer generation has the potential to revolutionise the field of aptamer design. We feel that further development of TMG-79 and validation in vitro will make it a viable candidate for diagnostic and research use in the future

DIANA-microT Web server upgrade supports Fly and Worm miRNA target prediction and bibliographic miRNA to disease association

microRNAs (miRNAs) are small endogenous RNA molecules that are implicated in many biological processes through post-transcriptional regulation of gene expression. The DIANA-microT Web server provides a user-friendly interface for comprehensive computational analysis of miRNA targets in human and mouse. The server has now been extended to support predictions for two widely studied species: Drosophila melanogaster and Caenorhabditis elegans. In the updated version, the Web server enables the association of miRNAs to diseases through bibliographic analysis and provides insights for the potential involvement of miRNAs in biological processes. The nomenclature used to describe mature miRNAs along different miRBase versions has been extensively analyzed, and the naming history of each miRNA has been extracted. This enables the identification of miRNA publications regardless of possible nomenclature changes. User interaction has been further refined allowing users to save results that they wish to analyze further. A connection to the UCSC genome browser is now provided, enabling users to easily preview predicted binding sites in comparison to a wide array of genomic tracks, such as single nucleotide polymorphisms. The Web server is publicly accessible in www.microrna.gr/microT-v4