27 research outputs found
DNA-origami-directed virus capsid polymorphism
No full text| openaire: EC/H2020/101002258/EU//ProCrystal Funding Information: The authors acknowledge financial support from the European Research Council (ERC) and ERA Chair MATTER under the European Union’s Horizon 2020 research and innovation programme (grant agreement numbers 101002258 (M.A.K.) and 856705 (V. Linko)), the Emil Aaltonen Foundation (V. Linko), the Sigrid Jusélius Foundation (V. Linko), the Academy of Finland (grant numbers 341057 (E.A.-P.) and 314671 (M.A.K)), the Finnish Foundation for Technology Promotion (V. Lampinen), and the Jane and Aatos Erkko Foundation (V. Linko and M.A.K.). This work was carried out under the Academy of Finland Centers of Excellence Program (2022-2029) in Life-Inspired Hybrid Materials (LIBER), project number number 346110 (M.A.K.). K. M. Nguyen and A. Kuzyk are acknowledged for providing the staple strands for the 13HR sample, P. Laurinmäki and B. Löflund for technical assistance with cryo-EM, M. Hankaniemi for support with NoV production, and M. Sammalkorpi and A. Scacchi for technical discussions. The facilities and expertise of the HiLIFE cryo-EM unit at the University of Helsinki, a member of Instruct-ERIC Centre Finland, FINStruct and Biocenter Finland are gratefully acknowledged. The authors also acknowledge CSC–IT Center of Science, Finland, for computational resources, Biocenter Finland for support of protein production and characterization infrastructure, and the provision of facilities and technical support by Aalto University Bioeconomy Facilities, OtaNanoNanomicroscopy Center (Aalto-NMC) and Micronova Nanofabrication Center. Publisher Copyright: © 2023, The Author(s).Viral capsids can adopt various geometries, most iconically characterized by icosahedral or helical symmetries. Importantly, precise control over the size and shape of virus capsids would have advantages in the development of new vaccines and delivery systems. However, current tools to direct the assembly process in a programmable manner are exceedingly elusive. Here we introduce a modular approach by demonstrating DNA-origami-directed polymorphism of single-protein subunit capsids. We achieve control over the capsid shape, size and topology by employing user-defined DNA origami nanostructures as binding and assembly platforms, which are efficiently encapsulated within the capsid. Furthermore, the obtained viral capsid coatings can shield the encapsulated DNA origami from degradation. Our approach is, moreover, not limited to a single type of capsomers and can also be applied to RNA–DNA origami structures to pave way for next-generation cargo protection and targeting strategies.Peer reviewe
Automated ion-selective measurement of lithium in serum. A practical approach to result-level verification in a two-way method validation
No full textLiquid-chromatographic analysis of a novel antitussive agent, 2′,4′-dimethyl-6′-methoxy-3-(2-methyl-piperidyl)propionanilide in human urine
No full textA European union and Canadian review of public health nursing preparation and practice.
No full textThis study explores the preparation and role of the public health nurse (PHN) across European Union (EU) countries (Finland, Sweden, and the United Kingdom) and Canadian provinces (Alberta, New Brunswick, and Prince Edward Island)
Kliinisen kemian tutkimusten analyyttiset laatuvaatimukset - mallinnus mittausepävarmuusbudjetilla
No full textClinical decision limits as criteria for setting analytical performance specifications for laboratory tests
No full textPeer reviewe
ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European In-Vitro-Diagnostics Regulation: Joint opinion of task force on European regulatory affairs and working group accreditation and ISO/CEN standards of the European Federation of Clinical Chemistry and Laboratory Medicine
No full textThe EU In-Vitro Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks
Validation and verification of examination procedures in medical laboratories : opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
No full textThis paper reflects the opinion of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO). It aims to provide guidance for drawing up local/national documents about validation and verification of laboratory methods. We demonstrate how risk evaluation can be used to optimize laboratory policies to meet intended use requirements as well as requirements of standards. This is translated in a number of recommendations on how to introduce risk evaluation in various stages of the implementation of new methods ultimately covering the whole process cycle
Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification
No full text© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo
