| 1. |
- van Bragt, JJMH, et al.
(författare)
-
Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
-
Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
|
|
| 2. |
- Theibich, Yusuf A., et al.
(författare)
-
Estimating the accuracy of calculated electron paramagnetic resonance hyperfine couplings for a lytic polysaccharide monooxygenase
- 2021
-
Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier BV. - 2001-0370. ; 19, s. 555-567
-
Tidskriftsartikel (refereegranskat)abstract
- Lytic polysaccharide monooxygenases (LPMOs) are enzymes that bind polysaccharides followed by an (oxidative) disruption of the polysaccharide surface, thereby boosting depolymerization. The binding process between the LPMO catalytic domain and polysaccharide is key to the mechanism and establishing structure-function relationships for this binding is therefore crucial. The hyperfine coupling constants (HFCs) from EPR spectroscopy have proven useful for this purpose. Unfortunately, EPR does not provide direct structural data and therefore the experimental EPR parameters have to be supported with parameters calculated with density functional theory. Yet, calculated HFCs are extremely sensitive to the employed computational setup. Using the LPMO Ls(AA9)A catalytic domain, we here quantify the importance of several choices in the computational setup, ranging from the use of specialized basis, the underlying structures, and the employed exchange-correlation functional. We show that specialized basis sets are an absolute necessity, and also that care has to be taken in the optimization of the underlying structure: only by allowing large parts of the protein around the active site to structurally relax could we obtain results that uniformly reproduced experimental trends. We compare our results to previously published X-ray structures and experimental HFCs for Ls(AA9)A as well as to recent experimental/theoretical results for another (AA10) family of LPMOs.
|
|
| 3. |
- Olsen, Jogvan Magnus Haugaard, et al.
(författare)
-
Dalton Project : A Python platform for molecular- and electronic-structure simulations of complex systems
- 2020
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 152:21
-
Tidskriftsartikel (refereegranskat)abstract
- The Dalton Project provides a uniform platform access to the underlying full-fledged quantum chemistry codes Dalton and LSDalton as well as the PyFraME package for automatized fragmentation and parameterization of complex molecular environments. The platform is written in Python and defines a means for library communication and interaction. Intermediate data such as integrals are exposed to the platform and made accessible to the user in the form of NumPy arrays, and the resulting data are extracted, analyzed, and visualized. Complex computational protocols that may, for instance, arise due to a need for environment fragmentation and configuration-space sampling of biochemical systems are readily assisted by the platform. The platform is designed to host additional software libraries and will serve as a hub for future modular software development efforts in the distributed Dalton community.
|
|
