Linköping University

About: Linköping University is a education organization based out in Linköping, Sweden. It is known for research contribution in the topics: Population & Health care. The organization has 15671 authors who have published 50013 publications receiving 1542189 citations.

The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress.

Abstract: SPECIFIC AIMSThe overall objective of the present study was to examine lysosomal stability during apoptosis and the relationship between caspase activation and the lysosomal proteases cathepsins D and B with regard to their effects on apoptosis.PRINCIPAL FINDINGS1. Naphthazarin-induced apoptosis is dependent on the lysosomal protease cathepsin DThe caspase-3-like activity increased after 12 h of treatment with the redox cycling quinone naphthazarine (NZ). By comparison, the activity of cathepsin D was augmented after 4 h of NZ treatment and peaked at 16 h (Fig. 1A⤻ , B⤻ ). Moreover, increased levels of p53, a transcription factor for cathepsin D, were detected after exposure to NZ for 4 h (Fig. 1D⤻ ). The total protein level did not change in response to p53 induction and was estimated to 8.2 ± 3.5, 8.0 ± 2.1, and 7.1 ± 1.4 μg protein/10 000 cells after 0, 12, and 20 h respectively. We also found that NZ caused a rapid decrease in the activity of the lysosomal cysteine protease cathepsin B (Fig. 1C⤻ ). Fi...

Variance-based sensitivity analysis of model outputs using surrogate models

Abstract: If a computer model is run many times with different inputs, the results obtained can often be used to derive a computationally cheaper approximation, or surrogate model, of the original computer code. Thereafter, the surrogate model can be employed to reduce the computational cost of a variance-based sensitivity analysis (VBSA) of the model output. Here, we draw attention to a procedure in which an adaptive sequential design is employed to derive surrogate models and estimate sensitivity indices for different sub-groups of inputs. The results of such group-wise VBSAs are then used to select inputs for a final VBSA. Our procedure is particularly useful when there is little prior knowledge about the response surface and the aim is to explore both the global variability and local nonlinear features of the model output. Our conclusions are based on computer experiments involving the process-based river basin model INCA-N, in which outputs like the average annual riverine load of nitrogen can be regarded as functions of 19 model parameters.

Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group.

Abstract: OBJECTIVE: To assess the effects of intra-articular injections of hyaluronan on symptoms of knee osteoarthritis (OA). METHODS: Two hundred and forty patients with symptomatic, radiological knee OA were randomly assigned to treatment with weekly injections for five weeks with either 25 mg of high molecular weight hyaluronan or vehicle. Results were evaluated at weeks 1, 2, 3, 4, 5, 13, and 20 by visual analogue scales (pain, function, motion, activity), algofunctional index, and global evaluation by patient and investigator. Analysis was by "intention to treat', "per protocol', and area under the curve principles on unstratified patient groups and for patients stratified into four groups of equal size by age and baseline algofunctional index. RESULTS: No serious side effects were reported. At 20 weeks both treatment groups were improved compared with baseline, with no difference between unstratified groups treated with placebo or hyaluronan. Comparison of treatment groups stratified by age and baseline algofunctional index revealed a significant difference in favour of hyaluronan over placebo (pain, activity, algofunctional index, global evaluations by patient and investigator) for patients older than 60 years and with a baseline algofunctional index greater than 10. There was no clinically relevant difference between the two treatments for the other three stratified subgroups of younger age or fewer symptoms. Similar results were obtained by area under the curve, intention to treat, and per protocol analysis. CONCLUSIONS: Patients older than 60 years with knee osteoarthritis and with significant symptoms corresponding to an index of severity of knee disease of 10 or more, comprise the group most likely to benefit from treatment with intra-articular hyaluronan injections.

An active inference theory of allostasis and interoception in depression

Abstract: In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding...