| 1. |
- Abdellah, Tebani, et al.
(author)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 2. |
- Bäck, Marcus, et al.
(author)
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Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease : use of cyclopentane and cyclopentene P2-motifs
- 2007
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:22, s. 7184-7202
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Journal article (peer-reviewed)abstract
- Several highly potent novel HCV NS3 protease inhibitors have been developed from two inhibitor series containing either a P2 trisubstituted macrocyclic cyclopentane- or a P2 cyclopentene dicarboxylic acid moiety as surrogates for the widely used N-acyl-(4R)-hydroxyproline in the P2 position. These inhibitors were optimized for anti HCV activities through examination of different ring sizes in the macrocyclic systems and further by exploring the effect of P4 substituent removal on potency. The target molecules were synthesized from readily available starting materials, furnishing the inhibitor compounds in good overall yields. It was found that the 14-membered ring system was the most potent in these two series and that the corresponding 13-, 15-, and 16-membered macrocyclic rings delivered less potent inhibitors. Moreover, the corresponding P1 acylsulfonamides had superior potencies over the corresponding P1 carboxylic acids. It is noteworthy that it has been possible to develop highly potent HCV protease inhibitors that altogether lack the P4 substituent. Thus the most potent inhibitor described in this work, inhibitor 20, displays a Ki value of 0.41 nM and an EC50 value of 9 nM in the subgenomic HCV replicon cell model on genotype 1b. To the best of our knowledge this is the first example described in the literature of a HCV protease inhibitor displaying high potency in the replicon assay and lacking the P4 substituent, a finding which should facilitate the development of orally active small molecule inhibitors against the HCV protease.
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| 3. |
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| 4. |
- Edenius, Lars, et al.
(author)
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Referensområden som verktyg för viltförvaltningsunderlag
- 2019
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In: Fakta. Skog. - 1400-7789.
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Other publication (pop. science, debate, etc.)abstract
- Referensområden är områden där vi följer populationer av älg och andra viltarter, samt förändringar i landskapet, mer intensivt.Referensområden är viktiga för att utveckla övervakningsmetoder och skaffa sig bra kunskap om hur systemet fungerar, för utbildning, samt som demonstrationsområden.Referensområden förväntas bli en viktig komponent i den nya ekosystembaserade viltförvaltningen.Slaktvikter, reproduktionsdata, åldersstruktur, älgtäthet, fodermängder, betestryck och skogsskador är exempel på data som är relevanta att samla in i referensområden för den nya älgförvaltningens behov.SLU har flera områden och försöksparker som kan utvecklas till nationella referensområden.Fördjupad övervakning inom referensområden är ett viktigt komplement till förvaltningsinventeringar inom miljöanalys och viltövervakning.
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| 5. |
- Gummesson, Anders, 1973, et al.
(author)
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Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes
- 2021
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In: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63
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Journal article (peer-reviewed)abstract
- Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
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| 6. |
- Gustafsson, Fredrik, et al.
(author)
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Particle Filters for Positioning, Navigation and Tracking
- 2001
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Reports (other academic/artistic)abstract
- A framework for positioning, navigation and tracking problems using particle filters (sequential Monte Carlo methods) is developed. It consists of a class of motion models and a general non-linear measurement equation in position. A general algorithm is presented, which is parsimonious with the particle dimension. It is based on marginalization, enabling a Kalman filter to estimate all position derivatives, and the particle filter becomes low-dimensional. This is of utmost importance for high-performance real-time applications. Automotive and airborne applications illustrate numerically the advantage over classical Kalman filter based algorithms. Here the use of non-linear models and non-Gaussian noise is the main explanation for the improvement in accuracy. More specifically, we describe how the technique of map matching is used to match an aircraft's elevation profile to a digital elevation map, and a car's horizontal driven path to a street map. In both cases, real-time implementations are available, and tests have shown that the accuracy in both cases is comparable to satellite navigation (as GPS), but with higher integrity. Based on simulations, we also argue how the particle filter can be used for positioning based on cellular phone measurements, for integrated navigation in aircraft, and for target tracking in aircraft and cars. Finally, the particle filter enables a promising solution to the combined task of navigation and tracking, with possible application to airborne hunting and collision avoidance systems in cars.
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| 7. |
- Gustafsson, Fredrik, et al.
(author)
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Particle Filters for Positioning, Navigation and Tracking
- 2002
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In: IEEE Transactions on Signal Processing. - : Institute of Electrical and Electronics Engineers (IEEE). - 1053-587X .- 1941-0476. ; 50:2, s. 425-437
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Journal article (peer-reviewed)abstract
- A framework for positioning, navigation and tracking problems using particle filters (sequential Monte Carlo methods) is developed. It consists of a class of motion models and a general non-linear measurement equation in position. A general algorithm is presented, which is parsimonious with the particle dimension. It is based on marginalization, enabling a Kalman filter to estimate all position derivatives, and the particle filter becomes low-dimensional. This is of utmost importance for high-performance real-time applications. Automotive and airborne applications illustrate numerically the advantage over classical Kalman filter based algorithms. Here the use of non-linear models and non-Gaussian noise is the main explanation for the improvement in accuracy. More specifically, we describe how the technique of map matching is used to match an aircraft's elevation profile to a digital elevation map, and a car's horizontal driven path to a street map. In both cases, real-time implementations are available, and tests have shown that the accuracy in both cases is comparable to satellite navigation (as GPS), but with higher integrity. Based on simulations, we also argue how the particle filter can be used for positioning based on cellular phone measurements, for integrated navigation in aircraft, and for target tracking in aircraft and cars. Finally, the particle filter enables a promising solution to the combined task of navigation and tracking, with possible application to airborne hunting and collision avoidance systems in cars.
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| 8. |
- Jansson, John-Olov, 1954, et al.
(author)
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The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions.
- 2023
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In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - 1471-2970. ; 378:1888
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Research review (peer-reviewed)abstract
- Body weight is tightly regulated when outside the normal range. It has been proposed that there are individual-specific lower and upper intervention points for when the homeostatic regulation of body weight is initiated. The nature of the homeostatic mechanisms regulating body weight at the lower and upper ends of the body weight spectrum might differ. Previous studies demonstrate that leptin is the main regulator of body weight at the lower end of the body weight spectrum. We have proposed that land-living animals use gravity to regulate their body weight. We named this homeostatic system the gravitostat and proposed that there are two components of the gravitostat. First, an obvious mechanism involves increased energy consumption in relation to body weight when working against gravity on land. In addition, we propose that there exists a component, involving sensing of the body weight by osteocytes in the weight-bearing bones, resulting in a feedback regulation of energy metabolism and body weight. The gravity-dependent homeostatic regulation is mainly active in obese mice. We, herein, propose the dual hypothesis of body weight regulation, including gravity-dependent actions (= gravitostat) at the upper end and leptin-dependent actions at the lower end of the body weight spectrum. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.
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| 9. |
- Mobini, Reza, 1965, et al.
(author)
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Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial
- 2017
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 19:4, s. 579-589
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Journal article (peer-reviewed)abstract
- Aims: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. Materials and methods: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (10(8) CFU/d) or high dose (10(10) CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. Results: Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. Conclusions: Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.
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| 10. |
- Nordlund, Per-Johan, et al.
(author)
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A Framework for Particle Filtering for Positioning, Navigation and Tracking
- 2001
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In: Proceedings of the 11th IEEE Signal Processing Workshop on Statistical Signal Processing. - : IEEE. - 0780370112 ; , s. 34-37
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Conference paper (peer-reviewed)abstract
- A framework for positioning, navigation and tracking problems using particle filters (recursive Monte Carlo methods) is developed. Automotive and airborne applications, approached in this framework, have proven a numerical advantage over classical Kalman filter based algorithms. Here the use of non-linear measurement models and non-Gaussian measurement noise is the main explanation for the improvement in accuracy, and models for relevant sensors are surveyed.
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