| 1. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)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. |
- Bereczky-Veress, Biborka, et al.
(författare)
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Host strain-dependent difference in susceptibility in a rat model of herpes simplex type 1 encephalitis.
- 2008
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Ingår i: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 14:2, s. 102-18
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is characterized by severe focal brain inflammation leading to substantial loss of nervous tissue. The authors established a model of Herpes simplex virus type 1 (HSV)-1-induced acute encephalitis in the rat by injecting into the whiskers' area a virus strain isolated from a fatal human HSE case. The model might resemble natural propagation of HSV-1 in humans; spreading from the mouth and lips via the trigeminal nerve to trigeminal ganglia and subsequently entering the central nervous system (CNS). HSV-1 infected Dark Agouti (DA) rats developed a well-synchronized disease and died 5 days after inoculation. HSV-1 detection by quantitative polymerase chain reaction (qPCR), virus isolation and immunohistochemistry, magnetic resonance imaging, and histopathological examination verified dramatic encephalitis mainly in the brainstem, but also in the olfactory bulb and other segments of the brain of diseased rats. In contrast, Piebald Virol Glaxo (PVG) rats were completely resistant to disease, displaying a more rapid clearance of peripheral infection and no evidence of virus entering into neither the trigeminal ganglia nor the CNS. These results suggest a regulation of susceptibility to HSV-1-induced encephalitis at the level of peripheral infection and subsequent neuronal uptake/transport of the virus. This provides a basis for future positioning of genetic polymorphisms regulating HSE and for dissection of important pathogenetic mechanisms of this severe human disease.
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| 3. |
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| 4. |
- Bergström, Andreas, 1978-
(författare)
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Timing-Based Localization using Multipath Information
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The measurements of radio signals are commonly used for localization purposes where the goal is to determine the spatial position of one or multiple objects. In realistic scenarios, any transmitted radio signal will be affected by the environment through reflections, diffraction at edges and corners etc. This causes a phenomenon known as multipath propagation, by which multiple instances of the transmitted signal having traversed different paths are heard by the receiver. These are known as Multi-Path Components (MPCs). The direct path (DP) between transmitter and receiver may also be occluded, causing what is referred to as non-Line-of-Sight (non-LOS) conditions. As a consequence of these effects, the estimated position of the object(s) may often be erroneous.This thesis focuses on how to achieve better localization accuracy by accounting for the above-mentioned multipath propagation and non-LOS effects. It is proposed how to mitigate these in the context of positioning based on estimation of the DP between transmitter and receiver. It is also proposed how to constructively utilize the additional information about the environment which they implicitly provide. This is all done in a framework wherein a given signal model and a map of the surroundings are used to build a mathematical model of the radio environment, from which the resulting MPCs are estimated.First, methods to mitigate the adverse effects of multipath propagation and non-LOS conditions for positioning based on estimation of the DP between transmitter and receiver are presented. This is initially done by using robust statistical measurement error models based on aggregated error statistics, where significant improvements are obtained without the need to provide detailed received signal information. The gains are seen to be even larger with up-to-date real-time information based on the estimated MPCs.Second, the association of the estimated MPCs with the signal paths predicted by the environmental model is addressed. This leads to a combinatorial problem which is approached with tools from multi-target tracking theory. A rich radio environment in terms of many MPCs gives better localization accuracy but causes the problem size to grow large—something which can be remedied by excluding less probable paths. Simulations indicate that in such environments, the single best association hypothesis may be a reasonable approximation which avoids the calculation of a vast number of possible hypotheses. Accounting for erroneous measurements is crucial but may have drawbacks if no such are occurring.Finally, theoretical localization performance bounds when utilizing all or a subset of the available MPCs are derived. A rich radio environment allows for good positioning accuracy using only a few transmitters/receivers, assuming that these are used in the localization process. In contrast, in a less rich environment where basically only the DP/LOS components are measurable, more transmitters/receivers and/or the combination of downlink and uplink measurements are required to achieve the same accuracy. The receiver’s capability of distinguishing between multiple MPCs arriving approximately at the same time also affects the localization accuracy.
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| 5. |
- Bergström, Andreas, 1978-, et al.
(författare)
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TOA Estimation Improvements in Multipath Environments by Measurement Error Models
- 2017
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Ingår i: Proceedings of the 2017 IEEE 28th Annual International Symposium on Personal, Indoor, and Mobile Radio Communications (PIMRC). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538635315 - 9781538635308 ; , s. 1-8
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Konferensbidrag (refereegranskat)abstract
- Many positioning systems rely on accuratetime of arrival measurements. In this paper, we addressnot only the accuracy but also the relevance of Time ofArrival (TOA) measurement error modeling. We discusshow better knowledge of these errors can improve relativedistance estimation, and compare the impact of differentlydetailed measurement error information. These models arecompared in simulations based on models derived froman Ultra Wideband (UWB) measurement campaign. Theconclusion is that significant improvements can be madewithout providing detailed received signal information butwith a generic and relevant measurement error model.
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| 6. |
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| 7. |
- Duong-Thi, Minh-Dao, et al.
(författare)
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Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules
- 2014
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 461, s. 57-59
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM-mu M) small molecule-protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant (K-D) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods (R-2 = 0.995, P < 0.0001). (C) 2014 Elsevier Inc. All rights reserved.
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| 8. |
- Engström, Patrik, et al.
(författare)
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Expansion of the Chlamydia trachomatis inclusion does not require bacterial replication
- 2015
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 305:3, s. 378-382
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis replication takes place inside of a host cell, exclusively within a vacuole known as the inclusion. During an infection, the inclusion expands to accommodate the increasing numbers of C. trachomatis. However, whether inclusion expansion requires bacterial replication and/or de novo protein synthesis has not been previously investigated in detail. Therefore, using a chemical biology approach, we herein investigated C. trachomatis inclusion expansion under varying conditions in vitro. Under normal cell culture conditions, inclusion expansion correlated with C trachomatis replication. When bacterial replication was inhibited using KSK120: an inhibitor that targets C. trachomatis glucose metabolism, inclusions expanded even in the absence of bacterial replication. In contrast, when bacterial protein synthesis was inhibited using chloramphenicol, expansion of inclusions was blocked. Together, these data suggest that de novo protein synthesis is necessary, whereas bacterial replication is dispensable for C trachomatis inclusion expansion. (C) 2015 The Authors. Published by Elsevier GmbH.
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| 9. |
- Gummesson, Anders, 1973, et al.
(författare)
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Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes
- 2021
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Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Karlsson, Fredrik, 1984, et al.
(författare)
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Gut metagenome in European women with normal, impaired and diabetic glucose control
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 498:7452, s. 99-103
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is a result of complex gene-environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence(1). Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity(2,3), diabetes(4) and cardiovascular disease(5). Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort(4) and show that the discriminant metagenomicmarkers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.
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