| 1. |
- Ahrentorp, Fredrik, et al.
(author)
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Effective particle magnetic moment of multi-core particles
- 2015
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In: Journal of Magnetism and Magnetic Materials. - : Elsevier BV. - 0304-8853 .- 1873-4766. ; 380, s. 221-226
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Journal article (peer-reviewed)abstract
- In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems BNF Starch from Micromod with a median particle diameter of 100 am and FeraSpin R from nanoPET with a median particle diameter of 70 nm - and one single-core particle system - SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm. (C) 2014 Elsevier B.V. All rights reserved.
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| 2. |
- Albert, J., et al.
(author)
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Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2014
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:10, s. 673-677
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Journal article (peer-reviewed)abstract
- The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.
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| 3. |
- Askerdal, Mikael, 1975, et al.
(author)
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Motion resistance modelling and validation in winter conditions with varying air drag
- 2024
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In: Vehicle System Dynamics. - 1744-5159 .- 0042-3114. ; In Press
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Journal article (peer-reviewed)abstract
- Range prediction is vital for battery electric vehicles, and the main source of errors in range prediction is often the uncertainty in motion resistance. Rig and wind tunnel measurements can be used to find the motion resistance of a specific vehicle combination under specified weather conditions. However, real-life variation of the operating conditions of heavy-duty vehicles makes testing impractical. This paper proposes and validates a model of motion resistance with parameters adapted to actual road weather conditions. The model is validated in winter conditions with varying wind, using a vehicle equipped with a wind sensor. The results show that the proposed model captures the motion resistance with high accuracy. Results also indicate that it is crucial to take weather effects into account when modelling motion resistance, particularly in winter conditions.
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| 4. |
- Bergstrand, Karl-Johan, et al.
(author)
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Nulägesanalys trädgård
- 2018
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Reports (pop. science, debate, etc.)abstract
- Rapporten Nulägesanalys - trädgård har genomförts inom ramen för projektgruppen Insatsstyrka trädgård. Syftet med inventeringen har varit att ge svar på vem som jobbar med trädgårdsvetenskap, vilka forskargrupper och med vilka forskningsämnen, samt identifiera framtida arbetsfält inom ämnet trädgårdsvetenskap och därmed ge uppslag för framtida utveckling av forskningsfält, utbildning och samverkan. I detta ingår att kartlägga trädgårdsvetenskaplig forskning, utbildning och samverkan vid SLU. Nulägesanalysen förväntas därmed ge en grund för fortsatt strategiskt arbete med att utveckla ämnet trädgårdsvetenskap (Horticultural Science) utifrån inventerade resurser och förutsättningar.
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| 5. |
- Bshara, Mussa, et al.
(author)
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Fingerprinting Localization in Wireless Networks Based on Received-Signal-Strength Measurements : A Case Study on WiMAX Networks
- 2010
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In: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 59:1, s. 283-294
-
Journal article (peer-reviewed)abstract
- This paper considers the problem of fingerprinting localization in wireless networks based on received-signal-strength (RSS) observations. First, the performance of static localization using power maps (PMs) is improved with a new approach called the base-station-strict (BS-strict) methodology, which emphasizes the effect of BS identities in the classical fingerprinting. Second, dynamic motion models with and without road network information are used to further improve the accuracy via particle filters. The likelihood-calculation mechanism proposed for the particle filters is interpreted as a soft version (called BS-soft) of the BS-strict approach applied in the static case. The results of the proposed approaches are illustrated and compared with an example whose data were collected from a WiMAX network in a challenging urban area in the capitol city of Brussels, Belgium.
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| 6. |
- Bshara, Mussa, et al.
(author)
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Robust Tracking in Cellular Networks Using HMM Filters and Cell-ID Measurements
- 2011
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In: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 60:3, s. 1016-1024
-
Journal article (peer-reviewed)abstract
- A localization algorithm based on cell identification (Cell-ID) information is proposed. Instead of building the localization decisions only on the serving base station, all the detected Cell-IDs (serving or nonserving) by the mobile station are utilized. The statistical modeling of user motion and the measurements are done via a hidden Markov model (HMM), and the localization decisions are made with maximum a posteriori estimation criterion using the posterior probabilities from an HMM filter. The results are observed and compared with standard alternatives on an example whose data were collected from a worldwide interoperability for microwave access network in a challenging urban area in the Brussels capitol city.
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| 7. |
- Bshara, Mussa, et al.
(author)
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Tracking in WiMAX Networks Depending on SCORE Measurements
- 2009
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In: Proceedings of the 6th Workshop on Positioning, Navigation and Communication. - 9781424432936 - 9781424432929 ; , s. 229-234
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Conference paper (peer-reviewed)abstract
- Tracking in WiMax networks is gaining a lot of interest; especially after the mobile WiMax became one of the emerging technologies that promote low-cost deployment and evolving to provide IP-based services of high mobility including providing location-based services (LBS). Therefore, locating users in a cheap way thatdepend on the available network resources is becoming more and more interesting and an active topic for researchers. In this paper we consider the problem of tracking in WiMAX networks depending on SCOREobservations. The provided examples show that with efficient measurement data processing and with the help of already available data (street maps), plausible results can be achieved.
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| 8. |
- Byrgazov, Konstantin, et al.
(author)
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Targeting aggressive osteosarcoma with a peptidase-enhanced cytotoxic melphalan flufenamide
- 2020
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In: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY. - : SAGE PUBLICATIONS LTD. - 1758-8340 .- 1758-8359. ; 12
-
Journal article (peer-reviewed)abstract
- Background: Low survival rates in metastatic high-grade osteosarcoma (HGOS) have remained stagnant for the last three decades. This study aims to investigate the role of aminopeptidase N (ANPEP) in HGOS progression and its targeting with a novel lipophilic peptidase-enhanced cytotoxic compound melphalan flufenamide (melflufen) in HGOS. Methods: Meta-analysis of publicly available gene expression datasets was performed to determine the impact ofANPEPgene expression on metastasis-free survival of HGOS patients. The efficacy of standard-of-care anti-neoplastic drugs and a lipophilic peptidase-enhanced cytotoxic conjugate melflufen was investigated in patient-derived HGOSex vivomodels and cell lines. The kinetics of apoptosis and necrosis induced by melflufen and doxorubicin were compared. Anti-neoplastic effects of melflufen were investigatedin vivo. Results: ElevatedANPEPexpression in diagnostic biopsies of HGOS patients was found to significantly reduce metastasis-free survival. In drug sensitivity assays, melflufen has shown an anti-proliferative effect in HGOSex vivosamples and cell lines, including those resistant to methotrexate, etoposide, doxorubicin, and PARP inhibitors. Further, HGOS cells treated with melflufen displayed a rapid induction of apoptosis and this sensitivity correlated with high expression ofANPEP. In combination treatments, melflufen demonstrated synergy with doxorubicin in killing HGOS cells. Finally, Melflufen displayed anti-tumor growth and anti-metastatic effectsin vivo. Conclusion: This study may pave the way for use of melflufen as an adjuvant to doxorubicin in improving the therapeutic efficacy for the treatment of metastatic HGOS.
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| 9. |
- Dela, Nicolas, et al.
(author)
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A pilot evaluation of using large movement driving simulator experiments to study driver behaviour influence on active safety systems for commercial heavy vehicles
- 2009
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In: Proceedings of the 21st International Symposium on Dynamics of Vehicles on Roads and Tracks (IAVSD'09), Stockholm, Sweden, August 17-21, 2009. - Linköping : ViP - Virtual prototyping and assessment by simulation.
-
Reports (other academic/artistic)abstract
- The evaluation of active safety functions like Electronic Stability Control (ESC) is of increasing importance, driven by legislation, to commercial heavy vehicle producers and to society as a whole to predict the potential benefits of the systems. Direct testing in real traffic with normal drivers of those functions are most often infeasible due to cost, repeatability and safety. This paper presents an attempt to explore the possibility of using large scale moving based driving simulators to evaluate functions like ESC. This is conducted through a simulator experiment where the subject drivers have been provoked in driving scenarios to ESC interventions. The experiment indicates the possibility of using driving simulators for evaluation purposes. This implies that studies of the benefits can be performed with higher accuracy regarding repeatability and evaluation testing of active safety functions can be made more cost efficient and without jeopardizing safety of involved driver and other road-users.
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| 10. |
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| 11. |
- Justice, Anne E., et al.
(author)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Journal article (peer-reviewed)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 12. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 13. |
- Karlsson, Fredrik, Docent, 1975-, et al.
(author)
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A within-subject comparison of face-to-face and telemedicine screening using the timed water swallow test (TWST) and the test of mastication and swallowing of solids (TOMASS)
- 2023
-
In: Dysphagia (New York. Print). - : Springer. - 0179-051X .- 1432-0460. ; 38, s. 483-490
-
Journal article (peer-reviewed)abstract
- The Timed Water Swallow Test (TWST) and the Test of Mastication of Solids (TOMASS) are dysphagia screening procedures that have been shown to be reliably assessed from video. The reliability of the procedures performed over telemedicine has not previously been assessed. TWST and TOMASS outcomes in two situations (both face-to-face and over telemedicine) were compared for 48 participants (aged 60-90; 27 with clinical conditions and 21 older persons). Both testing situation and test performed order were randomized, and all assessment procedures were performed within 3 h of each other. The results indicated a high level of agreement between face-to-face and telemedicine screening outcomes for TWST and TOMASS, respectively. The assessments indicated an 83% and 76% agreement in classifications of individual participants as within or outside normal limits for the TWST and TOMASS for the two test situations. The TWST showed a balanced distribution in differing classification in telemedicine (0.16-0.19 error rates). The TOMASS procedure classified more participants as outside normal limits over telemedicine compared to face-to-face administration. Agreement in the observed number of swallows was substantially lower than other outcome measures, which is attributed to increased difficulty in observing this property over video. Most participants (60%) reported that they would prefer telemedicine over face-to-face assessments, and 90% viewed the procedure as more accessible than expected. All participants were satisfied with the telemedicine procedures. The results suggest that clinical assessment of dysphagia over telemedicine using the TWST and TOMASS are viable alternatives to face-to-face administration of the procedures.
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| 14. |
- Leo, Christoph, et al.
(author)
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Holistic pedestrian safety assessment for average males and females
- 2023
-
In: Frontiers in Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
-
Journal article (peer-reviewed)abstract
- Objective: An integrated assessment framework that enables holistic safety evaluations addressing vulnerable road users (VRU) is introduced and applied in the current study. The developed method enables consideration of both active and passive safety measures and distributions of real-world crash scenario parameters. Methods: The likelihood of a specific virtual testing scenario occurring in real life has been derived from accident databases scaled to European level. Based on pre-crash simulations, it is determined how likely it is that scenarios could be avoided by a specific Autonomous Emergency Braking (AEB) system. For the unavoidable cases, probabilities for specific collision scenarios are determined, and the injury risk for these is determined, subsequently, from in-crash simulations with the VIVA+ Human Body Models combined with the created metamodel for an average male and female model. The integrated assessment framework was applied for the holistic assessment of car-related pedestrian protection using a generic car model to assess the safety benefits of a generic AEB system combined with current passive safety structures. Results: In total, 61,914 virtual testing scenarios have been derived from the different car-pedestrian cases based on real-world crash scenario parameters. Considering the occurrence probability of the virtual testing scenarios, by implementing an AEB, a total crash risk reduction of 81.70% was achieved based on pre-crash simulations. It was shown that 50 in-crash simulations per load case are sufficient to create a metamodel for injury prediction. For the in-crash simulations with the generic vehicle, it was also shown that the injury risk can be reduced by implementing an AEB, as compared to the baseline scenarios. Moreover, as seen in the unavoidable cases, the injury risk for the average male and female is the same for brain injuries and femoral shaft fractures. The average male has a higher risk of skull fractures and fractures of more than three ribs compared to the average female. The average female has a higher risk of proximal femoral fractures than the average male. Conclusions: A novel methodology was developed which allows for movement away from the exclusive use of standard-load case assessments, thus helping to bridge the gap between active and passive safety evaluations.
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| 15. |
- Leo, Fredrik, et al.
(author)
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Characterization of a highly conserved MUC5B-degrading protease, MdpL, from Limosilactobacillus fermentum
- 2023
-
In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 14
-
Journal article (peer-reviewed)abstract
- MUC5B is the predominant glycoprotein in saliva and is instrumental in the establishment and maintenance of multi-species eubiotic biofilms in the oral cavity. Investigations of the aciduric Lactobacillaceae family, and its role in biofilms emphasizes the diversity across different genera of the proteolytic systems involved in the nutritional utilization of mucins. We have characterized a protease from Limosilactobacillus fermentum, MdpL (Mucin degrading protease from Limosilactobacillus) with a high protein backbone similarity with commensals that exploit mucins for attachment and nutrition. MdpL was shown to be associated with the bacterial cell surface, in close proximity to MUC5B, which was sequentially degraded into low molecular weight fragments. Mapping the substrate preference revealed multiple hydrolytic sites of proteins with a high O-glycan occurrence, although hydrolysis was not dependent on the presence of O-glycans. However, since proteolysis of immunoglobulins was absent, and general protease activity was low, a preference for glycoproteins similar to MUC5B in terms of glycosylation and structure is suggested. MdpL preferentially hydrolyzed C-terminally located hydrophobic residues in peptides larger than 20 amino acids, which hinted at a limited sequence preference. To secure proper enzyme folding and optimal conditions for activity, L. fermentum incorporates a complex system that establishes a reducing environment. The importance of overall reducing conditions was confirmed by the activity boosting effect of the added reducing agents L-cysteine and DTT. High activity was retained in low to neutral pH 5.5-7.0, but the enzyme was completely inhibited in the presence of Zn2+. Here we have characterized a highly conserved mucin degrading protease from L. fermentum. MdpL, that together with the recently discovered O-glycanase and O-glycoprotease enzyme groups, increases our understanding of mucin degradation and complex biofilm dynamics.
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| 16. |
- Leo, Fredrik, et al.
(author)
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Characterization of MdpS: an in-depth analysis of a MUC5B-degrading protease from Streptococcus oralis
- 2024
-
In: FRONTIERS IN MICROBIOLOGY. - : Frontiers Media S.A.. - 1664-302X. ; 15
-
Journal article (peer-reviewed)abstract
- Oral biofilms, comprising hundreds of bacteria and other microorganisms on oral mucosal and dental surfaces, play a central role in oral health and disease dynamics. Streptococcus oralis, a key constituent of these biofilms, contributes significantly to the formation of which, serving as an early colonizer and microcolony scaffold. The interaction between S. oralis and the orally predominant mucin, MUC5B, is pivotal in biofilm development, yet the mechanism underlying MUC5B degradation remains poorly understood. This study introduces MdpS (Mucin Degrading Protease from Streptococcus oralis), a protease that extensively hydrolyses MUC5B and offers an insight into its evolutionary conservation, physicochemical properties, and substrate- and amino acid specificity. MdpS exhibits high sequence conservation within the species and also explicitly among early biofilm colonizing streptococci. It is a calcium or magnesium dependent serine protease with strict physicochemical preferences, including narrow pH and temperature tolerance, and high sensitivity to increasing concentrations of sodium chloride and reducing agents. Furthermore, MdpS primarily hydrolyzes proteins with O-glycans, but also shows activity toward immunoglobulins IgA1/2 and IgM, suggesting potential immunomodulatory effects. Significantly, MdpS extensively degrades MUC5B in the N- and C-terminal domains, emphasizing its role in mucin degradation, with implications for carbon and nitrogen sequestration for S. oralis or oral biofilm cross-feeding. Moreover, depending on substrate glycosylation, the amino acids serine, threonine or cysteine triggers the enzymatic action. Understanding the interplay between S. oralis and MUC5B, facilitated by MdpS, has significant implications for the management of a healthy eubiotic oral microenvironment, offering potential targets for interventions aimed at modulating oral biofilm composition and succession. Additionally, since MdpS does not rely on O-glycan removal prior to extensive peptide backbone hydrolysis, the MdpS data challenges the current model of MUC5B degradation. These findings emphasize the necessity for further research in this field.
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| 17. |
- Lu, Yingchang, et al.
(author)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 18. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Journal article (peer-reviewed)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 19. |
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| 20. |
- Niini, Tarja, et al.
(author)
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Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study
- 2012
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In: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 205:11, s. 588-593
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Journal article (peer-reviewed)abstract
- Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.
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| 21. |
- Oldefors, Fredrik, et al.
(author)
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PLC Verification and Monitoring Using 3D Graphical Simulation
- 2004
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In: Proceedings of the 21st international manufacturing conference. - Limerick : University of Limerick. Dept. of Manufacturing and Operations Engineering. - 1874653771 - 9781874653776 ; , s. 219-224
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Conference paper (other academic/artistic)
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| 22. |
- Pandis Iveroth, Sofie, 1975-
(author)
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Industrial ecology for sustainableurban development- the case of Hammarby Sjöstad
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- Today, more than half the world’s population lives in cities largely dependent on resources and ecosystem services from outside their physical boundaries. Correspondingly, urban resource needs and waste generation have serious worldwide ecological consequences, and urban areas have become a primary driver of environmental change. In response, various sustainable urban developments have been initiated worldwide. Quite a few of these rely on strategies giving urban areas the characteristics of ecosystems, i.e., fostering urban symbiosis by integrating infrastructural systems to optimise the environmental performance of the system as a whole.Whether or not the strategy of urban symbiosis actually contributes to sustainable urban development is, however, debated. It may support only short-term system optimisation, hindering the implementation of new technology crucial for the longterm environmental improvement of society, as that might require no symbiosis but substitution. Or it might actually support a complete transition to sustainable urban development.Consequently, this thesis explores the research question “How can urban symbiosis contribute to sustainable urban development?” using the implementation of urban symbiosis strategies in Hammarby Sjöstad, Stockholm, Sweden, as a single-case study. The choice of a single-case study approach was an attractive approach as the sustainable development strategy implemented in Hammarby Sjöstad was clear and consistent: the approach aimed at sustainable urban development by using innovative technical solutions such as urban symbiosis, and not by changing the behaviour of the inhabitants of the district. This fortuitous “natural experiment” was useful, as strategies for sustainable development are often difficult to evaluate since they are often not very clearly or consistently applied.Using results based on literature reviews, in-depth interviews, discussions with focus groups, and quantitative data, this thesis concludes that urban symbiosis strategies do not directly respond to path dependence, and that such strategies are as dependent on radical behavioural change as are transition management strategies. In addition, urban symbiosis strategies can optimise existing infrastructural systems and advance the planning of the sustainable urban district.
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| 23. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 24. |
- Simonds, Erin F., et al.
(author)
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Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma
- 2021
-
In: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 9:6
-
Journal article (peer-reviewed)abstract
- Background Glioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.Methods We used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.Results ICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.Conclusions Our data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.
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| 25. |
- Strandmark, Petter, et al.
(author)
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Shortest Paths with Curvature and Torsion
- 2013
-
In: Computer Vision (ICCV), 2013 IEEE International Conference on. - 1550-5499. - 9781479928392 ; , s. 2024-2031
-
Conference paper (peer-reviewed)abstract
- This paper describes a method of finding thin, elongated structures in images and volumes. We use shortest paths to minimize very general functionals of higher-order curve properties, such as curvature and torsion. Our globally optimal method uses line graphs and its runtime is polynomial in the size of the discretization, often in the order of seconds on a single computer. To our knowledge, we are the first to perform experiments in three dimensions with curvature and torsion regularization. The largest graphs we process have almost one hundred billion arcs. Experiments on medical images and in multi-view reconstruction show the significance and practical usefulness of regularization based on curvature while torsion is still only tractable for small-scale problems
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| 26. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 27. |
- Vicini, F. A., et al.
(author)
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A Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy
- 2022
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In: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016.
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Journal article (peer-reviewed)abstract
- Purpose: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT. Methods and Materials: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were classified into 3 biosignature risk groups using the decision score (DS) and the RRt category: (1) Low Risk (DS ≤2.8 without RRt), (2) Elevated Risk (DS >2.8 without RRt), and (3) Residual Risk (DS >2.8 with RRt). Total and invasive IBR rates were assessed by risk group and treatment. Results: In patients at low risk, there was no significant difference in IBR rates with or without RT (total, P = .8; invasive IBR, P = .7), and there were low overall 10-year rates (total, 5.1%; invasive, 2.7%). In patients with elevated risk, IBR rates were decreased with RT (total: hazard ratio [HR], 0.25; P < .001; invasive: HR, 0.28; P = .005); 10-year rates were 20.6% versus 4.9% (total) and 10.9% versus 3.1% (invasive). In patients with residual risk, although IBR rates decreased with RT after BCS (total: HR, 0.21; P < .001; invasive: HR, 0.29; P = .028), IBR rates remained significantly higher after RT compared with patients with elevated risk (HR, 2.5; 95% CI, 1.2-5.4; P = .018), with 10-year rates of 42.1% versus 14.7% (total) and 18.3% versus 6.5% (invasive). Conclusions: The novel biosignature identified patients with 3 distinct risk profiles: Low Risk patients with a low recurrence risk with or without adjuvant RT, Elevated Risk patients with excellent outcomes after BCS plus RT, and Residual Risk patients with an elevated recurrence risk remaining after BCS plus RT, warranting potential intensified or alternative treatment approaches. © 2022 The Authors
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| 28. |
- Weinmann, S., et al.
(author)
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Validation of a Ductal Carcinoma In Situ Biomarker Profile for Risk of Recurrence after Breast-Conserving Surgery with and without Radiotherapy
- 2020
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 26:15, s. 4054-4063
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Journal article (peer-reviewed)abstract
- PURPOSE: A major challenge in ductal carcinoma in situ (DCIS) treatment is selection of the most appropriate therapeutic approach for individual patients. We conducted an external prospective-retrospective clinical validation of a DCIS biologic risk signature, DCISionRT, in a population-based observational cohort of women diagnosed with DCIS and treated with breast-conserving surgery (BCS). EXPERIMENTAL DESIGN: Participants were 455 health plan members of Kaiser Permanente Northwest diagnosed with DCIS and treated with BCS with or without radiotherapy from 1990 to 2007. The biologic signature combined seven protein tumor markers assessed in formalin-fixed, paraffin-embedded tumor tissue with four clinicopathologic factors to provide a DCISionRT test result, termed decision score (DS). Cox regression and Kaplan-Meier analysis were used to measure the association of the DS, continuous (linear) or categorical (DS ≤ 3 vs. DS > 3), and subsequent total ipsilateral breast events and invasive ipsilateral breast events at least 6 months after initial surgery. RESULTS: In Cox regression, the continuous and categorical DS variables were positively associated with total and invasive breast event risk after adjustment for radiotherapy. In a subset analysis by treatment group, categorical Kaplan-Meier analyses showed at least 2-fold differences in 10-year risk of total breast events between the elevated-risk and low-risk DS categories. CONCLUSIONS: In this first external validation study of the DCISionRT test, the DS was prognostic for the risk of later breast events for women diagnosed with DCIS, following BCS. ©2020 American Association for Cancer Research.
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| 29. |
- Wigren, Julia, et al.
(author)
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At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021 : a retrospective cohort study
- 2023
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In: Eurosurveillance. - : European Centre for Disease Control and Prevention (ECDC). - 1025-496X .- 1560-7917. ; 28:13
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Journal article (peer-reviewed)abstract
- Background: The current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.Aim: The aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.Methods: We developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.Results: We demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.Conclusion: Implementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.
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