| 1. |
- Lindgren, Gustaf, et al.
(author)
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Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma.
- 2014
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Journal article (peer-reviewed)abstract
- Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.
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| 2. |
- Abu-Humaidan, Anas H.A., et al.
(author)
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EGFR modulates complement activation in head and neck squamous cell carcinoma
- 2020
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: The epidermal growth factor receptor (EGFR) is pivotal for growth of epithelial cells and is overexpressed in several epithelial cancers like head and neck squamous cell carcinoma (HNSCC). EGFR signalling is also involved in diverse innate immune functions in epithelia. We previously found a role for EGFR in modulating the complement system in skin, this prompted an investigation into EGFR role in complement modulation in HNSCC. Methods: We used patient derived HNSCC cell lines with varying sensitivities to EGFR inhibitors, and generated EGFR inhibition resistant cell lines to study the role of EGFR in modulating complement in HNSCC. Results: We found that HNSCC cell lines activate the complement system when incubated with human serum. This complement activation was increased in cell lines sensitive to EGFR inhibition following the use of the tyrosine kinase inhibitor Iressa. Sensitive cell line made resistant to EGFR-inhibitors displayed complement activation and a decrease in complement regulatory proteins even in the absence of EGFR-inhibitors. Complement activation did not cause lysis of HNSCC cells, and rather led to increased extracellular signal-regulated kinase (ERK) phosphorylation in one cell line. Conclusion: These data indicate that EGFR has a complement modulatory role in HNSCC, and that a prolonged EGFR-inhibition treatment in sensitive cancer cells increases complement activation. This has implications in understanding the response to EGFR inhibitors, in which resistance and inflammatory skin lesions are two major causes for treatment cessation.
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| 3. |
- Andersson, C David, et al.
(author)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Journal article (peer-reviewed)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 4. |
- Andersson, Hanna, et al.
(author)
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Natur på skolgården för lärande, hälsa och hållbarhet
- 2024. - 2024
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Reports (pop. science, debate, etc.)abstract
- Gröna och artrika utemiljöer främjar barns och ungas välbefinnande och kunskap, bådegenom hälsofördelar kopplade till biologisk mångfald och genom att skapa förutsättningarför lek och lärande om natur och miljöfrågor. Skolgården skulle kunna bidra till allt detta,men är idag i hög grad en outnyttjad plats för biologisk mångfald och klimatanpassningav städer. I denna policy brief presenteras huvudsakliga motiv och möjliga åtgärder för attutveckla gröna miljöer och biologisk mångfald på skolgårdar och förskolegårdar.
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| 5. |
- Andersson, Jan, 1965-, et al.
(author)
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Regeringsuppdrag synfält : utredning om förutsättningar för undantag från de medicinska kraven för individer med synfältsbortfall
- 2022
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Reports (other academic/artistic)abstract
- I regeringsuppdraget (I2021/ 02412) framgår att VTI, i samarbete med Trafikverket och Transportstyrelsen, ska utreda förutsättningarna för undantagshantering från de medicinska föreskrifterna med avseende på synfältsbortfall (B-körkort). Vidare ska tre aspekter beaktas: hur andra länder gör, konsekvenser för den enskilde samt samhällsekonomiska konsekvenser. Slutrapporten påvisar att Sverige med gällande rättsligt ramverk inte kan genomföra de förslag som slutrapporten föreslår. Det innebär att det kommer att krävas juridiska förändringar. Givet att dessa förändringar genomförs och att ett nytt förfaringssätt nyttjas visar slutrapporten på att a) positiva effekter för den enskilde individen uppstår, b) samhällsekonomiska vinster uppstår och c) en rättssäker och rättvis prövning är möjlig. Slutrapporten redovisar dessutom hur ett urval av andra länder har hanterat handläggningen av individer med synfältsbortfall givet samma EU-direktiv som Sverige regleras av. Det framgår också av undersökningen att samtliga länder, som en förutsättning för undantag från de föreskrivna kraven avseende synfält, tillämpar krav eller rekommendationer om att ett praktiskt körprov ska utgöra del i underlaget för bedömning av körförmågan. Kunskapsläget med avseende på körförmågebedömningar för individer med synfältsbortfall redovisas och där framgår med tydlighet att perimetrin som Sverige utnyttjar som underlag för återkallelse av körkort inte kan predicera individers körförmåga. Perimetrin är dock viktig eftersom individer med synfältsbortfall som grupp kan vara olämpliga förare. Slutsatsen som forskningslitteraturen enstämmigt lyfter är att det behövs förarprov (på väg eller i en simulator) för att kunna genomföra en valid bedömning. Slutligen innehåller slutrapporten vilka problem (aktiviteter) som kvarstår för att skapa en lämplig och kvalitetssäkrad process. Dessutom presenteras den kronologiska ordning på aktiviteter som behöver genomföras. Kronologin krävs eftersom resultatet av lämplig metod och aktör påverkar det vidare arbetet med avseende på utformning av körprov och rättsligt ramverk. Slutrapportens slutsats är att Sverige har möjligheten att genomföra en förändring med avsevärda nyttor. Detta eftersom de valda aktörerna och de valda metoderna existerar idag och därför endast behöver utvecklas i viss mån för att säkerställa att individer med synfältsbortfall erbjuds en kvalitetssäkrad, rättssäker och rättvis process som dessutom bedöms vara samhällsekonomiskt lönsam.
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| 6. |
- Baskaran, Karthikeyan, Senior Lecturer, 1983-, et al.
(author)
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Closed circuit driving performance in persons with quadrantanopia and hemianopia in Sweden
- 2016
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In: Scandinavian Journal of Optometry and Visual Science. - 1891-0882 .- 1891-0890. ; 9:2, s. 14-
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Journal article (peer-reviewed)abstract
- In Sweden, persons with homonymous visual field defects (HVFDs) are not allowed to drive and usually their driving licences are revoked. Although earlier studies (de Haan et al. 2014; Elgin et al. 2010) have shown that HVFDs do not necessarily impair practical fitness to drive, the Swedish transport agency does not allow them any on-road driving testing to prove their practical fitness to drive. The aim of this study was to evaluate driving performance in participants with visual field defects after acquired brain injury in a closed circuit driving track. Eleven former drivers with varying degrees of quadrantanopia and hemianopia after acquired brain damage were recruited for this study from the stroke rehabilitation department at Kalmar County Hospital. The median age of the participants was 55 years and their age ranged from 37 to 73 years. Driving performance was assessed by two experienced driving instructors. They graded the participants on a scale from 1 (major faults) to 5 (excellent) on the following five categories: manoeuvring the vehicle, risk assessment, traffic rules, visual scanning and situation awareness. The subject would pass the driving test only if they had scored 3 or more in each category. The subjects who passed the closed circuit driving track test were evaluated further with a driving simulator. Five (45%) out of 11 participants passed the driving test and were adjudged as fit to drive. The remaining six (55%) participants failed in at least one category. Three failed in visual scanning, two failed in manoeuvring and one failed in both the aforementioned categories as well as risk assessment. Three subjects who passed the closed circuit driving track test were also evaluated in a driving simulator. Out of the three subjects, only one was able to complete and pass the evaluation while the remaining two participants aborted the evaluation due to simulator sickness. Homonymous visual field defects do not necessarily impair fitness to drive. Therefore, an on-road assessment of practical fitness to drive should be allowed in Sweden for this population in the near future. The decision on practical fitness to drive cannot be based solely on the presence of visual field defects. A rehabilitation program aimed at improving safe driving should be put into practice with an on-road driving training and assessment procedure. It should be developed and implemented by experienced traffic inspectors as a complementary part of the decision to either issue or revoke a driving licence for this population.
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| 7. |
- Baskaran, Karthikeyan, Senior Lecturer, 1983-, et al.
(author)
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Driving performance in participants with quadrantanopia and hemianopia in Sweden : a closed circuit driving track study
- 2015
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Conference paper (peer-reviewed)abstract
- Background: The ability to drive a car is one of the important aspect of a person’s independent lifestyle. People with visual field defects after stroke or traumatic brain injury (TBI) have more limitations in driving. In Sweden, they are not allowed to drive and their driving licenses are revoked. The Swedish transport agency does not allow any on-road test for them to prove their practical fitness to drive. Therefore, the aim was to evaluate driving performance in participants with visual field defects after TBI in a closed circuit driving track.Methods: Eleven participants with varying degrees of quadrantanopia and hemianopia after TBI were recruited for this study. The mean age of the participants was 58 ±13.7 years (37 - 73 years). All participants underwent 10 weeks of explorative saccadic training at the hospital prior to driving assessment. Driving performance were assessed by two driving instructors and they graded the participants from 1 (fail) to 5 (excellent) on the following five categories: maneuvering the vehicle, safety margin, traffic rules, scanning for potential hazards and reacting to situations. The subject passed the driving test only if they scored 3 or more in each category.Results: Five (45%) out of 11 participants passed the driving test and they were adjudged as fit to drive. Remaining six (55%) participants failed at least in one category. Three of them failed in visual scanning, two failed in maneuvering and one failed in both the aforementioned categories as well as safety margin.Discussion: A rehabilitation program aimed at improving safe driving should be implemented and an on-road assessment of fitness to drive should be allowed in Sweden for this population in future.Conclusion: The decision on practical fitness to drive cannot be based solely on the presence of visual field defect and an on-road assessment is required.
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| 8. |
- de Frias Lopez, Ricardo, et al.
(author)
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A Numerical Study on the Permanent Deformation of Gap-Graded Granular Mixtures
- 2016
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In: Proceedings of the Third International Conference on Railway Technology. - Stirlingshire, UK : Civil-Comp Press.
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Conference paper (peer-reviewed)abstract
- Permanent deformation accumulation of unbound granular layers under traffic plays a critical role in the performance and need for maintenance of pavements and railway structures. In this paper, the discrete element method is used to study the permanent strain behaviour of binary mixtures of elastic spheres, as an idealization of gap-graded mixtures, under triaxial monotonic loading. The effects of stress level and soil fabric structure, based on a recently proposed classification system founded on micromechanical considerations, are assessed by subjecting mixtures with varying fines contents to different stress levels. Additionally, mixtures are loaded to static failure to study the dependency of the permanent strains on the closeness of the applied stress to failure stress, in accordance with existing empirical models. Numerical results are also compared with the experimentally determined behaviour of granular materials. The findings indicate that numerical mixtures are able to reproduce some of the most significant features observed in laboratory tests on granular materials, further encouraging the use of numerical simulations to enhance the understanding of granular media behaviour. Additionally, a good correlation between fabric structure and performance is obtained, giving additional support to the use of the studied fabric classification system for performance characterization.
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| 9. |
- de Frias Lopez, Ricardo
(author)
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Granular Materials for Transport Infrastructures : Mechanical performance of coarse–fine mixtures for unbound layers through DEM analysis
- 2016
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Licentiate thesis (other academic/artistic)abstract
- Granular materials are widely used as unbound layers within the infrastructure system playing a significant role on performance and maintenance. However, fields like pavement and railway engineering still heavily rely on empirically-based models owing to the complex behaviour of these materials, which partly stems from their discrete nature. In this sense, the discrete element method (DEM) presents a numerical alternative to study the behaviour of discrete systems with explicit consideration of the processes at particulate level governing the macroscopic response. This thesis aims at providing micromechanical insight into the effect of different particle sizes on the load-bearing structure of granular materials and its influence on the resilient modulus and permanent deformation response, both of which are greatly influenced by the stress level. In order to accomplish this, binary mixtures of elastic spheres under axisymmetric stress are studied using DEM as the simplest expression for gap-graded materials, which in turn also can be seen as a simplification of more complex mixtures.First, the effect of the fines content on the force transmission at contact level was studied. Results were used to define a soil fabric classification system where the roles of the coarse and fine fractions were defined and quantified in terms of force transmission.A behavioural correspondence between numerical mixtures and granular materials was established, where the mixtures were able to reproduce some of the most significant features regarding the resilient modulus and permanent strain dependency on stress level for granular materials.A good correlation between soil fabric and performance was also found. Generally, higher resilient modulus and lower deformation values were observed for interactive fabrics, whereas the opposite held for instable fabrics.Mixtures of elastic spheres are far from granular materials, where numerous additional factors should be considered. Nevertheless, it is the author’s belief that this work provides insight into the soil fabric structure and its effect on the macroscopic response of granular materials.
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| 10. |
- de Frias Lopez, Ricardo, et al.
(author)
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Resilient properties of binary granular mixtures: A numerical investigatio
- 2016
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In: Computers and geotechnics. - : Elsevier. - 0266-352X .- 1873-7633. ; 76, s. 222-233
-
Journal article (peer-reviewed)abstract
- The effect of stress level on the resilient modulus for binary mixtures of elastic spheres under triaxial loading is investigated using the discrete element method. The secant modulus during the first cycle of unloading is used as an estimate of the modulus after several load cycles due to computational time restrains. Later in the paper, its adequacy as an accurate and efficient estimator is shown. Numerical results are statistically compared with existing relations characterizing the stress dependency of the resilient modulus for real granular materials. It is concluded that the modulus prediction is significantly improved considering the effect of the deviator stress in addition to the confinement stress, obtaining a good correlation between the modulus and the confinement to deviator stress ratio for the numerical mixtures. The stress dependency of a recently proposed soil fabric classification system, based on force transmission considerations at particulate level, is also studied and its correlation with performance investigated. It is found that the relative load-bearing role of coarse and fine components is governed by the deviator to confinement stress ratio. However, the implemented fabric classification is fairly insensitive to changes in this ratio. Regarding resilient performance, interactive fabrics show the stiffest response whereas underfilled fabrics should be avoided due to a potential for instability.
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