| 1. |
- Al-Okshi, Ayman
(författare)
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Maxillofacial cone beam computed tomography (CBCT) : aspetcs on optimisation
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inom odontologisk såväl som inom medicinsk radiologi sker en snabb utveckling av nya tekniker. Nya metoder för att kunna diagnosticera och följa sjukdomsförlopp över tid introduceras. Cone-Beam Computed Tomography (CBCT) är en sådan ny teknik, som introducerades inom odontologin under sent 1990-tal. Tekniken innebär att man får en avbildning av kroppen i genomskärning i tre mot varandra vinkelräta plan. Efter en långsam start med få fabrikanter och typer av CBCT-maskiner har antalet tillverkare och modeller ökat och en snabb spridning av tekniken har skett. CBCT kan ge en utökad och bättre diagnostisk information än konventionell röntgenteknik, men till priset av högre stråldos. Eftersom utveckling av nya tekniker liksom försäljning av ny apparatur går snabbare än forskning som undersöker nyttan med de nya teknikerna, är det angeläget att vetenskapligt utvärdera i vilken utsträckning nya tekniker är till nytta för de patienter som undersöks. Alla undersökningar som görs med röntgenstrålning ska vara berättigade och optimerade dvs utföras med lägsta möjliga stråldos för en specifik klinisk frågeställning. Därför är det viktigt att forskning som rör nya tekniker beaktar olika aspekter av optimering av undersökningar som utförs vid olika kliniska indikationer. Denna avhandling behandlar några aspekter av hur undersökningar med CBCT kan optimeras. I det första delarbetet gjordes en systematisk granskning av den vetenskapliga litteratur som publicerats då det gäller hur stora stråldoser som en undersökning med CBCT av tänder, käkar och ansiktsskelett ger upphov till, samt hur dessa stråldoser beräknas. För att hitta all relevant litteratur gjordes en sökning i tre databaser vilket resulterade i att över 700 publikationer identifierades. Efter en första genomgång kvarstod 38 publikationer som handlade om dosmätningar vid CBCT undersökningar av tänder, käkar och ansiktsskelett. Få studier beskrev i tillräcklig omfattning hur stråldoser beräknats, vilka protokoll och mätmetoder som använts. Likaså var beskrivningen av hur stråldoser relateras till kvalitén på de röntgenbilder som undersökningen resulterade i, mestadels knapphändig. Det behövs mer forskning som beskriver hur beräkningar av stråldoser sker samt hur man kan använda den lägsta möjliga stråldosen för att uppnå den kvalitén på röntgenbilderna som är optimal för en given klinisk frågeställning. En modell för vilka parametrar som är nödvändiga vid rapportering av uppmätt stråldos för CBCT undersökningar av tänder, käkar och ansiktsskelett föreslås. Syftet med det andra delarbetet var att testa en metod för att beräkna stråldos, som inte tidigare använts i nämnvärd utsträckning för odontologiska undersökningar. Denna metod innebär att en röntgenkänslig film placeras i ett fantom som är sammansatt av material vilka simulerar biologisk vävnad. Stråldosen från tre CBCT apparater från olika tillverkare beräknades för tre olika kliniska frågeställningar. Därutöver jämfördes de uppmätta stråldoserna från de tre CBCT apparaterna med doser från tre konventionella röntgenapparater som ger två dimensionella bilder av tänder och käkar sk panoramaröntgenbilder. Stråldoserna från CBCT apparaterna varierade beroende på strålfält, samt energi och mängd av röntgenstrålning för de olika undersökningarna och var generellt högre än de uppmätta stråldoserna från panoramaröntgenapparaterna. I det tredje delarbetet var målet att relatera stråldos till bildkvalitet för en specifik klinisk frågeställning och en specifik CBCT apparat. Stråldoser uppmättes med en DAP-meter och bildkvalité utvärderades såväl fysikaliskt (objektivt) som subjektivt. För beräkning av den objektiva bildkvalitén användes ett fantom som tagits fram i ett tidigare EU-finansierat projekt (SEDENTEXCT) och för bedömning av den subjektiva bildkvalitén användes att fantom som var sammansatt av material liknande biologisk vävnad. Från resultaten av denna studie kunde ett undersökningsprotokoll föreslås för undersökning av tänder och omgivande vävnad som ger den bästa bildkvalitén med lägsta möjliga stråldos. I det fjärde delarbetet användes röntgenbilder tagna på unga individer som skulle genomgå behandling för att korrigera snedställda tänder. En sådan tandreglerings behandling kan ge upphov till vissa icke önskvärda sidoeffekter så som förkortade tandrötter och/eller att den benvävnad som omger tänderna till viss del blir förstörd. Det kan därför vara viktigt att utföra röntgenundersökningar på denna patientgrupp både innan behandlingen påbörjas och vid uppföljningar av behandlingen. Syftet med denna studie var att undersöka hur olika bedömare identifierar och mäter anatomiska strukturer (tandrötter och den benvävnad som omger tänderna) i röntgenbilder från CBCT undersökningar och jämföra med mätningar i röntgenbilder från två konventionella tekniker. Sex bedömare granskade röntgenbilderna och utförde mätningarna. Resultatet visar att i röntgenbilder från CBCT undersökningen var det lättare att identifiera de anatomiska strukturerna än i röntgenbilderna från de konventionella teknikerna. Likaså var samstämmigheten mellan och inom bedömare högst för CBCT undersökningen då det gäller mätning av rötternas längd. Då det gäller mätning av benvävnaden runt tänderna fanns ingen skillnad mellan de olika teknikerna. Sammanfattningsvis visar denna avhandling att det saknas studier av hög kvalitet då det gäller mätning av stråldos relaterat till optimal objektiv och subjektiv bildkvalitet för givna kliniska frågeställningar. Vidare förslås en modell som innehåller nödvändiga parametrar för att rapportera uppmätt stråldos vid undersökning med CBCT av tänder, käkar och ansiktsskelett. Ett protokoll för CBCT undersökning av tänder och omgivande benvävnad som ger bästa möjliga bildkvalitet med minsta möjliga stråldos föreslås liksom vilka aspekter som bör beaktas i vetenskapliga studier för röntgenologisk kartläggning av icke-önskvärda effekter av tandregleringsbehandling.
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| 2. |
- Arellano, Carlos
(författare)
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The influence of soil structure on microbial processes in microfluidic models
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The way microbes behave in nature can vary widely depending on the spatial characteristics of the habitats they are located in. The spatial structure of the microbial environment can determine whether and to which extent processes such as organic matter degradation, and synergistic or antagonistic microbial processes occur. Investigating how the different spatial characteristics of microhabitats influence microbes has been challenging due to methodological limitations. In the case of soil sciences, attempts to describe the inner structure of the soil pore space, and to connect it to microbial processes, such as to determine the access of nutrient limited soil microorganisms to soil organic matter pools, has been one of the main goals of the field in the last years. The present work aimed at answering the question of how spatial complexity affects microbial dispersal, growth, and the degradation of a dissolved organic substrate. Using microfluidic devices, designed to mimic the inner soil pore physical structures, we first followed the dispersal and growth of soil microbes in the devices, using soil inocula or burying the microfluidic devices in the top layer of a soil (Paper I). We found that inter-kingdom interactions can play an important role for the dispersal of water-dwelling organisms and that these physically modified their environment. To reveal the effect of the different structures on microbes in more detail we tested the influence of increasing spatial complexity in a porespace on the growth and substrate degradation of bacterial and fungal laboratory strains. The parameters we used to manipulate the pore space’s complexity were two: via the turning angle and turning order of pore channels (Paper II), and via the fractal order of a pore maze (Paper III). When we tested the effect of an increase in turning angle sharpness on microbial growth, we found that as angles became sharper, bacterial and fungal growth decreased, but fungi were more affected than bacteria. We also found that their substrate degradation was only affected when bacteria and fungi grew together, being lower as the angles were sharper. Our next series of experiments, testing the effect of maze fractal complexity, however, showed a different picture. The increase in maze complexity reduced fungal growh, similar to the previous experiments, but increased bacterial growth and substrate consumption, at least until a certain depth into the mazes, contrary to our initial hypothesis. To increase the relevance of our studies, we performed experiments in both microfluidic device designs inoculated with a soil microbial extract and followed the substrate degradation patterns over time (Paper IV). We found that as complexity increased, both in terms of angle sharpness and fractal order, substrate consumption also increased. Our results, specially in mazes, might be caused by a reduced competition among bacterial communities and individuals in complex habitats, allowing co-existence of different metabolic strategies and the onset of bacterial biofilm formation leading to a higher degradation efficiency, but further studies are required to confirm this. Our results show that the spatial characteristic of microhabitats is an important factor providing microbes with conditions for a wide variety of ecological interactions that determine their growth and their organic matter turnover.
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| 3. |
- Beckman, Svante, 1945-
(författare)
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Vilka är vägarna till kunskap?
- 1992
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Ingår i: Forskning och framsteg. - 0015-7937. ; 27:3, s. 52-53
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Artikeln framlägger teorin att individens kunskapsbestånd härrör ur fyra huvudkällor: hörsägen, erfarenhet, beräkning och medfödd kunskap.
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| 4. |
- Berndt, Jaqueline, Prof Dr, 1963-
(författare)
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Manga : Medium, Kunst und Material
- 2015
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Manga sind Vieles: Kulturindustrie und „Media-Mix“-Komponente, Instrument für „Cool-Japan“-Kampagnen seitens des japanischen Staates, Bildsprache einer globalen Fankultur und Quelle niedlicher Figuren. Aber sie sind auch Comics, serielle Bilderzählungen zumeist, deren Medienspezifik ebenjene Darstellungsleistungen beeinflusst, die aus geschichts- und geschlechtswissenschaftlicher Sicht vorrangig interessieren. Dieser Band versammelt deutsch- und englischsprachige Texte aus zehn Jahren Manga-Studien, die als Buch- oder Konferenzbeitrag für nicht comicspezifische Kontexte entstanden. Manga wird hier nicht einfach als kulturwissenschaftliches oder japanologisches Material benutzt, sondern vielmehr daraufhin befragt, welche ästhetisch-kulturellen Gegebenheiten und Diskurse für eine solche Indienststellung zu berücksichtigen sind. Hier steht der Manga selbst im Zentrum.
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| 5. |
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| 6. |
- Brinkman, Arie B., et al.
(författare)
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Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. However, the distribution of PMDs within and between tumor types, and their effects on key functional genomic elements including CGIs are poorly defined. We comprehensively show that loss of methylation in PMDs occurs in a large fraction of the genome and represents the prime source of DNA methylation variation. PMDs are hypervariable in methylation level, size and distribution, and display elevated mutation rates. They impose intermediate DNA methylation levels incognizant of functional genomic elements including CGIs, underpinning a CGI methylator phenotype (CIMP). Repression effects on tumor suppressor genes are negligible as they are generally excluded from PMDs. The genomic distribution of PMDs reports tissue-of-origin and may represent tissue-specific silent regions which tolerate instability at the epigenetic, transcriptomic and genetic level.
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| 7. |
- Brinkman, Herm Jan M., et al.
(författare)
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Pleiotropic anticoagulant functions of protein S, consequences for the clinical laboratory. Communication from the SSC of the ISTH
- 2021
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 19:1, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary deficiencies of protein S (PS) increase the risk of thrombosis. However, assessing the plasma levels of PS is complicated by its manifold physiological interactions, while the large inter-individual variability makes it problematic to establish reliable cut-off values. PS has multiple physiological functions, with only two appearing to have significant anticoagulant properties: the activated protein C (APC) and tissue factor pathway inhibitor alpha (TFPIα) cofactor activities. Current clinical laboratory investigations for deficiency in PS function rely only on the APC-dependent activity. This communication presents an argument for reclassifying the qualitative PS deficiencies to differentiate the two major anticoagulant functions of PS. Reliable assays are necessary for accurate evaluation of PS function when making a specific diagnosis of PS deficiency based on the anticoagulant phenotype alone. This report emphasizes the pleiotropic anticoagulant functions of PS and presents evidence-based recommendations for their implementation in the clinical laboratory.
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| 8. |
- Broecker, Verena, et al.
(författare)
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Uterus transplantation: Histological findings in explants at elective hysterectomy
- 2021
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 21:2, s. 798-808
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation has enabled women with absolute uterine factor infertility to carry a pregnancy. The first human uterus transplantation trial was initiated in 2013 in Gothenburg, Sweden. It was completed with 7 transplantations with long-term allograft survival and 9 children born from 6 women. In the present study we describe the histopathology of these 7 allografts, which were removed at 22-83 months after transplantation, and compare findings to control cases. Morphological findings in a subset of explants included linear subepithelial inflammation and perivascular stromal inflammation in the cervix, small inflammatory foci in the myometrium, and intimal inflammation in larger arteries. The average number of T cells, B cells, and macrophages was higher in transplants compared to normal controls, but variability was high among transplants. Chronic-active vascular rejection was seen in 2 of 7 transplants, both showed also inflammation in the cervix. Further, the inflammation seen in the cervix reflected the inflammation in the myometrium, suggesting that cervical biopsies are suitable to monitor rejection. However, the degree of inflammation and signs of rejection in explants did not reflect on the possibility to become pregnant in this limited series.
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| 9. |
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| 10. |
- Feiccabrino, James
(författare)
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Precipitation phase determination in cold region conceptual models - analysis and method development
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Precipitation phase uncertainty is a known source of error in conceptual models used for many hydrological, climatological, and environmental applications. These conceptual models often use the simple approach of calibrating an air temperature threshold (TRS) over a large area irrespective of physiographic characteristics such as distance to the ocean and topographic relief. Conceptual modeling requires empirical formulas to simplify physical processes. However, there is a plethora of literature against this TRS approach. The magnitude of uncertainty caused by the use of a set TRS is greatest in areas such as Scandinavia, where an average of 39% annual station precipitation occurs in the air temperature (TA) range of -3 to 5°C. One argument for the use of set threshold temperatures in conceptual models was the reduction of computational load, but this came at the cost of accuracy. To compound this error, surface conditions only have a minor contribution to the surface precipitation phase. Instead, microphysics (air-hydrometeor energy exchanges) and properties of the air in the lower atmosphere are the major influences on the observed precipitation phase. However, without adding atmospheric data, improvements to cold region conceptual model, precipitation phase can be achieved through the use of other reported surface data. Meteorological data from 169 observing stations were used to determine percent misclassified precipitation when air temperature (TA), Wet-bulb temperature 0.5°C (TW 0.5°C) thresholds, and an air temperature adjusted by relative humidity (TRH) = 0.75+0.085*(100-RH) formula were applied. The main dataset had roughly 400,000 precipitation events between TA -3 and 5°C. When analysed by country, Norwegian stations had average misclassified precipitation of 10.8% (1.2°C) for TA, 8.3% for TW 0.5°C, and 8.7% for TRH. In comparison, Swedish stations had misclassified precipitation totals of 9.3% (0.9°C) for TA, 8.2% for TW 0.5°C, and 8.7% for TRH. TW 0.5°C resulted in the least misclassified precipitation for both countries. However, saturation vapor pressure, relative humidity (RH), and other parameters required to calculate TW are often not reported by hydrological or meteorological stations. Therefore, improvement in TA methods is preferential over TW or RH methods. Cloud base height TA thresholds were found to increase with height and could be used as a proxy for RH. Cloud base height thresholds had 10.3%, and 9.1% misclassified precipitation in Norway and Sweden respectively. This method had greater error than RH, but performed better in low cloud conditions (100m in Norway and 300m in Sweden), so combining the methods is an option. However, cloud base height is not reported by all stations. If restricted to TA methods, sub-grouping stations by physiographic characteristics within a 15km radius decreased TA misclassified precipitation by 0.5% in Norway with little change in Sweden. This is a result of the Norwegian landscape varying to a greater extent than in Sweden. TA thresholds in Norway ranged from 2.4°C for ocean platforms to 0.9°C in the hills. Particularly high misclassified precipitation rates in mountains and hills can be reduced by nearly 10% when assigning TA for different station sub-groups using 1km maximum elevation or relief. For oceans/coast stations, TA assigned for water temperature sub-groups (reported by 16 stations) reduced misclassified precipitation by 17%. Models applying a daily TA threshold, had precipitation phase uncertainty reduced 10% with RH methods. Changing to an hourly timestep reduced error by more than 29%. Therefore, decreasing temporal resolution to 1-hour was more beneficial than adding parameters to the 24-hour model.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Nosko, A.L., et al.
(författare)
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Расчет нагрева тормозных устройств ПТМ
- 2007
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Ingår i: Construction and Road Building Machinery. - 0039-2391. ; :3, s. 38-43
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Schultzén, Joakim M.
(författare)
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On the Metrology of Birka and Early Sigtuna - Tools of Trade in the Viking Age Lake Mälaren Valley (Sweden)
- 2014
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Ingår i: Archäologisches Korrespondenzblatt. - 0342-734X. ; 44:1, s. 127-136
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Tidskriftsartikel (refereegranskat)abstract
- This paper analyses weights from the site of Birka, the main centre for trade in the Lake Malaren Valley during the Viking Age, as well as its successor, the medieval town of Sigtuna, with the purpose of identifying which weight system was employed for trade in the area and period. The results show that the system was a local variant (the Baltic Sea system) of the contemporary weight system of the Caliphate. Further, the paper deals with the reasons for implementing this system and why it remained in use in Sigtuna even after trade had shifted to areas where other weight systems were decreed. We propose that the increased trade with Western Europe in the late 10th century to a large extent was conducted via the Western Slavonic region, which would, at this time, still have employed the Baltic Sea system, and further that direct trade with monetary economies such as the Holy Roman Empire and England would have given little incentive for change.
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| 17. |
- Schultzén, Joakim, 1971-
(författare)
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Remodelling the past : Archaeometrological analysis applied on Birka weight material using a 3D scanner & Computer-Aided Design
- 2011
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 38:9, s. 2378-2386
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Tidskriftsartikel (refereegranskat)abstract
- Archaeometrological analysis has traditionally involved reconstructing the originally intended mass of a weight by hand; measuring with a calliper or a profile microscope, as well as using the artefact's displacement in water for factors such as volume and density. Ideally, corrosion was to be left intact, which is inconsistent with the goals of the conservationist. In all, the process was time consuming and may in some cases even have accelerated the deterioration of the artefacts. The CAD-method described in this article has been developed as a non-destructive alternative, employing a 3D scanner to create a virtual representation of the weight on which analysis can be performed. Density is calculated by dividing current mass with current volume, as supplied from the virtual model. Original volume is calculated by reconstructing the weight using basic geometrical shapes in a Computer-Aided Design program. Finally, to obtain the weight's original mass, the recreated original volume is multiplied by its current density. If the latter is found to have been altered through corrosion, a mean value of previously analysed weights in good condition (MNCA) may be applied instead. This new method for archaeometrological analysis is put to the test on a population of weights excavated at Birka. Four of these were previously analysed with the Traditional method, which makes it possible to compare results and draw conclusions on the accuracy of the CAD-method. An additional seven weights were analysed for further evaluation and also to investigate Sperber's theory of a 4.0 g standard unit in the metrology of Birka.
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| 18. |
- Schultzén, Joakim, 1971-
(författare)
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Report number 148 - Optical 3D-scanning of an Oil-painting
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This is the report from an optical 3D scanning of an oil-painting, attributed to the American artist James McNeill Whistler (1834-1903). The objective was to gather more information about the painting through the creation of 3D models of the surface structure, especially focusing on the signature area and the way in which the canvas was mounted onto the frame.
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| 19. |
- Servin, Martin, 1975-, et al.
(författare)
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Examining the smooth and nonsmooth discrete element approaches to granular matter
- 2014
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Ingår i: International Journal for Numerical Methods in Engineering. - : John Wiley & Sons. - 0029-5981 .- 1097-0207. ; 97:12, s. 878-902
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Tidskriftsartikel (refereegranskat)abstract
- The smooth and nonsmooth approaches to the discrete element method (DEM) are examined from a computational perspective. The main difference can be understood as using explicit versus implicit time integration. A formula is obtained for estimating the computational effort depending on error tolerance, system geometric shape and size, and on the dynamic state. For the nonsmooth DEM (NDEM), a regularized version mapping to the Hertz contact law is presented. This method has the conventional nonsmooth and smooth DEM as special cases depending on size of time step and value of regularization. The use of the projected Gauss-Seidel solver for NDEM simulation is studied on a range of test systems. The following characteristics are found. First, the smooth DEM is computationally more efficient for soft materials, wide and tall systems, and with increasing flow rate. Secondly, the NDEM is more beneficial for stiff materials, shallow systems, static or slow flow, and with increasing error tolerance. Furthermore, it is found that just as pressure saturates with depth in a granular column, due to force arching, also the required number of iterations saturates and become independent of system size. This effect make the projected Gauss-Seidel solver scale much better than previously thought.
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| 20. |
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| 21. |
- Sibiya, P., et al.
(författare)
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Hollow-Fibre Liquid-Phase Microextraction for the Determination of Polycyclic Aromatic Hydrocarbons in Johannesburg Jukskei River, South Africa
- 2013
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Ingår i: Chromatographia. - : Springer Science and Business Media LLC. - 0009-5893 .- 1612-1112. ; 76:7-8, s. 427-436
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Tidskriftsartikel (refereegranskat)abstract
- A simple, rapid and environmentally friendly hollow-fibre liquid-phase microextraction (HF-LPME) technique was developed for the quantitative determination of polycyclic aromatic hydrocarbons (PAHs) in aqueous samples. GC-MS was then used as the method of analysis. The HF-LPME technique involves extraction of PAHs from a 20-mL sample containing 20 % acetonitrile as a modifier. The PAHs were extracted into a 5-cm hollow fibre filled with heptane as organic solvent. At a stirring speed and extraction time of 600 rpm and 30 min, respectively, the acceptor solvent was then collected to be analysed. Parameters that affect the extraction efficiency were optimised in order to achieve high enrichment of the analytes. In order to evaluate the practical applicability of the HF-LPME technique, the performance of the method was compared to solid-phase extraction using spiked deionised water and real water samples. The obtained concentration enrichment factors ranged from 48 to 95 for HF-LPME and 81-135 for SPE, depending on the individual PAH. The detection limit ranged from 23 to 95 ng L-1 for HF-LPME and 20-52 ng L-1 for SPE. Water samples from the Johannesburg area, South Africa, were analysed using both extraction methods and the results were in good agreement. The relative standard deviations were less than 12 % for both methods. In this comparison, SPE was found to give high concentration enrichment factors and recovery, whereas faster and cheaper analyses were achieved with HF-LPME. The concentration of PAHs found could be arranged in the following order: phenanthrene > acenaphthene > fluoranthene > naphthalene > pyrene.
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| 22. |
- Staaf, Annika, et al.
(författare)
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Oförutsebar rättssäkerhet : En granskning av handläggning enligt LSS
- 2023
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Ingår i: Retfærd. - : Jurist- og Økonomforbundets Forlag. - 0105-1121. ; 46:4, s. 71-86
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Tidskriftsartikel (refereegranskat)abstract
- Artikelns resultat baserar sig på en enkätstudie till handläggare inom funktionshinderområdet i Sverige och redovisar deras arbetssituation, med fokus på konsekvenser for enskildas rättssäkerhet. Det övergripande syftet med artikeln ar att belysa aspekter av rättssäkerhet i ärenden enligt LSS. Rättssäkerhet är ett begrepp som givits flera betydelser, framfär allt en formell och en materiell definition (Peczenik, 1995). Vi argumenterar för att den materiella definitionen hör bättre samman med lagmotivens, liksom funktionsrättskonventionens (CRPD) fokus på mänsklig värdighet och likvärdigt bemötande vad avser LSS tillämpning. Resultaten visar att flera LSS-handläggare inte anser att deras hemkommuner fattar rättssäkra beslut och att utförda bedömningar är lite av gissningar eftersom tydliga riktlinjer saknas. Vidare anges att arbetsledare ger instruktioner om vilka insatser som får beviljas och vilka som ska avslås, utifrån budgethänsyn snarare än bedömningar av behov. Enkätsvaren redovisar också situationer där brukare blivit kränkande bemötta. Sammantaget leder detta till en oförutsebar rättssäkerhet for brukaren.
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| 23. |
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| 24. |
- Stolte, W. C., et al.
(författare)
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Inner-shell photoionization of atomic chlorine
- 2013
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Ingår i: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 88:5
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Tidskriftsartikel (refereegranskat)abstract
- Relative partial cross sections have been measured following photoexcitation of atomic chlorine near the Cl 2p and Cl 1s ionization thresholds. In addition, Breit-Pauli R-matrix calculations have been carried out in the region of the 2p thresholds, and the results are compared with experiment. Owing to angular-momentum considerations, it was found that the resonances associated with the higher 2p(-1) thresholds should be significantly wider than the lower ones, and this is borne out in both the experimental and the theoretical results. It is shown that a large number of resonance series contribute to the cross section, which make it difficult to untangle, and suggestions for further work to better understand the spectra are presented.
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| 25. |
- Uzelac, Ivana, et al.
(författare)
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A Structural Comparison Approach for Identifying Small Variations in Binding Sites of Homologous Proteins
- 2015
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Ingår i: Computational Molecular Bioscience. - : Scientific Research Publishing, Inc.. - 2165-3453 .- 2165-3445. ; 5:3, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- A method for analyzing the protein site similarity was devised aiming at understanding selectivity of homologous proteins and guiding the design of new drugs. The method is based on calculating Cα distances between selected pocket residues and subsequent analysis by multivariate methods. Five closely related serine proteases, the coagulation factors II, VII, IX, X, and XI, were studied and their pocket similarity was illustrated by PCA clustering. OPLS-DA was then applied to identify the residues responsible for the variation. By combining these two multivariate methods, we could successfully cluster the different proteases according to class and identify the important residues responsible for the observed variation.
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| 26. |
- Yang, Shanzheng
(författare)
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Mechanisms controlling midbrain dopaminergic neuron development
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The degeneration of midbrain dopaminergic (mDA) neurons accounts for some of the main motor symptoms of Parkinson’s disease (PD). Efforts during the last decades have focused on understanding how mDA neurons are generated and maintained with the hope of developing novel stem cell-based replacement therapies. In this thesis, I address some of these questions in four papers. Paper I: Wnt signaling controls multiple developmental processes in the embryo. Here we report that Wnt1 deletion causes the loss ofLmx1a and Ngn2 expression in the midbrain floorplate resulting in the loss of mDA progenitor specification and neurogenesis in this region. Only a few ectopic LMX1A+, NURR1 + and TH+ cells were transiently found in the basal plate. This phenotype and the morphogenesis defect found in Wnt5a−/− mice were worsened in Wnt1−/−;Wnt5a−/− mice, indicating the existence of a previously unsuspected cooperation between Wnt1 and Wnt5a in mDA neuron development in vivo. Based on these results, we developed a combined Wnt protocol to promote the generation of mDA neurons from neural and embryonic stem cells in vitro. We conclude that coordinated Wnt actions promote mDA neuron development in vivo and in stem cells. Paper II: In this study we report that the chemokine Cxcl12 is expressed in the meninges, surrounding the ventral midbrain (VM) and that its cognate receptor CXCR4, is present and activated in NURR1 + mDA precursors and neurons. We found that VM meninges or CXCL12 promoted migration and neuritogenesis of TH+ cells in a CXCR4-dependent manner in vitro. Consistently, pharmacological blockade of CXCR4 or genetic deletion of Cxcr4 resulted in an accumulation of TH+ cells in the lateral aspect of the intermediate zone in the VM. Moreover, the processes of TH+ cells in Cxcr4−/− mice were no longer radially distributed but disoriented. Thus our results indicate that CXCL12/CXCR4 regulate the radial migration of mDA neurons. Paper III: We report that the homeodomain transcription factor ZEB2, is present at a high level in progenitor cells of the ventricular zone in the midbrain floor plate and that its expression diminishes in NURR1 + post-mitotic precursors. We found that ZEB2 upregulated miR200c, which in turn repressed Zeb2, to form a negative feedback loop. Overexpression of Zeb2 reduced the levels of CXCR4 and NR4A2 in the developing VM in vivo, resulting in migration and mDA differentiation defects. This phenotype was phenocopied by mir200c knockdown, indicating that the Zeb2-miR200c loop prevents the premature differentiation of mDA progenitors into postmitotic cells and their migration. Paper IV: We demonstrate that the extracellular matrix protein, laminin 511 (LM511), promotes midbrain dopaminergic neuron survival and differentiation via binding to integrin α3β1 and activation of the Yes-Associated protein, YAP. We found that LM511-YAP enhances mDA neuron survival by inducing the expression of miR-130a, which reduces the levels of PTEN, a negative regulator of the Akt/PKB pro-survival pathway, both in vitro and in vivo. Additionally, YAP up-regulates the expression of mDA differentiation genes such as LMX1A, LMX1B and PITX3, and prevents the loss ofmDA neurons by oxidative stress. Thus our results suggest the LM511-YAP pathway as a possible target for the development of novel therapies for PD. In sum, the data presented in this thesis provide evidence that multiple factors control common aspects of mDA development such as neurogenesis, positively controlled by WNT1, WNT5A and miR200c and negatively by ZEB2. Similarly, the migration of mDA neurons is controlled by WNT5A, miR200c and CXCL12/CXCR4. Lastly, we found that the survival and differentiation of mDA neurons is not only controlled by neurotrophic factors, but also by the extracellular molecule, LM511, via YAP activation.
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