| 1. |
- Altai, Mohamed, et al.
(författare)
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188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
- 2014
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
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| 2. |
- Liu, Yu
(författare)
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Integrating life cycle assessment into simulation-based decision support
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Increasing marketing and legislative requirements put heavy demands on the environmental performance of future transportation solutions. The resulting need to reduce total environmental impacts presents both challenges and opportunities to the transport sector as a whole, including the automotive industry. Life cycle assessment (LCA) is commonly used to evaluate environmental performance in the automotive industry. However, the static nature of LCAlimits its usefulness for capturing dynamic environmental consequences in the manufacturing and operational phase. This thesis proposes a simulation-based approach to LCA that addresses this problem. Selected real-world case studies demonstrate the potential of the approach in both vehicle production processes and end-user applications. The work was preceded by a comprehensive review of the potential benefits and challenges of using simulation-based LCA in production processes. This review laid the foundation for the development and implementation of this method inthe automotive industry. Two real-world case studies demonstrate its value. The first was a waste collection case study in which LCA was integrated in an existing simulation-based decision support tool to optimize the company’s activities froma life cycle environmental impact perspective. A simultaneously developed simulation-based LCA model of an iron foundry production line extended the applicability of the method with a proposed decision support interpretation approach. The study shows that data and information from both simulation model and LCA databases can be integrated and utilized in the developed simulation-based LCA method. This allows different systems with different configurations to be combined to assess the relevant parameters, and eventually to provide information about overall environmental impacts to decision makers to improvethe environmental sustainability of the automotive industry.
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| 3. |
- Altai, Mohamed, et al.
(författare)
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Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
- 2014
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 87, s. 519-28
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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| 4. |
- Altai, Mohamed, et al.
(författare)
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Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with 188-Re
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:Suppl. 2, s. S219-S220
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1±0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172±32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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| 5. |
- Andersson, Jan, et al.
(författare)
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Traffic safety effects when overtaking 30 meter trucks
- 2012
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Ingår i: Advances in Human Factors and Ergonomics 2012- 14 Volume Set. - : Taylor & Francis. - 146655262X - 9781466552623
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Konferensbidrag (refereegranskat)abstract
- The purpose of this paper is to investigate if the introduction of extra-long and heavy trucks has an effect on traffic safety on Swedish roads, especially in relation to overtaking maneuvers. Traffic safety effects will be measured in terms of road user behavior concerning accelerations and time slots. First, focus group interviews with heavy truck drivers. Truck drivers that do not drive extra-long trucks believe that the introduction of extra-long trucks will create a number of traffic safety problems especially in terms of conflicts with ordinary road users. The drivers of extra-long trucks do not experience the problems that ordinary truck drivers predict. The problems they experience can be taken care of with more planning (thinking ahead). They also believe that the traffic sign on the back of the extra-long vehicle has a positive effect. The truck company, working environment and truck equipment are other important aspects mentioned by the drivers of the extra-long vehicles.The simulator study investigates overtaking situations on a 2+1-lane highway, with extra-long trucks (30.4 m) and ordinary trucks (18.75 m). The results reveal that the distance from the rear/front of the truck to the point where only one lane exists affects car drivers’ decision to overtake, independently of truck length. If the truck is in the relatively same position, the timeslot for a safe overtaking maneuver before next one-lane section was reduced significantly for extra-long trucks compared to ordinary trucks. The conclusion is that there exist small tendencies which point in the direction of enhanced traffic safety problems with the introduction of extra-long trucks. The results should, however, be interpreted with caution as the number of data points was few and collected in specific situations and in specific conditions. It was neither considered how the introduction of longer and heavier trucks, given a constant amount of goods, reduces the number of heavy trucks on the road network.
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| 6. |
- Andersson, Jan, et al.
(författare)
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Trafiksäkerhetspåverkan vid omkörning av 30-metersfordon
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trafikverket överväger att tillåta längre och tyngre fordon på vägarna förutsatt att de inte påverkar trafiksäkerheten negativt. Syftet med studien var att undersöka säkerhetseffekten av fordonslängd, speciellt med avseende på olycksrisken vid omkörningar. Intervjuade förare av en 30-meters timmerbil hade inte upplevt de farhågor som förare av normallånga lastbilar uttryckt i samband med trånga rondeller och korsningar, men de nämner betydelsen av stödjande åkeri, arbetsmiljö och fordonsutrustning. En simulatorstudie studerade bilförares omkörningar av ett 30- och ett 18,75-metersfordon på en 2+1-väg i situationen då två körfält går ihop till ett. Tidluckan till ett återstående körfält var i genomsnitt 0,2 s (sign.) kortare efter omkörningar av 30-metersfordonet i situationer då bakänden var i samma relativa position som för 18,75-metersfordonet vid början av omkörningen. En fältstudie analyserade videoinspelade omkörningar av en 30- och en 24-meters timmerbil på en 2+1-väg och en tvåfältig väg. Ingen signifikant skillnad i tidluckor kunde påvisas mellan omkörningar av de två fordonen för någon av vägtyperna. Det senare resultatet ska dock tolkas med försiktighet på grund av ojämnt distribuerad data som insamlats under specifika förhållanden. Slutsatserna är att det finns en liten tendens till negativ säkerhetseffekt vid omkörningar av längre fordon, och att fler fältstudier är nödvändiga.
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| 7. |
- Berndtsson, Mikael, et al.
(författare)
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A Fleet Management System Based on Complex Event Processing
- 2014
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Ingår i: DSS 2.0 – Supporting Decision Making with New Technologies. - : IOS Press. - 9781614993988 - 9781614993995 ; , s. 241-252
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Konferensbidrag (refereegranskat)abstract
- This paper describes our approach and experiences of applying techniques in complex event processing to fleet management systems. Current fleet management systems do not have support for complex event processing, hence they are limited to reacting to simple events such as door open, and vehicle reached waypoint. We argue that fleet management systems can benefit from having support for complex event processing. In this paper we present an implemented fleet management system that supports complex event processing.
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| 8. |
- Garkavij, Michael, et al.
(författare)
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Lu-177-[DOTA0,Tyr3] Octreotate Therapy in Patients With Disseminated Neuroendocrine Tumors: Analysis of Dosimetry With Impact on Future Therapeutic Strategy
- 2010
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1084-1092
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lu-177-(DOTAO,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan. METHODS: Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex. RESULTS: For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution. CONCLUSIONS: The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. Cancer 2010;116(4 suppl):1084-92. (C) 2010 American Cancer Society.
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| 9. |
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| 10. |
- Gudfinnsson, Kristens, et al.
(författare)
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Analyzing Business Intelligence Maturity
- 2015
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Ingår i: Journal of Decision Systems. - : Taylor & Francis Group. - 1246-0125 .- 2116-7052. ; 24:1, s. 37-54
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Tidskriftsartikel (refereegranskat)abstract
- Business intelligence has fundamentally changed how companiesconduct their business. In literature, the focus has been on volume-operationcompanies that provide services to millions of customers. In contrast, complexsystemscompanies have fewer customers and pursue customer needs byproviding more customized products and services. This paper presents the resultsof a case study conducted at a complex-systems company, with the overall aim toidentify how complex-systems companies may take advantage of businessintelligence. A framework was used to measure business intelligence maturity ofthe company. In addition, we also explain the current maturity level of the casecompany,based on critical factors for success adopted from the literature. Indoing so, we also contribute on important details regarding factors that must beconsidered by organizations, in order to leverage their analytical capability.Finally, we also propose topics that need to be further investigated, in order toincrease current knowledge regarding BI usage and maturity in complex-systemscompanies.
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