| 1. |
|
|
| 2. |
- Carlsson, Jörgen, et al.
(författare)
-
HER2 expression in breast cancer primary tumours and corresponding metastases : Original data and literature review
- 2004
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 90:12, s. 2344-2348
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.
|
|
| 3. |
- Djureinovic, Tatjana, et al.
(författare)
-
The CHEK2 1100delC variant in Swedish colorectal cancer
- 2006
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4885-4888
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.
|
|
| 4. |
- Elmlund, Hans, et al.
(författare)
-
A new cryo-EM single-particle Ab initio reconstruction method visualizes secondary structure elements in an ATP-Fueled AAA+ motor
- 2008
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 375:4, s. 934-947
-
Tidskriftsartikel (refereegranskat)abstract
- The generation of ab initio three-dimensional (3D) models is a bottleneck in the studies of large macromolecular assemblies by single-particle cryo-electron microscopy. We describe here a novel method, in which established methods for two-dimensional image processing are combined with newly developed programs for joint rotational 3D alignment of a large number of class averages (RAD) and calculation of 3D volumes from aligned projections (VolRec). We demonstrate the power of the method by reconstructing an 660-kDa ATP-fueled AAA+ motor to 7.5 Å resolution, with secondary structure elements identified throughout the structure. We propose the method as a generally applicable automated strategy to obtain 3D reconstructions from unstained single particles imaged in vitreous ice.
|
|
| 5. |
- Lundqvist, Joakim, et al.
(författare)
-
ATP-Induced Conformational Dynamics in the AAA plus Motor Unit of Magnesium Chelatase
- 2010
-
Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 18:3, s. 354-365
-
Tidskriftsartikel (refereegranskat)abstract
- Mg-chelatase catalyzes the first committed step of the chlorophyll biosynthetic pathway, the ATP-dependent insertion of Mg2+ into protoporphyrin IX (PPIX). Here we report the reconstruction using single-particle cryo-electron microscopy of the complex between subunits BchD and BchI of Rhodobacter capsulatus Mg-chelatase in the presence of ADP, the nonhydrolyzable ATP analog AMPPNP, and ATP at 7.5 angstrom, 14 angstrom, and 13 angstrom resolution, respectively. We show that the two AAA+ modules of the subunits form a unique complex of 3 dimers related by a three-fold axis. The reconstructions demonstrate substantial differences between the conformations of the complex in the presence of ATIP and ADP, and suggest that the C-terminal integrin-I domains of the BchD subunits play a central role in transmitting conformational changes of BchI to BchD. Based on these data a model for the function of magnesium chelatase is proposed.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Persson, Mikael, et al.
(författare)
-
[Lu-177]pertuzumab : Experimental therapy of HER-2-expressing xenografts
- 2007
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:1, s. 326-331
-
Tidskriftsartikel (refereegranskat)abstract
- Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy beta emitter Lu-177, might be a candidate for targeted radiotherapy of disseminated HER-2-positive micrometastases. The radiolabeled antibody [Lu-177]pertuzumab showed favorable targeting properties in BALB/c (nu/nu) mice with HER-2-overexpressing xenografts. The absorbed dose in tumors was more than five times higher than the absorbed dose in blood and more than seven times the absorbed dose in any other normal organ. Experimental therapy showed that [Lu-177]pertuzumab delayed tumor progression compared with controls (no treatment, P < 0.0001; nonlabeled pertuzumab antibody, P < 0.0001; and Lu-177-labeled irrelevant antibody, P < 0.01). No adverse side effects of the treatment could be detected. Thus, the experimental results support the planning of clinical studies applying [Lu-177]pertuzumab for therapy.
|
|
| 9. |
|
|
| 10. |
- Abbasinejad Enger, Shirin, 1975-
(författare)
-
Dosimetry Studies of Different Radiotherapy Applications using Monte Carlo Radiation Transport Calculations
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Developing radiation delivery systems for optimisation of absorbed dose to the target without normal tissue toxicity requires advanced calculations for transport of radiation. In this thesis absorbed dose and fluence in different radiotherapy applications were calculated by using Monte Carlo (MC) simulations.In paper I-III external neutron activation of gadolinium (Gd) for intravascular brachytherapy (GdNCB) and tumour therapy (GdNCT) was investigated. MC codes MCNP and GEANT4 were compared. MCNP was chosen for neutron capture reaction calculations. Gd neutron capture reaction includes both very short range (Auger electrons) and long range (IC electrons and gamma) products. In GdNCB the high-energetic gamma gives an almost flat absorbed dose delivery pattern, up to 4 mm around the stent. Dose distribution at the edges and inside the stent may prevent stent edge and in-stent restenosis. For GdNCT the absorbed dose from prompt gamma will dominate over the dose from IC and Auger electrons in an in vivo situation. The absorbed dose from IC electrons will enhance the total absorbed dose in the tumours and contribute to the cell killing.In paper IV a model for calculation of inter-cluster cross-fire radiation dose from β-emitting radionuclides in a breast cancer model was developed. GEANT4 was used for obtaining absorbed dose. The dose internally in cells binding the isotope (self-dose) increased with decreasing β-energy except for the radionuclides with substantial amounts of conversion electrons and Auger electrons. An effective therapy approach may be a combination of radionuclides where the high self-dose from nuclides with low β-energy should be combined with the inter-cell cluster cross-fire dose from high energy β-particles.In paper V MC simulations using correlated sampling together with importance sampling were used to calculate spectra perturbations in detector volumes caused by the detector silicon chip and its encapsulation. Penelope and EGSnrc were used and yielded similar results. The low energy part of the electron spectrum increased but to a less extent if the silicon detector was encapsulated in low z-materials.
|
|
| 11. |
|
|
| 12. |
- Abrahamsson, Maria, et al.
(författare)
-
Steric influence on the excited-state lifetimes of ruthenium complexes with bipyridyl-alkanylene-pyridyl ligands.
- 2008
-
Ingår i: Inorganic Chemistry. - : ACS. - 0020-1669 .- 1520-510X. ; 47:9, s. 3540-3548
-
Tidskriftsartikel (refereegranskat)abstract
- The structural effect on the metal-to-ligand charge transfer (MLCT) excited-state lifetime has been investigated in bis-tridentate Ru(II)-polypyridyl complexes based on the terpyridine-like ligands [6-(2,2'-bipyridyl)](2-pyridyl)methane (1) and 2-[6-(2,2'-bipyridyl)]-2-(2-pyridyl)propane (2). A homoleptic ([Ru(2)(2)](2+)) and a heteroleptic complex ([Ru(ttpy)(2)](2+)) based on the new ligand 2 have been prepared and their photophysical and structural properties studied experimentally and theoretically and compared to the results for the previously reported [Ru(1)(2)](2+). The excited-state lifetime of the homoleptic Ru-II complex with the isopropylene-bridged ligand 2 was found to be 50 times shorter than that of the corresponding homoleptic Ru-II complex of ligand 1, containing a methylene bridge. A comparison of the ground-state geometries of the two homoleptic complexes shows that steric interactions involving the isopropylene bridges make the coordination to the central Ru-II ion less octahedral in [Ru(2)(2)](2+) than in [Ru(1)(2))(2+). Calculations indicate that the structural differences in these complexes influence their ligand field splittings as well as the relative stabilities of the triplet metal-to-ligand charge transfer ((MLCT)-M-3) and metal-centered ((MC)-M-3) excited states. The large difference in measured excited-state lifetimes for the two homoleptic Ru-II complexes is attributed to a strong influence of steric interactions on the ligand field strength, which in turn affects the activation barriers for thermal conversion from (MLCT)-M-3 states to short-lived (MC)-M-3 states.
|
|
| 13. |
- Ahlgren, Ewa, et al.
(författare)
-
Driving performance of patients with coronary artery disease
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objectives To compare patients with coronary artery disease and healthy controls with respect to cognitive function and driving performance.Design and setting A controlled study conducted between April 1999 and January 2001.Subjects Forty-four patients with stable coronary artery disease scheduled for cardiac intervention with coronary artery bypass surgery or percutaneous coronary intervention. Forty volunteers of similar age without symptoms of coronary artery disease served as controls.Main outcome measures On-road driving scores in five specific test areas with a rating scale from 1 to 5. Neuropsychological test scores, including 12 tests.Results Compared with controls, patients with coronary artery disease had lower scores in all areas of the on-road driving test (p<0.05) and in the neuropsychological tests assessing psychomotor speed, visual and verbal memory, focused attention and simultaneous capacity (p<0.05). The difference between the groups in the on-road driving test appeared to be more pronounced among those above 65 years-of-age. Both patients and controls rated their performance significantly higher than the traffic inspector (p<0.05).Conclusions Cognitive function and driving performance may be impaired in patients with coronary artery disease.
|
|
| 14. |
- Ahlgren, Ewa, 1959-, et al.
(författare)
-
Neurocognitive impairment and driving performance after coronary artery bypass surgery
- 2003
-
Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 23:3, s. 334-340
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Neurocognitive impairment is common after cardiac surgery but few studies have examined the relationship between postoperative neuropsychological test performance and everyday behavior. The influence of postoperative cognitive impairment on car driving has previously not been investigated. The purpose of this study was to evaluate neurocognitive function and driving performance after coronary artery bypass grafting (CABG).Methods: Twenty-seven patients who underwent coronary artery bypass grafting with standard cardiopulmonary bypass technique and 20 patients scheduled for percutaneous coronary intervention (PCI) under local anesthesia (control group) were enrolled in this prospective study conducted from April 1999 to September 2000. Complete data were obtained in 23 and 19 patients, respectively. The patients underwent neuropsychological examination with a test battery including 12 tests, a standardized on-road driving test and a test in an advanced driving simulator before and 4–6 weeks after intervention.Results: More patients in the coronary artery bypass grafting group (n=11, 48%) than in the percutaneous coronary intervention group (n=2, 10%) showed a cognitive decline after intervention (P=0.01). In the on-road driving test, patients who underwent coronary artery bypass grafting deteriorated after surgery in the cognitive demanding parts like traffic behavior (P=0.01) and attention (P=0.04). Patients who underwent percutaneous intervention deteriorated in maneuvering of the vehicle (P=0.04). No deterioration was detected in the simulator in any of the groups after intervention. Patients with a cognitive decline after intervention also tended to drop in the on-road driving scores to a larger extent than did patients without a cognitive decline.Conclusion: This study indicates that cognitive functions important for safe driving may be influenced after cardiac surgery.
|
|
| 15. |
- Allmér, Hans, Lecturer, 1958-
(författare)
-
Servicescape for Digital Wellness Services for Young Elderly
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis digital wellness services (DWSs) are in focus. The DWSs are services provided through digital devices, such as smartphones, bracelets, and tablets, by using digital environments such as Internet, cloud services, and websites. They can provide users with information that has an impact on their wellness, such as pulse, nutrition, and training guidance. The focus for this work on DWSs is on the age group of young elderly (60 – 75 years old). They belong to a group who were born long before digital devices and environments emerged and this factor may affect their motivation and willingness to use and benefit from DWSs.This thesis offers a framework for a digital servicescape that enables young elderly to benefit from DWSs. DWSs are produced and offered in digital servicescapes, where the interaction between the service providers and the service users occurs. The interaction can take place in different spaces like fitness studios, shopping malls or banks. DWSs for large groups of young elderly will require an ecosystem of stakeholders to develop, distribute, maintain, support, and further develop these services. An ecosystem builds on policies, strategies, processes, information, technologies, applications and stakeholders, and includes people who build, sell, manage and use the system. In order to understand the ecosystem, it is necessary to have a holistic approach to work out how its context, technology, stakeholders, and use interact with each other. A digital servicescape offers the conceptual basis for the ecosystem to form, evolve, and survive and produces platforms on which it is easy, effective, and productive to access and use DWSs.The described interaction between digital servicescape and DWSs for improved health leads to the research question: How can a digital servicescape enhance young elderly’s use of Digital Wellness Services (DWSs)?In order to answer the research question, the thesis presents different approaches that influence the young elderly’s capabilities and willingness to use and benefit from DWSs. If the young elderly follow recommendations to apply DWSs they will benefit in terms of healthier aging, reduced ill health, and a better quality of life. For developers and providers of DWSs development work will open up business opportunities if they understand the needs and demands of the young elderly. In addition, DWSs can contribute to significant health, social, and economic benefits for society in general. Proactive wellness programs for young elderly will have cumulative effects on the conditions for good health. The digital servicescape is a conceptual framework for future work on actually building the necessary platforms for DWSs.The work on this thesis follows an explorative approach. The data collection was carried out through surveys, literature review, and focus groups after which the data was sorted, analysed and interpreted. As the work progressed, a need arose to obtain insights from additional perspectives with the consequence that the additional data contributed to a deeper knowledge of the young elderly, DWSs and digital servicescape.The young elderly are, as a group, a very large market consisting of almost 100 million people in Europe alone. For the young elderly, digitalisation has been a part of their lives and its development has provided them with new opportunities to communicate. To them the interface on their digital device is where the interaction with a service provider occurs. Behind the interface, a digital servicescape and an ecosystem provide the necessary tools for the young elderly to achieve the wellness they seek. Nevertheless, to understand the target group it is important to consider four wellness dimensions: i) physical wellness, ii) social wellness, iii) emotional wellness, and iv) intellectual wellness. Together, the four dimensions form a holistic wellness approach to motivate young elderly to use DWSs. The research results show that the young elderly need to be motivated to adopt the services offered. Motivation that affects the young elderly is both intrinsic and extrinsic and this should be considered when developing and providing DWSs and digital servicescapes. Therefore, the service providers have to meet the expectations, needs, and demands of the young elderly and develop services that are suited for the target group. However, this is not enough, as this research shows that the young elderly want to be in a context where they feel safe.Information systems offer a basis for communication and interaction with and through digital devices such as smartphones, tablets, and bracelets. The Internet constitutes a platform for service and social interaction. Services offered on the Web, make it possible to do shopping, be entertained, entertain, and be involved in education, research, business and much more. The internet forms an important part of the infrastructure for DWSs and digital servicescapes.An efficient and well-designed DWS and its servicescape can create a win-win-win situation. The first part is the young elderly who can benefit from DWSs by increasing their chances of a longer, healthier, and happier life and thereby achieve wellness. The second win situation concerns the service developers and providers who can build a business by designing well-working DWSs aimed at the young elderly. Finally, the third win situation is about family, friends, and society. Well-designed DWSs can be beneficial for family and friends to help the young elderly to achieve wellness and require less support from family and friends. For society in general, there are financial benefits, as healthier and happier young elderly will reduce the demand for health care and support. Together the three win-win-win scenarios build an opportunity for a better tomorrow for all concerned. This thesis has created a foundation for continued research, testing, and development of DWSs and digital servicescapes. It has shown that there is a need for deeper understanding of the benefits a well-designed servicescape for DWSs can bring to people in general and to the group of young elderly in particular. Furthermore, there is a need for further research in the win-win-win situations when young elderly get access to digital wellness devices. A particularly interesting avenue of research would be to investigate how that digital servicescape could be designed and whether society should provide devices free of charge, at discount or with some other business model.
|
|
| 16. |
- Almqvist, Ylva, et al.
(författare)
-
Biodistribution of At-211-Labeled humanized monoclonal antibody A33
- 2007
-
Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:4, s. 480-487
-
Tidskriftsartikel (refereegranskat)abstract
- Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.
|
|
| 17. |
- Almqvist, Ylva, et al.
(författare)
-
In vitro characterization of 211 At-labeled antibody A33 : a potential therapeutic agent against metastatic colorectal carcinoma
- 2005
-
Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 20:5, s. 514-523
-
Tidskriftsartikel (refereegranskat)abstract
- The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.
|
|
| 18. |
- Almqvist, Ylva, 1974-
(författare)
-
Targeted Therapy of Colorectal Cancer : Preclinical Evaluation of a Radiolabelled Antibody
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Targeted radiotherapy (TRT) of cancer is a promising approach that enables selective treatment of tumour cells, while sparing normal tissue. The humanized monoclonal antibody A33 (huA33) is a potential targeting agent for TRT of colorectal cancer, since its antigen is expressed in more than 95 % of all colorectal carcinomas. The aim of this thesis was to evaluate the therapeutic potential of the two huA33-based TRT-conjugates, 177Lu-huA33, and 211At-huA33. The conjugates 177Lu-huA33, and 211At-huA33, bound specifically to colorectal cancer cells, both in vitro and in vivo. A dose dependent cytotoxic effect of 211At-huA33 was also demonstrated in vitro. From a therapeutic perspective, both conjugates had a favourable biodistribution in tumour-bearing nude mice, with high tumour uptake and a low uptake in normal organs (with the exception of an expected thyroid uptake of 211At). After injection of 211At-huA33, the blood absorbed a slightly higher dose than the tumour, but for 177Lu-huA33, the tumour received a 12 times higher dose than blood. Two days after intravenous injection of 177Lu-huA33 in tumour-bearing mice, the tumours could be clearly visualised by gamma camera imaging, with very low interference from normal tissue radioactivity. In an experimental therapy study, also performed in tumour-bearing mice, there was an excellent therapeutic effect of 177Lu-huA33. About 50 % of the treated animals were tumour free 140 days after injection of 177Lu-huA33, while none of the non-radioactive controls survived beyond 20 days after injection of treatment substances. In conclusion, this thesis demonstrates that the therapeutic conjugates 177Lu-huA33, and 211At-huA33, are promising targeting agents that might help improve therapy of colorectal cancer.
|
|
| 19. |
|
|
| 20. |
- Alp, Dennis, et al.
(författare)
-
The 30 Year Search for the Compact Object in SN 1987A
- 2018
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 864:2
-
Tidskriftsartikel (refereegranskat)abstract
- Despite more than 30 years of searching, the compact object in Supernova (SN) 1987A has not yet been detected. We present new limits on the compact object in SN 1987A using millimeter, near-infrared, optical, ultraviolet, and X-ray observations from ALMA, VLT, HST, and Chandra. The limits are approximately 0.1 mJy (0.1 x 10(-26) erg s(-1) cm(-2) Hz(-1)) at 213 GHz, 1 L-circle dot (6 x 10(-29) erg s(-1) cm(-2) Hz(-1)) in the optical if our line of sight is free of ejecta dust, and 10(36) erg s(-1) (2 x 10(-30) erg s(-1) cm(-2) Hz(-1) ) in 2-10 keV X-rays. Our X-ray limits are an order of magnitude less constraining than previous limits because we use a more realistic ejecta absorption model based on three-dimensional neutrino-driven SN explosion models. The allowed bolometric luminosity of the compact object is 22 L-circle dot if our line of sight is free of ejecta dust, or 138L(circle dot) if dust-obscured. Depending on assumptions, these values limit the effective temperature of a neutron star (NS) to <4-8 MK and do not exclude models, which typically are in the range 3-4 MK. For the simplest accretion model, the accretion rate for an efficiency 77 is limited to <10(-11) eta(-1) M-circle dot yr(-1), which excludes most predictions. For pulsar activity modeled by a rotating magnetic dipole in vacuum, the limit on the magnetic field strength (B) for a given spin period (P) is B less than or similar to 10(14) P-2 G s(-2), which firmly excludes pulsars comparable to the Crab. By combining information about radiation reprocessing and geometry, we infer that the compact object is a dust-obscured thermally emitting NS, which may appear as a region of higher-temperature ejecta dust emission.
|
|
| 21. |
- Alänge, Sverker, 1951, et al.
(författare)
-
PROJECT OPEN ARENAS - The evolution of the Lindholmen and Innovatum ‘"arenas’" and their role for innovation in vehicle technology
- 2005
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The the Lindholmen and Innovatum "arenas" in Göteborg and Trollhättan were planted on the soil of former industrial giants as shipbuilding industry in Göteborg and heavy manufacturing industries in Trollhättan in Region Västra Götaland. This study describes the evolution these "arenas" and their role and function for innovation and economic renewal in Swedish automotive industry. The case study has two purposes: First, to tell the story of two such public-private mobilisations in a regional Swedish and global context, and second, to discuss the broader policy implications of this on-going restructuring towards "glocal innovation". The case takes its starting point from a historical perspective following the development of arenas and local mobilization over a period of time including the recent intermezzo in 2004 of the multinational car manufacturer "General Motors" causing one of the larger Swedish innovation policy interventions in decades. The case is analysed with respect to seven issues: The question of how historical processes intervene in current initiatives; The role of systemic features of technology and how this in turn create a need for system innovation; The increasing role of the local-global("glocal") dimension in innovation processes and what this may mean for actors at a national level; The role of Arenas(and "arenas", which was our more encompassing term) as a new and emerging nexus for public-private partnership; The function of arenas in this respect to provide a structure for innovation processes; The role of these emerging structures, in the form of two Arenas, to develop different characteristics due to adaptation to local circumstances; And finally, we note that the work to establish arenas have created a local/regional preparedness to influence and to take a proactive role for innovation.
|
|
| 22. |
- Andersson, Anders, et al.
(författare)
-
Describing fish passage in a river confluence with telemetry and CFD
- 2016
-
Konferensbidrag (refereegranskat)abstract
- The confluence between hydropower tailrace and the old river bed in Stornorrfors in the river Umeälven in the northern part of Sweden has shown to be the largest obstacle for upstream migrating salmon and sea trout during the migrating season. Fish are attracted to the high flow rate from the tailrace and will not migrate upstream in the old river bed being the passage to the fishway leading past the hydropower dam. By triangulating the movements of radio tagged fish using eight antennas in the confluence, it is here possible to describe the individual fish tracks left by radio tagged fish during the migrating season. These tracks are then compared with three-dimensional Computational Fluid Dynamics (CFD) simulations of the confluence. By simulating the most common combinations of turbine flow and spill flow in the old river bed it is then possible to find correlations between individual fish movements and flow parameters such as velocity, turbulence intensity or vorticity for different flow combinations. It was previously assumed that fish had trouble locating the old river bed, the results of the triangulation however shows that most fish finds the old river bed within a few days but does not chose to migrate until several days (or weeks) later. The main issue to be solved is therefore not how to attract the fish to the old river bed but rather how to create favorable conditions in the old river bed so that migrating fish are more inclined to take that path upstream.
|
|
| 23. |
- Andersson, Anders G., et al.
(författare)
-
A numerical study of the location and function of the entrance of a fishway in a regulated river
- 2010
-
Ingår i: 8th International Symposium on ECOHYDRAULICS. ; , s. 277-284
-
Konferensbidrag (refereegranskat)abstract
- Simulation driven design with Computational Fluid Dynamics has been used to evaluate the flow downstream a hydropower plant with regards to upstream migrating fish. Field measurements with an Acoustic Doppler Current Profiler were performed and the measurements were used to validate the simulations. The measurements indicate a more unstable flow than the simulations and the tailrace jet from the turbines is stronger in the simulations. The simulations are however considered to capture the important features of the flow in a way that makes them viable for attraction water simulations. A fishway entrance was included in the simulations and the subsequent attraction water was evaluated for two positions and two angles of the entrance at different turbine discharges. Results show that both positions are viable and that a position where the flow from the fishway does not have to compete with the flow from the power plant will generate superior attraction water. Simulations were also performed further downstream where the flow from the turbines meets the old river bed which is the current fish passage for upstream migrating fish. A modification of the old river bed was made in the model as one scenario to generate better attraction water. This considerably increases the attraction water although it cannot compete with the flow from the tailrace tunnel.
|
|
| 24. |
- Andersson, Anders G., et al.
(författare)
-
A study of the location of the entrance of a fishway in a regulated river with CFD and ADCP
- 2012
-
Ingår i: Modelling and Simulation in Engineering. - : Hindawi Limited. - 1687-5591 .- 1687-5605. ; 2012
-
Tidskriftsartikel (refereegranskat)abstract
- Simulation-driven design with computational fluid dynamics has been used to evaluate the flow downstream of a hydropower plant with regards to upstream migrating fish. Field measurements with an Acoustic Doppler Current Profiler were performed, and the measurements were used to validate the simulations. The measurements indicate a more unstable flow than the simulations, and the tailrace jet from the turbines is stronger in the simulations. A fishway entrance was included in the simulations, and the subsequent attraction water was evaluated for two positions and two angles of the entrance at different turbine discharges. Results show that both positions are viable and that a position where the flow from the fishway does not have to compete with the flow from the power plant will generate superior attraction water. Simulations were also performed for further downstream where the flow from the turbines meets the old river bed which is the current fish passage for upstream migrating fish. A modification of the old river bed was made in the model as one scenario to generate better attraction water. This considerably increases the attraction water although it cannot compete with the flow from the tailrace tunnel.
|
|
| 25. |
- Anund Vogel, Jonas, 1981-
(författare)
-
Incentivising Innovation in the Swedish Construction Industry
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Almost 40 percent of global final energy use and CO2 emissions are connected to buildings and building-related activities; it is therefore important to incentivise the design and construction of resource-efficient buildings. Unfortunately, energy demand and associated emissions in the sector continue to grow. Such incentives will help achieve energy and environmental targets, reduce costs, and make smart and sustainable buildings and cities possible at a larger scale. Because novel technologies carry risks alongside their advantages, developers, contractors and consultants must have incentives to reduce and share those risks in a rational way if we are to meet the crucial long-term societal goals of reduced use of resources and emissions. I hypothesise that there are legal and institutional frameworks (rules, building codes, regulations, standard contracts, etc.) that result in weak or negative incentives for construction industry actors to invest in, propose, and install resource-efficient technologies. If the hypothesis holds true, then the goal is to identify ways to better incentivise construction industry actors to fully engage in the design and construction of smart and sustainable buildings. To tackle this, four studies were carried out using a mixed-method approach. Paper 1 identifies 38 barriers to energy efficiency in Swedish multifamily buildings. The next study (Paper 2) develops a categorisation framework in order to understand where to engage to overcome or bypass barriers to energy efficiency. Paper 3 and 4 are devoted to analysing two sets of barriers and propose possible solutions to overcome or avoid them: (1) how the current legal framework guiding start and operation of housing co-operatives (mainly the Co-operative Act) influences incentives for engaging in resource-efficient construction, and (2) how the legal instrument for collaboration between developers and consultants incentivises resource-efficient construction. In this case, the contract under investigation is the General Conditions of Contract for Consulting Agreements for Architectural and Engineering Assignments (ABK 09)”. Changes to these two sets of legal and institutional frameworks could have a significant impact on how buildings are designed, produced and used. The changes proposed could incentivise construction industry actors to fully pursue the creation of smart, sustainable buildings that deliver services to users and reduce negative environmental impacts stemming from both the building construction and operation phases.
|
|
| 26. |
- Anund Vogel, Jonas, 1981-, et al.
(författare)
-
Who is Governing the Commons : Studying Swedish Housing Cooperatives
- 2016
-
Ingår i: Housing, Theory and Society. - : Taylor & Francis. - 1403-6096 .- 1651-2278. ; 33:4, s. 424-444
-
Tidskriftsartikel (refereegranskat)abstract
- This study examines current governance structures related to multifamily buildings designed by single actors (developers) and operated in cooperative forms. The study analyses the long-term sustainability of the resource regime of study (multifamily buildings) and inked governance structures by applying Ostrom’s eight design principles for long-term survival of self-organized resource regimes (Common-pool resources or CPR’s). The study also searches for signs of movement towards social innovation and collective action in current governance structures. We argue that the structures governing planning, production and operation of housing cooperatives in Sweden do not fulfil the eight design principles for the long-term survival of the resource regime of study, nor do they encourage movement towards social innovation or collective action. In order to ensure the long-term survival of the resource regime of study and to increase innovation in governance structures, five adjustments are proposed; changes in the structures governing risk/profit distribution, communication, collaboration and information between actors in the Swedish cooperative housing sector.
|
|
| 27. |
|
|
| 28. |
- Becher, Nina, et al.
(författare)
-
Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24 h
- 2024
-
Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 45:10, s. 837-849
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHRE) ≥ 24 hours and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared to no anticoagulation in these patients.METHODS: This secondary prespecified analysis of NOAH-AFNET 6 examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared to placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and ECG-diagnosed atrial fibrillation.RESULTS: AHRE ≥24 hours were present at baseline in 259/2389 patients enrolled in NOAH-AFNET 6 (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc score 4). Clinical characteristics were not different from patients with shorter AHRE. During a median follow-up of 1.8 years, the primary outcome occurred in 9/132 patients with AHRE ≥24 hours (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). AHRE duration did not interact with the efficacy (p-interaction = 0.65) or safety (p-interaction = 0.98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 hours developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; p < 0.001).CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.
|
|
| 29. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 30. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 31. |
- Bergström, Beatrice, et al.
(författare)
-
The Rheumatoid Arthritis Risk Gene AIRE Is Induced by Cytokines in Fibroblast-Like Synoviocytes and Augments the Pro-inflammatory Response
- 2019
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The autoimmune regulator AIRE controls the negative selection of self-reactive T-cells as well as the induction of regulatory T-cells in the thymus by mastering the transcription and presentation of tissue restricted antigens (TRAs) in thymic cells. However, extrathymic AIRE expression of hitherto unknown clinical significance has also been reported. Genetic polymorphisms of AIRE have been associated with rheumatoid arthritis (RA), but no specific disease-mediating mechanism has been identified. Rheumatoid arthritis is characterized by a systemic immune activation and arthritis. Activated fibroblast-like synoviocytes (FLS) are key effector cells, mediating persistent inflammation, and destruction of joints. In this study, we identified AIRE as a cytokine-induced RA risk gene in RA FLS and explored its role in these pathogenic stroma cells. Using RNA interference and RNA sequencing we show that AIRE does not induce TRAs in FLS, but augments the pro-inflammatory response induced by tumor necrosis factor and interleukin-1 beta by promoting the transcription of a set of genes associated with systemic autoimmune disease and annotated as interferon-gamma regulated genes. In particular, AIRE promoted the production and secretion of a set of chemokines, amongst them CXCL10, which have been associated with disease activity in RA. Finally, we demonstrate that AIRE is expressed in podoplanin positive FLS in the lining layer of synovial tissue from RA patients. These findings support a novel pro-inflammatory role of AIRE at peripheral inflammatory sites and provide a potential pathological mechanism for its association with RA.
|
|
| 32. |
- Beshara, Soheir, et al.
(författare)
-
Kinetic analysis of 52Fe-labelled iron(III) hydroxide-sucrose complex following bolus administration using positron emission tomography
- 1999
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 104:2, s. 288-295
-
Tidskriftsartikel (refereegranskat)abstract
- Kinetic analysis of a single intravenous injection of 100 mg iron(III) hydroxide-sucrose complex (Venofer) mixed with 52Fe(III) hydroxide-sucrose as a tracer was followed for 3-6 h in four generally anaesthetized, artificially ventilated minipigs using positron emission tomography (PET). The amount of injected radioactivity ranged from 30 to 200 MBq. Blood radioactivity, measured by PET in the left ventricle of the heart, displayed a fast clearance phase followed by a slow one. In the liver and bone marrow a fast radioactivity uptake occurred during the first 30 min, followed by a slower steady increase. In the liver a slight decrease in radioactivity uptake was noted by the end of the study. A kinetic analysis using a three-compartment (namely blood pool, reversible and irreversible tissue pools) model showed a fairly high distribution volume in the liver as compared with the bone marrow. In conclusion, the pharmacokinetics of the injected complex was clearly visualized with the PET technique. The organs of particular interest, namely the heart (for blood kinetics), liver and bone marrow could all be viewed by a single setting of a PET tomograph with an axial field of view of 10 cm. The half-life (T1/2) of 52Fe (8.3 h) enables a detailed kinetic study up to 24 h. A novel method was introduced to verify the actual 52Fe contribution to the PET images by removing the interfering radioactive daughter 52mMn positron emissions. The kinetic data fitted the three-compartment model, from which rate constants could be obtained for iron transfer from the blood to a pool of iron in bone marrow or liver to which it was bound during the study period. In addition, there was a reversible tissue pool of iron, which in the liver slowly equilibrated with the blood, to give a net efflux from the liver some hours after i.v. administration. The liver uptake showed a relatively long distribution phase, whereas the injected iron was immediately incorporated into the bone marrow. Various transport mechanisms seem to be involved in the handling of the injected iron complex.
|
|
| 33. |
- Beshara, Soheir, et al.
(författare)
-
Pharmacokinetics and red cell utilization of 52Fe/59Fe-labelled iron polymaltose in anaemic patients using positron emission tomography
- 2003
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 120:5, s. 853-859
-
Tidskriftsartikel (refereegranskat)abstract
- Parenteral iron-polysaccharide complexes are increasingly applied. The pharmacokinetics of iron sucrose have been assessed by our group using positron emission tomography (PET). A single intravenous injection of 100 mg iron as iron (III) hydroxide-polymaltose complex, labelled with a tracer in the form of 52Fe/59Fe, was similarly assessed in six patients using PET for about 8 h. Red cell utilization was followed for 4 weeks. Iron polymaltose was similarly distributed to the liver, spleen and bone marrow. However, a larger proportion of this complex was rapidly distributed to the bone marrow. The shorter equilibration phase for the liver, about 25 min, indicates the minimal role of the liver for direct distribution. Splenic uptake also reflected the reticuloendothelial handling of this complex. Red cell utilization ranged from 61% to 99%. Despite the relatively higher uptake by the bone marrow, there was no saturation of marrow transport systems at this dose level. In conclusion, high red cell utilization of iron polymaltose occurred in anaemic patients. The major portion of the injected dose was rapidly distributed to the bone marrow. In addition, the reticuloendothelial uptake of this complex may reflect the safety of polysaccharide complexes. Non-saturation of transport systems to the bone marrow indicated the presence of a large interstitial transport pool, which might possibly be transferrin.
|
|
| 34. |
- Beshara, Soheir, et al.
(författare)
-
Pharmacokinetics and red cell utilization of iron(III) hydroxide- sucrose complex in anaemic patients: a study using positron emission tomography
- 1999
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 104:2, s. 296-302
-
Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetics of a single intravenous injection of 100 mg iron hydroxide-sucrose complex labelled with a tracer in the form of 52Fe/59Fe was followed in six anaemic patients for a period ranging from 6 to 8 3 h using positron emission tomography (PET). Red cell utilization of the labelled iron was followed for 4 weeks. PET data showed radioactive uptake by the liver, spleen and bone marrow. The uptake by the macrophage-rich spleen demonstrated the reticuloendothelial uptake of this iron preparation, with subsequent effective release of that iron for marrow utilization. Red cell utilization, followed for 4 weeks, ranged from 59% to 97%. The bone marrow influx rate constant was independent of blood iron concentration, indicating non-saturation of the transport system in bone marrow. This implied that higher doses of the iron complex can probably be used in the same setting. A higher influx rate into the marrow compared with the liver seemed to be consistent with higher red cell utilization. This would indicate that early distribution of the injected iron complex may predict the long-term utilization.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Bornefalk, Hans, et al.
(författare)
-
Dual-energy imaging using a photon counting detector with electronic spectrum-splitting - art. no. 61421H
- 2006
-
Ingår i: Medical Imaging 2006: Physics of Medical Imaging, Pts 1-3. - : SPIE. - 9780819461858 ; , s. H1421-H1421
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a dual-energy imaging technique optimized for contrast-enhanced mammography using a photon counting detector. Each photon pulse is processed separately in the detector and the addition of an electronic threshold near the middle of the energy range of the x-ray spectrum allows discrimination of high and low energy photons. This effectively makes the detector energy sensitive, and allows the acquisition of high- and low-energy images simultaneously. These high- and low-energy images can be combined to dual-energy images where the anatomical clutter has been suppressed. By setting the electronic threshold close to 33.2 keV (the k-edge of iodine) the system is optimized for dual-energy contrast-enhanced imaging of breast tumors. Compared to other approaches, this method not only eliminates the need for separate exposures that might lead to motion artifacts, it also eliminates the otherwise deteriorating overlap between high- and low-energy spectra. We present phantom dual-energy images acquired on a prototype system to illustrate that the technique is already operational, albeit in its infancy. We also present a theoretical estimation of the potential gain in tumor signal-difference-to-noise ratio when using this electronic spectrum-splitting method as opposed to acquiring the high- and low-energy images separately with double exposures with separate x-ray spectra. Assuming ideal energy sensitive photon counting detectors, we arrive at the conclusion that the signal-difference-to-noise ratio could be increased by 145% at constant dose. We also illustrate our results on synthetic images.
|
|
| 38. |
|
|
| 39. |
- Bornefalk, Hans, et al.
(författare)
-
Single-shot dual-energy subtraction mammography with electronic spectrum splitting : Feasibility
- 2006
-
Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 60:2, s. 275-278
-
Tidskriftsartikel (refereegranskat)abstract
- We present a single-shot dual-energy subtraction mammography technique using an energy sensitive photon counting detector. An electronic threshold near the middle of the X-ray spectrum discriminates between high- and low-energy photons, and allows the simultaneous acquisition of high- and low-energy images which can be combined to suppress anatomical clutter. By setting the electronic threshold close to 33.2 keV (the k-edge of iodine) the system is optimized for dual-energy contrast-enhanced imaging of breast tumors. This method eliminates the need for separate exposures which might otherwise lead to motion artifacts. The method is illustrated in phantom images.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Bruskin, Alexander, et al.
(författare)
-
Radiobromination of monoclonal antibody using potassium [76Br] (4 isothiocyanatobenzyl-ammonio)-bromo-decahydro-closo-dodecaborate (Bromo-DABI)
- 2004
-
Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 31:2, s. 205-11
-
Tidskriftsartikel (refereegranskat)abstract
- The use of charged linkers in attaching radiohalogens to tumor-seeking biomolecules may improve intracellular retention of the radioactive label after internalization and degradation of targeting proteins. Derivatives of polyhedral boron clusters, such as closo-dodecaborate (2-) anion, might be possible charged linkers. In this study, a bifunctional derivative of closo-dodecaborate, (4-isothiocyanatobenzyl-ammonio)-undecahydro-closo-dodecaborate (DABI) was labeled with positron-emitting nuclide (76)Br (T 1/2 = 16.2 h) and coupled to anti-HER2/neu humanized antibody Trastuzumab. The overall labeling yield at optimized conditions was 80.7 +/- 0.6%. The label was proven to be stable in vitro in physiological and a set of denaturing conditions. The labeled antibody retained its capacity to bind to HER-2/neu antigen expressing cells. The results of the study demonstrated feasibility for using derivatives of closo-dodecaborate in indirect labeling of antibodies for radioimmunoPET.
|
|
| 44. |
- Bruskin, Alexander, et al.
(författare)
-
Separation of two labeled components of [111In] -OctreoScan by HPLC
- 2001
-
Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - 0236-5731 .- 1588-2780. ; 247:1, s. 95-99
-
Tidskriftsartikel (refereegranskat)abstract
- [111In]-DTPA-D-Phe1-octreotide (OctreoScan®, Mallinkrodt) is widely used for detection of neuroendocrine tumors and has lately been proposed for radionuclide therapy. We found, using HPLC and a GF-250 column (Zorbax®, Hewlett Packard), that OctreoScan® can be separated in two radiolabeled components of about equal amount. The analytical conditions for a quantitative isolation indicate that the two-peptide components of OctreoScan®have different lipophilicity. The isolated components are stable and do not transform into each other at room temperature during 6 hours (shelf-life of OctreoScan®).
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Carlsson, Jörgen, et al.
(författare)
-
Conjugate chemistry and cellular processing of EGF-dextran
- 1999
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 313-321
-
Tidskriftsartikel (refereegranskat)abstract
- Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.
|
|
| 49. |
- Carlsson, Jörgen, et al.
(författare)
-
Planning for intracavitary anti-EGFR radionuclide therapy of gliomas : Literature review and data on EGFR expression
- 2006
-
Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:1, s. 33-45
-
Tidskriftsartikel (refereegranskat)abstract
- Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.
|
|
| 50. |
- Carlsson, Jörgen, et al.
(författare)
-
Requirements regarding dose rate and exposure time for killing of tumour cells in beta particle radionuclide therapy
- 2006
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 33:10, s. 1185-1195
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to identify combinations of dose rate and exposure time that have the potential to provide curative treatment with targeted radionuclide therapy applying low dose rate beta irradiation. Methods: Five tumour cell lines, U-373MG and U-118MG gliomas, HT-29 colon carcinoma, A-431 cervical squamous carcinoma and SKBR-3 breast cancer, were used. An experimental model with 10(5) tumour cells in each sample was irradiated with low dose rate beta particles. The criterion for successful treatment was absence of recovery of cells during a follow-up period of 3 months. The initial dose rates were in the range 0.1-0.8 Gy/h, and the cells were continuously exposed for 1, 3 or 7 days. These combinations covered dose rates and doses achievable in targeted radionuclide therapy. Results: Continuous irradiation with dose rates of 0.2-0.3 and 0.4-0.6 Gy/h for 7 and 3 days, respectively, could kill all cells in each tumour cell sample. These treatments gave total radiation doses of 30-40 Gy. However, when exposed for just 24 h with about 0.8 Gy/h, only the SKBR-3 cells were successfully treated; all the other cell types recovered. There were large cell type-dependent variations in the growth delay patterns for the cultures that recovered. The U-118MG cells were most resistant and the U-373MG and SKBR-3 cells most sensitive to the treatments. The HT-29 and A-431 cells were intermediate. Conclusion: The results serve as a guideline for the combinations of dose rate and exposure time necessary to kill tumour cells when applying low dose rate beta irradiation. The shift from recovery to "cure" fell within a narrow range of dose rate and exposure time combinations.
|
|
