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- Eriksson, Emma, et al.
(author)
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Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment
- 2017
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In: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 24:2, s. 92-103
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Journal article (peer-reviewed)abstract
- CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. TMZ-CD40L was a potent stimulator of human myeloid cells and T-cell responses. Further, CD40L-mediated stimulation increased tumor-infiltrating T cells in vivo, which may be due to a direct activation of endothelial cells to upregulate receptors for lymphocyte attachment and transmigration. In conclusion, CD40L-mediated gene therapy is an interesting concept for the treatment of tumors with high levels of M2 macrophages, such as pancreatic cancer, and an oncolytic virus as carrier of CD40L may further boost tumor killing and immune activation.
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| 4. |
- Chan, T., et al.
(author)
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DECOVALEX III BMT3/BENCHPAR WP4 : The thermo-hydro-mechanical responses to a glacial cycle and their potential implications for deep geological disposal of nuclear fuel waste in a fractured crystalline rock mass
- 2005
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In: International Journal of Rock Mechanics And Mining Sciences. - : Elsevier BV. - 1365-1609 .- 1873-4545. ; 42:5-6, s. 805-827
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Journal article (peer-reviewed)abstract
- A number of studies related to past and on-going deep repository performance assessments have identified glaciation/ deglaciation as major future events in the next few hundred thousand years capable of causing significant impact on the long term performance of the repository system. Benchmark Test 3 (BMT3) of the international DECOVALEX III project has been designed to provide an illustrative example that explores the mechanical and hydraulic response of a fractured crystalline rock mass to a period of glaciation. The primary purpose of this numerical study is to investigate whether transient events associated with a glacial cycle could significantly influence the performance of a deep geological repository in a crystalline Shield setting. A conceptual site-scale (tens of kilometres) hydro-mechanical (HM) model was assembled based primarily on site-specific litho-structural, hydrogeological and geomechanical data from the Whiteshell Research Area in the Canadian Shield, with simplification and generalization. Continental glaciological modelling of the Laurentide ice sheet through the last glacial cycle lasting approximately 100,000 years suggests that this site was glaciated at about 60 ka and between about 22.5 and 11 ka before present with maximum ice sheet thickness reaching 2500 m and maximum basal water pressure head reaching 2000m. The ice-sheet/drainage model was scaled down to generate spatially and temporally variable hydraulic and mechanical glaciated surface boundary conditions for site-scale subsurface HM modelling and permafrost modelling. Under extreme periglacial conditions permafrost was able to develop down to the assumed 500-m repository horizon. Two- and three-dimensional coupled HM finite-element simulations indicate: during ice-sheet advance there is rapid rise in hydraulic head, high transient hydraulic gradients and high groundwater velocities 2-3 orders of magnitude higher than under nonglacial conditions; surface water recharges deeper than under nonglacial conditions; upon ice-sheet retreat, the gradients reverse; fracture zone network geometry, interconnectivity and hydraulic properties significantly influence flow domain response; residual elevated heads are preserved for 10,000s in the low-diffusivity rock; and no hydraulic jacking or shear failure occurs at depth. It was found that transient coupled modelling is necessary to capture the essence of glacial effects on Performance Assessment. Model dimensionality also significantly affects simulated results.
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| 5. |
- Christiansson, Maria, et al.
(author)
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OSL in NaCl vs. TL in LiF for absorbed dose measurements and radiation quality assessment in the photon energy range 20 keV to 1.3 MeV
- 2018
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In: Radiation Measurements. - : Elsevier BV. - 1350-4487. ; 112, s. 11-15
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Journal article (peer-reviewed)abstract
- The aim of this study was to determine the photon energy dependence of absorbed dose measurements, in a comparison of optically stimulated luminescence (OSL) in NaCl with thermoluminescence (TL) in LiF:Mg,Cu,P. The comparisons were made at exposure to ionizing radiation in the photon energy range 20 keV to 1.3 MeV. Specially designed dosemeter kits containing both NaCl and LiF were used under i) laboratory conditions using defined radiation fields, ii) laboratory conditions using sealed point sources mimicking unintentional exposures, and iii) field conditions in areas in Japan that were affected by the Fukushima Daiichi nuclear disaster in 2011. The dosemeter kits used in Japan showed that absorbed doses as low as 100 μGy can be assessed from the OSL signal in NaCl. The ratio of the dosemeter readings using OSL in NaCl and TL in LiF increases after irradiation at lower photon energies (less than a few hundred keV) as determined under laboratory conditions. Compensating for this energy dependence of the absorbed dose determinations obtained from OSL in NaCl would thus require an energy-dependent conversion factor for photon energies below 600 keV. On the other hand, the difference in the photon energy dependence between NaCl and LiF may be used to assess the mean effective energy of the photon field. The signal ratios between NaCl and LiF after exposure to radiation in the Fukushima Dashii contaminated areas in Japan, 1.67 ± 0.26 (2013) and 1.63 ± 0.32 (2015), indicate that the mean photon energy in this area was 300–400 keV during the years of the survey.
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| 6. |
- Christiansson, M., et al.
(author)
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Retrospective dosimetry using salted snacks and nuts : A feasibility study
- 2017
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In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 174:1, s. 1-5
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Journal article (peer-reviewed)abstract
- The possibility of using ordinary household table salt for dosimetry is suggested by its high sensitivity to ionising radiation, which generates a readout of optically stimulated luminescence (OSL). However, to exploit this finding for retrospective human dosimetry, it would be needed to find salt in close proximity to the exposed individual. Finding salty snacks frequently tucked into handbags, backpacks or pockets seemed to be a possibility; these items therefore became the test materials of the present study. The aluminium or cardboard packages used to exclude the moisture that makes crisps and nuts go soft and stale also helps to retain the induced OSL signal. Therefore, different snacks, either their salt component alone or mixed with the snack, are exposed to ionising radiation and then were assessed for their dosimetric properties. The results indicate the feasibility of using some salty snacks for dosimetry, with a minimum detectable dose as low as 0.2 mGy.
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| 7. |
- Geber-Bergstrand, Therése, et al.
(author)
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Optically stimulated luminescence (OSL) dosimetry in irradiated alumina substrates from mobile phone resistors
- 2018
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In: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 57:1, s. 69-75
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Journal article (peer-reviewed)abstract
- In this study the dosimetric properties of alumina (Al2O3) substrates found in resistors retrieved from mobile phones were investigated. Measurements of the decline of optically stimulated luminescence (OSL) generated following exposure of these substrates to ionising radiation showed that 16% of the signal could still be detected after 2 years (735 days). Further, the magnitude of the regenerative dose (calibration dose; Di) had no impact on the accuracy of dose estimates. Therefore, it is recommended that the Di be set as low as is practicable, so as to accelerate data retrieval. The critical dose, DCL, and dose limit of detection, DDL, taking into account the uncertainty in the dose–response relation as well as the uncertainty in the background signal, was estimated to be 7 and 13 mGy, respectively, 1 h after exposure. It is concluded that given the significant long-term component of fading, an absorbed dose of 0.5 Gy might still be detectable up to 6 years after the exposure. Thus, OSL from alumina substrates can be used for dosimetry for time periods far in excess of those previously thought.
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