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- Backlund, Sandra
(författare)
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Efficient improvement of energy efficiency in small and medium- sized Swedish firms
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This is a dissertation about efficient implementation of energy efficiency measures in small and medium-sized Swedish firms. The aim is to investigate the potential for economically efficient implementation of energy efficiency improvement measures in small and medium-sized firms. The thesis contains five papers that analyse different aspects that have been put forth in policy documents and academic debate as methods to improve energy efficiency in non-energy intensive sectors.By reading policy documents, interviewing representatives of small and medium- sized firms and energy auditors as well as analysing data from the Swedish energy audit program, different aspects of energy management practices, energy services and energy audits are considered. The thesis is the product of an interdisciplinary context but economic theory is at the foundation of the analysis and has helped formulate questions and hypotheses that have been tested and explored with the data.The results show that while the potential for improving energy efficiency in the small and medium- sized sector in Sweden is large there are challenges to realizing it in each individual firm. There is potential for improving energy efficiency in the sector and not just for investments in new technology but also for adjusting existing machinery and changing behaviour, but costs for investigating the potential and implementing the measures are large relative to the improvement potential in each company. Energy management practices in this sector are lacking and energy services will only be demanded if reduction in production cost is estimated larger than transaction costs of the service. The Swedish energy audit program has led to the implementation of energy efficiency improvements in the participating firms but compared to other policy instruments it has been a less cost-efficient way to improve energy efficiency in Sweden.
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| 2. |
- Bengtsson Ryberg, Johanna, et al.
(författare)
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The Effects of Wind Power on Human Interests : A Synthesis
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- PrefaceThere is a great need for knowledge concerning the impacts of wind power on humans, landscapes, the marine environment, birds, bats and other mammals.Previous studies of these environmental impacts have lacked an overall view of the effects. This has led to deficiencies in the processes surrounding the establishment of new wind farms. Vindval is a knowledge programme undertaken as a collaboration between the Swedish Energy Agency and the Swedish Environmental Protection Agency. Its aim is to gather and communicate scientific knowledge about the impacts of wind power on people and the natural environment. The programme continues until 2013.Vindval comprises some 30 individual research projects, together with four synthesis projects. Syntheses are prepared by experts, who compile and assess overall research results and experience regarding the effects of wind power in four different areas – humans, birds/bats, marine life and terrestrial mammals.The results of this research and synthesis work will provide a basis for environmental impact assessments and for the planning and permitting processes associated with wind power installations. Vindval requires high standards in the review and approval of research proposals, in order to ensure high-quality reports. The same high standards apply to the reporting, approval and publication of research results from the projects.This report was written by Johanna Bengtsson Ryberg, Gösta Bluhm, Karl Bolin, Bosse Bodén, Kristina Ek, Karin Hammarlund, Marianne Henningsson, Inga-Lena Hannukka, Carina Johansson, Sofia Jönsson, Sanna Mels, Tom Mels, Mats Nilsson, Erik Skärbäck, Patrik Söderholm, Åsa Waldo, Ingegärd Widerström, Niklas Åkerman.This report is a translation of the previous report in Swedish “Vindkraftens påverkan på människors intressen” (Naturvårdsverket report no 6497). Translated by Sofia Jönsson.The contents of the report are the responsibility of the authors.
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| 6. |
- Borgegard, Tomas, et al.
(författare)
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Alzheimers Disease: Presenilin 2-Sparing gamma-Secretase Inhibition Is a Tolerable A beta Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Secretase inhibition represents a major therapeutic strategy for lowering amyloid beta (A beta) peptide production in Alzheimers disease (AD). Progress toward clinical use of gamma-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The gamma-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between A beta production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1(PS1) over PS2 subclass of gamma-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain A beta levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious gamma-secretase targeting strategy for AD.
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| 7. |
- Borgegård, Tomas, et al.
(författare)
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Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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| 8. |
- Boza-Serrano, Antonio, et al.
(författare)
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The role of Galectin-3 in α-synuclein-induced microglial activation
- 2014
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
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Forskningsöversikt (refereegranskat)abstract
- Background: Parkinson's disease (PD) is the most prevalent neurodegenerative motor disorder. The neuropathology is characterized by intraneuronal protein aggregates of α-synuclein and progressive degeneration of dopaminergic neurons within the substantia nigra. Previous studies have shown that extracellular α-synuclein aggregates can activate microglial cells, induce inflammation and contribute to the neurodegenerative process in PD. However, the signaling pathways involved in α-synuclein-mediated microglia activation are poorly understood. Galectin-3 is a member of a carbohydrate-binding protein family involved in cell activation and inflammation. Therefore, we investigated whether galectin-3 is involved in the microglia activation triggered by α-synuclein. Results: We cultured microglial (BV2) cells and induced cell activation by addition of exogenous α-synuclein monomers or aggregates to the cell culture medium. This treatment induced a significant increase in the levels of proinflammatory mediators including the inducible Nitric Oxide Synthase (iNOS), interleukin 1 Beta (IL-1β) and Interleukin-12 (IL-12). We then reduced the levels of galectin-3 expression using siRNA or pharmacologically targeting galectin-3 activity using bis-(3-deoxy-3-(3-fluorophenyl-1H-1,2,3-triazol-1-yl)-β-D-galactopyranosyl)-sulfane. Both approaches led to a significant reduction in the observed inflammatory response induced by α-synuclein. We confirmed these findings using primary microglial cells obtained from wild-type and galectin-3 null mutant mice. Finally, we performed injections of α-synuclein in the olfactory bulb of wild type mice and observed that some of the α-synuclein was taken up by activated microglia that were immunopositive for galectin-3. Conclusions: We show that α-synuclein aggregates induce microglial activation and demonstrate for the first time that galectin-3 plays a significant role in microglia activation induced by α-synuclein. These results suggest that genetic down-regulation or pharmacological inhibition of galectin-3 might constitute a novel therapeutic target in PD and other synucleinopathies.
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- Brodin, N. Patrik, et al.
(författare)
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Life years lost-comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale
- 2012
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 118:21, s. 5432-5440
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The authors developed a framework for estimating and comparing the risks of various long-term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach, and thyroid cancer; heart failure, and myocardial infarction were derived from large published clinical series. Combined with age-specific and sex-specific hazards in the US general population, the dose-response analysis yielded excess hazards of complications for a cancer survivor as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication for 3-dimensional conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction, and stomach cancer. The estimates of breast or thyroid cancer incidence were higher than those for lung and stomach cancer incidence, but LYL were lower because of the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years for IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty, but including prognosis and attained age at an event to obtain the more informative LYL estimate added relatively little to this uncertainty. Cancer 2012. (c) 2012 American Cancer Society.
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| 10. |
- Brodin, N Patrik, et al.
(författare)
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Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma.
- 2011
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50:6, s. 806-16
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc(®) (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007-2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WR(neutron)). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.
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