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| 2. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 4. |
- Leimalm, Ulrika, et al.
(författare)
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Off-gas dust in an experimental blast furnace part 1: Characterization of flue dust, sludge and shaft fines
- 2010
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Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 50:11, s. 1560-1569
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Tidskriftsartikel (refereegranskat)abstract
- In blast furnace (BF) ironmaking, efforts are made to decrease coke consumption, which can be done by increasing the pulverized coal injection rate (PCR). This will cause changes in ¡n-furnace reduction conditions, burden distribution, demands on raw material strength, etc. In order to maintain stable operation, but also to obtain low amounts of material losses through the off-gas, it is important to understand fines generation and behaviour in the BF Off-gas dust and shaft fines generated in the LKAB Experimental Blast Furnace (EBF) were sampled during operation with olivine pellets and mixtures of acid pellets and sinter as iron-bearing materials. Characterization using XRD, SEM and LOM was focused on fines from iron-bearing materials, coke and slag formers. The results showed that flue dust, mainly <0.5 mm, was mechanically formed and created in the same manner for all investigated samples. Carbon-containing particles dominated in the fractions >0.075 mm and consisted mainly of coke particles from the shaft. Fe-containing particles, as Fe2O 3 from the top of the shaft, formed the major part of flue dust fractions <0.063 mm. Particles from slag formers such as quartzite and limestone were observed in flue dust when slag formers were utilized in the feed. Sludge consisted mainly of chemically formed spherical particles <1 μm precipitated from the ascending gas as the temperature decreased. © 2010 ISIJ.
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| 6. |
- Lundgren, Maria, et al.
(författare)
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Off-gas dust in an experimental blast furnace part 2: Relation to furnace conditions
- 2010
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Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 50:11, s. 1570-1580
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Tidskriftsartikel (refereegranskat)abstract
- In the blast furnace process, material losses are caused by particles that are blown out of the furnace by the off-gas. In order to reduce these losses, it is important to understand the correlations between furnace conditions and off-gas dust formation. Off-gas dust, as flue dust and sludge, were collected during shaft probe sampling in LKAB Experimental Blast Furnace (EBF). Process data was used to evaluate the relationship between off-gas dust amounts and furnace conditions. The graphitization degree (Lc value) of shaft coke and coke in flue dust was determined using XRD measurements. Solution loss in the shaft had a negligible effect on coke degradation and the coke particles which ended up in the flue dust were mainly derived from abrasion at low temperatures. The amount of alkali and SiO2 in sludge increased with higher PCR and flame temperature, which confirmed that submicron spherical particles in sludge originated from the high temperature area around the raceway. Theoretical critical particle diameters of materials, which could be blown out with the off-gas, were estimated. Flow conditions in the top of the shaft as well as and the properties of fine particles in terms of size and density are important when outflow of mechanical dust, such as flue dust, is concerned. Low off-gas temperatures, and thus lower off-gas velocities, are favourable for low flue dust amounts expelled from the blast furnace. © 2010 ISIJ.
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| 7. |
- Mesfun, Sennai, et al.
(författare)
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Black liquor fractionation for biofuels production : A techno-economic assessment
- 2014
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 166, s. 508-517
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Tidskriftsartikel (refereegranskat)abstract
- The hemicelluloses fraction of black liquor is an underutilized resource in many chemical pulp mills. It is possible to extract and separate the lignin and hemicelluloses from the black liquor and use the hemicelluloses for biochemical conversion into biofuels and chemicals. Precipitation of the lignin from the black liquor would consequently decrease the thermal load on the recovery boiler, which is often referred to as a bottleneck for increased pulp production. The objective of this work is to techno-economically evaluate the production of sodium-free lignin as a solid fuel and butanol to be used as fossil gasoline replacement by fractionating black liquor. The hydrolysis and fermentation processes are modeled in Aspen Plus to analyze energy and material balances as well as to evaluate the plant economics. A mathematical model of an existing pulp and paper mill is used to analyze the effects on the energy performance of the mill subprocesses.
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| 9. |
- Nilsson, Robert, et al.
(författare)
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Techno-economics of carbon preserving butanol production using a combined fermentative and catalytic approach
- 2014
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 161, s. 263-269
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a novel process for n-butanol production which combines a fermentation consuming carbon dioxide (succinic acid fermentation) with subsequent catalytic reduction steps to add hydrogen to form butanol. Process simulations in Aspen Plus have been the basis for the techno-economic analyses performed. The overall economy for the novel process cannot be justified, as production of succinic acid by fermentation is too costly. Though, succinic acid price is expected to drop drastically in a near future. By fully integrating the succinic acid fermentation with the catalytic conversion the need for costly recovery operations could be reduced. The hybrid process would need 22% less raw material than the butanol fermentation at a succinic acid fermentation yield of 0.7 g/g substrate. Additionally, a carbon dioxide fixation of up to 13 ktonnes could be achieved at a plant with an annual butanol production of 10 ktonnes
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| 10. |
- Olofsson, Roger, 1978, et al.
(författare)
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Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
- 2014
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 317-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.
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