| 1. |
- 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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| 2. |
- Svensson, Ingrid, et al.
(författare)
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Styrelsemöte - en ny examinationsmetod
- 2005
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Ingår i: [Host publication title missing]. - 9789163187728 ; , s. 124-127
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Konferensbidrag (refereegranskat)abstract
- Under en genomfattande renovering av en befintlig fortsättningskurs i hållfasthetslära har en ny examinationmetod utarbetats. Syftet med såväl hela omarbetningen av kursen som den nya examinationsmetoden, har varit att öka studenternas förmåga att göra snabba överslagsberäkningar. Studenterna delas in i grupper och varje grupp utgör en styrelse som skall ta ställning till ett designförslag. Den snabba analysförmågan tränas och hela styrelsen måste vara överens så att sekreteraren kan skriva ned beslutet i protokollet som alla måste skriva under vid styrelsemötets slut.
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| 3. |
- Svensson, Johan, 1978-, et al.
(författare)
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Rollspelsövningar för undervisning av matematiska modeller
- 2017
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Ingår i: Universitetspedagogiska konferensen 2017. - Umeå : Universitetspedagogik och lärandestöd (UPL), Umeå universitet. ; , s. 52-53
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna presentation är att redovisa och diskutera resultat från ett pågående PUNKTUM-projekt med syfte att utveckla och utvärdera rollspel som metod för undervisning i högre matematik och statistik.
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| 4. |
- Svensson, Mats, et al.
(författare)
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Biodiversity in sustainable forestry.
- 2002
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Ingår i: Developing principles and models for sustainable forestry in Sweden. - 1402009992 ; , s. 273-296
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Svensson, Marie, et al.
(författare)
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Osmotic stability of the cell membrane of Escherichia coli from a temperature-limited fed-batch process
- 2005
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 67:3, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- The temperature-limited fed-batch (TLFB) process is a technique where the oxygen consumption rate is controlled by a gradually declining temperature profile rather than a growth-limiting glucose-feeding profile. In Escherichia coli cultures, it has been proven to prevent an extensive release of endotoxins, i.e. lipopolysaccharides, that occurs in the glucose-limited fed-batch (GLFB) processes at specific growth rates below 0.1 h(-1). The TLFB and the GLFB process were compared to each other when applied to produce the periplasmic, constitutively expressed, enzyme beta-lactamase. The extraction of the enzyme was performed by osmotic shock. A higher production of beta-lactamase was achieved with the TLFB technique while no difference in the endotoxin release was found during the extraction procedure. Furthermore, it was found that growth at declining temperature, generated by the TLFB technique, gradually stabilizes the cytoplasmic membrane, resulting in a significantly increased product quality in the extract from the TLFB cultures in the osmotic shock treatment.
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| 6. |
- Adolfsson, Per, 1967-, et al.
(författare)
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Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
- 2000
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Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 6:9, s. 835-842
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α2/β2-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.
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| 7. |
- Ahadi, Aylin, et al.
(författare)
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Simulation of a Friction Stir Welding Process using FE technique
- 2006
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Ingår i: Report TVSM. - 0281-6679.
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Konferensbidrag (refereegranskat)abstract
- In this paper a three dimensional FE model of the friction stir welding (FSW) is presented and the FSW process is simulated. The model has been implemented in FE code Abaqus with user subroutines DLOAD, DFLUX and UMASFL. The material data used to describe the welded panels is from an aluminium alloy called AL-2024-T3 and the material is assumed to be isotropic with temperature dependent yield stress and elastic modulus. A nonlinear-coupled thermo-mechanical analysis was performed in order to study the temperature and stress distribution.
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| 8. |
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| 9. |
- Alriksson-Schmidt, Ann, et al.
(författare)
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Improving the Health of Individuals With Cerebral Palsy: Protocol for the Multidisciplinary Research Program MOVING ON WITH CP
- 2019
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Ingår i: Jmir Research Protocols. - Toronto, Canada : JMIR Publications Inc.. - 1929-0748. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral palsy (CP) is one of the most common early onset disabilities globally. The causative brain damage in CP is nonprogressive, yet secondary conditions develop and worsen over time. Individuals with CP in Sweden and most of the Nordic countries are systematically followed in the national registry and follow-up program entitled the Cerebral Palsy Follow-Up Program (CPUP). CPUP has improved certain aspects of health care for individuals with CP and strengthened collaboration among professionals. However, there are still issues to resolve regarding health care for this specific population. Objective: The overall objectives of the research program MOVING ON WITH CP are to (1) improve the health care processes and delivery models; (2) develop, implement, and evaluate real-life solutions for Swedish health care provision; and (3) evaluate existing health care and social insurance benefit programs and processes in the context of CP. Methods: MOVING ON WITH CP comprises 9 projects within 3 themes. Evaluation of Existing Health Care (Theme A) consists of registry studies where data from CPUP will be merged with national official health databases, complemented by survey and interview data. In Equality in Health Care and Social Insurance (Theme B), mixed methods studies and registry studies will be complemented with focus group interviews to inform the development of new processes to apply for benefits. In New Solutions and Processes in Health Care Provision (Theme C), an eHealth (electronic health) procedure will be developed and tested to facilitate access to specialized health care, and equipment that improves the assessment of movement activity in individuals with CP will be developed. Results: The individual projects are currently being planned and will begin shortly. Feedback from users has been integrated. Ethics board approvals have been obtained. Conclusions: In this 6-year multidisciplinary program, professionals from the fields of medicine, social sciences, health sciences, and engineering, in collaboration with individuals with CP and their families, will evaluate existing health care, create conditions for a more equal health care, and develop new technologies to improve the health care management of people with CP.
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| 10. |
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