| 1. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Berglund, Anna-Karin, 1979, et al.
(författare)
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Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA. : Mapping ribonucleotides in mitochondrial DNA
- 2017
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.
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| 3. |
- 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. |
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Kommunerna och hållbar utveckling : Demokrati, välfärd och lokal utveckling
- 2022
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- I 25 år har Centrum för kommunstrategisk forskning, CKS, varit ett nav för forskning och samverkan kring kommunal och regional utveckling. Den här boken är en del i uppmärksammandet av 25-årsjubiléet.Boken är en antologi som belyser frågor om hållbar utveckling utifrån kommunernas olika roller och ansvar för samhällsstrukturer och samhällsprocesser. Författarna till de olika kapitlen är forskare vid CKS och forskare som ingår i CKS samarbetsnätverk. I de olika kapitlen sammanfattas i flera fall forskning som har sträckt sig över många år. På så sätt visar vi genom den här boken hur kontinuiteten genom vår centrumbildning har bidragit till en livskraftig struktur för fördjupad kommunstrategisk och regionstrategisk forskning som tagit stöd i dialoger med miljöer utanför och innanför forskarsamhället.Redaktör för boken är Brita Hermelin, professor i kulturgeografi vid CKS. Övriga författare är Magnus Dahlstedt, David Ekholm, Gissur Ó Erlingsson, Ida Grundel, Sara Gustafsson, Robert Jonsson, Martin Klinthäll, Dick Magnusson, Kristina Trygg, Susanne Wallman Lundåsen, Emanuel Wittberg, Johan Wänström och Richard Öhrvall.
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| 5. |
- Aref, Thomas, 1980, et al.
(författare)
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Andreev tunneling in charge pumping with SINIS turnstiles
- 2011
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Ingår i: Europhysics Letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 96:3
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements on hybrid single-electron turnstiles with superconducting leads contacting a normal island (SINIS). We observe Andreev tunneling of electrons influencing the current plateau characteristics of the turnstiles under radio-frequency pumping. The data is well accounted for by numerical simulations. We verify the dependence of the Andreev tunneling rate on the turnstile's charging energy. Increasing the charging energy effectively suppresses the Andreev current.
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| 6. |
- Aref, Thomas, 1980, et al.
(författare)
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Quantum Acoustics with Surface Acoustic Waves
- 2016
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Ingår i: Superconducting Devices in Quantum Optics. - Cham : Springer International Publishing. - 9783319240916 ; , s. 217-244
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- It has recently been demonstrated that surface acoustic waves (SAWs) can interact with superconducting qubits at the quantum level. SAW resonators in the GHz frequency range have also been found to have low loss at temperatures compatible with superconducting quantum circuits. These advances open up new possibilities to use the phonon degree of freedom to carry quantum information. In this chapter, we give a description of the basic SAW components needed to develop quantum circuits, where propagating or localized SAW-phonons are used both to study basic physics and to manipulate quantum information. Using phonons instead of photons offers new possibilities which make these quantum acoustic circuits very interesting. We discuss general considerations for SAW experiments at the quantum level and describe experiments both with SAW resonators and with interaction between SAWs and a qubit. We also discuss several potential future developments.
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| 7. |
- Batista, P.D., et al.
(författare)
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Acousto-electric single-photon detector
- 2007
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 6583, s. 658304-
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Tidskriftsartikel (refereegranskat)abstract
- We propose a novel concept for a semiconductor-based single-photon detector for quantum information processing, which is capable of discriminating the number of photons in a light pulse. The detector exploits the charge transport by a surface acoustic wave (SAW) in order to combine a large photon absorption area (thus providing high photon collection efficiency) with a microscopic charge detection area, where the photo generated charge is detected with resolution at the single electron level using single electron transistors (SETs). We present preliminary results on acoustic transport measured in a prototype for the detector as well as on the fabrication of radio-frequency single-electron transistors (RFSETs) for charge detection. The photon detector is a particular example of acousto-electric nanocircuits that are expected to be able to control both the spatial and the spin degrees of freedom of single electrons. If realized, these circuits will contribute substantially to a scalable quantum information technology.
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| 8. |
- Christiernin-Gustafsson, Linn, 1979-, et al.
(författare)
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A multi-Layered aesthetical web-portal interface for governmental integration issues
- 2010
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Ingår i: Proceedings of the Workshop on Advanced Visual Interfaces AVI 2010. - Rome : ACM. - 9781450300766 ; , s. 341-344
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Konferensbidrag (refereegranskat)abstract
- The County Administrative Board, a governmental authority in The West Region of Sweden, has in collaboration with the local Counties asked us for advice in presenting information in an official and simple way on the web for the foreign person or refugee, just arrived in Sweden. Administrator officers and social workers are taking part in their introduction. In this paper, we describe our investigation and study in how to present a web design for a "newcomer" in Sweden through a multi-Layered design concept, a kind of design which will interact with each person's needs. In this multipurpose concept and portal, it has been important to consider aesthetical values, layout and graphic design. It has also been important to design a layout that provides different users with different contents. Copyright © 2010 ACM.
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| 9. |
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| 10. |
- Gustafsson, Johan E., 1979-
(författare)
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Essays on value, preference and freedom
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay I develops a new framework for preference relations, that makes further preference relations beyond the trichotomy of preference, dispreference and indifference conceptually possible. The new framework models relations in terms of swaps, which are conceived of as transfers from one alternative state to another. With this new preference framework the essay presents a fitting-attitude analysis of new value relations that avoids some problems of earlier proposals. Essay II examines the small-improvement argument that is usually considered the most powerful argument against comparability, that is, the view that for any two alternatives an agent is rationally required to either prefer one of the alternatives to the other or be indifferent between them. The essay argues that while there might be reasons to believe each of the premises in the small-improvement argument, there is a conflict between these reasons. The conflict is such that we are not provided with a reason to believe the conjunction of the premises. Essay III develops a new measure of freedom of choice based on the proposal that a set offers more freedom of choice than another if, and only if, the expected degree of dissimilarity between a random alternative from the set of possible alternatives and the most similar offered alternative in the set is smaller. Furthermore, a version of this measure is developed that is able to take into account the values of the possible options.
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