| 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. |
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| 3. |
- Palmborg, Cecilia, et al.
(författare)
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Odling av rörflen - Sortförsök, odlingsåtgärder och klimatpåverkan : Projekt Bioenergigårdar i ett nytt landskap - Slutrapport 1 Delprojekt FoU
- 2011
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Rapport (populärvet., debatt m.m.)abstract
- Projekt Bioenergigårdar i ett nytt landskap var ett utvecklingsprojekt som drevs av länsstyrelsen Västerbotten 2008-2011. Ett delprojekt, delprojekt FoU, drevs av institutionen för norrländsk jordbruksvetenskap och enheten för biomassateknologi och kemi på SLU Umeå. Delprojektet har i huvudsak finansierats av Kempestiftelserna, men också av SLU och EU. Forskning kring rörflen som energigröda har bedrivits vid SLU Umeå sedan senare delen av 1980-talet. Det är dock först genom projektet "Ökad produktion av biobränsleråvara - minskat oljeberoende" 2006-2007 och Bioenergigårdar som odling i länet kommit igång i kommersiell skala. Tidigare forskningsinsatser vid SLU och erfarenheter och önskemål från pågående verksamhet med rörflensodling har lett fram till fem aktivitetsområden och huvudinriktningar. Alla delrapporter från undersökningar och experiment har sammanställts till två slutrapporter. Rapport 1 publiceras av institutionen för norrländsk jordbruksvetenskap, SLU Umeå: 1. Sortprövning av rörflen- Provning av kommersiella sorter och lovande nummersorter på fler platser än förut. 2. Produktion av åkerbränsle- Hur kan man minska gödslingskostnaderna och varför drabbas produktionen ibland av svackor? 3. Åkerbränsle miljöaspekter- Hur mycket kol lagrar rörflen i rötter och jord och hur påverkar rörflensodling koldioxidavgången från dikad torvmark? Rapport 2 publiceras av enheten för biomassateknologi och kemi, SLU Umeå: 4. Skörd och transportsystem- Vilka skördesystem och transportsystem är effektivast och billigast för att få fram dels lös hackad rörflen, dels balad rörflen som kan lagras? 5. Bränsleförädling och förbränning- Studier av brikettering, tillsatser, bränslemixar och pannor.
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| 4. |
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| 5. |
- Al-Adili, Ali, et al.
(författare)
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Analysis of prompt fission neutrons in U-235(nth,f) and fission fragment distributions for the thermal neutron induced fission of U-234
- 2016
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Ingår i: CNR*15 - 5th International Workshop On Compound-Nuclear Reactions And Related Topics. - : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- This paper presents the ongoing analysis of two fission experiments. Both projects are part of the collaboration between the nuclear reactions group at Uppsala and the JRC-IRMM. The first experiment deals with the prompt fission neutron multiplicity in the thermal neutron induced fission of U-235(n,f). The second, on the fission fragment properties in the thermal fission of U-234(n,f). The prompt fission neutron multiplicity has been measured at the JRC-IRMM using two liquid scintillators in coincidence with an ionization chamber. The first experimental campaign focused on U-235(nth,f) whereas a second experimental campaign is foreseen later for the same reaction at 5.5 MeV. The goal is to investigate how the so-called saw-tooth shape changes as a function of fragment mass and excitation energy. Some harsh experimental conditions were experienced due to the large radiation background. The solution to this will be discussed along with preliminary results. In addition, the analysis of thermal neutron induced fission of U-234(n,f) will be discussed. Currently analysis of data is ongoing, originally taken at the ILL reactor. The experiment is of particular interest since no measurement exist of the mass and energy distributions for this system at thermal energies. One main problem encountered during analysis was the huge background of U-235(nth, f). Despite the negligible isotopic traces in the sample, the cross section difference is enormous. Solution to this parasitic background will be highlighted.
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| 6. |
- Al-Adili, Ali, et al.
(författare)
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Fission Activities of the Nuclear Reactions Group in Uppsala
- 2015
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Ingår i: Scientific Workshop on Nuclear Fission Dynamics and the Emission of Prompt Neutrons and Gamma Rays, THEORY-3. - : Elsevier BV. ; , s. 145-149
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Konferensbidrag (refereegranskat)abstract
- This paper highlights some of the main activities related to fission of the nuclear reactions group at Uppsala University. The group is involved for instance in fission yield experiments at the IGISOL facility, cross-section measurements at the NFS facility, as well as fission dynamics studies at the IRMM JRC-EC. Moreover, work is ongoing on the Total Monte Carlo (TMC) methodology and on including the GEF fission code into the TALYS nuclear reaction code. Selected results from these projects are discussed.
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| 7. |
- Al-Adili, Ali, et al.
(författare)
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Ion counting efficiencies at the IGISOL facility
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- At the IGISOL-JYFLTRAP facility, fission mass yields can be studied at high precision. Fission fragments from a U target are passing through a Ni foil and entering a gas filled chamber. The collected fragments are guided through a mass separator to a Penning trap where their masses are identified. This simulation work focuses on how different fission fragment properties (mass, charge and energy) affect the stopping efficiency in the gas cell. In addition, different experimental parameters are varied (e. g. U and Ni thickness and He gas pressure) to study their impact on the stopping efficiency. The simulations were performed using the Geant4 package and the SRIM code. The main results suggest a small variation in the stopping efficiency as a function of mass, charge and kinetic energy. It is predicted that heavy fragments are stopped about 9% less efficiently than the light fragments. However it was found that the properties of the U, Ni and the He gas influences this behavior. Hence it could be possible to optimize the efficiency.
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| 8. |
- Al-Adili, Ali, et al.
(författare)
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Neutron-multiplicity experiments for enhanced fission modelling
- 2017
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 9782759890200
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Konferensbidrag (refereegranskat)abstract
- The nuclear de-excitation process of fission fragments (FF) provides fundamental information for the understanding of nuclear fission and nuclear structure in neutron-rich isotopes. The variation of the prompt-neutron multiplicity, ν(A), as a function of the incident neutron energy (En) is one of many open questions. It leads to significantly different treatments in various fission models and implies that experimental data are analyzed based on contradicting assumptions. One critical question is whether the additional excitation energy (Eexc) is manifested through an increase of ν(A) for all fragments or for the heavy ones only. A systematic investigation of ν(A) as a function of En has been initiated. Correlations between prompt-fission neutrons and fission fragments are obtained by using liquid scintillators in conjunction with a Frisch-grid ionization chamber. The proof-of-principle has been achieved on the reaction 235U(nth,f) at the Van De Graff (VdG) accelerator of the JRC-Geel using a fully digital data acquisition system. Neutrons from 252Cf(sf) were measured separately to quantify the neutron-scattering component due to surrounding shielding material and to determine the intrinsic detector efficiency. Prelimenary results on ν(A) and spectrum in correlation with FF properties are presented.
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| 9. |
- Al-Adili, Ali, et al.
(författare)
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Simulations of the fission-product stopping efficiency in IGISOL
- 2015
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:59, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- At the Jyväskylä Ion Guide Isotope Separator On-Line (IGISOL) facility, independent fission yields are measured employing the Penning-trap technique. Fission products are produced, e.g. by impinging protons on a uranium target, and are stopped in a gas-filled chamber. The products are collected by a flow of He gas and guided through a mass separator to a Penning trap, where their masses are identified. This work investigates how fission-product properties, such as mass and energy, affect the ion stopping efficiency in the gas cell. The study was performed using the Geant4 toolkit and the SRIM code. The main results show a nearly mass-independent ion stopping with regard to the wide spread of ion masses and energies, with a proper choice of uranium target thickness. Although small variations were observed, in the order of 5%, the results are within the systematic uncertainties of the simulations. To optimize the stopping efficiency while reducing the systematic errors, different experimental parameters were varied; for instance material thicknesses and He gas pressure. Different parameters influence the mass dependence and could alter the mass dependencies in the ion stopping efficiency.
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| 10. |
- Al-Adili, Ali, et al.
(författare)
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Studying fission neutrons with 2E-2v and 2E
- 2018
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Ingår i: SCIENTIFIC WORKSHOP ON NUCLEAR FISSION DYNAMICS AND THE EMISSION OF PROMPT NEUTRONS AND GAMMA RAYS (THEORY-4). - : EDP Sciences. - 9782759890316
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Konferensbidrag (refereegranskat)abstract
- This work aims at measuring prompt-fission neutrons at different excitation energies of the nucleus. Two independent techniques, the 2E-2v and the 2E techniques, are used to map the characteristics of the mass-dependent prompt fission neutron multiplicity, 7(A), when the excitation energy is increased. The VERDI 2E-2v spectrometer is being developed at JRC-GEEL. The Fission Fragment (FF) energies are measured using two arrays of 16 silicon (Si) detectors each. The FFs velocities are obtained by time-of-flight, measured between micro-channel plates (MCP) and Si detectors. With MCPs placed on both sides of the fission source, VERDI allows for independent timing measurements for both fragments. Cf-252(sf) was measured and the present results revealed particular features of the 2E-2v technique. Dedicated simulations were also performed using the GEF code to study important aspects of the 2E-2v technique. Our simulations show that prompt neutron emission has a non-negligible impact on the deduced fragment data and affects also the shape of 17(A). Geometrical constraints lead to a total-kinetic energy-dependent detection efficiency. The 2E technique utilizes an ionization chamber together with two liquid scintillator detectors. Two measurements have been performed, one of Cf-252(sf) and another one of thermal-neutron induced fission in U-235(n,f). Results from Cf-252(sf) are reported here.
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