| 21. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 22. |
- Ladds, Marcus J. G. W., et al.
(författare)
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A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
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| 23. |
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| 24. |
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| 25. |
- Saygi, B., et al.
(författare)
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Reduced transition probabilities along the yrast line in W-166
- 2017
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of excited states in the yrast band of the neutron-deficient nuclide W-166 have been measured utilizing the DPUNS plunger device at the target position of the JUROGAM II gamma-ray spectrometer in conjunction with the RITU gas-filled separator and the GREAT focal-plane spectrometer. Excited states in W-166 were populated in the Mo-92(Kr-78, 4p) reaction at a bombarding energy of 380 MeV. The measurements reveal a low value for the ratio of reduced transitions probabilities for the lowest-lying transitions B(E2; 4(+)-> 2(+)) / B(E2; 2(+)-> 0(+)) = 0.33(5), compared with the expected ratio for an axially deformed rotor (B-4/2 = 1.43).
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| 26. |
- Doncel, Maria, et al.
(författare)
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Lifetime measurements of excited states in W-162 and W-164 and the evolution of collectivity in rare-earth nuclei
- 2017
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 95:4
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of the first excited 2(+) states in the extremely neutron- deficient W-162 and W-164 nuclei have been measured using the recoil distance Doppler shift technique. Experimental B(E2) data for the isotopic chains of hafnium, tungsten, and osmium, from the midshell region near the beta-stability line towards the N = 82 closed shell and the most neutron-deficient nuclides, are compared with predictions of nuclear deformations and 2(1)(+) -> 0(g.s)(.+) reduced transition strengths from different classes of state-of-the-art theoretical model calculations. The results reveal striking differences and deficiencies in the predictive power of current nuclear structure models.
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| 27. |
- Hamilton, B. R., et al.
(författare)
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Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement
- 2021
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Ingår i: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 51:7, s. 1401-1415
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Tidskriftsartikel (refereegranskat)abstract
- Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.
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| 28. |
- Li, Hongjie, et al.
(författare)
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Recoil-decay tagging spectroscopy of W-162(74)88
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:1
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the highly neutron-deficient nucleus W-162 have been investigated via the Mo-92(Kr-78, 2 alpha) W-162 reaction. Prompt gamma rays were detected by the JUROGAM II high-purity germanium detector array and the recoiling fusion-evaporation products were separated by the recoil ion transport unit (RITU) gas-filled recoil separator and identified with the gamma recoil electron alpha tagging (GREAT) spectrometer at the focal plane of RITU. gamma rays from W-162 were identified uniquely using mother-daughter and mother-daughter-granddaughter alpha-decay correlations. The observation of a rotational-like ground-state band is interpreted within the framework of total Routhian surface (TRS) calculations, which suggest an axially symmetric ground-state shape with a gamma-soft minimum at beta(2) approximate to 0.15. Quasiparticle alignment effects are discussed based on cranked shell model calculations. New measurements of the W-162 ground-state alpha-decay energy and half-life were also performed. The observed alpha-decay energy agrees with previous measurements. The half-life of W-162 was determined to be t(1/2) = 990(30) ms. This value deviates significantly from the currently adopted value of t(1/2) = 1360(70) ms. In addition, the alpha-decay energy and half-life of Os-166 were measured and found to agree with the adopted values.
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| 29. |
- Mills, James A., et al.
(författare)
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Archiving Primary Data : Solutions for Long-Term Studies
- 2015
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 30:10, s. 581-589
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Tidskriftsartikel (refereegranskat)abstract
- The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (PIs) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.
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| 30. |
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