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- Gad, Helge, et al.
(author)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Journal article (peer-reviewed)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. |
- Jeppsson, Lennart, et al.
(author)
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High-resolution Late Silurian correlations between Gotland, Sweden and the Broken River region, NE Australia: Lithologies, conodonts and isotopes
- 2007
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In: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 245:1-2, s. 115-137
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Conference paper (peer-reviewed)abstract
- High-resolution correlations, partly with a precision better than 10 ka, are achieved between late Ludfordian sequences on Gotland, Sweden (on Baltica), and a section (COG) through the Coral Gardens Formation along the Broken River, northeastern Australia (on Gondwana), despite these sections having been on different palaeocontinents facing different oceans. The interval is characterised by rapid, very large faunal, isotopic, and lithologic changes. Lithologies are remarkably similar in the two areas, consisting of, in order from below: marls with thin limestone beds, flaggy limestones, oncoidal crinoidal limestone, oncoidal marls, terrigenous clastics (silty clay, mudstone, sandstone), oolite, and cliff-/gorge-forming limestones. Further, independent correlation dates several of the lithological changes as coeval. The 813 C excursion in whole rock carbonates is one of the three largest ones known during the Phanerozoic. The increase in delta C-13 is very similar in the two areas, from below + 1 parts per thousand to c. + 9 parts per thousand VPDB though two Gotland samples yielded + 9.71 parts per thousand and + 10.54 parts per thousand (the corresponding COG interval included fewer carbonate layers than needed to definitely exclude that this difference is due to a lack of suitable rocks for sampling). Compared with the lithologies and the delta C-13 curves, the conodont faunas display some divergence, but key taxa permit precise correlations for much of the studied interval. The conodont assemblages change stepwise from very diverse in the Polygnathoides siluricus Zone to a low diversity fauna dominated markedly by a single taxon (Upper Icriodontid Subzone), returning abruptly to a comparatively diverse Ozarkodina snajdri Zone fauna. A method resembling graphic correlation in some respects is used to propose a similarly high-resolution correlation through a longer interval for future testing. (c) 2006 Elsevier B.V. All rights reserved.
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- Khuyagbaatar, J., et al.
(author)
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New Short-Lived Isotope 221U and the Mass Surface Near N=126
- 2015
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In: Physical Review Letters. - 1079-7114. ; 115:24
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Journal article (peer-reviewed)abstract
- Two short-lived isotopes 221U and 222U were produced as evaporation residues in the fusion reaction 50Ti+176Yb at the gas-filled recoil separator TASCA. An α decay with an energy of Eα=9.31(5) MeV and half-life T1/2=4.7(7) μs was attributed to 222U. The new isotope 221U was identified in α-decay chains starting with Eα=9.71(5) MeV and T1/2=0.66(14) μs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.
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| 6. |
- Nygård, K., et al.
(author)
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ForMAX – a beamline for multiscale and multimodal structural characterization of hierarchical materials
- 2024
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In: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 31:Pt 2, s. 363-377
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Journal article (peer-reviewed)abstract
- The ForMAX beamline at the MAX IV Laboratory provides multiscale and multimodal structural characterization of hierarchical materials in the nanometre to millimetre range by combining small- and wide-angle X-ray scattering with full-field microtomography. The modular design of the beamline is optimized for easy switching between different experimental modalities. The beamline has a special focus on the development of novel fibrous materials from forest resources, but it is also well suited for studies within, for example, food science and biomedical research.
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| 7. |
- Cramer, Bradley D., et al.
(author)
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Testing the limits of Paleozoic chronostratigraphic correlation via high-resolution (<500 k.y.) integrated conodont, graptolite, and carbon isotope (delta C-13(carb)) biochemostratigraphy across the Llandovery-Wenlock (Silurian) boundary: Is a unified Phanerozoic time scale achievable?
- 2010
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In: Geological Society of America Bulletin. - 0016-7606. ; 122:9-10, s. 1700-1716
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Journal article (peer-reviewed)abstract
- The resolution and fidelity of global chronostratigraphic correlation are direct functions of the time period under consideration. By virtue of deep-ocean cores and astrochronology, the Cenozoic and Mesozoic time scales carry error bars of a few thousand years (k.y.) to a few hundred k. y. In contrast, most of the Paleozoic time scale carries error bars of plus or minus a few million years (m. y.), and chronostratigraphic control better than +/- 1 m. y. is considered "high resolution." The general lack of Paleozoic abyssal sediments and paucity of orbitally tuned Paleozoic data series combined with the relative incompleteness of the Paleozoic stratigraphic record have proven historically to be such an obstacle to intercontinental chronostratigraphic correlation that resolving the Paleozoic time scale to the level achieved during the Mesozoic and Cenozoic was viewed as impractical, impossible, or both. Here, we utilize integrated graptolite, conodont, and carbonate carbon isotope (delta C-13 carb) data from three paleocontinents (Baltica, Avalonia, and Laurentia) to demonstrate chronostratigraphic control for upper Llandovery through middle Wenlock (TelychianSheinwoodian, similar to 436-426 Ma) strata with a resolution of a few hundred k.y. The interval surrounding the base of the Wenlock Series can now be correlated globally with precision approaching 100 k.y., but some intervals (e. g., uppermost Telychian and upper Shein-woodian) are either yet to be studied in sufficient detail or do not show sufficient biologic speciation and/or extinction or carbon isotopic features to delineate such small time slices. Although producing such resolution during the Paleozoic presents an array of challenges unique to the era, we have begun to demonstrate that erecting a Paleozoic time scale comparable to that of younger eras is achievable.
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| 8. |
- Helander, A, et al.
(author)
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Improved HPLC method for carbohydrate-deficient transferrin in serum
- 2003
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 49:11, s. 1881-1890
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Journal article (peer-reviewed)abstract
- Background: There is need for a reference method for transferrin glycoforms in serum to which routine immunologic methods for the alcohol marker carbohydrate-deficient transferrin (CDT) can be traceable. We describe an improved HPLC method for transferrin glycoforms. Methods: Transferrin was iron-saturated by mixing the serum with ferric nitrilotriacetic acid, and lipoproteins were precipitated with dextran sulfate and calcium chloride. Separation of glycoforms was performed on a SOURCE 15Q anion-exchange column using salt gradient elution. Quantification relied on selective absorbance of the iron-transferrin complex at 470 run. The relative amount of each glycoform was calculated as a percentage of the area under the curve, using baseline integration. Results: The HPLC system provided reproducible separation and quantification of the asialo-, monosialo-, disialo-, trisialo-, tetrasialo-, pentasialo-, and hexasialotransferrin glycoforms. Most importantly, disialo- and trisialotransferrin were almost baseline separated. The intra- and interassay CV for disialotransferrin were <5%. Serum and the pretreated samples were stable for at least 2 days at 22 or 4 degreesC. Sera from 132 healthy controls contained [mean (SD)] 1.16 (0.25)% disialotransferrin, 4.77 (1.36)% trisialotransferrin, 80.18 (2.01)% tetrasialotransferrin, and 13.88 (1.69)% pentasialo- + hexasialotransferrin. In some cases of a high (>6%) trisialotransferrin, monosialotransferrin was detected at <0.25%. Asialotransferrin was not detected in control sera, but was detected in 57% of chronic heavy drinkers and in 62% of sera with greater than or equal to2% disialotransferrin. Conclusions: The HPLC method fulfills the requirements of a preliminary reference method for CDT and should work for any combination of serum transferrin glycoforms. This method could also be useful for confirming positive CDT results by immunoassays in medico-legal cases. (C) 2003 American Association for Clinical Chemistry.
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| 9. |
- Khuyagbaatar, J., et al.
(author)
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Fission in the landscape of heaviest elements: Some recent examples
- 2016
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In: Nobel Symposium NS 160 – Chemistry and Physics of Heavy and Superheavy Elements. - : EDP Sciences. - 9782759890118 ; 131
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Conference paper (peer-reviewed)abstract
- The fission process still remains a main factor that determines the stability of the atomic nucleus of heaviest elements. Fission half-lives vary over a wide range, 10^−19 to 10^24 s. Present experimental techniques for the synthesis of the superheavy elements that usually measure α-decay chains are sensitive only in a limited range of half-lives, often 10^5 to 10^3 s. In the past years, measurement techniques for very short-lived and very long-lived nuclei were significantly improved at the gas-filled recoil separator TASCA at GSI Darmstadt. Recently, several experimental studies of fission-related phenomena have successfully been performed. In this paper, results on 254−256Rf and 266Lr are presented and corresponding factors for retarding the fission process are discussed.
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| 10. |
- Olsson, Gustaf, et al.
(author)
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Instrumentation, control and automation in wastewater – from London 1973 to Narbonne 2013
- 2014
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In: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 69:7, s. 1373-1385
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Journal article (peer-reviewed)abstract
- Key developments of instrumentation, control and automation (ICA) applications in wastewater systems during the past 40 years are highlighted in this paper. From the first ICA conference in 1973 through to today there has been a tremendous increase in the understanding of the processes, instrumentation, computer systems and control theory. However, many developments have not been addressed here, such as sewer control, drinking water treatment and water distribution control. It is hoped that this review can stimulate new attempts to more effectively apply control and automation in water systems in the coming years.
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