| 1. |
- Rofors, E., et al.
(författare)
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Response of a Li-glass/multi-anode photomultiplier detector to focused proton and deuteron beams
- 2020
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 984
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Tidskriftsartikel (refereegranskat)abstract
- The response of a position-sensitive Li-glass based scintillation detector being developed for thermal-neutron detection with 6 mm position resolution has been investigated using focused beams of 2.5MeV protons and deuterons. The beams were scanned across the detector in 0.5 mm horizontal and vertical steps perpendicular to the beams. Scintillation light was registered using an 8 × 8 pixel multi-anode photomultiplier tube. The signal amplitudes were recorded for each pixel on an event-by-event basis. Several pixels generally registered considerable signals at each beam location. To optimize planned detector operation at the European Spallation Source, the number of pixels above set thresholds was investigated, with the maximization of the single-hit efficiency over the largest possible area as the primary goal. For both beams, at a threshold of ∼50% of the mean of the full-deposition peak, ∼80% of the events were registered in a single pixel, resulting in an effective position resolution of ∼5 mm in X and Y. Lower thresholds resulted in higher pixel multiplicities. These events could also be localized with the same effective position resolution.
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| 2. |
- Dahl, F, et al.
(författare)
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Imaging single DNA molecules for high precision NIPT
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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| 3. |
- Giovannucci, TA, et al.
(författare)
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Inhibition of the ubiquitin-proteasome system by an NQO1-activatable compound
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:10, s. 914-
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Tidskriftsartikel (refereegranskat)abstract
- Malignant cells display an increased sensitivity towards drugs that reduce the function of the ubiquitin-proteasome system (UPS), which is the primary proteolytic system for destruction of aberrant proteins. Here, we report on the discovery of the bioactivatable compound CBK77, which causes an irreversible collapse of the UPS, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death. CBK77 caused accumulation of ubiquitin-dependent, but not ubiquitin-independent, reporter substrates of the UPS, suggesting a selective effect on ubiquitin-dependent proteolysis. In a genome-wide CRISPR interference screen, we identified the redox enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) as a critical mediator of CBK77 activity, and further demonstrated its role as the compound bioactivator. Through affinity-based proteomics, we found that CBK77 covalently interacts with ubiquitin. In vitro experiments showed that CBK77-treated ubiquitin conjugates were less susceptible to disassembly by deubiquitylating enzymes. In vivo efficacy of CBK77 was validated by reduced growth of NQO1-proficient human adenocarcinoma cells in nude mice treated with CBK77. This first-in-class NQO1-activatable UPS inhibitor suggests that it may be possible to exploit the intracellular environment in malignant cells for leveraging the impact of compounds that impair the UPS.
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| 4. |
- Goderis, Steven, et al.
(författare)
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Globally distributed iridium layer preserved within the Chicxulub impact structure
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- The Cretaceous-Paleogene (K-Pg) mass extinction is marked globally by elevated concentrations of iridium, emplaced by a hypervelocity impact event 66 million years ago. Here, we report new data from four independent laboratories that reveal a positive iridium anomaly within the peak-ring sequence of the Chicxulub impact structure, in drill core recovered by IODP-ICDP Expedition 364. The highest concentration of ultrafine meteoritic matter occurs in the post-impact sediments that cover the crater peak ring, just below the lowermost Danian pelagic limestone. Within years to decades after the impact event, this part of the Chicxulub impact basin returned to a relatively low-energy depositional environment, recording in unprecedented detail the recovery of life during the succeeding millennia. The iridium layer provides a key temporal horizon precisely linking Chicxulub to K-Pg boundary sections worldwide.
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| 7. |
- Elfman, LHM, et al.
(författare)
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IgE binding capacity of synthetic and recombinant peptides of the major storage mite (Lepidoglyphus destructor) allergen, Lep d 2
- 1998
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 117:3, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- <b>Background:</b> Lepidoglyphus destructor is an important non–pyroglyphid mite species in Europe and a dominant allergen in farming environments. The major allergen of L. destructor, Lep d 2, is a protein of 13.2 kD that is recognised by about 90% of sera RAST positive to this mite species. <b>Methods:</b> The cDNA of two isoallergens of the Lep d 2 has previously been sequenced and the protein expressed in different protein expression systems. In order to map the B–cell epitopes, the full length protein and the truncated forms of the protein have been expressed in Escherichia coli as glutathione–S–transferase (GST) fusion proteins. Recombinant Lep d 2 fragments and synthetic overlapping 15 mer peptides spanning Lep d 2 were probed with sera from patients allergic to storage mite. <b>Results:</b> The full–length (125 amino acids) GST fusion protein reacted strongly with patient IgE in Western blots and dot blots. Synthetic peptides failed to react with IgE antibodies from mite–allergic patients and the truncated fusion proteins displayed weak IgE–binding capacity. <b>Conclusion:</b> We conclude that there are no dominant linear IgE–binding epitopes in Lep d 2. Recombinant or synthetic Lep d 2 fragments may, however, be further evaluated as hypoallergenic candidate molecules for specific immunotherapy.
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| 8. |
- Frost, Robert J. W., et al.
(författare)
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Preliminary results from a study of luminescent materials : For application in the beam imaging system at the ESS
- 2023
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier. - 0168-583X .- 1872-9584. ; 540, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- As part of the development of the beam imaging system at the European Spallation Source, luminescent screens have been fabricated by the flame spraying of scintillating materials onto stainless steel backings. A total of seven screens were produced, three of chromia alumina (Al2O3:Cr), two of YAG (Y3Al5O12:Ce) and two of a 50/50 mix of these. The properties of these screens under proton irradiation were evaluated using a2.55 MeV proton beam at currents of up to 10 μA. Irradiation times were up to 25 h per sample, during which luminescence-, spectrographic-, thermal- and current-data was sampled at a rate of 1 Hz. Preliminary results of these measurements are reported here; with a quantitative analysis presented for one of the chromia alumina screens and a qualitative comparison of all three material types. The luminescent yield for chromia alumina was determined to be around 2000 photons/MeV for a virgin screen, and was found to drop to 1.5% after 167 mC of proton irradiation. A recovery of the luminescence of chromia alumina to >60% was observed after beam current was reduced for an 8 h period. Observations indicate that the YAG and mixed composition screens retain higher luminescence than the chromia alumina even at temperatures of over 200 ◦C. It is indicated that the luminescence from YAG feeds the R-lines of chromia alumina in the mixed composition screens.
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