| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 15. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 16. |
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| 19. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 20. |
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| 21. |
- Blachucki, Wojciech, et al.
(författare)
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Approaching the Attosecond Frontier of Dynamics in Matter with the Concept of X-ray Chronoscopy
- 2022
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Ingår i: Applied Sciences. - : MDPI AG. - 2076-3417. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Featured Application Herein, an innovative methodology, called X-ray chronoscopy, is proposed for exploration of ultrafast processes in matter with attosecond precision using current XFEL sources. The method is based on measuring the change in an X-ray pulse temporal profile induced by interaction with a medium. X-ray free electron lasers (XFELs) have provided scientists opportunities to study matter with unprecedented temporal and spatial resolutions. However, access to the attosecond domain (i.e., below 1 femtosecond) remains elusive. Herein, a time-dependent experimental concept is theorized, allowing us to track ultrafast processes in matter with sub-fs resolution. The proposed X-ray chronoscopy approach exploits the state-of-the-art developments in terahertz streaking to measure the time structure of X-ray pulses with ultrahigh temporal resolution. The sub-femtosecond dynamics of the saturable X-ray absorption process is simulated. The employed rate equation model confirms that the X-ray-induced mechanisms leading to X-ray transparency can be probed via measurement of an X-ray pulse time structure.
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| 22. |
- Blachucki, W., et al.
(författare)
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Inception of electronic damage of matter by photon-driven post-ionization mechanisms
- 2019
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Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- "Probe-before-destroy" methodology permitted diffraction and imaging measurements of intact specimens using ultrabright but highly destructive X-ray free-electron laser (XFEL) pulses. The methodology takes advantage of XFEL pulses ultrashort duration to outrun the destructive nature of the X-rays. Atomic movement, generally on the order of >50 fs, regulates the maximum pulse duration for intact specimen measurements. In this contribution, we report the electronic structure damage of a molecule with ultrashort X-ray pulses under preservation of the atoms' positions. A detailed investigation of the X-ray induced processes revealed that X-ray absorption events in the solvent produce a significant number of solvated electrons within attosecond and femtosecond timescales that are capable of coulombic interactions with the probed molecules. The presented findings show a strong influence on the experimental spectra coming from ionization of the probed atoms' surroundings leading to electronic structure modification much faster than direct absorption of photons. This work calls for consideration of this phenomenon in cases focused on samples embedded in, e.g., solutions or in matrices, which in fact concerns most of the experimental studies.
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| 23. |
- Blachucki, Wojciech, et al.
(författare)
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Resonant X-ray Emission Spectroscopy with a SASE Beam
- 2021
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Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 11:18
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Tidskriftsartikel (refereegranskat)abstract
- Featured Application In the present work, RXES planes are reconstructed with high energy resolution from the experimental spectra of the X-ray radiation emitted from a sample and of incident X-ray pulses delivered by an XFEL operated in the raw SASE mode. The dependence of the reconstructed RXES planes' quality on the number of recorded XFEL shots is studied. Aqueous iron (III) oxide nanoparticles were irradiated with pure self-amplified spontaneous emission (SASE) X-ray free-electron laser (XFEL) pulses tuned to the energy around the Fe K-edge ionization threshold. For each XFEL shot, the incident X-ray pulse spectrum and Fe K beta emission spectrum were measured synchronously with dedicated spectrometers and processed through a reconstruction algorithm allowing for the determination of Fe K beta resonant X-ray emission spectroscopy (RXES) plane with high energy resolution. The influence of the number of X-ray shots employed in the experiment on the reconstructed data quality was evaluated, enabling the determination of thresholds for good data acquisition and experimental times essential for practical usage of scarce XFEL beam times.
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| 24. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 25. |
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| 26. |
- Czapla-Masztafiak, Joanna, et al.
(författare)
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Investigating DNA Radiation Damage Using X-Ray Absorption Spectroscopy
- 2016
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:6, s. 1304-1311
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Tidskriftsartikel (refereegranskat)abstract
- The biological influence of radiation on living matter has been studied for years; however, several questions about the detailed mechanism of radiation damage formation remain largely unanswered. Among all biomolecules exposed to radiation, DNA plays an important role because any damage to its molecular structure can affect the whole cell and may lead to chromosomal rearrangements resulting in genomic instability or cell death. To identify and characterize damage induced in the DNA sugar-phosphate backbone, in this work we performed x-ray absorption spectroscopy at the P K-edge on DNA irradiated with either UVA light or protons. By combining the experimental results with theoretical calculations, we were able to establish the types and relative ratio of lesions produced by both UVA and protons around the phosphorus atoms in DNA.
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| 27. |
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| 28. |
- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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| 29. |
- Dunham, I, et al.
(författare)
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The DNA sequence of human chromosome 22
- 1999
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
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Tidskriftsartikel (refereegranskat)
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| 30. |
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| 31. |
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| 33. |
- Haas, CB, et al.
(författare)
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Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 18852-
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene–environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case–control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E−4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E−4), and Aspartylglucosaminidase (AGA: p = 4.5E−4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.
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| 34. |
- Kayser, Yves, et al.
(författare)
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Core-level nonlinear spectroscopy triggered by stochastic X-ray pulses
- 2019
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Stochastic processes are highly relevant in research fields as different as neuroscience, economy, ecology, chemistry, and fundamental physics. However, due to their intrinsic unpredictability, stochastic mechanisms are very challenging for any kind of investigations and practical applications. Here we report the deliberate use of stochastic X-ray pulses in two-dimensional spectroscopy to the simultaneous mapping of unoccupied and occupied electronic states of atoms in a regime where the opacity and transparency properties of matter are subject to the incident intensity and photon energy. A readily transferable matrix formalism is presented to extract the electronic states from a dataset measured with the monitored input from a stochastic excitation source. The presented formalism enables investigations of the response of the electronic structure to irradiation with intense X-ray pulses while the time structure of the incident pulses is preserved.
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| 35. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 39. |
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| 41. |
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| 42. |
- Sá, Jacinto, et al.
(författare)
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Temperature-programmed reduction of NiO nanoparticles followed by time-resolved RIXS.
- 2014
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 16:17, s. 7692-6
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of nano-NiO was determined using resonant inelastic X-ray scattering (RIXS) spectroscopy. The nanosized NiO particles were reduced in situ, leading to the formation of metallic Ni in a single step. Time-resolved RIXS elucidated in real time the changes on the occupied and unoccupied electronic structure of the material, which are dramatically affected by the reduction process.
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| 43. |
- Sá, Jacinto, et al.
(författare)
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Transient mid-IR study of electron dynamics in TiO2 conduction band.
- 2013
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Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 138:7, s. 1966-70
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Tidskriftsartikel (refereegranskat)abstract
- The dynamics of TiO2 conduction band electrons were followed with a novel broadband synchrotron-based transient mid-IR spectroscopy setup. The lifetime of conduction band electrons was found to be dependent on the injection method used. Direct band gap excitation results in a lifetime of 2.5 ns, whereas indirect excitation at 532 nm via Ru-N719 dye followed by injection from the dye into TiO2 results in a lifetime of 5.9 ns.
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| 44. |
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| 45. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 46. |
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| 47. |
- Szlachetko, Jakub, et al.
(författare)
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Establishing nonlinearity thresholds with ultraintense X-ray pulses
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- X-ray techniques have evolved over decades to become highly refined tools for a broad range of investigations. Importantly, these approaches rely on X-ray measurements that depend linearly on the number of incident X-ray photons. The advent of X-ray free electron lasers (XFELs) is opening the ability to reach extremely high photon numbers within ultrashort X-ray pulse durations and is leading to a paradigm shift in our ability to explore nonlinear X-ray signals. However, the enormous increase in X-ray peak power is a double-edged sword with new and exciting methods being developed but at the same time well-established techniques proving unreliable. Consequently, accurate knowledge about the threshold for nonlinear X-ray signals is essential. Herein we report an X-ray spectroscopic study that reveals important details on the thresholds for nonlinear X-ray interactions. By varying both the incident X-ray intensity and photon energy, we establish the regimes at which the simplest nonlinear process, two-photon X-ray absorption (TPA), can be observed. From these measurements we can extract the probability of this process as a function of photon energy and confirm both the nature and sub-femtosecond lifetime of the virtual intermediate electronic state.
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| 48. |
- Szlachetko, Jakub, et al.
(författare)
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Subsecond and in situ chemical speciation of Pt/Al(2)O(3) during oxidation-reduction cycles monitored by high-energy resolution off-resonant X-ray spectroscopy.
- 2013
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:51, s. 19071-4
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Tidskriftsartikel (refereegranskat)abstract
- We report an in situ time-resolved high-energy resolution off-resonant spectroscopy study with subsecond resolution providing insight into the oxidation and reduction steps of a Pt catalyst during CO oxidation. The study shows that the slow oxidation step is composed of two characteristic stages, namely, dissociative adsorption of oxygen followed by partial oxidation of Pt subsurface. By comparing the experimental spectra with theoretical calculations, we found that the intermediate chemisorbed O on Pt is adsorbed on atop position, which suggests surface poisoning by CO or surface reconstruction.
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| 49. |
- Tyrala, Krzysztof, et al.
(författare)
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State-Population Narrowing Effect in Two-Photon Absorption for Intense Hard X-ray Pulses
- 2017
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Ingår i: Applied Sciences. - : MDPI AG. - 1454-5101 .- 2076-3417. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- We report on studies of state-populations during the two-photon absorption process using intense X-ray pulses. The calculations were performed in a time-dependent manner using a simple three-level model expressed by coupled rate equations. We show that the proposed approach describes well the measured rates of X-rays excited in the one-photon and two-photon absorption processes, and allows detailed investigation of the state population dynamics during the course of the incident X-ray pulse. Finally, we demonstrate that the nonlinear interaction of X-ray pulses with atoms leads to a time-narrowing of state populations. This narrowing-effect is attributed to a quadratic incidence X-ray intensity dependence characteristic for nonlinear interactions of photons with matter.
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| 50. |
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