| 1. |
- Jiao, Xiang, et al.
(författare)
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PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 102769-102782
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Tidskriftsartikel (refereegranskat)abstract
- Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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| 2. |
- Lundin, Susanne, et al.
(författare)
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Fieldwork in Grey Zones : A case study on organ trafficking in the Philippines
- 2016
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Ingår i: Global Bodies in Grey Zones : Health, Hope, Bioeconomy - Health, Hope, Bioeconomy. - 9781928357193
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Bokkapitel (refereegranskat)abstract
- In this chapter I present a multi-sited fieldwork set in the Philippines that examines trade in organs from living individuals. The organ commerce generally involves organs harvested from living persons. Since humans have two kidneys and can survive with one, it is primarily kidneys that are transplanted, but also illegally traded. Here, my focus is solely on kidney transplantation. The ambition is to capture some fundamental features of what enables transplants in society's legal and moral outskirts, that is to follow the specific question, in Nordstrom͛s sense (2004:13) about what makes organ trade work as well as what social anthropologists Lawrence Cohen and Nancy Scheper Huges term the ͚Rotten Trade͛ (Cohen and Scheper-Hughes 2009). The method is primarily ethnography, making use of observations and interviews.
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| 3. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 4. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 5. |
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| 6. |
- Antunes, V. G., et al.
(författare)
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Influence of the magnetic field on the extension of the ionization region in high power impulse magnetron sputtering discharges
- 2023
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Ingår i: Plasma sources science & technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 32:7
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Tidskriftsartikel (refereegranskat)abstract
- The high power impulse magnetron sputtering (HiPIMS) discharge brings about increased ionization of the sputtered atoms due to an increased electron density and efficient electron energization during the active period of the pulse. The ionization is effective mainly within the electron trapping zone, an ionization region (IR), defined by the magnet configuration. Here, the average extension and the volume of the IR are determined based on measuring the optical emission from an excited level of the argon working gas atoms. For particular HiPIMS conditions, argon species ionization and excitation processes are assumed to be proportional. Hence, the light emission from certain excited atoms is assumed to reflect the IR extension. The light emission was recorded above a 100 mm diameter titanium target through a 763 nm bandpass filter using a gated camera. The recorded images directly indicate the effect of the magnet configuration on the average IR size. It is observed that the shape of the IR matches the shape of the magnetic field lines rather well. The IR is found to expand from 10 and 17 mm from the target surface when the parallel magnetic field strength 11 mm above the racetrack is lowered from 24 to 12 mT at a constant peak discharge current.
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| 7. |
- Arab, Khelifa, et al.
(författare)
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Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A
- 2014
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 55:4, s. 604-614
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.
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| 8. |
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| 9. |
- Babu, Swetha Suresh, et al.
(författare)
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Modeling of high power impulse magnetron sputtering discharges with tungsten target
- 2022
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Ingår i: Plasma sources science & technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 31:6, s. 065009-
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Tidskriftsartikel (refereegranskat)abstract
- The ionization region model (IRM) is applied to model a high power impulse magnetron sputtering discharge with a tungsten target. The IRM gives the temporal variation of the various species and the average electron energy, as well as internal discharge parameters such as the ionization probability and the back-attraction probability of the sputtered species. It is shown that an initial peak in the discharge current is due to argon ions bombarding the cathode target. After the initial peak, the W+ ions become the dominating ions and remain as such to the end of the pulse. We demonstrate how the contribution of the W+ ions to the total discharge current at the target surface increases with increased discharge voltage for peak discharge current densities J (D,peak) in the range 0.33-0.73 A cm(-2). For the sputtered tungsten the ionization probability increases, while the back-attraction probability decreases with increasing discharge voltage. Furthermore, we discuss the findings in terms of the generalized recycling model and compare to experimentally determined deposition rates and find good agreement.
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| 10. |
- Barynova, Kateryna, et al.
(författare)
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On working gas rarefaction in high power impulse magnetron sputtering
- 2024
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Ingår i: Plasma sources science & technology. - : IOP Publishing. - 0963-0252 .- 1361-6595. ; 33:6
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Tidskriftsartikel (refereegranskat)abstract
- The ionization region model (IRM) is applied to explore working gas rarefaction in high power impulse magnetron sputtering discharges operated with graphite, aluminum, copper, titanium, zirconium, and tungsten targets. For all cases the working gas rarefaction is found to be significant, the degree of working gas rarefaction reaches values of up to 83%. The various contributions to working gas rarefaction, including electron impact ionization, kick-out by the sputtered species or hot argon atoms, and diffusion, are evaluated and compared for the different target materials, and over a range of discharge current densities. The relative importance of the various processes varies between different target materials. In the case of a graphite target with argon as the working gas at 1 Pa, electron impact ionization (by both primary and secondary electrons) is the dominating contributor to working gas rarefaction, with over 90% contribution, while the contribution of sputter wind kick-out is small < 10 %. In the case of copper and tungsten targets, the kick-out dominates, with up to ∼60% contribution at 1 Pa. For metallic targets the kick-out is mainly due to metal atoms sputtered from the target, while for the graphite target the small kick-out contribution is mainly due to kick-out by hot argon atoms and to a smaller extent by carbon atoms. The main factors determining the relative contribution of the kick-out by the sputtered species to working gas rarefaction appear to be the sputter yield and the working gas pressure.
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