| 1. |
- Hinke, C. B., et al.
(author)
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Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7403, s. 341-345
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Journal article (peer-reviewed)abstract
- The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During beta(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of Sn-100, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the beta-decay of Sn-100, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear beta-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, In-100, are well reproduced by modern, large-scale shell model calculations.
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| 2. |
- Klionsky, DJ, et al.
(author)
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Autophagy in major human diseases
- 2021
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In: The EMBO journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 40:19, s. e108863-
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Journal article (peer-reviewed)
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| 3. |
- Grawe, H., et al.
(author)
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The (6+) isomer in 102Sn revisited : Neutron and proton effective charges close to the double shell closure
- 2021
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In: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 820
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Journal article (peer-reviewed)abstract
- In a high-energy fragmentation experiment at GSI an Iπ = (6+) isomer and its γ-decay are identified in 102Sn, the two-neutron neighbour of the doubly-magic 100Sn. Its half-life is measured to be T1/2 = 367(11) ns. The possible existence of further isomers is discussed in the framework of large-scale shell model (LSSM) calculations including up to five particle-hole excitations of the 100Sn core. From the precise B(E2; 6+ → 4+) strength and the recently remeasured value for B(E2; 8+ → 6+) in the two-proton hole neighbour 98Cd effective E2 polarization charges for protons and neutrons were inferred including LSSM corrections within the full N=4 0hω space. The results are discussed in comparison to predicted and empirically determined effective operators.
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| 4. |
- Michel, M., et al.
(author)
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Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
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In: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
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Journal article (peer-reviewed)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
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| 5. |
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| 6. |
- Meister, Mikael, 1969, et al.
(author)
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High-energy breakup of 8B
- 2003
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In: Nucl. Phys. A. ; 718, s. 431-433
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Conference paper (peer-reviewed)
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| 7. |
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| 8. |
- Anders, S., et al.
(author)
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European roadmap on superconductive electronics - Status and perspectives
- 2010
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In: Physica C: Superconductivity and its Applications. - : Elsevier BV. - 0921-4534. ; 470:23-24, s. 2079-2126
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Journal article (peer-reviewed)abstract
- For four decades semiconductor electronics has followed Moore's law: with each generation of integration the circuit features became smaller, more complex and faster. This development is now reaching a wall so that smaller is no longer any faster. The clock rate has saturated at about 3-5 GHz and the parallel processor approach will soon reach its limit. The prime reason for the limitation the semiconductor electronics experiences is not the switching speed of the individual transistor, but its power dissipation and thus heat. Digital superconductive electronics is a circuit- and device-technology that is inherently faster at much less power dissipation than semiconductor electronics. It makes use of superconductors and Josephson junctions as circuit elements, which can provide extremely fast digital devices in a frequency range - dependent on the material - of hundreds of GHz: for example a flip-flop has been demonstrated that operated at 750 GHz. This digital technique is scalable and follows similar design rules as semiconductor devices. Its very low power dissipation of only 0.1 mu W per gate at 100 GHz opens the possibility of three-dimensional integration. Circuits like microprocessors and analogue-to-digital converters for commercial and military applications have been demonstrated. In contrast to semiconductor circuits, the operation of superconducting circuits is based on naturally standardized digital pulses the area of which is exactly the flux quantum Phi(0). The flux quantum is also the natural quantization unit for digital-to-analogue and analogue-to-digital converters. The latter application is so precise, that it is being used as voltage standard and that the physical unit 'Volt' is defined by means of this standard. Apart from its outstanding features for digital electronics, superconductive electronics provides also the most sensitive sensor for magnetic fields: the Superconducting Quantum Interference Device (SQUID). Amongst many other applications SQUIDs are used as sensors for magnetic heart and brain signals in medical applications, as sensor for geological surveying and food-processing and for non-destructive testing. As amplifiers of electrical signals. SQUIDs can nearly reach the theoretical limit given by Quantum Mechanics. A further important field of application is the detection of very weak signals by 'transition-edge' bolo-meters, superconducting nanowire single-photon detectors, and superconductive tunnel junctions. Their application as radiation detectors in a wide frequency range, from microwaves to X-rays is now standard. The very low losses of superconductors have led to commercial microwave filter designs that are now widely used in the USA in base stations for cellular phones and in military communication applications. The number of demonstrated applications is continuously increasing and there is no area in professional electronics, in which superconductive electronics cannot be applied and surpasses the performance of classical devices. Superconductive electronics has to be cooled to very low temperatures. Whereas this was a bottleneck in the past, cooling techniques have made a huge step forward in recent years: very compact systems with high reliability and a wide range of cooling power are available commercially, from microcoolers of match-box size with milli-Watt cooling power to high-reliability coolers of many Watts of cooling power for satellite applications. Superconductive electronics will not replace semiconductor electronics and similar room-temperature techniques in standard applications, but for those applications which require very high speed, low-power consumption, extreme sensitivity or extremely high precision, superconductive electronics is superior to all other available techniques. To strengthen the European competitiveness in superconductor electronics research projects have to be set-up in the following field: - Ultra-sensitive sensing and imaging. - Quantum measurement instrumentation. - Advanced analogue-to-digital converters. - Superconductive electronics technology.
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| 9. |
- Cirulli, Elizabeth T., et al.
(author)
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A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury
- 2019
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In: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 156:6, s. 1707-1716
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility.METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings.RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01.CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
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| 10. |
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| 11. |
- Cortina-Gil, D., et al.
(author)
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One-neutron knockout of O-23
- 2005
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 25, s. 343-346
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Conference paper (peer-reviewed)abstract
- Breakup reactions were used to study the ground-state configuration of the neutron-rich isotope O-23. The O-22 fragments produced in one-nucleon removal from O-23 at 938 MeV/nucleon in a carbon target were detected in coincidence with de-exciting gamma rays, allowing to discern between 220 ground-state and excited-states contributions. From the comparison of exclusive experimental momentum distributions for the one-neutron removal channel to theoretical momentum distributions calculated in an Eikonal model for the knockout process, and spin and parity assignment of I-pi = 1/2(+) was deduced for the 230 ground state. This result solved the existent experimental discrepancy.
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| 12. |
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| 13. |
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| 14. |
- Errichetti, E., et al.
(author)
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Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society
- 2020
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 182:2, s. 454-467
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Journal article (peer-reviewed)abstract
- Background Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. Objectives We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. Methods The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. Results Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) 'other structures' (including colour and morphology); and (v) 'specific clues'. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). Conclusions This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.
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| 15. |
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| 16. |
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| 17. |
- Fabbri, L. M., et al.
(author)
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COPD and multimorbidity: recognising and addressing a syndemic occurrence
- 2023
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In: Lancet Respiratory Medicine. - 2213-2600. ; 11:11, s. 1020-1034
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Journal article (peer-reviewed)abstract
- Most patients with chronic obstructive pulmonary disease (COPD) have at least one additional, clinically relevant chronic disease. Those with the most severe airflow obstruction will die from respiratory failure, but most patients with COPD die from non-respiratory disorders, particularly cardiovascular diseases and cancer. As many chronic diseases have shared risk factors (eg, ageing, smoking, pollution, inactivity, and poverty), we argue that a shift from the current paradigm in which COPD is considered as a single disease with comorbidities, to one in which COPD is considered as part of a multimorbid state-with co-occurring diseases potentially sharing pathobiological mechanisms-is needed to advance disease prevention, diagnosis, and management. The term syndemics is used to describe the co-occurrence of diseases with shared mechanisms and risk factors, a novel concept that we propose helps to explain the clustering of certain morbidities in patients diagnosed with COPD. A syndemics approach to understanding COPD could have important clinical implications, in which the complex disease presentations in these patients are addressed through proactive diagnosis, assessment of severity, and integrated management of the COPD multimorbid state, with a patient-centred rather than a single-disease approach.
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| 18. |
- Gattinger, Pia, et al.
(author)
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Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes
- 2022
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:1, s. 230-242
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Journal article (peer-reviewed)abstract
- Background: The determinants of successful humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of critical importance for the design of effective vaccines and the evaluation of the degree of protective immunity conferred by exposure to the virus. As novel variants emerge, understanding their likelihood of suppression by population antibody repertoires has become increasingly important.Methods: In this study, we analyzed the SARS-CoV-2 polyclonal antibody response in a large population of clinically well-characterized patients after mild and severe COVID-19 using a panel of microarrayed structurally folded and unfolded SARS-CoV-2 proteins, as well as sequential peptides, spanning the surface spike protein (S) and the receptor-binding domain (RBD) of the virus.Results: S- and RBD-specific antibody responses were dominated by immunoglobulin G (IgG), mainly IgG1, and directed against structurally folded S and RBD and three distinct peptide epitopes in S2. The virus neutralization activity of patients´ sera was highly correlated with IgG antibodies specific for conformational but not sequential RBD epitopes and their ability to prevent RBD binding to its human receptor angiotensin-converting enzyme 2 (ACE2). Twenty percent of patients selectively lacked RBD-specific IgG. Only immunization with folded, but not with unfolded RBD, induced antibodies against conformational epitopes with high virus-neutralizing activity. Conformational RBD epitopes required for protection do not seem to be altered in the currently emerging virus variants.Conclusion: These results are fundamental for estimating the protective activity of antibody responses after natural infection or vaccination and for the design of vaccines, which can induce high levels of SARS-CoV-2–neutralizing antibodies conferring sterilizing immunity.
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| 19. |
- Liopyris, Konstantinos, et al.
(author)
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Expert agreement on the presence and spatial localization of melanocytic features in dermoscopy.
- 2023
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In: The Journal of investigative dermatology. - 1523-1747. ; 144:3
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Journal article (peer-reviewed)abstract
- Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. Herein we attempted to evaluate agreement among experts on 'exemplar images' not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least one of 31 melanocytic-specific features were submitted by 25 world experts as 'exemplars'. Using a web-based platform that allows for image mark-up of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with 8 achieving excellent agreement (Gwet's AC >0.75) and 7 of them being melanoma-specific features. These features were: 'Peppering /Granularity' (0.91); 'Shiny White Streaks' (0.89); 'Typical Pigment network' (0.83); 'Blotch Irregular' (0.82); 'Negative Network' (0.81); 'Irregular Globules' (0.78); 'Dotted Vessels' (0.77) and 'Blue Whitish Veil' (0.76). By utilizing an exemplar dataset, good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication and machine learning experiments.
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| 20. |
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| 21. |
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| 22. |
- Muller, N. F., et al.
(author)
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Bayesian inference of reassortment networks reveals fitness benefits of reassortment in human influenza viruses
- 2020
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 117:29, s. 17104-17111
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Journal article (peer-reviewed)abstract
- Reassortment is an important source of genetic diversity in seg-mented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based infer-ence framework. Here, we introduce a coalescent-based model that allows us to explicitly model the joint coalescent and reas-sortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. This algorithm provides the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full-genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks show-ing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.
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| 23. |
- Nicoletti, Paola, et al.
(author)
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Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study
- 2017
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In: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 152:5, s. 1078-1089
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for druginduced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A* 33: 01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9 - 3.8; P = 2.4 x 10(-8)) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6 - 2.5; P = 9.7 x 10(-9)). The association with A* 33: 01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A* 33: 01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6 - 2.7; P = 4.8 x 10(-9)). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0 - 9.5; P = 7.1 x 10(-9)). We validated the association between A* 33: 01 terbinafine-and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A* 33: 01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors.
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| 24. |
- Polimeni, A., et al.
(author)
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Hydrogen related effects in diluted nitrides
- 2003
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In: 22nd Int. Conf. on Defects in Semiconductors,2003. - : Elsevier. ; , s. 371-
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Conference paper (peer-reviewed)abstract
- Hydrogen irradiation leads to the passivation of the electronic activity of nitrogen in Ga(AsN), thus allowing a fine tuning of the material optical properties. Here, some recent results on the effects that hydrogen irradiation has on the electronic properties of diluted III-N-V alloys are presented. In Ga(AsN), both the increase in the electron effective mass and exciton wave function localization induced by nitrogen are reversed in a fully controllable manner by hydrogen irradiation. In Ga(PN), hydrogen widens the band gap and exposes gradually in the gap nitrogen complex states formerly resonant with the conduction band.
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