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| 7. |
- Das, A., et al.
(författare)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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| 8. |
- Heuer, V. B., et al.
(författare)
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Temperature limits to deep subseafloor life in the Nankai Trough subduction zone
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6521, s. 1230-1234
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms in marine subsurface sediments substantially contribute to global biomass. Sediments warmer than 40 degrees C account for roughly half the marine sediment volume, but the processes mediated by microbial populations in these hard-to-access environments are poorly understood. We investigated microbial life in up to 1.2-kilometer-deep and up to 120 degrees C hot sediments in the Nankai Trough subduction zone. Above 45 degrees C, concentrations of vegetative cells drop two orders of magnitude and endospores become more than 6000 times more abundant than vegetative cells. Methane is biologically produced and oxidized until sediments reach 80 degrees to 85 degrees C. In 100 degrees to 120 degrees C sediments, isotopic evidence and increased cell concentrations demonstrate the activity of acetate-degrading hyperthermophiles. Above 45 degrees C, populated zones alternate with zones up to 192 meters thick where microbes were undetectable.
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| 9. |
- Andersen, M. R., et al.
(författare)
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Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88
- 2011
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 21:6, s. 885-897
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Tidskriftsartikel (refereegranskat)abstract
- The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook wholegenome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi
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| 10. |
- Pawlowski, P., et al.
(författare)
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Neutron recognition in the LAND detector for large neutron multiplicity
- 2012
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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. ; 694, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- The performance of the LAND neutron detector is studied. Using an event-mixing technique based on one-neutron data obtained in the S107 experiment at the GSI laboratory, we test the efficiency of various analytic tools used to determine the multiplicity and kinematic properties of detected neutrons. A new algorithm developed recently for recognizing neutron showers from spectator decays in the ALADIN experiment S254 is described in detail. Its performance is assessed in comparison with other methods. The properties of the observed neutron events are used to estimate the detection efficiency of LAND in this experiment. (C) 2012 Elsevier B.V. All rights reserved.
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| 11. |
- Lukasik, J., et al.
(författare)
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Discriminant analysis and secondary-beam charge recognition
- 2008
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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. ; 587:2-3, s. 413-419
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Tidskriftsartikel (refereegranskat)abstract
- The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around La-124 and Sn-107 were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable Sn-124 projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.
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| 12. |
- Trautmann, W., et al.
(författare)
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Isotopic dependence of the caloric curve
- 2009
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Ingår i: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410. ; 62:2, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- Isotopic effects in projectile fragmentation at relativistic energies have been studied with the ALADIN forward spectrometer at SIS. Stable and radioactive Sn and La beams with an incident energy of 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z ratio of the produced spectator sources, consistent with predictions for expanded systems. Consequences for the proposed interpretation of chemical breakup temperatures as representing the limiting temperatures predicted by microscopic models are discussed. (C) 2009 Elsevier B.V. All rights reserved.
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| 13. |
- Guninski, R. S., et al.
(författare)
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Efficacy and safety of SBRT for spine metastases : A systematic review and meta-analysis for preparation of an ESTRO practice guideline
- 2023
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Ingår i: Radiotherapy and Oncology. - 0167-8140.
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Advances in characterizing cancer biology and the growing availability of novel targeted agents and immune therapeutics have significantly changed the prognosis of many patients with metastatic disease. Palliative radiotherapy needs to adapt to these developments. In this study, we summarize the available evidence for stereotactic body radiotherapy (SBRT) in the treatment of spinal metastases. Materials and methods: A systematic review and meta-analysis was performed using PRISMA methodology, including publications from January 2005 to September 2021, with the exception of the randomized phase III trial RTOG-0631 which was added in April 2023. Re-irradiation was excluded. For meta-analysis, a random-effects model was used to pool the data. Heterogeneity was assessed with the I2-test, assuming substantial and considerable as I2 > 50 % and I2 > 75 %, respectively. A p-value < 0.05 was considered statistically significant. Results: A total of 69 studies assessing the outcomes of 7236 metastases in 5736 patients were analyzed. SBRT for spine metastases showed high efficacy, with a pooled overall pain response rate of 83 % (95 % confidence interval [CI] 68 %-94 %), pooled complete pain response of 36 % (95 % CI: 20 %-53 %), and 1-year local control rate of 94 % (95 % CI: 86 %-99 %), although with high levels of heterogeneity among studies (I2 = 93 %, I2 = 86 %, and 86 %, respectively). Furthermore, SBRT was safe, with a pooled vertebral fracture rate of 9 % (95 % CI: 4 %-16 %), pooled radiation induced myelopathy rate of 0 % (95 % CI 0–2 %), and pooled pain flare rate of 6 % (95 % CI: 3 %-17 %), although with mixed levels of heterogeneity among the studies (I2 = 92 %, I2 = 0 %, and 95 %, respectively). Only 1.7 % of vertebral fractures required surgical stabilization. Conclusion: Spine SBRT is characterized by a favorable efficacy and safety profile, providing durable results for pain control and disease control, which is particularly relevant for oligometastatic patients.
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| 14. |
- Klug, Stefanie J, et al.
(författare)
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TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies
- 2009
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
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| 15. |
- Poon, Lok Y. J., et al.
(författare)
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Psychometric Properties of the Internet Gaming Disorder Scale-Short-Form (IGDS9-SF) : Systematic Review
- 2021
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Ingår i: Journal of Medical Internet Research. - : JMIR PUBLICATIONS, INC. - 1438-8871. ; 23:10
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Forskningsöversikt (refereegranskat)abstract
- Background: The Internet Gaming Disorder Scale-Short-Form (IGDS9-SF) is among the best with regard to its psychometric properties. Therefore, clinical psychologists are likely guided to use the IGDS9-SF if they want to assess or screen the disordered gaming in their practice. However, the information, especially psychometric evidence, concerning the IGDS9-SF has not been fully examined and summarized. Objective: This systematic review evaluated the psychometric properties of different language versions of the IGDS9-SF and assessed its methodological quality in order to improve the clinicians' understanding of the IGDS9-SF and facilitate its use. Methods: Systematic literature searches were carried out using Embase, MEDLINE, PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science. The review included English-language studies of any research design that have reported at least one psychometric property of the IGDS9-SF, as defined by the COnsensus-based Standards for the selection of health status Measurement INstrument (COSMIN), and have aimed at testing the psychometric properties of the IGDS9-SF. Results: In total, 21 studies comprising 15 language versions of the IGDS9-SF were included. Overall, the IGDS9-SF showed adequate internal consistency (although some items did not have satisfactory item-total correlation [IT]), excellent criterion validity, and the ability to distinguish different subgroups with measurement invariance being supported across gender and age. In terms of factor structure, the IGDS9-SF was shown to have a unidimensional factor structure across all 21 studies. Conclusions: Although there is insufficient evidence regarding the responsiveness and properties of the IGDS9-SF using item response theory, the existing evidence supports its use in assessing disordered gaming among individuals.
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| 16. |
- Yoo, S. J. B., et al.
(författare)
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Spectral phase encoded time spread optical code division multiple access technology for next generation communication networks Invited
- 2007
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Ingår i: Journal of Optical Networking. - 1536-5379. ; 6:10, s. 1210-1227
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Tidskriftsartikel (refereegranskat)abstract
- We overview and summarize the progress of the spectral phase encoded time spreading (SPECTS) optical code division multiple access (O-CDMA) technology. Recent progress included a demonstration of a 320 Gbit/s (32-user x 10 Gbit/s) all-optical passive optical network testbed based on the SPECTS O-CDMA technology and a theoretical prediction of the spectral efficiency at 100% and above. In particular, InP-based integrated photonics allows implementation of SPECTS O-CDMA transmitters and receivers monolithically integrated on a chip. The integrated InP chip technology not only allows robust and compact configurations for practical and low-cost O-CDMA network deployments but also offers code reconfigurations at rapid rates for secure communication applications.
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| 17. |
- Alimoradi, Z., et al.
(författare)
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Is alexithymia associated with sleep problems? : A systematic review and meta-analysis
- 2022
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier. - 0149-7634 .- 1873-7528. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- Alexithymia, a difficulty identifying and expressing emotions experienced by oneself or others, measurably harms quality of sleep. Research has observed the association between alexithymia and sleep problems; however, the cumulative effect of this association is still unknown. Therefore, this systematic review and meta-analysis was conducted to present scientific evidence regarding the relationship between alexithymia and sleep quality. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, and using relevant keywords, we searched six databases: Scopus, PubMed Central, ProQuest, ISI Web of Knowledge, EMBASE, and Science Direct. We selected observational studies on the association between alexithymia and sleep. We conducted meta-analysis using a random-effect model to calculate the effect size (ES) with Fisher's z transformation. Eligible studies (N = 26) in 24 papers included 7546 participants from 12 countries. The entire ES for the association between alexithymia and sleep was 0.44 (95 % CI: 0.31, 0.56). Additionally, patient populations had a larger ES (ES = 0.55; 95 % CI: 0.30, 0.79) than healthy populations (ES = 0.30; 95 % CI: 0.20, 0.41). The results of the present systematic review and meta-analysis revealed a significant association between alexithymia and sleep problems, especially among people with any medical condition.
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| 18. |
- Brown, K. W., et al.
(författare)
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Observation of Long-Range Three-Body Coulomb Effects in the Decay of Ne-16
- 2014
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 113:23, s. Art. no. 232501-
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of an E/A = 57.6-MeV Ne-17 beam with a Be target is used to populate levels in Ne-16 following neutron knockout reactions. The decay of 16Ne states into the three-body O-14 + p + p continuum is observed in the High Resolution Array (HiRA). For the first time for a 2p emitter, correlations between the momenta of the three decay products are measured with sufficient resolution and statistics to allow for an unambiguous demonstration of their dependence on the long-range nature of the Coulomb interaction. Contrary to previous measurements, our measured limit Gamma
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| 20. |
- Soares, Francisco M., et al.
(författare)
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Monolithic InP 100-Channel X 10-GHz Device for Optical Arbitrary Waveform Generation
- 2011
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Ingår i: IEEE Photonics Journal. - 1943-0655. ; 3:6, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate monolithic integration of a 100-channel arrayed-waveguide grating (AWG) with 10-GHz channel spacing and 100 optically controlled Michelson-interferometer-based phase and amplitude modulators. The high-resolution AWG showed better than -15-dB crosstalk, and the modulator extinction ratio was better than 20 dB with either electrical or optical modulation control. The twin-integrated devices comprise a 50-mm diameter InP wafer with 1200 independent optoelectronic components.
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| 25. |
- Rutqvist, J., et al.
(författare)
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A numerical study of THM effects on the near-field safety of a hypothetical nuclear waste repository - BMT1 of the DECOVALEX III project. Part 3 : Effects of THM coupling in sparsely fractured rocks
- 2005
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Ingår i: International Journal of Rock Mechanics And Mining Sciences. - : Elsevier BV. - 1365-1609 .- 1873-4545. ; 42:5-6, s. 745-755
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Tidskriftsartikel (refereegranskat)abstract
- As a part of the international DECOVALEX III project, and the European BENCHPAR project, the impact of thermal-hydrological-mechanical (THM) couplings on the performance of a bentonite-back-filled nuclear waste repository in near-field crystalline rocks is evaluated in a Bench-Mark Test problem (BMT1) and the results are presented in a series of three companion papers in this issue. This is the third paper with focuses on the effects of THM processes at a repository located in a sparsely fractured rock. Several independent coupled THM analyses presented in this paper show that THM couplings have the most significant impact on the mechanical stress evolution, which is important for repository design, construction and post-closure monitoring considerations. The results show that the stress evolution in the bentonite-back-filled excavations and the surrounding rock depends on the post-closure evolution of both fields of temperature and fluid pressure. It is further shown that the time required to full resaturation may play an important role for the mechanical integrity of the repository drifts. In this sense, the presence of hydraulically conducting fractures in the near-field rock might actually improve the mechanical performance of the repository. Hydraulically conducting fractures in the near-field rocks enhances the water supply to the buffers/back-fills, which promotes a more timely process of resaturation and development of swelling pressures in the back-fill, thus provides timely confining stress and support to the rock walls. In one particular case simulated in this study, it was shown that failure in the drift walls could be prevented if the compressive stresses in back-fill were fully developed within 50 yr, which is when thermally induced rock strain begins to create high differential (failure-prone) stresses in the near-field rocks. Published by Elsevier Ltd.
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| 26. |
- Rutqvist, Jonny, et al.
(författare)
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Evaluation of the Impact of Thermal-Hydrological-Mechanical Couplings in Bentonite and Near-Field Rock Barriers of a Nuclear Waste Repository in Sparsely Fractured Hard Rock
- 2004
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Ingår i: Coupled Thermo-Hydro-Mechanical-Chemical Processes in Geo-Systems — Fundamentals, Modelling, Experiments and Applications. - : Elsevier. ; , s. 217-223
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Bokkapitel (refereegranskat)abstract
- As part of the international DECOVALEX III project and the European BENCHPAR project, this paper evaluates the impact of thermal-hydrological-mechanical (THM) couplings on the performance of a bentonite back-filled nuclear waste repository in sparsely fractured hard rock. The significance of THM coupling on the performance of a hypothetical repository is evaluated by several independent coupled numerical analyses. Moreover, the influence of a discrete fracture intersecting a deposition hole is discussed. The analysis shows that THM couplings have the most impact on the mechanical behaviour of bentonite-rock system, which is important for repository design considerations.
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