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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 5. |
- Singh, A., et al.
(författare)
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Solar Assisted Gasification
- 2019. - 1
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Ingår i: Advances in Solar Energy Research. - Singapore : Springer. - 9789811333019 - 9789811333026 ; , s. 551-576
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Bokkapitel (refereegranskat)
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| 6. |
- Mishra, A., et al.
(författare)
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Solar Thermal Powered Bakery Oven
- 2019. - 1
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Ingår i: Advances in Solar Energy Research. - Singapore : Springer. - 9789811333019 - 9789811333026 ; , s. 577-592
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Bokkapitel (refereegranskat)
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| 7. |
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| 8. |
- Kaundal, S., et al.
(författare)
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Solar-Assisted Gasification Based Cook Stoves
- 2018. - 1
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Ingår i: Coal and Biomass Gasification. - Singapore : Springer. - 9789811073342 - 9789811073359 ; , s. 403-422
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Bokkapitel (refereegranskat)
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| 9. |
- Provino, Alessia, et al.
(författare)
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Stability, Crystal Chemistry, and Magnetism of U2+xN21-xB6 and Nb3-yNi20+yB6 and the Role of Uranium in the Formation of the Quaternary U2-zNbzNi21B6 and U delta Nb3-delta Ni20B6 Systems
- 2019
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 58:22, s. 15045-15059
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the U-Ni-B and Nb-Ni-B systems to search for possible new heavy fermion compounds and superconducting materials. The formation, crystal chemistry, and physical properties of U2Ni21B6 and Nb3-yNi20+yB6 [ternary derivatives of the cubic Cr23C6-type (cF116, Fm3m)] have been studied; the formation of the hypothetical U3Ni20B6 and Nb2Ni21B6 has been disproved. U2Ni21B6 [a = 10.6701(2) angstrom] crystallizes in the ordered W2Cr21C6-type, whereas Nb3-yNi20+yB6 [a = 10.5842(1) angstrom] adopts the Mg3Ni20B6-type. Ni in U2Ni21B6 can be substituted by U, leading to the solid solution U2-xNi21+yB6 (0 <= x <= 0.3); oppositely, Nb in Nb3Ni20B6 is partially replaced by Ni, forming the solution Nb3-yNi20+yB6 (0 <= y <= 0.5), none of them reaching the limit corresponding to the hypothetically ordered U3Ni20B6 and Nb2Ni21B6. These results prompted us to investigate quaternary compounds U2-zNbzNi21B6 and U6Nb3-delta Ni20B6: strong competition in the occupancy of the 4a and 8c sites by U, Nb, and Ni atoms has been observed, with the 4a site occupied by U/Ni atoms only and the 8c site filled by U/Nb atoms only. U2Ni21B6, U2.3Ni20.7B6, and Nb3Ni20B6 are Pauli paramagnets. Interestingly, Nb2.5Ni20.5B6 shows ferromagnetism with T-c approximate to 11 K; the Curie-Weiss fit gives an effective magnetic moment of 2.78 mu(B)/Ni, suggesting that all Ni atoms in the formula unit contribute to the total magnetic moment. The M(H) data at 2 K further corroborate the ferromagnetic behavior with a saturation moment of 10 mu(B)/fu (approximate to 0.49 mu(B)/Ni). The magnetic moment of Ni at the 4a site induces a moment in all of the Ni atoms of the whole unit cell (32f and 48h sites), with all atoms ordering ferromagnetically at 11 K. Density functional theory (DFT) shows that the formation of U2Ni21B6 and Nb3Ni20B6 is energetically preferred. The various electronic states generating ferromagnetism on Nb2.5Ni20.5B6 and Pauli paramagnetism on U2Ni21B6 and Nb3Ni20B6 have been identified.
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| 11. |
- Singh, Vinayak, et al.
(författare)
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Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria.
- 2017
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 103:1, s. 13-25
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need to discover new anti-tubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that has potent, bactericidal activity against M. tuberculosis. Mutations in APYS1-resistant M. tuberculosis mapped exclusively to wag31, a gene that encodes a scaffolding protein thought to orchestrate cell elongation. Recombineering confirmed that a Gln201Arg mutation in Wag31 was sufficient to cause resistance to APYS1, however, neither overexpression nor conditional depletion of wag31 impacted M. tuberculosis susceptibility to this compound. In contrast, expression of the wildtype allele of wag31 in APYS1-resistant M. tuberculosis was dominant and restored susceptibility to APYS1 to wildtype levels. Time-lapse imaging and scanning electron microscopy revealed that APYS1 caused gross malformation of the old pole of M. tuberculosis, with eventual lysis. These effects resembled the morphological changes observed following transcriptional silencing of wag31 in M. tuberculosis. These data show that Wag31 is likely not the direct target of APYS1, but the striking phenotypic similarity between APYS1 exposure and genetic depletion of Wag31 in M. tuberculosis suggests that APYS1 might indirectly affect Wag31 through an as yet unknown mechanism.
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