| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 4. |
- Ali, R., et al.
(författare)
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Computational analysis of PT/CT contact behavior for a heavy water reactor at high temperature and pressure
- 2018
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Ingår i: Proceedings of 2018 15th International Bhurban Conference on Applied Sciences and Technology, IBCAST 2018. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538635643 ; , s. 645-650
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Konferensbidrag (refereegranskat)abstract
- A computational model has been developed for a heavy water reactor (HWR) reactor to analyze the temperature distribution of the moderator and pressure tube and to determine the thermal stress analysis of pressure tube (PT) using the non linear elastic model for thermal expansion. For an IAEA ICSP problem, the experimental set up and model were developed by the Fuel Channel High Temperature Heat Transfer (FCHTHT) laboratory in Canada. In case of LOCA or primary heat transfer failure, PT experiences a significant heat flux that results in ballooning of PT. Following the PT deformation, PT/CT contact may occur and thus there is spike in heat flux at calandria tube (CT) resulting in the local dryout of CT. The study was divided into two parts, pre-contact phase and contact phase. The analysis is made by using the COMSOL multiphysics software. The results reveal the effect of buoyancy and support the validation of experimental set up where the graphite heater is offset below the centre to account for the buoyancy effects. The PT was deformed at higher temperature and came in contact at 74.4 seconds.
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| 5. |
- Abhinand, P. A., et al.
(författare)
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Insights on the structural perturbations in human MTHFR Ala222Val mutant by protein modeling and molecular dynamics
- 2016
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : Informa UK Limited. - 0739-1102 .- 1538-0254. ; 34:4, s. 892-905
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Tidskriftsartikel (refereegranskat)abstract
- Methylenetetrahydrofolate reductase (MTHFR) protein catalyzes the only biochemical reaction which produces methyltetrahydrofolate, the active form of folic acid essential for several molecular functions. The Ala222Val polymorphism of human MTHFR encodes a thermolabile protein associated with increased risk of neural tube defects and cardiovascular disease. Experimental studies have shown that the mutation does not affect the kinetic properties of MTHFR, but inactivates the protein by increasing flavin adenine dinucleotide (FAD) loss. The lack of completely solved crystal structure of MTHFR is an impediment in understanding the structural perturbations caused by the Ala222Val mutation; computational modeling provides a suitable alternative. The three-dimensional structure of human MTHFR protein was obtained through homology modeling, by taking the MTHFR structures from Escherichia coli and Thermus thermophilus as templates. Subsequently, the modeled structure was docked with FAD using Glide, which revealed a very good binding affinity, authenticated by a Glide XP score of-10.3983 (kcal mol-1). The MTHFR was mutated by changing Alanine 222 to Valine. The wild-type MTHFR-FAD complex and the Ala222Val mutant MTHFR-FAD complex were subjected to molecular dynamics simulation over 50 ns period. The average difference in backbone root mean square deviation (RMSD) between wild and mutant variant was found to be ~.11 Å. The greater degree of fluctuations in the mutant protein translates to increased conformational stability as a result of mutation. The FAD-binding ability of the mutant MTHFR was also found to be significantly lowered as a result of decreased protein grip caused by increased conformational flexibility. The study provides insights into the Ala222Val mutation of human MTHFR that induces major conformational changes in the tertiary structure, causing a significant reduction in the FAD-binding affinity.
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| 6. |
- Delville, J., et al.
(författare)
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The WALLTURB joined experiment to assess the large scale structures in a high reynolds number turbulent boundary layer
- 2011
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Ingår i: ERCOFTAC Series. - Dordrecht : Springer Netherlands. - 1382-4309 .- 2215-1826. - 9789048196029 ; 14, s. 64-73
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Konferensbidrag (refereegranskat)abstract
- Experiments, involving the joint effort of three European teams and aiming at using the state-of-the-art techniques to study the dynamics of the high Reynolds turbulent boundary layer, have been performed in June 2006 in the LML large wind tunnel. A set of four stereoscopic PIV systems and a rake of 143 hot wires were used to provide synchronised measurements. This paper summarises these ex-periments, presents sample results of both PIV and hot-wire rake data and illustrates the complementarity of such a coupled approach that combines the advantages of each technique.
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| 7. |
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| 8. |
- Faraz, S. M., et al.
(författare)
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Voltage- and Frequency-Dependent Electrical Characteristics and Interface State Density of Ni/ZnO Schottky Diodes
- 2022
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Ingår i: Acta Physica Polonica. A. - : POLISH ACAD SCIENCES INST PHYSICS. - 0587-4246 .- 1898-794X. ; 141:2, s. 99-104
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Tidskriftsartikel (refereegranskat)abstract
- Frequency and voltage dependent electrical characteristics are reported for Ni/ZnO Schottky diodes. Schottky diodes are realized from nano-structured ZnO thin films grown by DC magnetron sputtering. Electrical characterizations are performed by current-voltage (I-V), capacitance-voltage (C-V) and conductance-voltage (G/omega-V) measurements. The diode parameters are extracted, such as barrier height (phi(B)), ideality factor (n) and carrier concentration (N-D). The diodes exhibited a non-linear rectifying behaviour with a barrier height of 0.68 eV and an ideality factor greater than unity. Charge transport mechanism and possible reasons responsible for non-idealities are investigated. The density of interface states (N-SS) below the conduction band are extracted from the measured values of I-V and C-V as a function of E-C - E-SS. From E-C- 0.51 to E-C - 0.64 eV below the conduction band edge, the interface state density N-SS is found to be in the range 1.74 x 10(12)-1.87 x 10(11) eV cm. The interface states density obtained from capacitance-frequency (C-f) characteristics varied from 0.53 x 10(12)-0.12 x 10(12) eV cm from E-C 0.82 eV to E-C 0.89 eV below the conduction band. A complete description of current transport and interface properties is important for the realization of good quality Schottky diodes and for the design and implementation of high performance electronic circuits and systems.
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| 9. |
- Grenn, Francis P., et al.
(författare)
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The Parkinson's Disease Genome-Wide Association Study Locus Browser
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered.
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| 10. |
- Lazowski, K., et al.
(författare)
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Strand specificity of ribonucleotide excision repair in Escherichia coli
- 2023
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 51:4
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Tidskriftsartikel (refereegranskat)abstract
- In Escherichia coli, replication of both strands of genomic DNA is carried out by a single replicase-DNA polymerase III holoenzyme (pol III HE). However, in certain genetic backgrounds, the low-fidelity TLS polymerase, DNA polymerase V (pol V) gains access to undamaged genomic DNA where it promotes elevated levels of spontaneous mutagenesis preferentially on the lagging strand. We employed active site mutants of pol III (pol III alpha_S759N) and pol V (pol V_Y11A) to analyze ribonucleotide incorporation and removal from the E. coli chromosome on a genome-wide scale under conditions of normal replication, as well as SOS induction. Using a variety of methods tuned to the specific properties of these polymerases (analysis of lacI mutational spectra, lacZ reversion assay, HydEn-seq, alkaline gel electrophoresis), we present evidence that repair of ribonucleotides from both DNA strands in E. coli is unequal. While RNase HII plays a primary role in leading-strand Ribonucleotide Excision Repair (RER), the lagging strand is subject to other repair systems (RNase HI and under conditions of SOS activation also Nucleotide Excision Repair). Importantly, we suggest that RNase HI activity can also influence the repair of single ribonucleotides incorporated by the replicase pol III HE into the lagging strand.
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