| 1. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 4. |
- Dobritzsch, Doreen, 1972-, et al.
(författare)
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beta-Ureidopropionase deficiency due to novel and rare UPB1 mutations affecting pre-mRNA splicing and protein structural integrity and catalytic activity
- 2022
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier. - 1096-7192 .- 1096-7206. ; 136:3, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- beta-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyses the conversion of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid to beta-alanine and beta-aminoisobutyric acid, ammonia and CO2. To date, only a limited number of genetically confirmed patients with a complete beta-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 10 newly identified beta-ureidopropionase deficient individuals. Patients presented mainly with neurological abnormalities and markedly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in urine. Analysis of UPB1, encoding beta-ureidopropionase, showed 5 novel missense variants and two novel splice-site variants. Functional expression of the UPB1 variants in mammalian cells showed that recombinant beta-ureidopropionase carrying the p.Ala120Ser, p.Thr129Met, p.Ser300Leu and p.Asn345Ile variant yielded no or significantly decreased beta-ureidopropionase activity. Analysis of the crystal structure of human beta-ureidopropionase indicated that the point mutations affect substrate binding or prevent the proper subunit association to larger oligomers and thus a fully functional beta-ureidopropionase. A minigene approach showed that the intronic variants c.[364 + 6 T > G] and c.[916 + 1_916 + 2dup] led to skipping of exon 3 and 8, respectively, in the process of UPB1 pre-mRNA splicing. The c.[899C > T] (p.Ser300Leu) variant was identified in two unrelated Swedish beta-ureidopropionase patients, indicating that beta-ureidopropionase deficiency may be more common than anticipated.
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| 5. |
- Bogdan, Cristian, et al.
(författare)
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Generating an Abstract User Interface from a Discourse Model Inspired by Human Communication
- 2008
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Ingår i: Proceedings of the 41st Annual Hawaii International Conference on System Sciences. ; , s. 36-46
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Konferensbidrag (refereegranskat)abstract
- Inspired by Human Communication Cristian Bogdan, Jürgen Falb, Hermann Kaindl, Sevan Kavaldjian, Roman Popp, Helmut Horacek, Edin Arnautovic and Alexander Szep Vienna University of Technology, Institute of Computer Technology A 1040 Vienna, Austria {bogdan, falb, kaindl, kavaldjian, popp, horacek, arnautovic, szep}@ict.tuwien.ac.at Abstract Programming user interfaces is hard, error-prone and expensive, but recent advances allow generating them from interaction design models. We present an approach for modeling interaction design that is inspired by human com- munication. Our interaction design models are discourse models, more precisely models of dialogues. They are based on theories of human communication and should, therefore, be more understandable to humans than programs imple- menting user interfaces. The main ingredients of our mod- els are communicative acts (Speech Act Theory), which are connected as adjacency pairs (Conversation Analysis) and via RST relations (Rhetorical Structure Theory). While RST provides useful means for modeling discourse in the sense of monologue, a dialogue results from connecting monologues via adjacency pairs. This paper presents a new metamodel that integrates these approaches. Based on it, we show how abstract user interfaces can be generated from such dis- course models. In a nutshell, we generate finite-state ma- chinery and employ rules devised by us to map parts of a discourse model to abstract widgets.
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| 6. |
- Dean, J., et al.
(författare)
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Microglial MyD88 signaling regulates acute neuronal toxicity of LPS-stimulated microglia in vitro
- 2010
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Ingår i: Brain, Behavior, and Immunity. - : Elsevier BV. - 0889-1591. ; 24:5, s. 776-83
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Tidskriftsartikel (refereegranskat)abstract
- Although the role of microglial activation in neural injury remains controversial, there is increasing evidence for a detrimental effect in the immature brain, which may occur in response to release of neurotoxic substances including pro-inflammatory cytokines. However, the signaling mechanisms involved in microglial-induced neuronal cell death are unclear. Microglia isolated from the brains of wild-type (WT) or MyD88 knockout (KO) mice were exposed to PBS or the TLR4-ligand LPS (100 ng/mL) for 2, 6, 14, or 24 h, and the microglia-conditioned medium (MCM) collected. Detection of multiple inflammatory molecules in MCM was performed using a mouse 22-plex cytokine microbead array kit. Primary neuronal cultures were supplemented with the 14 h or 24 h MCM, and the degree of neuronal apoptosis examined after exposure for 24 h. Results showed a rapid and sustained elevation in multiple inflammatory mediators in the MCM of WT microglia exposed to LPS, which was largely inhibited in MyD88 KO microglia. There was a significant increase in apoptotic death measured at 24 h in cultured neurons exposed to CM from either 14 h or 24 h LPS-stimulated WT microglia (p < .05 vs. WT control). By contrast, there was no increase in apoptotic death in cultured neurons exposed to CM from 14 h or 24 h LPS-stimulated MyD88 KO microglia (p = .15 vs. MyD88 KO control). These data suggest that MyD88-dependent activation of microglia by LPS causes release of factors directly toxic to neurons.
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| 7. |
- Dini, P., et al.
(författare)
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Proceedings - 5th International Conference on Software Engineering Advances, ICSEA 2010 : Preface
- 2010
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Ingår i: International Conference on Software Engineering Advances (ICSEA). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. xii-xiii
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Presents the introductory welcome message from the conference proceedings. May include the conference officers' congratulations to all involved with the conference event and publication of the proceedings record.
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| 8. |
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| 9. |
- Kaindl, H., et al.
(författare)
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Robot-Supported Cooperative Work : A Shared-Shopping Scenario
- 2011
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Ingår i: System Sciences (HICSS), 2011 44th Hawaii International Conference on. - 9780769542829 ; , s. 5718472-
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Konferensbidrag (refereegranskat)abstract
- Computer-support cooperative work has been studied extensively and achieved applications that are widely useful. However, there was not much emphasis on support through robots for cooperative work. So, there is no deep understanding of what is needed to support tasks that involve individually moving communication partners and for which the physical context is relevant. This work shows an example of robot-supported cooperative work, where two robots communicate with each other to indirectly support communication between their human users. This example is a shared-shopping scenario. For its realization, we make use of high-level discourse models both for specifying communication between a robot shopping cart and its human user, and between two robot carts. The emerging communication from such intertwined discourses supports a shared (shopping) task of their two human users, who collaborate based on the shopping list shared in this way. Such support is important in a setting where the physical context is relevant, e.g., the vicinity to products.
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| 10. |
- Kolczewski, C., et al.
(författare)
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Detailed study of pyridine at the C1s and N1s ionization thresholds : The influence of the vibrational fine structure
- 2001
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 115:14, s. 6426-6437
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Tidskriftsartikel (refereegranskat)abstract
- High resolution, vibrationally resolved, near-edge x-ray absorption fine structure (NEXAFS) spectra at the C 1s and N 1s ionization thresholds of pyridine and deuterated d(5)-pyridine in the gas phase have been recorded. The high resolution of 65 meV (150 meV) at the C s (N 1s) ionization thresholds reveals vibrational structures in the spectra. Detailed ab initio and density functional theory (DFT) calculations were performed to interpret the experimental spectra and to assign the observed peaks. In particular we focused on the previously unexplained intensity ratio for the two components of the C1s -->1 pi* transition. For this transition the vibrational structure is included through a linear coupling model in the DFT calculations and leads to the experimentally observed similar to2:3 intensity ratio between the two pi* components in the C1s spectrum rather than the similar to3:2 ratio obtained without vibrational effects. After inclusion of relaxation effects in the excited states, in addition to the vibrational effects, both theoretical methods yield almost perfect agreement with experiment.
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