| 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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| 2. |
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| 3. |
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| 4. |
- Stack, K. M., et al.
(författare)
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Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
- 2024
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 129:2
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low-angle cross stratified sandstone, thin-bedded granule sandstone, and thick-bedded granule-pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment-deformed sandstone interbedded with broad, unconfined coarser-grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft-sediment deformed laminated, sulfate-bearing mudstone with lenses of low-angle cross-stratified and scoured sandstone; and FA3, comprised of dipping planar, thin-bedded sand-gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand-dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long-lived, habitable lacustrine and deltaic environment within Jezero crater.
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| 5. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 6. |
- Chavanne, A. V., et al.
(författare)
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Individual-Level Prediction of Exposure Therapy Outcome Using Structural and Functional MRI Data in Spider Phobia: A Machine-Learning Study
- 2023
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Ingår i: Depression and Anxiety. - 1091-4269. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Machine-learning prediction studies have shown potential to inform treatment stratification, but recent efforts to predict psychotherapy outcomes with clinical routine data have only resulted in moderate prediction accuracies. Neuroimaging data showed promise to predict treatment outcome, but previous prediction attempts have been exploratory and reported small clinical sample sizes. Herein, we aimed to examine the incremental predictive value of neuroimaging data in contrast to clinical and demographic data alone (for which results were previously published), using a two-level multimodal ensemble machine-learning strategy. We used pretreatment structural and task-based fMRI data to predict virtual reality exposure therapy outcome in a bicentric sample of N=190 patients with spider phobia. First, eight 1st-level random forest classifications were conducted using separate data modalities (clinical questionnaire scores and sociodemographic data, cortical thickness and gray matter volumes, functional activation, connectivity, connectivity-derived graph metrics, and BOLD signal variance). Then, the resulting predictions were used to train a 2nd-level classifier that produced a final prediction. No 1st-level or 2nd-level classifier performed above chance level except BOLD signal variance, which showed potential as a contributor to higher-level prediction from multiple regions across the brain (1st-level balanced accuracy=0.63). Overall, neuroimaging data did not provide any incremental accuracy for treatment outcome prediction in patients with spider phobia with respect to clinical and sociodemographic data alone. Thus, we advise caution in the interpretation of prediction performances from small-scale, single-site patient samples. Larger multimodal datasets are needed to further investigate individual-level neuroimaging predictors of therapy response in anxiety disorders.
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| 7. |
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| 8. |
- Buldyreva, J, et al.
(författare)
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Linewidth modelling of C2H2-N-2 mixtures tested by rotational CARS measurements
- 2006
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Ingår i: Journal of Raman Spectroscopy. - : Wiley. - 1097-4555 .- 0377-0486. ; 37:6, s. 647-654
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Tidskriftsartikel (refereegranskat)abstract
- The acetylene-nitrogen system is investigated in a combined theoretical and experimental effort in view of its thermometry applications. Accurate values of the rotational Raman linewidths of acetylene are of crucial importance for the computation of spectra from rotational coherent anti-Stokes Raman scattering (CARS) used for temperature and concentration evaluations. Since the direct measurements of these linewidths are not available, they are rigorously calculated by a semi-classical Robert-Bonamy formalism employing exact trajectories. The computed linewidths are used as input parameters in the theoretical spectra simulation, which is also improved by the inclusion of an interbranch interference with coherent Stokes Raman scattering (CSRS). These theoretical spectra are used to evaluate the temperature from experimental CARS spectra of acetylene-nitrogen mixtures recorded in the pressure range 0.1-0.6 MPa. The new linewidths (NLWs) and the CSRS interference inclusion result in a clear improvement of spectral fitting as well as in reasonable values of evaluated temperatures. Copyright (c) 2006 John Wiley & Sons, Ltd.
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| 9. |
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| 10. |
- Kiefer, J., et al.
(författare)
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Gas diagnostics by laser-induced breakdown spectroscopy employing polarization filtering
- 2010
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Ingår i: Laser Applications to Chemical, Security and Environmental Analysis, LACSEA 2010. - 2162-2701. - 9781557528803
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Konferensbidrag (refereegranskat)abstract
- In this work we present a setup for laser-induced breakdown spectroscopy (LIBS) employing a polarization filtering approach and use it for gas diagnostics. A one parts-per-million (ppm) detection sensitivity is achieved for hydrogen atoms.
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| 11. |
- Kiefer, J., et al.
(författare)
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Laser-induced breakdown spectroscopy in gases using ungated detection in combination with polarization filtering and online background correction
- 2010
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Ingår i: Measurement Science & Technology. - : IOP Publishing. - 0957-0233 .- 1361-6501. ; 21:6
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative and fast analysis of gas mixtures is an important task in the field of chemical, security and environmental analysis. In this paper we present a diagnostic approach based on laser-induced breakdown spectroscopy (LIBS). A polarization filter in the signal collection system enables sufficient suppression of elastically scattered light which otherwise reduces the dynamic range of the measurement. Running the detector with a doubled repetition rate as compared to the laser online background correction is obtained. Quantitative measurements of molecular air components in synthetic, ambient and expiration air are performed and demonstrate the potential of the method. The detection limits for elemental oxygen and hydrogen are in the order of 15 ppm and 10 ppm, respectively.
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| 12. |
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| 14. |
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| 15. |
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| 16. |
- Tal, Tamara, et al.
(författare)
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New approach methods to assess developmental and adult neurotoxicity for regulatory use : a PARC work package 5 project
- 2024
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.
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| 17. |
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| 18. |
- Custodio, TF, et al.
(författare)
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Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5588-
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC50 of 0.6 µg/ml. A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the ‘up’ ACE2-binding conformation. The combined approach represents an alternative, fast workflow to select binders with neutralizing activity against newly emerging viruses.
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| 19. |
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| 20. |
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| 21. |
- Gao, Yi, et al.
(författare)
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In situ determination of N-2 broadening coefficients in flames for rotational CARS thermometry
- 2013
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 34, s. 3637-3644
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Tidskriftsartikel (refereegranskat)abstract
- Total N-2 S-branch broadening coefficients have been measured in situ as a function of radial position in a highly sooting ethylene diffusion flame by the use of time-resolved dual-broadband picosecond pure rotational CARS (RCARS). Time-domain measurements of the J-dependent N-2 rotational coherence decays in the flame were used to determine the broadening coefficients, and these coefficients were then used in the spectral fitting routine for the determination of temperature and [O-2]/[N-2] ratio in the flame. Corrections of up to 125 K are found when compared to spectral fitting using an ECS self-broadened N-2 linewidth model. The presented technique effectively takes into account contributions to the N-2 linewidths from all collision partners without any a priori knowledge of relative species concentrations. Published by Elsevier Inc. on behalf of The Combustion Institute.
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| 22. |
- Geitmann, Matthis, et al.
(författare)
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Identification of a Novel Scaffold for Allosteric Inhibition of Wild Type and Drug Resistant HIV-1 Reverse Transcriptase by Fragment Library Screening
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:3, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- A novel scaffold inhibiting wild type and drug resistant variants of human immunodeficiency virus type 1 reverse transcriptase (HIV-1RT) has been identified in a library consisting of 1040 fragments. The fragments were significantly different from already known non-nucleoside reverse transcriptase inhibitors (NNRTIs), as indicated by a Tversky similarity analysis. A screening strategy involving SPR biosensor-based interaction analysis and enzyme inhibition was used. Primary biosensor-based screening, using short concentration series, was followed by analysis of nevirapine competition and enzyme inhibition, thus identifying inhibitory fragments binding to the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding site. Ten hits were discovered, and their affinities and resistance profiles were evaluated with wild type and three drug resistant enzyme variants (K103N, Y181C, and L100I). One fragment exhibited submillimolar K(D) and IC(50) values against all four tested enzyme variants. A substructure comparison between the fragment and 826 structurally diverse published NNRTIs confirmed that the scaffold was novel. The fragment is a bromoindanone with a ligand efficiency of 0.42 kcal/mol(-1).
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Kiefer, J., et al.
(författare)
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OH-thermometry using laser polarization spectroscopy and laser-induced fluorescence spectroscopy in the OH A-X (1,0) band
- 2009
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Ingår i: Journal Of Raman Spectroscopy. - : Wiley. - 0377-0486 .- 1097-4555. ; 40:7, s. 828-835
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Konferensbidrag (refereegranskat)abstract
- Laser-induced fluorescence (LIF) and polarization spectroscopy (PS) is used for OH-thermometry utilizing the off-diagonal A-X (1,0) band. Both techniques are used simultaneously in order to allow a comparison of the results. For deriving temperature information from the spectra, three methods are employed: (1) a contour fit method comparing experimental and calculated spectra, (2) spectral fitting of a single highly resolved spectral line and (3) a two-line intensity ratio approach. In general, both spectroscopic techniques gave similar results. The high-resolution approach (2) did not deliver reasonable results in our experiments. The most accurate but also most time consuming method was the contour fit (1). For future two-dimensional temperature measurements, the 2-line-method (3) was identified to be the method of choice. The present study contains, to the best of our knowledge, the first polarization spectroscopic study in the A-X (1,0) band of OH. Copyright (C) 2009 John Wiley & Sons, Ltd.
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| 27. |
- Kiefer, J, et al.
(författare)
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Planar laser-induced fluorescence of HCO for instantaneous flame front imaging in hydrocarbon flames
- 2009
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 32, s. 921-928
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Tidskriftsartikel (refereegranskat)abstract
- The detection of the formyl radical (HCO) is of great interest in the field of combustion research since it can provide information about the local heat release (HR) rate which is a key parameter in the understanding of combustion processes. Unfortunately, due to the low signal level, HCO planar laser-induced fluorescence (PLTF) has so far not been applicable for single-shot imaging, which is necessary in particular for studying turbulent flames. In the present paper for the first time, to the best of our knowledge, single-shot PLIF imaging of HCO in flames is demonstrated by employing-a multimode frequency-tripled alexandrite laser. Oil the basis of long pulse duration along with a spectrally broad bandwidth enabling multi-line excitation a sufficient signal-to-noise ratio is achieved. In detail, excitation in the B-X system around 258.69 nm is applied and subsequent fluorescence detection in the spectral range 300-400 nm is performed. A series of experiments concerning spectral interferences, saturation behavior and the influence of flame stoichiometry (in the range phi = 0.6-2) have been conducted. Two typical fuels have been employed: methane (CH4) as conventional hydrocarbon as well as dimethyl ether (DME) as modern bio fuel. Single-shot HCO imaging is finally demonstrated in a laminar DME/air Bunsen flame and in a slightly turbulent methane/oxygen welding torch flame. The results indicate that the developed HCO PLIF technique offers a strong potential for improved flame Studies particularly in turbulent flames, In general, the approach to employ laser sources with reasonably broader bandwidth and longer pulse duration compared to conventional Nd:YAG pumped systems for PLIF will open up new possibilities in the field of Combustion diagnostics. (c) 2009 The Combustion Institute. Published by Elsevier file. All rights reserved.
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| 28. |
- Meier, Gianmarco, et al.
(författare)
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Deep mutational scan of a drug efflux pump reveals its structure–function landscape
- 2023
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 19, s. 440-450
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Tidskriftsartikel (refereegranskat)abstract
- Drug efflux is a common resistance mechanism found in bacteria and cancer cells, but studies providing comprehensive functional insights are scarce. In this study, we performed deep mutational scanning (DMS) on the bacterial ABC transporter EfrCD to determine the drug efflux activity profile of more than 1,430 single variants. These systematic measurements revealed that the introduction of negative charges at different locations within the large substrate binding pocket results in strongly increased efflux activity toward positively charged ethidium, whereas additional aromatic residues did not display the same effect. Data analysis in the context of an inward-facing cryogenic electron microscopy structure of EfrCD uncovered a high-affinity binding site, which releases bound drugs through a peristaltic transport mechanism as the transporter transits to its outward-facing conformation. Finally, we identified substitutions resulting in rapid Hoechst influx without affecting the efflux activity for ethidium and daunorubicin. Hence, single mutations can convert EfrCD into a drug-specific ABC importer. [Figure not available: see fulltext.]
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| 29. |
- Ochs, E, et al.
(författare)
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Electrical noise in nanocrystalline films
- 1998
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Ingår i: PHYSICA STATUS SOLIDI A-APPLIED RESEARCH. - 0031-8965. ; 168:2, s. R9-R10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Pandya, Nikhil J, et al.
(författare)
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Noelin1 Affects Lateral Mobility of Synaptic AMPA Receptors
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 24:5, s. 1218-1230
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Tidskriftsartikel (refereegranskat)abstract
- Lateral diffusion on the neuronal plasma membrane of the AMPA-type glutamate receptor (AMPAR) serves an important role in synaptic plasticity. We investigated the role of the secreted glycoprotein Noelin1 (Olfactomedin-1 or Pancortin) in AMPAR lateral mobility and its dependence on the extracellular matrix (ECM). We found that Noelin1 interacts with the AMPAR with high affinity, however, without affecting rise- and decay time and desensitization properties. Noelin1 co-localizes with synaptic and extra-synaptic AMPARs and is expressed at synapses in an activity-dependent manner. Single-particle tracking shows that Noelin1 reduces lateral mobility of both synaptic and extra-synaptic GluA1-containing receptors and affects short-term plasticity. While the ECM does not constrain the synaptic pool of AMPARs and acts only extrasynaptically, Noelin1 contributes to synaptic potentiation by limiting AMPAR mobility at synaptic sites. This is the first evidence for the role of a secreted AMPAR-interacting protein on mobility of GluA1-containing receptors and synaptic plasticity.
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| 31. |
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| 33. |
- Undabarrena, A., et al.
(författare)
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Complete genome sequence of the marine Rhodococcus sp H-CA8f isolated from Comau fjord in Northern Patagonia, Chile
- 2018
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Ingår i: Marine Genomics. - : Elsevier BV. - 1874-7787. ; 40, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- Rhodococcus sp. H-CA8f was isolated from marine sediments obtained from the Comau fjord, located in Northern Chilean Patagonia. Whole-genome sequencing was achieved using PacBio RS II platform, comprising one closed, complete chromosome of 6,19 Mbp with a 62.45% G + C content. The chromosome harbours several metabolic pathways providing a wide catabolic potential, where the upper biphenyl route is described. Also, Rhodococcus sp. H-CA8f bears one linear mega-plasmid of 301 Kbp and 62.34% of G + C content, where genomic analyses demonstrated that it is constituted mostly by putative ORFs with unknown functions, representing a novel genetic feature. These genetic characteristics provide relevant insights regarding Chilean marine actinobacterial strains.
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| 34. |
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