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| 2. |
- Brinson, Robert G., et al.
(author)
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Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics
- 2019
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In: mAbs. - : Informa UK Limited. - 1942-0862 .- 1942-0870. ; 11:1, s. 94-105
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Journal article (peer-reviewed)abstract
- The increased interest in using monoclonal antibodies (mAbs) as a platform for biopharmaceuticals has led to the need for new analytical techniques that can precisely assess physicochemical properties of these large and very complex drugs for the purpose of correctly identifying quality attributes (QA). One QA, higher order structure (HOS), is unique to biopharmaceuticals and essential for establishing consistency in biopharmaceutical manufacturing, detecting process-related variations from manufacturing changes and establishing comparability between biologic products. To address this measurement challenge, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) methods were introduced that allow for the precise atomic-level comparison of the HOS between two proteins, including mAbs. Here, an inter-laboratory comparison involving 26 industrial, government and academic laboratories worldwide was performed as a benchmark using the NISTmAb, from the National Institute of Standards and Technology (NIST), to facilitate the translation of the 2D-NMR method into routine use for biopharmaceutical product development. Two-dimensional H-1,N-15 and H-1,C-13 NMR spectra were acquired with harmonized experimental protocols on the unlabeled Fab domain and a uniformly enriched-N-15, 20%-C-13-enriched system suitability sample derived from the NISTmAb. Chemometric analyses from over 400 spectral maps acquired on 39 different NMR spectrometers ranging from 500 MHz to 900 MHz demonstrate spectral fingerprints that are fit-for-purpose for the assessment of HOS. The 2D-NMR method is shown to provide the measurement reliability needed to move the technique from an emerging technology to a harmonized, routine measurement that can be generally applied with great confidence to high precision assessments of the HOS of mAb-based biotherapeutics.
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| 3. |
- Kaucka, Marketa, et al.
(author)
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Analysis of neural crest-derived clones reveals novel aspects of facial development
- 2016
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In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 2:8
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Journal article (peer-reviewed)abstract
- Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth.
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| 4. |
- Margalith, Ilan, et al.
(author)
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Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates
- 2012
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In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 287:23, s. 18872-18887
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Journal article (peer-reviewed)abstract
- Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.
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| 5. |
- Morenzoni, Elvezio, et al.
(author)
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Low-Energy Muons at PSI: Examples of Investigations of Superconducting Properties in Near-Surface Regions and Heterostuctures
- 2014
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In: Proceedings of the International Symposium on Science Explored by Ultra Slow Muon (USM2013). - : The Physical Society of Japan.
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Conference paper (peer-reviewed)abstract
- With the advent of polarized low-energy muons, with tunable energy in the kiloelectronvolt range, it is possible to use the sensitivity and the local-probe character of µSR to perform depth-dependent investigations on the nanometer scale of magnetic and superconducting properties of materials. Here, after a brief summary of the present status of LE-µSR at PSI, we give some examples of investigations of superconducting properties in the near-surface regions of single crystals and thin-film materials.
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| 7. |
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| 8. |
- Sugiyama, Jun, et al.
(author)
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Li-ion diffusion in Li4Ti5O12 and LiTi2O4 battery materials detected by muon spin spectroscopy
- 2015
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 92:1
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Journal article (peer-reviewed)abstract
- Lithium diffusion in spinel Li4Ti5O12 and LiTi2O4 compounds for future battery applications has been studied with muon spin relaxation (mu+SR). Measurements were performed on both thin-film and powder samples in the temperature range between 25 and 500 K. For Li4Ti5O12 and above about similar to 200 K, the field distribution width (Delta) is found to decrease gradually, while the field fluctuation rate (nu) increases exponentially with temperature. For LiTi2O4, on the contrary, the Delta(T) curve shows a steplike decrease at similar to 350 K, around which the nu(T) curve exhibits a local maximum. These behaviors suggest that Li+ starts to diffuse above around 200 K for both spinels. Assuming a jump diffusion of Li+ at the tetrahedral 8a site to the vacant octahedral 16c site, diffusion coefficients of Li+ at 300 K in the film samples are estimated as (3.2 +/- 0.8) x 10(-11) cm(2)/s for Li4Ti5O12 and (3.6 +/- 1.1) x 10(-11) cm(2)/s for LiTi2O4. Further, some small differences are found in both thermal activation energies and Li-ion diffusion coefficients between the powder and thin-film samples.
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| 9. |
- Sugiyama, Jun, et al.
(author)
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Search for a space charge layer in thin film battery materials with low-energy muons
- 2023
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 2462:1
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Conference paper (peer-reviewed)abstract
- In an all solid state Li-ion battery, it is crucial to reduce ionic resistivity at the interface between the electrode and the electrolyte in order to enhance Li+ mobility across the interface. Recent first principles calculations predict the presence of a space-charge layer (SCL) at the interface due to the difference in the Li+ chemical potential at the interface between two different materials, as in the metal-semiconductor junction in electronic devices. However, the presence of SCL has never been experimentally observed. Our first attempt in a fresh multilayer sample, Cu(10 nm)/Li3PO4(50 nm)/LiCoO2(100 nm) on a sapphire substrate, with low-energy μ +SR (LE μ +SR) revealed a gradual change in the nuclear magnetic field distribution width as a function of implantation depth even across the interface between Li3PO4 and LiCoO2. This implies that the change in the field distribution width at SCL of the sample is too small to be detected by LE μ +SR.
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| 10. |
- Suter, Andreas, et al.
(author)
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Two-Dimensional Magnetic and Superconducting Phases in Metal-Insulator La2−xSrxCuO4 Superlattices Studied by Low-Energy Muon-Spin Rotation
- 2014
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In: Proceedings of the International Symposium on Science Explored by Ultra Slow Muon (USM2013). - : Physical society of Japan. ; , s. 010204-010204
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Conference paper (peer-reviewed)abstract
- We show, by means of low-energy muon-spin-rotation measurements, that few-unit-cells thick La2CuO4 layers synthesized digitally by molecular beam epitaxy are antiferromagnetically ordered. Below a thickness of about 5 CuO2 layers the long-range ordered state breaks down, and a magnetic state appears with enhanced quantum fluctuations and a reduced spin stiffness. This magnetic state can exist in close proximity (few Å) to high-temperature superconducting layers, without transmitting supercurrents. Charge-transfer effects and potential softening of the antiferromagnetic state due to the proximity to the superconducting state are discussed.
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