| 1. |
- Fritschi, Sarah K, et al.
(författare)
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Highly potent soluble amyloid-β seeds in human Alzheimer brain but not cerebrospinal fluid.
- 2014
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 137:11, s. 2909-2915
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Tidskriftsartikel (refereegranskat)abstract
- The soluble fraction of brain samples from patients with Alzheimer's disease contains highly biologically active amyloid-β seeds. In this study, we sought to assess the potency of soluble amyloid-β seeds derived from the brain and cerebrospinal fluid. Soluble Alzheimer's disease brain extracts were serially diluted and then injected into the hippocampus of young, APP transgenic mice. Eight months later, seeded amyloid-β deposition was evident even when the hippocampus received subattomole amounts of brain-derived amyloid-β. In contrast, cerebrospinal fluid from patients with Alzheimer's disease, which contained more than 10-fold higher levels of amyloid-β peptide than the most concentrated soluble brain extracts, did not induce detectable seeding activity in vivo. Similarly, cerebrospinal fluid from aged APP-transgenic donor mice failed to induce cerebral amyloid-β deposition. In comparison to the soluble brain fraction, cerebrospinal fluid largely lacked N-terminally truncated amyloid-β species and exhibited smaller amyloid-β-positive particles, features that may contribute to the lack of in vivo seeding by cerebrospinal fluid. Interestingly, the same cerebrospinal fluid showed at least some seeding activity in an in vitro assay. The present results indicate that the biological seeding activity of soluble amyloid-β species is orders of magnitude greater in brain extracts than in the cerebrospinal fluid.
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| 2. |
- Zhu, Geyunjian H., et al.
(författare)
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Feasibility of Coacervate-Like Nanostructure for Instant Drug Nanoformulation
- 2023
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Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 15:14, s. 17485-17494
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Tidskriftsartikel (refereegranskat)abstract
- Despite the enormous advancements in nanomedicine research, a limited number of nanoformulations are available on the market, and few have been translated to clinics. An easily scalable, sustainable, and cost-effective manufacturing strategy and long-term stability for storage are crucial for successful translation. Here, we report a system and method to instantly formulate NF achieved with a nanoscale polyelectrolyte coacervate-like system, consisting of anionic pseudopeptide poly(L-lysine isophthalamide) derivatives, polyethylenimine, and doxorubicin (Dox) via simple "mix-and-go" addition of precursor solutions in seconds. The coacervate-like nanosystem shows enhanced intracellular delivery of Dox to patient-derived multidrug-resistant (MDR) cells in 3D tumor spheroids. The results demonstrate the feasibility of an instant drug formulation using a coacervate-like nanosystem. We envisage that this technique can be widely utilized in the nanomedicine field to bypass the special requirement of large-scale production and elongated shelf life of nanomaterials.
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| 3. |
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| 4. |
- Darvishi, Sorour, et al.
(författare)
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Advances in the Sensing and Treatment of Wound Biofilms
- 2022
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 61:13
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Forskningsöversikt (refereegranskat)abstract
- Wound biofilms represent a particularly challenging problem in modern medicine. They are increasingly antibiotic resistant and can prevent the healing of chronic wounds. However, current treatment and diagnostic options are hampered by the complexity of the biofilm environment. In this review, we present new chemical avenues in biofilm sensors and new materials to treat wound biofilms, offering promise for better detection, chemical specificity, and biocompatibility. We briefly discuss existing methods for biofilm detection and focus on novel, sensor-based approaches that show promise for early, accurate detection of biofilm formation on wound sites and that can be translated to point-of-care settings. We then discuss technologies inspired by new materials for efficient biofilm eradication. We focus on ultrasound-induced microbubbles and nanomaterials that can both penetrate the biofilm and simultaneously carry active antimicrobials and discuss the benefits of those approaches in comparison to conventional methods.
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| 5. |
- Gallardo, Rodrigo, et al.
(författare)
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De novo design of a biologically active amyloid
- 2016
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 354:6313, s. 720-
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Tidskriftsartikel (refereegranskat)abstract
- Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional-determined by VEGFR2 loss of function in a biological context in which target protein function is essential.
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| 6. |
- Gaspar, Ricardo, et al.
(författare)
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Secondary nucleation of monomers on fibril surface dominates α-synuclein aggregation and provides autocatalytic amyloid amplification
- 2017
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Ingår i: Quarterly Reviews of Biophysics. - 0033-5835. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.
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| 7. |
- Hult, Johan, et al.
(författare)
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Quantitative three-dimensional imaging of soot volume fraction in turbulent non-premixed flames
- 2002
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Ingår i: Experiments in Fluids. - : Springer Science and Business Media LLC. - 1432-1114 .- 0723-4864. ; 33:2, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- A three-dimensional (3-D) imaging system for studies of reactive and non-reactive flows is described. It can be used to reveal the topology of turbulent structures and to extract 3-D quantities, such as concentration gradients. Measurements are performed using a high repetition rate laser and detector system in combination with a scanning mirror. In this study, the system is used for laser-induced incandescence measurements to obtain quantitative 3-D soot volume fraction distributions in both laminar and turbulent non-premixed flames. From the acquired data, iso-concentration surfaces are visualised and concentration gradients calculated.
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| 8. |
- Kaminski, Clemens, et al.
(författare)
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Development of high speed spectroscopic imaging techniques for the time resolved study of spark ignition phenomena
- 2000
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Ingår i: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on the development of novel time resolved spectroscopic imaging techniques for the study of spark ignition phenomena in combustion cells and an SI-engine. The techniques are based on planar laser induced fluorescence imaging (PLIF) of OH radicals, on fuel tracer PLIF, and on chemiluminescence. The techniques could be achieved at repetition rates reaching several hundreds of kilo-Hz and were cycle resolved. These techniques offer a new path along which engine related diagnostics can be undertaken, providing a wealth of information on turbulent spark ignition.
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| 9. |
- Kaminski, Clemens, et al.
(författare)
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Flame growth and wrinkling in a turbulent flow
- 2000
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Ingår i: Applied physics. B, Lasers and optics (Print). - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 71:5, s. 711-716
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Tidskriftsartikel (refereegranskat)abstract
- High-speed planar laser-induced fluorescence (PLIF) and 3-D large eddy simulations (LES) are used to study turbulent flame kernel growth, wrinkling and the formation of separated flame pockets in methane/air mixtures. Turbulence was effected by a set of rotary fans situated in a cylindrical enclosure. Flame wrinkling was followed on sequential 2-D OH images captured at kHz repetition rates. Under stoichiometric conditions and low turbulence levels the flame kernel remains singly connected and close to spherical in shape. By increasing turbulence or reducing the stoichiometry of the mixture the formation of separated pockets could be observed and studied. The mechanisms behind these phenomena are investigated qualitatively by LES of a level-set G-equation describing the flame surface propagation in turbulent flows.
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| 10. |
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