9 research outputs found

    Thinking in Terms of Structure-Activity-Relationships (T-SAR): A Tool to Better Understand Nanofiltration Membranes

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    A frontier to be conquered in the field of membrane technology is related to the very limited scientific base for the rational and task-specific design of membranes. This is especially true for nanofiltration membranes with properties that are based on several solute-membrane interaction mechanisms. “Thinking in terms of Structure-Activity-Relationships” (T-SAR) is a methodology which applies a systematic analysis of a chemical entity based on its structural formula. However, the analysis become more complex with increasing size of the molecules considered. In this study, T-SAR was combined with classical membrane characterization methods, resulting in a new methodology which allowed us not only to explain membrane characteristics, but also provides evidence for the importance of the chemical structure for separation performance. We demonstrate an application of the combined approach and its potential to discover stereochemistry, molecular interaction potentials, and reactivity of two FilmTec nanofiltration membranes (NF-90 and NF-270). Based on these results, it was possible to predict both properties and performance in the recovery of hydrophobic ionic liquids from aqueous solution

    Amyloidogenicity assessment of transthyretin gene variants

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    Objective: Hereditary transthyretin-mediated amyloidosis is a treatable condition caused by amyloidogenic variants in the transthyretin-gene resulting in severe peripheral neuropathy or cardiomyopathy. Only about a third of over 130 known variants are clearly pathogenic, most are classified as variants of uncertain significance. A clear delineation of these into pathogenic or non-pathogenic is highly desirable but hampered by low frequency and penetrance. We thus sought to characterize their amylogenic potential by an unbiased in vitro approach. Methods: Thioflavin T and turbidity assays were used to compare the potential of mammalian cell expressed wt-transthyretin and 12 variant proteins (either variants of uncertain significance, benign, pathogenic) to aggregate and produce amyloid fibrils in vitro. As proof of principle, the assays were applied to transthyretin-Ala65Val, a variant that was newly detected in a family with peripheral neuropathy and amyloid deposits in biopsies. In silico analysis was performed to compare the position of the benign and pathogenic variants. Results: Transthyretin-Ala65Val showed a significantly higher amyloidogenic potential than wt-transthyretin, in both turbidity- and Thioflavin T-assays, comparable to known pathogenic variants. The other eight tested variants did not show an increased amyloidogenic potential. In silico structural analysis further confirmed differences between pathogenic and benign variants in position and interactions. Interpretation: We propose a biochemical approach to assess amyloidogenic potential of transthyretin variants. As exemplified by transthyretin-Ala65Val, data of three assays together with histopathology clearly demonstrates its amyloidogenicity

    Strange Hadron Spectroscopy with Secondary KL Beam in Hall D

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    Final version of the KLF Proposal [C12-19-001] approved by JLab PAC48. The intermediate version of the proposal was posted in arXiv:1707.05284 [hep-ex]. 103 pages, 52 figures, 8 tables, 324 references. Several typos were fixedWe propose to create a secondary beam of neutral kaons in Hall D at Jefferson Lab to be used with the GlueX experimental setup for strange hadron spectroscopy. The superior CEBAF electron beam will enable a flux on the order of 1×104 KL/sec1\times 10^4~K_L/sec, which exceeds the flux of that previously attained at SLAC by three orders of magnitude. The use of a deuteron target will provide first measurements ever with neutral kaons on neutrons. The experiment will measure both differential cross sections and self-analyzed polarizations of the produced Λ\Lambda, Σ\Sigma, Ξ\Xi, and Ω\Omega hyperons using the GlueX detector at the Jefferson Lab Hall D. The measurements will span CM cosθ\cos\theta from 0.95-0.95 to 0.95 in the range W = 1490 MeV to 2500 MeV. The new data will significantly constrain the partial wave analyses and reduce model-dependent uncertainties in the extraction of the properties and pole positions of the strange hyperon resonances, and establish the orbitally excited multiplets in the spectra of the Ξ\Xi and Ω\Omega hyperons. Comparison with the corresponding multiplets in the spectra of the charm and bottom hyperons will provide insight into he accuracy of QCD-based calculations over a large range of masses. The proposed facility will have a defining impact in the strange meson sector through measurements of the final state KπK\pi system up to 2 GeV invariant mass. This will allow the determination of pole positions and widths of all relevant K(Kπ)K^\ast(K\pi) SS-,PP-,DD-,FF-, and GG-wave resonances, settle the question of the existence or nonexistence of scalar meson κ/K0(700)\kappa/K_0^\ast(700) and improve the constrains on their pole parameters. Subsequently improving our knowledge of the low-lying scalar nonet in general

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