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The development of inhibitors of islet amyloid formation is important as pancreatic amyloid deposition contributes to type-2 diabetes and islet transplant failure. The Alzheimer's Aβ peptide and human amylin (h-amylin), the polypeptide responsible for amyloid formation in type-2 diabetes, share common physio-chemical features and some inhibitors of Aβ also inhibit amyloid formation by h-amylin and vice versa. Thus, a popular and potentially useful strategy to find lead compounds for anti-amylin amyloid agents is to examine compounds that have effects on Aβ amyloid formation. The triphenylmethane dye, brilliant blue G (BBG, Sodium;3-[[4-[(E)-[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]-2-methylcyclohexa-2,5-dien-1-ylidene]methyl]-N-ethyl-3-methylanilino]methyl]benzenesulfonate) has been shown to modulate Aβ amyloid formation and inhibit Aβ induced toxicity. However, the effects of BBG on h-amylin have not been examined, although other triphenylmethane derivatives inhibit h-amylin amyloid formation. The compound has only a modest impact on h-amylin amyloid formation unless it is added in significant excess. BBG also remodels preformed h-amylin amyloid fibrils if added in excess, however BBG has no significant effect on h-amylin induced toxicity towards cultured β-cells or cultured CHO-T cells except at high concentrations. BBG is shown to interfere with standard thioflavin-T assays of h-amylin amyloid formation and disaggregation, highlighting the difficulty of interpreting such experiments in the absence of other measurements. BBG also interferes with ANS based assays of h-amylin amyloid formation. The work highlights the differences between inhibition of Aβ and h-amylin amyloid formation, illustrates the limitation of using Aβ inhibitors as leads for h-amylin amyloid inhibitors, and reinforces the difficulties in interpreting dye binding assays of amyloid formation.

A novel and highly efficient photocatalyst of a AgBiO3/BiOCl heterojunction has been developed via a facile water bath and in situ precipitation method. The photocatalytic activities of the catalysts were investigated by the degradation of ciprofloxacin (CIP) under visible-light irradiation (>420 nm). The experiment results revealed that the photocatalytic performance of the optimized AgBiO3/BiOCl heterojunction was much higher than pure AgBiO3 and BiOCl. The degradation efficiency of the as-prepared AgBiO3/BiOCl heterojunction (ABC-30) for CIP could reach 88% within 160 min, with 2.89 and 3.76 times higher activity than pure AgBiO3 and BiOCl, respectively. The improved photocatalytic performance of AgBiO3/BiOCl was attributed to the synergistic effect of the enhanced light absorption range and effective separation and transfer of the photo-induced charge carrier. The optimized heterojunction showed broad-spectrum catalytic activities towards various organic contaminants. The degradation efficiencies varied with the nature of the pollutant and decreased in the following order: Lanasol Red 5B (100%) > methyl orange (99%) > methylene blue (98%) > tetracycline (92%) > ciprofloxacin (88%) > ofloxacin (85%) > norfloxacin (78%) > rhodamine B (59%) > metronidazole (43%) > phenol (40%) > carbamazepine (20%). Furthermore, the trapping experiments and ESR indicated that superoxide radicals and holes were the main reactive species. [ABSTRACT FROM AUTHOR]

The parameter identification problem of linear discrete period time‐varying (LDPV) systems is studied in this paper and a two‐step identification algorithm based on the recursive least squares principle is proposed. The recursive principle‐based identification algorithm is mostly used to deal with the parameter identification of time‐invariant systems. Combine with the cyclic reconstruction method, the LDPV system is converted to a linear time‐invariant system. Then, based on this and combined with recursive least squares identification, a discrimination algorithm is proposed for the parameter estimation of the LDPV system. Finally, a numerical simulation example is given to demonstrate the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Proteinnative state aggregation, a major problem in pharmaceuticaland biological processes, has been addressed pharmacologically bythe addition of protein-binding excipients. Heparin (Hp), a highlysulfated polysaccharide, interacts with numerous proteins with moderateto high affinity, but reports about its effect on protein aggregationare contradictory. We studied the pH dependence of the aggregationof antithrombin (AT) and bovine serum albumin (BSA) in the presenceand absence of heparin. High-precision turbidimetry showed strongaggregation for both AT and BSA in I= 10 mM NaCl,conditions at which electrostatically driven Hp binding and aggregationboth occur, with more obvious aggregation of heparin-free AT appearingas larger aggregate size. Aggregation of AT was dramatically inhibitedat Hp: protein 6:1 (mole ratio); however, the effect at 0.5:1 Hp:proteinwas greater for BSA. Frontal analysis capillary electrophoresis showeda much larger equilibrium association constant Kobsbetween Hp and AT, in accord with the onset of Hp bindingat a higher pH; both effects are explained by the higher charge densityof the positive domain for AT as revealed by modeling with DelPhi.The corresponding modeling images showed that these domains persistat high salt only for AT, consistent with the 160-fold drop in Kobsat 100 mM salt for BSA–Hp binding.The smaller inhibition effect for AT arises from the tendency of itsuncomplexed monomer to form larger aggregates more rapidly, but thestronger binding of Hp to AT does not facilitate Hp-induced aggregatedissolution which occurs more readily for BSA. This can be attributedto the higher density of AT aggregates evidenced by higher fractaldimensions. Differences between inhibition and reversal by Hp arisebecause the former may depend on the stage at which Hp enters theaggregation process and the latter on aggregate size and morphology. [ABSTRACT FROM AUTHOR]