This article proposes a systematic method for the optimal design of sensor locations for an automated Coordinate Checking Fixture (CCF). The fixture can be employed for making at-machine assessments of the dimensional accuracy of manufactured components. Coordinate measurements obtained by the sensors built into the fixture can be utilized in estimating geometric parameters of a manufactured part. Two important issues that arise in the design of a CCF are the optimal number of sensors to be used and the best locations for each sensor. The proposed method uses statistical analyses of the Fisher information matrix and the prediction matrix to obtain an optimal set of sensors from an initial candidate set. Sensors are placed at locations that maximize the determinant of the Fisher information matrix for best parameter estimation, while the sensor of the least contribution to the measurement objective is iteratively eliminated. With the benefit of physical insight, the design procedure results in a balanced decision for the optimal placement of sensors. The developed method also addresses the problem of selection of part locators for part localization in the CCF. Examples are provided for illustration of the developed procedure for automotive space frame extrusion parts.
l-Cysteine is a ubiquitous and unique sulfur-containing amino acid with numerous applications in agricultural and food industries. The efficient production of l-cysteine via microbial fermentation has received a great deal of attention. In this study, the fitness of different Escherichia coli K-12 strains harboring plasmid pLH03 was investigated. The enhancement of the precursor synthetic pathway and thiosulfate assimilation pathway resulted in the good performance of the E. coli BW25113 strain. The expression levels of synthetic pathway genes were optimized by two constitutive promoters to assess their effects on cysteine production. In conjunction, the main degradation pathway genes were also deleted for more efficient production of cysteine. l-Cysteine production was further increased through the manipulation of the sulfur transcription regulator cysB and sulfur supplementation. After process optimization in a 1.5 L bioreactor, LH2A1M0BΔYTS-pLH03 [BW25113 Ptrc2-serA Ptrc1-cysMPtrc-cysBΔyhaMΔtnaAΔsdaA-(pLH03)] accumulated 8.34 g/L cysteine, laying a foundation for application in the cysteine fermentation industry.
Myricetin is a natural flavonol found in many grapes, berries, fruits, vegetables, and herbs as well as other plants. Recent studies have identified potential antiamyloidogenic activity for this compound. In this study, the kinetics of amyloid fibril formation by hen egg white lysozyme (HEWL) and the antifibril-forming activity of myricetin were investigated. We demonstrate that myricetin significantly inhibits the fibrillation of HEWL and the inhibitory effect is dose-dependent. Interestingly, the inhibitory effect toward HEWL fibrillation was stronger than that exerted by the previously characterized fibril-forming inhibitor quercetin, which has high structural similarity with myricetin. Spectrofluorometric and computational studies suggest that the mechanism underlying the inhibitory action of myricetin at a molecular level is to reduce the population of partially unfolded HEWL intermediates. This action is achieved by the tight binding of myricetin to the aggregation-prone region of the β-domain of HEWL and linking to the relatively stable α-domain, thus resulting in the inhibition of amyloid fibril formation. KEYWORDS: myricetin, lysozyme, amyloid, molecular dynamics simulation, molecular docking ■ INTRODUCTIONAmyloid diseases are characterized by conformational changes of certain proteins, which lead to intracellular or extracellular aggregation, eventually resulting in fibrillar amyloid deposits in the affected tissue. Currently there are approximately 30 extracellular fibril proteins known to be associated with human amyloidosis. 1 The so-called "hereditary non-neuropathic systemic amyloidosis" is associated with two lysozyme variants (I56T and D67H), which were identified in the early 1990s 2 and other naturally occurring amyloidogenic variants (F57I, F57I/ T70N, W64R, and T70N/W112R) discovered more recently. 3−5 The pathological characteristics of these amyloidoses includes the deposition of the full-length protein variants in organs, such as liver, spleen, and kidneys. 2 At present there are still no effective treatments for amyloid diseases such as Alzheimer's disease, systemic amyloidosis, familial amyloid polyneuropathy, and Creutzfeldt-Jakob disease, and all drugs in development that target Alzheimer's disease have failed at various stages of clinical trials. 6 However, the identification and development of small molecules that inhibit fibril formation by amyloidogenic proteins is a promising area of research. 7,8 Among the most promising small-molecule inhibitors, the naturally occurring polyphenols show the most effective antiamyloidogenic activity. 9 A group of polyphenols found in green tea (GTPs) including (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECG), and (−)-epigallocatechin gallate (EGCG) have been reported as effective inhibitors of alkali-saltinduced fibrillogenesis of hen egg white lysozyme (HEWL) with ECG as the most potent polyphenol. 10 A previous report demonstrated that curcumin can also inhibit the aggregation and formation of amyloid fibrillation of HEWL ...
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