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Ion mobility spectrometry was utilized to corroborate the identity of streptorubin B (2) as the natural product produced by Streptomyces coelicolor. Natural product 2was initially assigned as butylcycloheptylprodigiosin (3), and only relatively recently was this assignment clarified. We present additional evidence of this assignment by comparing collisional cross sections (Ω) of synthetic standards of 2, 3, and metacycloprodigiosin (4) to the cyclic prodiginine produced by S. coelicolor. Calculated theoretical Ω values demonstrate that cyclic prodiginines could be identified without standards. This work highlights ion mobility as an efficient tool for the dereplication of natural products.

BackgroundAlthough a meta-analysis has confirmed the association between antidepressant exposure in utero and subsequent poor neonatal adaptation, few identified studies included drug levels or standardized measures and only two studies followed up children who developed symptoms beyond infancy.MethodsThe study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 42 women/infant pairs at delivery. In all, 31 women continued to take antidepressants until delivery and 11 ceased earlier in pregnancy. Poor neonatal adaptation was assessed twice daily for up to 6 days by using the Neonatal Abstinence Scoring System (NASS). Drug levels were analyzed in umbilical cord blood and maternal blood obtained at delivery.ResultsIn total, 76% (32 of 42) of neonates exposed to antidepressants had symptoms observed on the NASS. These symptoms occurred up to 5 days postpartum with 25% having symptoms that persisted for more than 3 days. The most frequent symptoms were correlated most closely to antidepressant drug levels. Elevated NASS scores were found to be associated with poorer fine motor development at 6 months of age.ConclusionsPoor neonatal adaptation may be more common than previously recognized. The NASS was observed to be an effective assessment and monitoring measure. Research following symptomatic infants beyond the neonatal period is required.

Background:The Depression, Anxiety, and Stress Scale –21 (DASS-21) is a frequently used measure of emotional disturbance symptoms in Parkinson’s disease (PD). However, the factor structure of the DASS-21 in PD has yet to be explored. Objective:To assess whether the scale is measuring these symptoms in PD in the same way as the general population. Methods:The present study fit a series of established DASS-21 factor structures with both confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM) using data from 251 participants with PD. Results:The 3-factor ESEM provided the best fit. The depression and stress scales fit well, however, few items on the anxiety subscale loaded clearly, with several items significantly loading onto the depression or stress factors. Conclusions:Whilst the depression and stress subscales appear suitable in PD, poor loadings and internal consistency indicate the anxiety subscale may not accurately assess anxiety symptomology in PD. This may be due to the scale’s reliance on physiological symptoms as indicators of anxiety, when many of these are present in PD. Thus, the anxiety subscale of the DASS-21 may not be a suitable measure of anxiety in PD.

Natural products exhibit a broad range of biological properties and have been a crucial source of therapeutic agents and novel scaffolds. Although bacterial secondary metabolomes are widely explored, they remain incompletely cataloged by current isolation and characterization strategies. To identify metabolites residing in unexplored chemical space, we have developed an integrated discovery approach that combines bacterial growth perturbation, accurate mass spectrometry, comparative mass spectra data analysis, and fragmentation spectra clustering for the identification of low-abundant, novel compounds from complex biological matrices. In this investigation, we analyzed the secreted metabolome of the extensively studied Actinomycete, Streptomyces coelicolorM145, and discovered a low-abundant suite of 15 trihydroxamate, amphiphilic siderophores. Compounds in this class have primarily been observed in marine microorganisms making their detection in the soil-dwelling S. coelicolorM145 significant. At least 10 of these ferrioxamine-based molecules are not known to be produced by any organism, and none have previously been detected from S. coelicolorM145. In addition, we confirmed the production of ferrioxamine D1, a relatively hydrophilic family member that has not been shown to be biosynthesized by this organism. The identified molecules are part of only a small list of secondary metabolites that have been discovered since sequencing of S. coelicolorM145 revealed that it possessed numerous putative secondary metabolite-producing gene clusters with no known metabolites. Thus, the identified siderophores represent the unexplored metabolic potential of both well-studied and new organisms that could be uncovered with our sensitive and robust approach.

Chromatography is a technique used to separate and quantify the components in a complex chemical mixture. We have created a 3D visualization system capable of comparing the chemical properties of chromatographic systems. The visualization system combines scatter plots, parallel coordinates, and specialized glyphs to assist in the analysis of chromatographic data and comparisons of multiple systems. Using this tool, numerous separation systems can be readily compared simultaneously - greatly facilitating the ability to select systems that are likely to produce desired separations during method development.

It is now well known that smart fluids [electrorheological (ER) and magnetorheological (MR)] can form the basis of controllable vibration damping devices. With both types of fluid, however, the force/velocity characteristic of the resulting damper is significantly non-linear, possessing the general form associated with a Bingham plastic. In a previous paper the authors showed that by using a linear feedback control strategy it is possible to produce the equivalent of a viscous damper with a continuously variable damping coefficient. In the present paper the authors illustrate an extension of the technique, by showing how the shape of the force/velocity characteristic can be controlled through feedback control. This is achieved by using a polynomial function to generate a set point based upon the damper velocity. The response is investigated for polynomial functions of zero, 1st and 2nd order. It is shown how the damper can accurately track higher order polynomial shaping functions, while the zero-order function is particularly useful in illustrating the dynamics of the closed-loop system.

The optimization of roadway safety design by experimental means is expensive and time consuming. Computer simulation of such complex engineering systems improves understanding of how and why the system behaves as it does, aids in decision making, and reduces development costs and time involved. The simulation presented is based on a computer model developed from a study of the results of full-scale experiments of impact on the Brifen wire-rope safety fence (WRSF). The code comprises a dynamic vehicle model and a quasi-static fence model interacting in time through the important collapse mechanisms of the system. The principles governing them are described and their inclusion is validated by demonstrating good correlation between the predictions of the simulation and the experimental test data. Sensitivity studies show that the performance of a WRSF is particularly sensitive to the impact conditions of vehicle speed and angle and the design parameters offence height, post spacing, post strength, and rope pre-tension. The sensitivity work is extended to show that for fences installed with a low rope pre-tension, performance may not be significantly impaired if rope pre-tension is not maintained. However, significant gains in fence performance may be made should a fence be installed and maintained with a high rope pre-tension. The use of the simulation in assessing cost-effectiveness of alternative designs in achieving a target performance is also demonstrated.