Internal standard signal suppression by co-eluting analyte in isotope dilution LC-ESI-MS

The suppression of the internal standard by increasing concentrations of the co-eluting analyte in calibration series and plasma samples analysed by LC-ESI-MS was studied using the isotope dilution technique. A series of three analyte/deuterated analyte pairs including fexofenadine/d6-fexofenadine, dapsone/d4-dapsone and peudoephedrine/d3-ephedrine were investigated. Suppression of the internal standard signal was noticed in extracted plasma samples containing fexofenadine and d6-fexofenadine as internal standard, as well as in solvent based calibration solutions of the three pair of compounds noted above during LC-ESI-MS analysis at flow rates greater than 100 microL min(-1). This signal suppression effect was described by invoking Enke's model of electrospray ion generation. This model suggests that signal suppression can be ascribed to the competition between ionic species for charged surface sites present on the generated droplets during the electrospray process. The slopes of the calibration curves of the three analytes were close to unity (fexofenadien/d6-fexofenadine 0.964 +/- 0.008, pseudoephedrine/d3-ephedrine 1.02 +/- 0.080 and dapsone/d4-dapsone 0.905 +/- 0.048) as predicted by the model, indicating that quantitation should not be affected by the variation in the peak area of the internal standard.     

Molecular tagging thermometry with adjustable temperature sensitivity

We report an extension to the technique of molecular tagging thermometry which allows for adjustable temperature sensitivity. The temperature dependence of laser-induced phosphorescence of the water-soluble phosphorescent triplex (1-BrNp•Mβ-CD•ROH) is used to conduct temperature measurements in aqueous flows. It is shown that the temperature sensitivity of phosphorescence intensity can be adjusted by changing the time delay between the laser excitation pulse and the start of the phosphorescence emission acquisition. For example, for a phosphorescence integration period of 1 ms, the temperature sensitivity of the measured phosphorescence intensity varies in the range 8.15–18.2% per °C at 25°C as the time delay changes from 1 to7 ms. This temperature sensitivity is much higher than that of most fluorescent dyes used for temperature measurements (e.g. less than about 2% per °C for Rhodamine B). The implementation and application of this new approach are demonstrated by conducting temperature measurements in the wake of a heated cylinder.     

High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters

Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature—which assume a diverse ‘chemical space’—have significant potential as a source of anthelmintic compounds. In the present study, we screened a collection of extracts (n = 7616) derived from marine invertebrates sampled from Australian waters in a high throughput bioassay for in vitro anti-parasitic activity against the barber’s pole worm (Haemonchus contortus)—an economically important parasitic nematode of livestock animals. In this high throughput screen (HTS), we identified 58 active extracts that reduced larval motility by ≥70% (at 90 h), equating to an overall ‘hit rate’ of ~0.8%. Of these 58 extracts, 16 also inhibited larval development by ≥80% (at 168 h) and/or induced ‘non-wild-type’ (abnormal) larval phenotypes with reference to ‘wild-type’ (normal) larvae not exposed to extract (negative controls). Most active extracts (54 of 58) originated from sponges, three from chordates (tunicates) and one from a coral; these extracts represented 37 distinct species/taxa of 23 families. An analysis of samples by ¹H NMR fingerprinting was utilised to dereplicate hits and to prioritise a set of 29 sponge samples for future chemical investigation. Overall, these results indicate that a range of sponge species from Australian waters represents a rich source of natural compounds with nematocidal or nematostatic properties. Our plan now is to focus on in-depth chemical investigations of the sample set prioritised herein.     

Second-layer polysilicon structures for gate end-around leakage-current compensation in bulk CMOS ICs

CMOS integrated circuits (ICs) operating in space or other radiation environments can suffer from three different reliability problems due to the radiation: total dose effects, dose rate effects, and single event effects. The two most significant total-dose reliability problems are subthreshold, gate, end-around leakage current and threshold voltage shift. This article documents the theory, design, implementation, and testing of new, second-layer polysilicon structures that can compensate for radiation-induced, subthreshold, gate, end-around, leakage current. Second-layer polysilicon is available in many commercial, bulk CMOS processes and is normally used for floating-gate devices, such as EEPROMs and FPLAs, and charge-coupled devices such as CCD focal plan arrays. The use of the described structures in CMOS ICs would allow radiation tolerant ICs to be fabricated with commercial, bulk CMOS processes, greatly reducing manufacturing costs when compared to the cost of fabricating ICs on dedicated, radiation-hardened process lines.     

GaAs-AlGaAs multiquantum well reflection modulators grown on GaAsand silicon substrates

Measurements of GaAs-AlGaAs multiple-quantum-well (MQW) reflection modulators grown simultaneously on GaAs and silicon substrates are presented. Comparable electroabsorption is observed, with contrast ratios of about 4:1 for both modulators at 20 V. The absorption spectrum of the GaAs-on-Si quantum well shows a single exciton peak, which leads to certain improvements in modulator performance. This study is very encouraging for the growth of GaAs MQW modulators on silicon integrated circuit chips for off-chip communication     

Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates

The endocannabinoids 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamine (anandamide) are principally degraded by monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), respectively. The recent discovery of O-aryl carbamates such as JZL184 as selective MAGL inhibitors has enabled functional investigation of 2-AG signaling pathways in vivo. Nonetheless, JZL184 and other reported MAGL inhibitors still display low-level cross-reactivity with FAAH and peripheral carboxylesterases, which can complicate their use in certain biological studies. Here, we report a distinct class of O-hexafluoroisopropyl (HFIP) carbamates that inhibits MAGL in vitro and in vivo with excellent potency and greatly improved selectivity, including showing no detectable cross-reactivity with FAAH. These findings designate HFIP carbamates as a versatile chemotype for inhibiting MAGL and should encourage the pursuit of other serine hydrolase inhibitors that bear reactive groups resembling the structures of natural substrates.     

Wood property relationships and survival models in reliability

We study the relationship between lumber strength properties and their visual grading characteristics. This topic is central to the analysis of the reliability of lumber products in that it underlies the calculation of structural design values. The approaches described in the paper are adaptations of survival analysis methods commonly used in medical studies. Because each piece of lumber can only be tested to destruction with one method (i.e., each piece cannot be broken twice), modeling these strengths distributions simultaneously can be challenging. In the past, this kind of problem has been solved by subjectively matching pieces of lumber, but the quality of this approach is then an issue. The objective of our analysis is to build a predictive model that relates the strength properties to the recorded characteristics. The paper concludes that type of wood defect (knot), a lumber grade status (off‐grade: yes/no), and a lumber's module of elasticity have statistically significant effects on wood strength. We find that the Weibull accelerated failure time model provides a better fit than the Cox proportional hazards model in our dataset. Copyright © 2016 John Wiley & Sons, Ltd.     

CO2 laser cutting of MDF: 2. Estimation of power distribution

Part 2 of this paper details an experimentally-based method to evaluate the power distribution for both CW and PM cutting. Variations in power distribution with different cutting speeds, material thickness and pulse ratios are presented. The paper also provides information on both the cutting efficiency and absorptivity index for MDF, and comments on the beam dispersion characteristics after the cutting process.     

Computer aided measurement of biomechanical characteristics of cadaverous lumbar spines

Special computer-aided equipment was designed for measurement of biomechanical characteristics of lower part of the spine (L1-L5). When the stress is applied, it is necessary to observe the shift of the sample elements, together with measurement of the spine rigidity. This shift is determined with the help of circular targets fitted to the appropriate vertebra. The targets, illuminated by lamp or laser light, are monitored and their digitalized images are scanned by CCD camera is stored as computer media. The two dimensional Fourier transform of the digital optical signal is obtained by the fast Fourier transform algorithm. The period and direction of the interference fringes determine the size and the direction of the sample shift.