Measurement uncertainty from physical sample preparation: estimation including systematic error

A methodology is proposed, which employs duplicated primary sampling and subsequent duplicated physical preparation coupled with duplicated chemical analyses. Sample preparation duplicates should be prepared under conditions that represent normal variability in routine laboratory practice. The proposed methodology requires duplicated chemical analysis on a minimum of two of the sample preparation duplicates. Data produced from the hierarchical design is treated with robust analysis of variance (ANOVA) to generate uncertainty estimates, as standard uncertainties ('u' expressed as standard deviation), for primary sampling (ssamp), physical sample preparation (sprep) and chemical analysis (sanal). The ANOVA results allow the contribution of the sample preparation process to the overall uncertainty to be assessed. This methodology has been applied for the first time to a case study of pesticide residues in retail strawberry samples. Duplicated sample preparation was performed under ambient conditions on two consecutive days. Multi-residue analysis (quantification by GC-MS) was undertaken for a range of incurred pesticide residues including those suspected of being susceptible to loss during sample preparation procedures. Sampling and analytical uncertainties dominated at low analyte concentrations. The sample preparation process contributed up to 20% to the total variability and had a relative uncertainty (Uprep%) of up to 66% (for bupirimate at 95% confidence). Estimates of systematic errors during physical sample preparation were also made using spike recovery experiments. Four options for the estimation of measurement uncertainty are discussed, which both include and exclude systematic error arising from sample preparation and chemical analysis. A holistic approach to the combination and subsequent expression of uncertainty is advised.     

Oxaziridine-mediated amination of primary amines: scope and application to a one-pot pyrazole synthesis

Electrophilic amination of primary aliphatic and aromatic amines is reported using a diethylketomalonate-derived oxaziridine to afford the corresponding N-Boc hydrazines in good to excellent yields. The method allows a one-pot synthesis of pyrazoles from primary amines. [Reaction: see text]     

Reactive Chemical Probes: Beyond the Kinase Cysteinome

The reaction of small‐molecule chemical probes with proteins has been harnessed to develop covalent inhibitor drugs and protein‐profiling technologies. This Essay discusses some of the recent enhancements to the chemical biology toolkit that are enabling the study of previously unchartered areas of chemoproteomic space. An analysis of the kinome is used to illustrate the potential for these approaches enable the pursuit of new targets using reactive chemical probes.     

Copper‐Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol‐substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl‐protected enol, since the corresponding acetyldiazoimide failed to provide any cross‐products in metal‐catalyzed reactions with sulfur ylides. This copper‐catalyzed cycloaddition is initiated with the generation of enol‐substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six‐membered ring formation, C?O and C?S bond cleavage, and silyl and acetyl group migration.     

Electrochemical and Surface Analysis Studies on the Carbon Dioxide Corrosion of X‐65 Carbon Steel

A comprehensive study of the CO₂ corrosion of carbon steel (X‐65) at low partial pressures of CO₂ is reported in this paper. Field emission scanning electron microscopy (FESEM), Raman spectroscopy (RS), synchrotron radiation‐grazing incidence X‐ray diffraction (SR‐GIXRD), and electrode kinetic studies have confirmed that chukanovite, magnetite and siderite are the main corrosion products at low partial pressures of CO₂. Chukanovite forms predominantly in the presence of CO₂, while magnetite was found to be the major corrosion product in the absence of CO₂, although the majority of previous work based on conventional ex‐situ materials characterization techniques has implied that siderite is the main corrosion product. Here, it is shown that the nature of corrosion products is strongly dependent on the experimental conditions at low pressures of CO₂, which has not been elucidated in previous studies. Accordingly, this study has made a significant contribution to identifying the true nature of corrosion scales formed at low partial pressures of CO₂ allowing the development of effective anti‐corrosive agents for the control and prevention of carbon steel corrosion at low CO₂ partial pressures.     

Optimised uncertainty at minimum overall cost to achieve fitness-for-purpose in food analysis.

An optimised uncertainty (OU) methodology is described, that balances the uncertainty of measurements on food against the cost of the measurements and the other expenditure that may arise as a consequence of the possible misclassification of the food. Measurement uncertainty from the sources of primary sampling and chemical analysis is estimated using an existing technique, which is based on the taking of duplicated samples and duplicated analyses. The input information required for the OU method is the actual costs of sampling and analysis, and the expected costs that could arise from either the 'false positive' or 'false negative' classification of batches of food. A loss function is then constructed that calculates the 'expectation of loss' which will arise for a given uncertainty of measurement. This function has a minimum value of cost at an optimal value of uncertainty, which can be estimated numerically. Application of this OU method to a case study on the determination of aflatoxin levels in pistachio nuts has demonstrated this minimum value. Below the optimum value of uncertainty, the costs increased due to higher measurement costs. Above the optimum value, the costs increased due to increasing probability of expenditure on consequences such as unnecessary rejection of the batch, potential litigation or loss of corporate reputation because of undetected contamination. A second stage of the OU method optimises the division of the expenditure on the measurement between that on sampling and that on analysis. The technique is demonstrated as a useful new approach for judging the fitness-for-purpose of chemical measurements in the food industry. Several areas for further development of the technique are identified. By matching the expenditure on the measurement against that caused by the misclassification of the food, the OU method has the potential to reduce overall expenditure whilst ensuring an appropriate reliability of measurement.     

Trends in the evolution of models & modeling perspectives on mathematical learning and problem solving

In this paper we briefly outline the models and modelling (M&M) perspective of mathematical thinking and learning relevant for the 21st century. Models and modeling (M&M) research often investigates the nature of understandings and abilities that are needed in order for students to be able to use what they have (presumably) learned in the classroom in “real life” situations beyond school Nonetheless, M&M perspectives evolved out of research on concept development more than research on problem solving; and, rather than being preoccupied with the kind of word problems emphasized in textbooks and standardized tests, we focus on (simulations of) problem solving “in the wild.” Also, we give special attention to the fact that, in a technology-basedage of information, significant changes are occurring in the kinds of “mathematical thinking” that is coming to be needed in the everyday lives of ordinary people in the 21^st century—as well as in the lives of productive people in future-oriented fields that are heavy users of mathematics, science, and technology.     

Hafnium binding to rat serum transferrin

Using the TDPAC-technique binding parameters for Hf were determined afterin vivo uptake of¹⁸¹Hf in rat plasma. As much as 98.5% of the metal ions proved to be bound to protein, essentially to transferrin. The main fraction of the¹⁸¹Hf ions experiences a well defined electric quadrupole perturbation frequency (vQ1=(1516 ± 15)MHz, δ₁=(5.3 ± 0.8)%) connected with a marked relaxation damping (λ = (46 ± 8)MHz). The remaining Hf nuclei are subject to a fairly broad distribution of electric field gradients (v_Q2=(1014 ± 37)MHz, δ₂=(16±3)%). The results are compared with data obtained within vitro ¹⁸¹Hf-labeled human transferrin.