A structured approach to cope with impurities during industrial crystallization development

The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development

On separable Fokker-Planck equations with a constant diagonal diffusion matrix

We classify (1+3)-dimensional Fokker-Planck equations with a constant diagonal diffusion matrix that are solvable by the method of separation of variables. As a result, we get possible forms of the drift coefficients $B_1(\vec x),B_2(\vec x),B_3(\vec x)$ providing separability of the corresponding Fokker-Planck equations and carry out variable separation in the latter. It is established, in particular, that the necessary condition for the Fokker-Planck equation to be separable is that the drift coefficients $\vec B(\vec x)$ must be linear. We also find the necessary condition for R-separability of the Fokker-Planck equation. Furthermore, exact solutions of the Fokker-Planck equation with separated variables are constructedComment: 20 pages, LaTe

Transgenic Potatoes for Potato Cyst Nematode Control Can Replace Pesticide Use without Impact on Soil Quality

Current and future global crop yields depend upon soil quality to which soil organisms make an important contribution. The European Union seeks to protect European soils and their biodiversity for instance by amending its Directive on pesticide usage. This poses a challenge for control of Globodera pallida (a potato cyst nematode) for which both natural resistance and rotational control are inadequate. One approach of high potential is transgenically based resistance. This work demonstrates the potential in the field of a new transgenic trait for control of G. pallida that suppresses root invasion. It also investigates its impact and that of a second transgenic trait on the non-target soil nematode community. We establish that a peptide that disrupts chemoreception of nematodes without a lethal effect provides resistance to G. pallida in both a containment and a field trial when precisely targeted under control of a root tip-specific promoter. In addition we combine DNA barcoding and quantitative PCR to recognise nematode genera from soil samples without microscope-based observation and use the method for nematode faunal analysis. This approach establishes that the peptide and a cysteine proteinase inhibitor that offer distinct bases for transgenic plant resistance to G. pallida do so without impact on the non-target nematode soil community

Impact of impurities on crystallization and product quality : a case study with paracetamol

A thorough, systematic study into the effect that structurally related impurities have on both the process and product quality during the crystallization of an active pharmaceutical ingredient is presented. The presence of acetanilide and metacetamol influences the crystallization and product quality of paracetamol. Where high concentrations of either impurity were present in the crystallization feed, product recovery decreased by up to 15%. Acetanilide is included in the final product through adsorption onto the particle surface in concentrations up to 0.79 mol%, which can be reduced to acceptable levels through product reslurrying. The presence of metacetamol results in much higher concentrations—up to 6.78 mol% in the final product, of which approximately 1 mol% is incorporated into the crystal lattice, resulting in the perturbation of the unit-cell dimensions. The incidental crystallization and subsequent isolation of metastable Form II paracetamol increased product purity in the presence of a low metacetamol concentration. This metastable product converts to stable paracetamol Form I through reslurrying, offering an efficient metacetamol impurity rejection route. The morphology of the product is modified consistently by both impurities. An elongation of the normal prismatic shape is observed, which in the extreme case of high metacetamol contamination results in the isolation of fine, fragile needles. This problematic morphology is also improved by a reslurrying of the crystallization product to give a more equilateral shape. This systematic study of the influence of acetanilide and metacetamol on the crystallization of paracetamol builds a well-rounded picture of the concomitant impact of impurities on the principal quality attributes of a crystallization product

Obstruction Results in Quantization Theory

We define the quantization structures for Poisson algebras necessary to generalise Groenewold and Van Hove's result that there is no consistent quantization for the Poisson algebra of Euclidean phase space. Recently a similar obstruction was obtained for the sphere, though surprising enough there is no obstruction to the quantization of the torus. In this paper we want to analyze the circumstances under which such obstructions appear. In this context we review the known results for the Poisson algebras of Euclidean space, the sphere and the torus.Comment: 34 pages, Latex. To appear in J. Nonlinear Scienc

The coherence of autism

There is a growing body of opinion that we should view autism as fractionable into different, largely independent sets of clinical features. The alternative view is that autism is a coherent syndrome in which principal features of the disorder stand in intimate developmental relationship with each other. Studies of congenitally blind children offer support for the latter position and suggest that a source of coherence in autism is restriction in certain forms of perceptually dependent social experience

From the Shell-shocked Soldier to the Nervous Child: Psychoanalysis in the Aftermath of the First World War

This article investigates the development of child analysis in Britain between the wars, as the anxious child succeeded the shell-shocked soldier as a focus of psychoanalytic enquiry. Historians of psychoanalysis tend to regard the Second World War as a key moment in the discovery of the ‘war within’ the child, but it was in the aftermath of the First War that the warring psyche of the child was observed and elaborated. The personal experience of war and its aftermath, and the attention given to regression in the treatment of war neuroses, encouraged Melanie Klein, Anna Freud and others to turn their attention to children. At the same time, however, the impact of the First World War as a traumatic event, with inter-generational consequences, remained largely unaccounted for within psychoanalysis as Klein and others focused on the child's riven internal world