Differential evolution for the offline and online optimization of fed-batch fermentation processes

The optimization of input variables (typically feeding trajectories over time) in fed-batch fermentations has gained special attention, given the economic impact and the complexity of the problem. Evolutionary Computation (EC) has been a source of algorithms that have shown good performance in this task. In this chapter, Differential Evolution (DE) is proposed to tackle this problem and quite promising results are shown. DE is tested in several real world case studies and compared with other EC algorihtms, such as Evolutionary Algorithms and Particle Swarms. Furthermore, DE is also proposed as an alternative to perform online optimization, where the input variables are adjusted while the real fermentation process is ongoing. In this case, a changing landscape is optimized, therefore making the task of the algorithms more difficult. However, that fact does not impair the performance of the DE and confirms its good behaviour.(undefined

Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma

Background Pathogenic germline variants in subunits of succinate dehydrogenase (SDHB, SDHC and SDHD) are broadly associated with disease subtypes of phaeochromocytoma-paraganglioma (PPGL) syndrome. Our objective was to investigate the role of variant type (ie, missense vs truncating) in determining tumour phenotype.Methods Three independent datasets comprising 950 PPGL and head and neck paraganglioma (HNPGL) patients were analysed for associations of variant type with tumour type and age-related tumour risk. All patients were carriers of pathogenic germline variants in the SDHB, SDHC or SDHD genes.Results Truncating SDH variants were significantly over-represented in clinical cases compared with missense variants, and carriers of SDHD truncating variants had a significantly higher risk for PPGL (p<0.001), an earlier age of diagnosis (p<0.0001) and a greater risk for PPGL/HNPGL comorbidity compared with carriers of missense variants. Carriers of SDHB truncating variants displayed a trend towards increased risk of PPGL, and all three SDH genes showed a trend towards over-representation of missense variants in HNPGL cases. Overall, variant types conferred PPGL risk in the (highest-to-lowest) sequence SDHB truncating, SDHB missense, SDHD truncating and SDHD missense, with the opposite pattern apparent for HNPGL (p<0.001).Conclusions SDHD truncating variants represent a distinct group, with a clinical phenotype reminiscent of but not identical to SDHB. We propose that surveillance and counselling of carriers of SDHD should be tailored by variant type. The clinical impact of truncating SDHx variants is distinct from missense variants and suggests that residual SDH protein subunit function determines risk and site of disease.Diabetes mellitus: pathophysiological changes and therap

On a uniformly accurate finite difference approximation of a singularly perturbed reaction-diffusion problem using grid equidistribution

We examine the convergence properties of a finite difference approximation of a singularly perturbed reaction-diffusion boundary value problem using a nonuniform grid. The grid is based on the equidistribution of a positive monitor function that is a linear combination of a constant floor and a power of the second derivative of the solution. Analysis shows how the monitor function can be chosen to ensure that the accuracy of the numerical approximation is insensitive to the size of the singular perturbation parameter. The use of equidistribution principles appears in many practical grid adaption schemes and our analysis provides insight into the convergence behaviour on such grids. Numerical results are given that confirm the uniform convergence rates

Romantic love: a mammalian brain system for mate choice

Mammals and birds regularly express mate preferences and make mate choices. Data on mate choice among mammals suggest that this behavioural ‘attraction system’ is associated with dopaminergic reward pathways in the brain. It has been proposed that intense romantic love, a human cross-cultural universal, is a developed form of this attraction system. To begin to determine the neural mechanisms associated with romantic attraction in humans, we used functional magnetic resonance imaging (fMRI) to study 17 people who were intensely ‘in love’. Activation specific to the beloved occurred in the brainstem right ventral tegmental area and right postero-dorsal body of the caudate nucleus. These and other results suggest that dopaminergic reward and motivation pathways contribute to aspects of romantic love. We also used fMRI to study 15 men and women who had just been rejected in love. Preliminary analysis showed activity specific to the beloved in related regions of the reward system associated with monetary gambling for uncertain large gains and losses, and in regions of the lateral orbitofrontal cortex associated with theory of mind, obsessive/compulsive behaviours and controlling anger. These data contribute to our view that romantic love is one of the three primary brain systems that evolved in avian and mammalian species to direct reproduction. The sex drive evolved to motivate individuals to seek a range of mating partners; attraction evolved to motivate individuals to prefer and pursue specific partners; and attachment evolved to motivate individuals to remain together long enough to complete species-specific parenting duties. These three behavioural repertoires appear to be based on brain systems that are largely distinct yet interrelated, and they interact in specific ways to orchestrate reproduction, using both hormones and monoamines. Romantic attraction in humans and its antecedent in other mammalian species play a primary role: this neural mechanism motivates individuals to focus their courtship energy on specific others, thereby conserving valuable time and metabolic energy, and facilitating mate choice