Process modelling of protein crystallisation: A case study of lysozyme

With the rise in interest of protein crystallisation as a purification step in downstream processing, there is significant interest in the process modelling of these crystallisation steps. Herein, we demonstrate and compare the applicability of “traditional” nucleation and growth models, commonly used to model small molecule crystallisation, for the successful population balance modelling of lysozyme crystallisation at the 100 mL and 1 L scales. Results show that both empirical power-law and first-principles models for nucleation and growth provide good fits to experimental data. Results from parameter estimation highlight a high degree of model sensitivity to initial guesses and stress the importance of providing particle size estimates in order to extract sensible data from the models. Estimates obtained for the 100 mL scale provided suitable initial guesses for the 1 L scale, despite significant differences in the final values obtained at each scale. For future work, further investigation into model validation upon scale-up is recommended. The work performed demonstrates the effectiveness of population balance modelling in the prediction of protein crystallisation behaviour, regardless of the underlying physical phenomena

Shedding Light Onto the Nature of Iron Decorated Graphene and Graphite Oxide Nanohybrids for CO₂ Conversion at Atmospheric Pressure

We report on the design and testing of new graphite and graphene oxide‐based extended π‐conjugated synthetic scaffolds for applications in sustainable chemistry transformations. Nanoparticle‐functionalised carbonaceous catalysts for new Fischer Tropsch and Reverse GasWater Shift (RGWS) transformations were prepared: functional graphene oxides emerged from graphite powders via an adapted Hummer's method and subsequently impregnated with uniform‐sized nanoparticles. Then the resulting nanomaterials were imaged by TEM, SEM, EDX, AFM and characterised by IR, XPS and Raman spectroscopies prior to incorporation of Pd(II) promoters and further microscopic and spectroscopic analysis. Newly synthesised 2D and 3D layered nanostructures incorporating carbon‐supported iron oxide nanoparticulate pre‐catalysts were tested, upon hydrogen reduction in situ, for the conversion of CO2 to CO as well as for the selective formation of CH4 and longer chain hydrocarbons. The reduction reaction was also carried out and the catalytic species isolated and fully characterised. The catalytic activity of a graphene oxide‐supported iron oxide pre‐catalyst converted CO2 into hydrocarbons at different temperatures (305, 335, 370 and 405 °C), and its activity compared well with that of the analogues supported on graphite oxide, the 3‐dimensional material precursor to the graphene oxide. Investigation into the use of graphene oxide as a framework for catalysis showed that it has promising activity with respect to reverse gas water shift (RWGS) reaction of CO2 to CO, even at the low levels of catalyst used and under the rather mild conditions employed at atmospheric pressure. Whilst the γ‐Fe2O3 decorated graphene oxide‐based pre‐catalyst displays fairly constant activity up to 405 °C, it was found by GC‐MS analysis to be unstable with respect to decomposition at higher temperatures. The addition of palladium as a promoter increased the activity of the iron functionalised graphite oxide in the RWGS. The activity of graphene oxide supported catalysts was found to be enhanced with respect to that of iron‐functionalised graphite oxide with, or without palladium as a promoter, and comparable to that of Fe@carbon nanotube‐based systems tested under analogous conditions. These results display a significant step forward for the catalytic activity estimations for the iron functionalised and rapidly processable and scalable graphene oxide. The hereby investigated phenomena are of particular relevance for the understanding of the intimate surface morphologies and the potential role of non‐covalent interactions in the iron oxide‐graphene oxide networks, which could inform the design of nano‐materials with performance in future sustainable catalysis applications

Uniform electroactive fiber-like micelle nanowires for organic electronics

AbstractMicelles formed by the self-assembly of block copolymers in selective solvents have attracted widespread attention and have uses in a wide variety of fields, whereas applications based on their electronic properties are virtually unexplored. Herein we describe studies of solution-processable, low-dispersity, electroactive fibre-like micelles of controlled length from π-conjugated diblock copolymers containing a crystalline regioregular poly(3-hexylthiophene) core and a solubilizing, amorphous regiosymmetric poly(3-hexylthiophene) or polystyrene corona. Tunnelling atomic force microscopy measurements demonstrate that the individual fibres exhibit appreciable conductivity. The fibres were subsequently incorporated as the active layer in field-effect transistors. The resulting charge carrier mobility strongly depends on both the degree of polymerization of the core-forming block and the fibre length, and is independent of corona composition. The use of uniform, colloidally stable electroactive fibre-like micelles based on common π-conjugated block copolymers highlights their significant potential to provide fundamental insight into charge carrier processes in devices, and to enable future electronic applications.</jats:p

A contingent valuation study to estimate the parental willingness-to-pay for childhood diarrhoea and gender bias among rural households in India

We used contingent valuation technique to estimate the parental willingness to pay for an episode of diarrhoea among 324 children of both sexes aged between five and seven years in two rural villages of Chennai in India. The aim was to examine if there was any gender bias in the parental willingness to treat children for a diarrhoeal episode, and if so to what extent. The willingness to pay was specified as a hedonic function of the duration and severity of an episode, and of parents' socioeconomic characteristics. The findings suggest that parents were willing to pay more to protect their male child compared to the female child suffering from a diarrhoeal episode. The median willingness to pay to avoid an episode for male and female children were calculated at Rs. 33.7 (approx. US$0.72) and Rs. 25.2 (approx. US$ 0.54) respectively – a difference of around 34%. After adjusting for the greater duration and severity of the illness, it was found that the difference between the two medians increased to 51%

Local Competition Between Foraging Relatives: Growth and Survival of Bruchid Beetle Larvae

Kin selection theory states that when resources are limited and all else is equal, individuals will direct competition away from kin. However, when competition between relatives is completely local, as is the case in granivorous insects whose larval stages spend their lives within a single seed, this can reduce or even negate the kin-selected benefits. Instead, an increase in competition may have the same detrimental effects on individuals that forage with kin as those that forage with non-kin. In a factorial experiment we assessed the effects of relatedness and competition over food on the survival and on fitness-related traits of the bruchid beetle Callosobruchus maculatus. Relatedness of competitors did not affect the survival of larvae. Larval survival substantially decreased with increasing larval density, and we found evidence that beetles maturing at a larger size were more adversely affected by competition, resulting in lower survival rates. Furthermore, females showed a reduction in their growth rate with increasing larval density, emerging smaller after the same development time. Males increased their growth rate, emerging earlier but at a similar size when food was more limited. Our results add to the growing number of studies that fail to show a relationship between relatedness and a reduction in competition between relatives in closed systems, and emphasize the importance of the scale at which competition between relatives occurs

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Attitudes About COVID-19 and Health (ATTACH): Online Survey and Mixed Methods Study

Background: Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. / Objective: In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. / Methods: The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper–Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively. / Results: By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (Ps<.05), had more preexisting mental health disorders and medical conditions, and were younger than 65 years (all Ps<.001). / Conclusions: Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics

Enhancing security and dependability of industrial networks with opinion dynamics

Opinion Dynamics poses a novel technique to accurately locate the patterns of an advanced attack against an industrial infrastructure, compared to traditional intrusion detection systems. This distributed solution provides pro table information to identify the most a ected areas within the network, which can be leveraged to design and deploy tailored response mechanisms that ensure the continuity of the service. In this work, we base on this multi-agent collaborative approach to propose a response technique that permits the secure delivery of messages across the network. For such goal, our contribution is twofold: rstly, we rede ne the existing algorithm to assess not only the compromise of nodes, but also the security and quality of service of communication links; secondly, we develop a routing protocol that prioritizes the secure paths throughout the topology considering the information obtained from the detection system.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Uniform “Patchy” Platelets by Seeded Heteroepitaxial Growth of Crystallizable Polymer Blends in Two Dimensions

Rectangular platelets formed by the self-assembly of block copolymers in selective solvents are of interest for a range of applications. Recently, we showed that the seeded growth of crystallizable blends of a block copolymer and homopolymer yields well-defined, low area dispersity examples of these two-dimensional (2D) structures. The key feature was the use of the same crystallizable polymer segment in the seed and blend components to enable an efficient homoepitaxial growth process. Herein we demonstrate that this 2D crystallization-driven self-assembly approach can be extended to <i>heteroepitaxial</i> growth by the use of different crystallizable polymers with compatible crystal structures. This allows the formation of well-defined “patchy” rectangular platelets and platelet block comicelles with different core chemistries. The use of scanning transmission electron microscopy–energy-dispersive X-ray spectroscopy provided key information on the spatial location of the components in the resulting assemblies and thereby valuable insight into the 2D heteroepitaxial growth process