Opportunities for Process Control and Quality Assurance Using Online NIR Analysis to a Continuous Wet Granulation Tableting Line

This paper investigates the application of online near-infrared measurements as a means to measure blend uniformity in a continuous tableting line. Underlying all the monitoring and control methods is the ability to measure key tablet properties online at a rate suitable for control purposes. The use of NIR to determine any deviations in blend uniformity is demonstrated by interpreting the relevant spectral signature allowing quantitative information to be acquired for process monitoring and quality assurance. In addition to demonstrating the functionality of the NIR probe, the practical issues arising in the application are discussed. The composition of the blend was measured using an NIR probe over a range of concentrations and the results were calculated comparing sub unit dose scale of scrutiny of small populations. This was compared with predicted product quality for whole tablets over the whole production period. This technique has demonstrated how data collected online can be used to successfully predict the quality of the whole production run for the purposes of real-time product quality assurance

Constraining magma storage conditions at a restless volcano in the Main Ethiopian Rift using phase equilibria models

This work is a contribution to the Natural Environment Research Council (NERC) funded RiftVolc project (NE/L013932/1, Rift volcanism: past, present, and future). W.H., T.A.M., and D.M.P. are supported by and contribute to the NERC Centre for the Observation and Modelling of Earthquakes, Volcanoes, and Tectonics (COMET). W.H. M.J.S. were supported by a NERC studentships NE/J5000045/1 and NE/K500811/01 respectively.The Main Ethiopian Rift hosts a number of peralkaline volcanic centres, with many showing signs of recent unrest. Due, in part, to the low number of historical eruptions recorded in the region, volcanism in the Main Ethiopian Rift remains understudied relative to other volcanic settings and conditions of magma storage remain almost entirely unknown. Aluto is one of these restless caldera systems and identifying magma storage conditions is vital for evaluating the risks posed by recent periods of unrest. In this study, we ran ~ 150 fractional crystallisation models, using the Rhyolite-MELTS thermodynamic software, within the range P = 50–300 MPa, starting H2O = 0.5–3 wt% and fO2 = QFM-2 − QFM + 1. This represents a realistic range of potential magma storage conditions at Aluto. We assessed the fractionation trends produced using two different starting compositions, which represent different estimates of the parental melt feeding the system. The predicted liquid lines of descent produced by these models are compared with Aluto whole-rock data from the literature, and are presented along with new observations of the natural phase assemblage and erupted mineral compositions to provide information on the magma storage conditions. Using a new, quantitative statistical approach to compare empirical data and thermodynamic model-outputs, we find that the compositions of evolved peralkaline rhyolites from Aluto are best reproduced by isobaric fractional crystallisation from a rift-related basaltic composition, without the need for significant crustal assimilation. Around 90% protracted fractional crystallisation is required to produce these compositions. This indicates that the magmatic system is likely to exist as a highly crystalline mush. The best agreement between models and natural samples is at low pressures (150 MPa), low initial H2O concentrations (0.5 wt%) and relatively high oxygen fugacity (QFM). The depth of magma storage derived from these results (~ 5.6 ± 1 km) agrees well with the source depths modelled from measured ground deformation at Aluto in 2008. Data from other peralkaline volcanic centres in the Main Ethiopian Rift, such as Boset and Gedemsa, and at other locations globally (e.g. Pantelleria, Italy) suggest that these storage conditions are a common feature of many peralkaline volcanic centres. Our data is consistent with the formation of a Daly Gap at Aluto due to compositional stratification of the magma reservoir beneath the caldera, and the non-linear relationship between temperature and SiO2 concentration during magmatic differentiation.PostprintPeer reviewe

Microbial Communities in a High Arctic polar desert landscape

The High Arctic is dominated by polar desert habitats whose microbial communities are poorly understood. In this study, we used next generation sequencing to describe the α- and β-diversity of polar desert soils from the Kongsfjorden region of Svalbard. Ten phyla consistently dominated the soils and accounted for 95 % of all sequences, with Proteobacteria, Actinobacteria and Chloroflexi being the dominant lineages. In contrast to previous investigations of Arctic soils, Acidobacterial relative abundances were low as were the Archaea throughout the Kongsfjorden polar desert landscape. Lower Acidobacterial abundances were attributed to the circumneutral soil pH in this region which has resulted from the weathering of the underlying carbonate geology. In addition, we correlated previously measured geochemical variables to determine potential controls on the communities. Soil phosphorus, pH, nitrogen and calcium significantly correlated with β-diversity indicating a landscape scale lithological control of soil nutrients which in turn influenced community composition. In addition, soil phosphorus and pH significantly correlated with α- diversity, specifically the Shannon diversity and Chao 1 richness indices

Participation and satisfaction after spinal cord injury: results of a vocational and leisure outcome study

Study design: Survey. Objectives: Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. Design: Descriptive analysis of data from a questionnaire. Setting: Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. Subjects: A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. Main outcome measures: Changes in participation in activities; current life satisfaction; support and unmet needs. Results: Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60% of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. Conclusions: Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation

Temporal dynamics of aquatic communities and implications for pond conservation

Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups

Inverting the handedness of circularly polarized luminescence from light-emitting polymers using film thickness

The emission of circularly polarized light is central to many applications, including data storage, optical quantum computation, biosensing, environmental monitoring, and display technologies. An emerging method to induce (chiral) circularly polarized (CP) electroluminescence from the active layer of polymer light-emitting diodes (polymer OLEDs; PLEDs) involves blending achiral polymers with chiral small-molecule additives, where the handedness/sign of the CP light is controlled by the absolute stereochemistry of the small molecule. Through the in-depth study of such a system we report an interesting chiroptical property: the ability to tune the sign of CP light as a function of active layer thickness for a fixed enantiomer of the chiral additive. We demonstrate that it is possible to achieve both efficient (4.0 cd/A) and bright (8000 cd/m2) CP-PLEDs, with high dissymmetry of emission of both left-handed (LH) and right-handed (RH) light, depending on thickness (thin films, 110 nm: gEL = 0.51, thick films, 160 nm: gEL = -1.05, with the terms "thick" and "thin" representing the upper and lower limits of the thickness regime studied), for the same additive enantiomer. We propose that this arises due to an interplay between localized CP emission originating from molecular chirality and CP light amplification or inversion through a chiral medium. We link morphological, spectroscopic, and electronic characterization in thin films and devices with theoretical studies in an effort to determine the factors that underpin these observations. Through the control of active layer thickness and device architecture, this study provides insights into the mechanisms that result in CP luminescence and high performance from CP-PLEDs, as well as demonstrating new opportunities in CP photonic device design

Development and validation of a RAD-Seq target-capture based genotyping assay for routine application in advanced black tiger shrimp (Penaeus monodon) breeding programs

Background: The development of genome-wide genotyping resources has provided terrestrial livestock and crop industries with the unique ability to accurately assess genomic relationships between individuals, uncover the genetic architecture of commercial traits, as well as identify superior individuals for selection based on their specific genetic profile. Utilising recent advancements in de-novo genome-wide genotyping technologies, it is now possible to provide aquaculture industries with these same important genotyping resources, even in the absence of existing genome assemblies. Here, we present the development of a genome-wide SNP assay for the Black Tiger shrimp (Penaeus monodon) through utilisation of a reduced-representation whole-genome genotyping approach (DArTseq). Results: Based on a single reduced-representation library, 31,262 polymorphic SNPs were identified across 650 individuals obtained from Australian wild stocks and commercial aquaculture populations. After filtering to remove SNPs with low read depth, low MAF, low call rate, deviation from HWE, and non-Mendelian inheritance, 7542 high-quality SNPs were retained. From these, 4236 high-quality genome-wide loci were selected for baits-probe development and 4194 SNPs were included within a finalized target-capture genotype-by-sequence assay (DArTcap). This assay was designed for routine and cost effective commercial application in large scale breeding programs, and demonstrates higher confidence in genotype calls through increased call rate (from 80.2 ± 14.7 to 93.0% ± 3.5%), increased read depth (from 20.4 ± 15.6 to 80.0 ± 88.7), as well as a 3-fold reduction in cost over traditional genotype-by-sequencing approaches. Conclusion: Importantly, this assay equips the P. monodon industry with the ability to simultaneously assign parentage of communally reared animals, undertake genomic relationship analysis, manage mate pairings between cryptic family lines, as well as undertake advance studies of genome and trait architecture. Critically this assay can be cost effectively applied as P. monodon breeding programs transition to undertaking genomic selection

Highly selective high-speed circularly polarized photodiodes based on π-conjugated polymers

Chiral π-conjugated molecular systems that are intrinsically sensitive to the handedness of circularly polarized (CP) light potentially allow for miniaturized, low-cost CP detection devices. Such devices promise to transform several technologies, including biosensing, quantum optics, and communication of data encrypted by exploiting the spin angular momentum of light. Here a simple, bilayer organic photodiode (CP OPD) comprising an achiral π-conjugated polymer–chiral additive blend as the electron donor layer and an achiral C60 electron acceptor layer is realized. These devices exhibit considerable photocurrent dissymmetry gph, with absolute values as high as 0.85 and dark currents as low as 10 pA. Impressively, they showcase a linear dynamic range of 80 dB, and rise and fall times of ≈7 µs, which significantly outperforms all previously reported CP selective photodetectors. Mechanistically, it is shown that the gph is sensitive to the thickness of both the chiral donor and achiral acceptor layers and that a trade-off exists between the external quantum efficiency and gph. The fast-switching speeds of these devices, coupled with their large dynamic range and highly selective response to CP light, opens up the possibility of their direct application in CP sensing and optical communications

Postpandemic rebound of adeno-associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom

Over 1000 cases of unexplained severe acute hepatitis in children have been reported to date worldwide. An association with adeno-associated virus type 2 (AAV2) infection, a human parvovirus, prompted us to investigate the epidemiology of AAV in the United Kingdom. Three hundred pediatric respiratory samples collected before (April 03, 2009–April 03, 2013) and during (April 03, 2022) the COVID-19 pandemic were obtained. Wastewater samples were collected from 50 locations in London (August 2021–March 2022). Samples were tested for AAV using real-time polymerase chain reaction followed by sequencing. Selected adenovirus (AdV)-positive samples were also sequenced. The detection frequency of AAV2 was a sevenfold higher in 2022 samples compared with 2009–2013 samples (10% vs. 1.4%) and highest in AdV-positive samples compared with negatives (10/37, 27% vs. 5/94, 5.3%, respectively). AAV2-positive samples displayed high genetic diversity. AAV2 sequences were either very low or absent in wastewater collected in 2021 but increased in January 2022 and peaked in March 2022. AAV2 was detected in children in association with AdV of species C, with a highest frequency in 2022. Our findings are consistent with the expansion of the population of children unexposed to AAV2, leading to greater spread of the virus once distancing restrictions were lifted

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically