Reverse Monte Carlo studies of CeO2 using neutron and synchrotron radiation techniques

A reverse Monte Carlo analysis method was employed to extract the structure of CeO2 from Neutron total scattering (comprising both neutron diffraction (ND) and pair-distribution functions (PDF) and Ce L3- and K-edge EXAFS data. Here it is shown that there is a noticeable difference between using short ranged x-ray absorption spectroscopy data and using medium-long range PDF and ND data in regards to the disorder of the cerium atoms. This illustrates the importance of considering multiple length scales and radiation sources

The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

Structure of Nano-sized CeO2 Materials: Combined Scattering and Spectroscopic Investigations

The structure of several nano‐sized ceria, CeO2, systems was investigated using neutron and X‐ray diffraction and X‐ray absorption spectroscopy. Whilst both diffraction and total pair distribution functions (PDFs) revealed that in all of the samples the occupancy of both Ce4+ and O2− are very close to the ideal stoichiometry, the analysis using Reverse Monte Carlo technique revealed significant disorder around oxygen atoms in the nano‐sized ceria samples in comparison to the highly crystalline NIST standard. In addition, the analysis revealed that the main differences observed in the pair correlations from various X‐ray and neutron diffraction techniques were attributable to the particle size of the CeO2 prepared by the reported three methods. Furthermore, detailed analysis of the Ce L3‐ and K‐edge EXAFS data support this finding; in particular the decrease in higher shell coordination numbers with respect to the NIST standard, is attributed to differences in particle size

Personalized Drug Dosage – Closing the Loop

A brief account is given of various approaches to the individualization of drug dosage, including the use of pharmacodynamic markers, therapeutic monitoring of plasma drug concentrations, genotyping, computer-guided dosage using ‘dashboards’, and automatic closed-loop control of pharmacological action. The potential for linking the real patient to his or her ‘virtual twin’ through the application of physiologically-based pharmacokinetic modeling is also discussed

Preliminary Evidence for the Cross-Cultural Utility of the Type D Personality Construct in the Ukraine

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Masked mRNA is stored with aggregated nuclear speckles and its asymmetric redistribution requires a homolog of mago nashi

<p>Abstract</p> <p>Background</p> <p>Many rapidly developing systems rely on the regulated translation of stored transcripts for the formation of new proteins essential for morphogenesis. The microspores of the water fern <it>Marsilea vestita </it>dehydrate as they mature. During this process both mRNA and proteins required for subsequent development are stored within the microspores as they become fully desiccated and enter into senescence. At this point microspores become transcriptionally silent and remain so upon rehydration and for the remainder of spermatogenesis. Transcriptional silencing coupled with the translation of preformed RNA makes the microspore of <it>M. vestita </it>a useful system in which to study post-transcriptional regulation of RNA.</p> <p>Results</p> <p>We have characterized the distribution of mRNA as well as several conserved markers of subnuclear bodies within the nuclei of desiccating spores. During this period, nuclear speckles containing RNA were seen to aggregate forming a single large coalescence. We found that aggregated speckles contain several masked mRNA species known to be essential for spermatogenesis. During spermatogenesis masked mRNA and associated speckle proteins were shown to fragment and asymmetrically localize to spermatogenous but not sterile cells. This asymmetric localization was disrupted by RNAi knockdown of the <it>Marsilea </it>homolog of the Exon Junction Complex core component Mago nashi.</p> <p>Conclusions</p> <p>A subset of masked mRNA is stored in association with nuclear speckles during the dormant phase of microspore development in <it>M. vestita</it>. The asymmetric distribution of specific mRNAs to spermatogenous but not sterile cells mirrors their translational activities and appears to require the EJC or EJC components. This suggests a novel role for nuclear speckles in the post-transcriptional regulation of transcripts.</p

Characterising within-hospital SARS-CoV-2 transmission events using epidemiological and viral genomic data across two pandemic waves

Hospital outbreaks of COVID19 result in considerable mortality and disruption to healthcare services and yet little is known about transmission within this setting. We characterise within hospital transmission by combining viral genomic and epidemiological data using Bayesian modelling amongst 2181 patients and healthcare workers from a large UK NHS Trust. Transmission events were compared between Wave 1 (1st March to 25th July 2020) and Wave 2 (30th November 2020 to 24th January 2021). We show that staff-to-staff transmissions reduced from 31.6% to 12.9% of all infections. Patient-to-patient transmissions increased from 27.1% to 52.1%. 40%-50% of hospital-onset patient cases resulted in onward transmission compared to 4% of community-acquired cases. Control measures introduced during the pandemic likely reduced transmissions between healthcare workers but were insufficient to prevent increasing numbers of patient-to-patient transmissions. As hospital-acquired cases drive most onward transmission, earlier identification of nosocomial cases will be required to break hospital transmission chains

Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe