Hydrodynamic modeling of tidal-fluvial flows in a large river estuary

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe transition between riverine and estuarine environments is characterised by a change from unidirectional to bidirectional flows, in a region referred to herein as the Tidally-Influenced Fluvial Zone (TIFZ). In order to improve our understanding of the hydrodynamics and morphodynamics of this zone, we present a combined field and numerical modelling study of the Columbia River Estuary (CRE), USA, tidally-influenced fluvial zone. The CRE is large measuring 40 km in length and between 5 and 10 km wide. A shallow water model (Delft3D) was applied in both 2D and 3D configurations and model sensitivity to the key process parameterizations was investigated. Our results indicate that a 2D model constrained within the estuary can sufficiently reproduce depth-averaged flow within the TIFZ of a stratified estuary. Model results highlight the interactions between tidal-, fluvial- and topographic-forcing that result in depth dependent tidal rectification, and thus zones of residual sediment transport that: i) may be flood-directed along shallow channel margins and in the lee of bars, and simultaneously ii) is ebb-directed within deeper channel thalwegs. This condition is enhanced at lower discharges, but increased fluvial discharge reduces the number and size of regions with net flood-directed sediment transport and flow. These sediment transport patterns provide a mechanism to extend the bar/island topography downstream, and generate flood-directed, ebb-directed, and symmetrical bedforms, all within the same channel. Analysis of the model data reveals flood-directed sediment transport is due to both tidal variability and mean flow. These results highlight the need to include the mean flow component (M0) when considering the long-term morphodynamic evolution in a TIFZ. Model results highlight the interactions between tidal-, fluvial- and topographic-forcing that result in depth dependent tidal rectification, and thus zones of residual sediment transport that: i) may be flood-directed along shallow channel margins and in the lee of bars, and simultaneously ii) is ebb-directed within deeper channel thalwegs. This condition is enhanced at lower discharges, but increased fluvial discharge reduces the number and size of regions with net flood-directed sediment transport and flow. These sediment transport patterns provide a mechanism to extend the bar/island topography downstream, and generate flood-directed, ebb-directed, and symmetrical bedforms, all within the same channel. Analysis of the model data reveals flood-directed sediment transport is due to both tidal variability and mean flow. These results highlight the need to include the mean flow component (M0) when considering the long-term morphodynamic evolution in a TIFZ

The Catalytic Site Atlas 2.0: cataloging catalytic sites and residues identified in enzymes.

Understanding which are the catalytic residues in an enzyme and what function they perform is crucial to many biology studies, particularly those leading to new therapeutics and enzyme design. The original version of the Catalytic Site Atlas (CSA) (http://www.ebi.ac.uk/thornton-srv/databases/CSA) published in 2004, which catalogs the residues involved in enzyme catalysis in experimentally determined protein structures, had only 177 curated entries and employed a simplistic approach to expanding these annotations to homologous enzyme structures. Here we present a new version of the CSA (CSA 2.0), which greatly expands the number of both curated (968) and automatically annotated catalytic sites in enzyme structures, utilizing a new method for annotation transfer. The curated entries are used, along with the variation in residue type from the sequence comparison, to generate 3D templates of the catalytic sites, which in turn can be used to find catalytic sites in new structures. To ease the transfer of CSA annotations to other resources a new ontology has been developed: the Enzyme Mechanism Ontology, which has permitted the transfer of annotations to Mechanism, Annotation and Classification in Enzymes (MACiE) and UniProt Knowledge Base (UniProtKB) resources. The CSA database schema has been re-designed and both the CSA data and search capabilities are presented in a new modern web interface

A Tablet-based Virtual Environment for Neurosurgery Training

Published in Presence: Teleoperators and Virtual Environments, Spring 2015No. 2, Pages 155-162 Posted Online October 15, 2015. doi:10.1162/PRES_a_00224The requirement for training surgical procedures without exposing the patient to additional risk is well accepted and is part of a national drive in the UK and internationally. Computer-based simulations are important in this context, including neurosurgical resident training. The objective of this study is to evaluate the effectiveness of a custom built virtual environment in assisting training of a ventriculostomy procedure. The training tool (called VCath) has been developed as an app for a tablet platform to provide easy access and availability to trainees. The study was conducted at the first boot camp organized for all year one trainees in neurosurgery in the UK. The attendees were randomly distributed between the VCath training group and the Control group. Efficacy of performing ventriculostomy for both groups was assessed at the beginning and end of the study using a simulated insertion task. Statistically significant changes in performance of selecting the burr hole entry point, the trajectory length and duration metrics for the VCath group, together with a good indicator of improved normalized jerk (representing the speed and smoothness of arm motion), all suggest that there has been a higher level cognitive benefit to using VCath. The app is successful as it is focused on the cognitive task of ventriculostomy, encouraging the trainee to rehearse the entry point and use anatomical landmarks to create a trajectory to the target. In straight-line trajectory procedures such as ventriculostomy, cognitive task based education is a useful adjunct to traditional methods and may reduce the learning curve and ultimately improve patient safety

The planform mobility of river channel confluences: Insights from analysis of remotely sensed imagery

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.River channel confluences are widely acknowledged as important geomorphological nodes that control the downstream routing of water and sediment, and which are locations for the preservation of thick fluvial deposits overlying a basal scour. Despite their importance, there has been little study of the stratigraphic characteristics of river junctions, or the role of confluence morphodynamics in influencing stratigraphic character and preservation potential. As a result, although it is known that confluences can migrate through time, models of confluence geomorphology and sedimentology are usually presented from the perspective that the confluence remains at a fixed location. This is problematic for a number of reasons, not least of which is the continuing debate over whether it is possible to discriminate between scour that has been generated by autocyclic processes (such as confluence scour) and that driven by allocyclic controls (such as sea-level change). This paper investigates the spatial mobility of river confluences by using the 40-year record of Landsat Imagery to elucidate the styles, rates of change and areal extent over which large river confluence scours may migrate. On the basis of these observations, a new classification of the types of confluence scour is proposed and applied to the Amazon and Ganges-Brahmaputra-Meghna (GBM) basins. This analysis demonstrates that the drivers of confluence mobility are broadly the same as those that drive channel change more generally. Thus in the GBM basin, a high sediment supply, large variability in monsoonal driven discharge and easily erodible bank materials result in a catchment where over 80% of large confluences are mobile over this 40-year window; conversely this figure is < 40% for the Amazon basin. These results highlight that: i) the potential areal extent of confluence scours is much greater than previously assumed, with the location of some confluences on the Jamuna (Brahmaputra) River migrating over a distance of 20 times the tributary channel width; ii) extensive migration in the confluence location is more common than currently assumed, and iii) confluence mobility is often tied to the lithological and hydrological characteristics of the drainage basins that determine sediment yield.This work was funded by NERC grant NE/I023228/1 to Sambrook Smith, Bull, Nicholas and Best

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics

Imaging Atherosclerosis.

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). M.D is supported by the British Heart Foundation (FS/14/78/31020). N.R.E. is supported by a research training fellowship from the Dunhill Medical Trust (RTF44/0114). A.J.B. is supported by the British Heart Foundation. J.H.F.R. is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust.This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/CIRCRESAHA.115.30624

The phylogenetically-related pattern recognition receptors EFR and XA21 recruit similar immune signaling components in monocots and dicots

During plant immunity, surface-localized pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs). The transfer of PRRs between plant species is a promising strategy for engineering broad-spectrum disease resistance. Thus, there is a great interest in understanding the mechanisms of PRR-mediated resistance across different plant species. Two well-characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs) EFR and XA21 from Arabidopsis thaliana (Arabidopsis) and rice, respectively. Interestingly, despite being evolutionary distant, EFR and XA21 are phylogenetically closely related and are both members of the sub-family XII of LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of these related PRRs to engage immune signaling across the monocots-dicots taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show that the kinase domain of the rice XA21 is functional in triggering elf18-induced signaling and quantitative immunity to the bacteria Pseudomonas syringae pv. tomato (Pto) DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore, the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with known components of the EFR complex. Conversely, EFR associates with Arabidopsis orthologues of rice XA21-interacting proteins, which appear to be involved in EFR-mediated signaling and immunity in Arabidopsis. Our work indicates the overall functional conservation of immune components acting downstream of distinct LRR-RK-type PRRs between monocots and dicots

The Use of Stereoscopy in a Neurosurgery Training Virtual Environment

Published in Presence: Teleoperators and Virtual EnvironmentsWe have previously investigated the effectiveness of a custom built virtual environment in assisting training of a ventriculostomy procedure, which is a commonly performed procedure by a neurosurgeon and a core task for trainee surgeons. The training tool (called VCath) was initially developed as a low fidelity app for a tablet platform to provide easy access and availability to trainees. Subsequently we have developed a high fidelity version of VCath that uses a stereoscopic display to immerse the trainee in the virtual environment. This paper reports on two studies that have been carried out to compare the low and high fidelity versions of VCath, particularly to assess the value of stereoscopy. Study 1 was conducted at the second annual boot camp organized for all year one trainees in neurosurgery in the UK. Study 2 was performed on lay people, with no surgical experience. Our hypothesis was that using stereoscopy in the training task would be beneficial. Results from Study 1 demonstrated that performance improved for both the control group and the group trained with the tablet version of VCath. The group trained on the high fidelity version of VCath with a stereoscopic display showed no performance improvement. The indication is that our hypothesis is false. In Study 2, six different conditions were investigated that covered the use of training with VCath on a tablet, a mono display at two different sizes, a stereo display at two different sizes, and a control group who received no training. Results from this study with lay people show that stereoscopy can make a significant improvement to the accuracy of needle placement. The possible reasons for these results and the apparent contradiction between the two studies are discussed

Meso-mechanical model for intergranular stress corrosion cracking and implications for microstructure engineering

The microstructure determines the resistance of polycrystalline materials to intergranular stress corrosion cracking to a large extent. The random grain boundaries are prone to sensitisation and form paths of low resistance for intergranular cracks to follow. The non-sensitised special grain boundaries, such as twin boundaries, are observed to encourage crack bridging ligament formation. Computational models of intergranular cracking have been developed to investigate crack bridging and its effects on crack propagation in microstructures with different fractions of special boundaries. Grain refinement has been shown to be beneficial through experimental studies, but was not described by the model. This work introduces a two-dimensional model and presents results for microstructures with grain sizes that differ by a factor of two. A synergetic effect of grain size and special boundaries fraction is demonstrated. It is shown that the crack bridging zone size depends on the grain size, and the shielding contribution depends on the relative size of the bridging zone compared to the crack length. It is concluded that both grain refinement and increase in the fraction of special boundaries are important for improving microstructure resistance. These observations are consistent with the effects of grain boundary engineering on stress corrosion cracking resistance