Protoptype integrated design (Pride) system reference manual. Volume 2: Schema definition

An initial description of an evolving relational database schema is presented for the management of finite element model design and analysis data. The report presents a description of each relation including attribute names, data types, and definitions. The format of this report is such that future modifications and enhancements may be easily incorporated

Numerical Modeling of Mantle Flow Beneath Madagascar to Constrain Upper Mantle Rheology Beneath Continental Regions

Over the past few decades, azimuthal seismic anisotropy measurements have been widely used proxy to study past and present‐day deformation of the lithosphere and to characterize convection in the mantle. Beneath continental regions, distinguishing between shallow and deep sources of anisotropy remains difficult due to poor depth constraints of measurements and a lack of regional‐scale geodynamic modeling. Here, we constrain the sources of seismic anisotropy beneath Madagascar where a complex pattern cannot be explained by a single process such as absolute plate motion, global mantle flow, or geology. We test the hypotheses that either Edge‐Driven Convection (EDC) or mantle flow derived from mantle wind interactions with lithospheric topography is the dominant source of anisotropy beneath Madagascar. We, therefore, simulate two sets of mantle convection models using regional‐scale 3‐D computational modeling. We then calculate Lattice Preferred Orientation that develops along pathlines of the mantle flow models and use them to calculate synthetic splitting parameters. Comparison of predicted with observed seismic anisotropy shows a good fit in northern and southern Madagascar for the EDC model, but the mantle wind case only fits well in northern Madagascar. This result suggests the dominant control of the measured anisotropy may be from EDC, but the role of localized fossil anisotropy in narrow shear zones cannot be ruled out in southern Madagascar. Our results suggest that the asthenosphere beneath northern and southern Madagascar is dominated by dislocation creep. Dislocation creep rheology may be dominant in the upper asthenosphere beneath other regions of continental lithosphere

Numerical Modeling of Mantle Flow Beneath Madagascar to Constrain Upper Mantle Rheology Beneath Continental Regions

Over the past few decades, azimuthal seismic anisotropy measurements have been widely used proxy to study past and present‐day deformation of the lithosphere and to characterize convection in the mantle. Beneath continental regions, distinguishing between shallow and deep sources of anisotropy remains difficult due to poor depth constraints of measurements and a lack of regional‐scale geodynamic modeling. Here, we constrain the sources of seismic anisotropy beneath Madagascar where a complex pattern cannot be explained by a single process such as absolute plate motion, global mantle flow, or geology. We test the hypotheses that either Edge‐Driven Convection (EDC) or mantle flow derived from mantle wind interactions with lithospheric topography is the dominant source of anisotropy beneath Madagascar. We, therefore, simulate two sets of mantle convection models using regional‐scale 3‐D computational modeling. We then calculate Lattice Preferred Orientation that develops along pathlines of the mantle flow models and use them to calculate synthetic splitting parameters. Comparison of predicted with observed seismic anisotropy shows a good fit in northern and southern Madagascar for the EDC model, but the mantle wind case only fits well in northern Madagascar. This result suggests the dominant control of the measured anisotropy may be from EDC, but the role of localized fossil anisotropy in narrow shear zones cannot be ruled out in southern Madagascar. Our results suggest that the asthenosphere beneath northern and southern Madagascar is dominated by dislocation creep. Dislocation creep rheology may be dominant in the upper asthenosphere beneath other regions of continental lithosphere

Biologically important artificial Light at night on the seafloor

Accelerating coastal development is increasing the exposure of marine ecosystems to nighttime light pollution, but is anthropogenic light reaching the seafloor in sufficient quantities to have ecological impacts? Using a combination of mapping, and radiative transfer modelling utilising in situ measurements of optical seawater properties, we quantified artificial light exposure at the sea surface, beneath the sea surface, and at the sea floor of an urbanised temperate estuary bordered by an LED lit city. Up to 76% of the three-dimensional seafloor area was exposed to biologically important light pollution. Exposure to green wavelengths was highest, while exposure to red wavelengths was nominal. We conclude that light pollution from coastal cities is likely having deleterious impacts on seafloor ecosystems which provide vital ecosystem services. A comprehensive understanding of these impacts is urgently needed

Sensitivity of shelf sea marine ecosystems to temporal resolution of meteorological forcing

Phytoplankton phenology and the length of the growing season have implications that cascade through trophic levels and ultimately impact the global carbon flux to the seafloor. Coupled hydrodynamic‐ecosystem models must accurately predict timing and duration of phytoplankton blooms in order to predict the impact of environmental change on ecosystem dynamics. Meteorological conditions, such as solar irradiance, air temperature and wind‐speed are known to strongly impact the timing of phytoplankton blooms. Here, we investigate the impact of degrading the temporal resolution of meteorological forcing (wind, surface pressure, air and dew point temperatures) from 1‐24 hours using a 1D coupled hydrodynamic‐ecosystem model at two contrasting shelf‐sea sites: one coastal intermediately stratified site (L4) and one offshore site with constant summer stratification (CCS). Higher temporal resolutions of meteorological forcing resulted in greater wind stress acting on the sea surface increasing water column turbulent kinetic energy. Consequently, the water column was stratified for a smaller proportion of the year producing a delayed onset of the spring phytoplankton bloom by up to 6 days, often earlier cessation of the autumn bloom, and shortened growing season of up to 23 days. Despite opposing trends in gross primary production between sites, a weakened microbial loop occurred with higher meteorological resolution due to reduced dissolved organic carbon production by phytoplankton caused by differences in resource limitation: light at CCS and nitrate at L4. Caution should be taken when comparing model runs with differing meteorological forcing resolutions. Recalibration of hydrodynamic‐ecosystem models may be required if meteorological resolution is upgraded

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors

Using site-directed mutagenesis to further the understanding of insulin receptor-insulin like growth factor-1 receptor heterodimer structure

Type 2 diabetes is characterised by the disruption of insulin and insulin-like growth factor (IGF) signalling. The key hubs of these signalling cascades - the Insulin receptor (IR) and Insulin-like growth factor 1 receptor (IGF1R) – are known to form functional IR-IGF1R hybrid receptors which are insulin resistant. However, the mechanisms underpinning IR-IGF1R hybrid formation are not fully understood, hindering the ability to modulate this for future therapies targeting this receptor. To pinpoint suitable sites for intervention, computational hotspot prediction was utilised to identify promising epitopes for targeting with point mutagenesis. Specific IGF1R point mutations F450A, R391A and D555A show reduced affinity of the hybrid receptor in a BRET based donor-saturation assay, confirming hybrid formation could be modulated at this interface. These data provide the basis for rational design of more effective hybrid receptor modulators, supporting the prospect of identifying a small molecule that specifically interacts with this target

Delivering NEET policy packages? A decade of NEET policy in England

This article explores the way in which government policy shapes the lives of young people who are not in education, employment or training (NEET). In particular it examines how the concept of NEETs is set within a specific infrastructure and discourse for managing and supporting young people. The article provides a brief history of the NEET concept and NEET initiatives, before moving on to scrutinise the policies of the Coalition Government. A key distinction is made between those policies and practices that seek to prevent young people becoming NEET from those that seek to re-engage those who are NEET. It is argued that the Coalition has drawn on a similar active labour market toolkit to the previous Labour administration, but that this has been implemented with fewer resources and less co-ordination. It concludes that there is little reason to believe that Coalition policy will be any more successful than that of the previous government, and some reason to be concerned that it will lead to young people becoming more entrenched within NEET

Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

Correction to: Scientific Reports https://doi.org/10.1038/srep29179, published online 14 July 201