A summary of the methodology for the seismic stratigraphic interpretation for the 'GlaciStore' bid to IODP

This report summarises the methodology followed for the seismic interpretation of sedimentary strata that are the overburden sequence and the Palaeogene strata that are prospective CO2 storage formations, in the UK Central North Sea. The interpretation of selected 2D and 3D seismic reflection, well and borehole data in the UK North and Central North Sea is targeted to inform the preparation of the ‘GlaciStore’ proposal for scientific drilling submitted to the International Ocean Discovery Programme (IODP). Drilling sites proposed to IODP lie within the UK and Norwegian sectors of the North Sea. The methodology is described for the interpretation of seismic data for proposed sites within UK waters. The seismic interpretation was undertaken in collaboration with Norwegian members of the GlaciStore consortium. The seismic interpretation was divided into two teams according to depth, into ‘shallower and ‘deeper’ seismic interpretation activities, appropriate to the fields of expertise and experience of the interpreters. The ‘shallower seismic’ interpreters considered strata of latest Neogene and Quaternary age which were deposited during major glacial and interglacial cycles. The ‘deeper seismic’ interpreters considered slightly older strata of Mid Eocene to Quaternary in age. Seven potential UK drill sites were selected to address the scientific objectives in the proposal. 2D and 3D seismic, well, borehole and bathymetry data were used to map buried and open tunnel valleys and to identify any evidence for the presence of shallow gas in the ‘shallower seismic’ interpretation at each drill site. Only sites without any indication of shallow gas features were considered as these pose a serious hazard for drilling. 2D and 3D seismic and well datasets and existing interpretations were collated for the ‘deeper seismic’ interpretation. The hydrocarbon exploration well log data, which were found to be of variable quality, were used to identify and map a number of stratigraphical surfaces of Cenozoic age, and included Quaternary strata, around the grid of seismic lines. Maps from some of the key stratigraphical surfaces are presented, selected to inform the drilling proposal. A plot of acoustic velocity data was prepared to inform future conversion of the seismic interpretation to true vertical depth. Future work, based on the seismic interpretation undertaken to underpin the drilling proposal, is identified. Features observed within the ‘shallower’ and ‘deeper’ seismic interpretations that warrant further investigation are: a chaotic zone within the Quaternary sequence; prograding units within the Eocene Horda Formation; basin centre sandstone bodies as prospective CO2 storage strata within the Horda Formation; systematic mapping of cross-cutting, buried tunnel valleys in the Quaternary sequence from 3D seismic data

Microwave Gaseous Discharges

Contains research objectives and reports on five research projects

Congestion, Capacity, Carbon: Priorities for National Infrastructure - Consultation Response: SCCS response to the National Infrastructure Commission consultation on priorities for national infrastructure

Carbon capture and storage (CCS) is a set of technologies that can reduce emissions of carbon dioxide (CO2) at source to prevent increased atmospheric concentrations of the gas, which cause climate change. The approach of SCCS is to consider that the UK future ambition on reducing carbon emissions requires a CO2 removal and storage service for industry, heat, transport, and power. That requires infrastructure consisting of pipelines, shipping, and associated gas compression and gas separation facilities. There is a market failure in the UK to provide these facilities commercially. Consequently, state intervention is needed to create these initial networks, suitable for later privatisation.Carbon capture and storage (CCS) is a set of technologies that can reduce emissions of carbon dioxide (CO2) at source to prevent increased atmospheric concentrations of the gas, which cause climate change. The approach of SCCS is to consider that the UK future ambition on reducing carbon emissions requires a CO2 removal and storage service for industry, heat, transport, and power. That requires infrastructure consisting of pipelines, shipping, and associated gas compression and gas separation facilities. There is a market failure in the UK to provide these facilities commercially. Consequently, state intervention is needed to create these initial networks, suitable for later privatisation

Whole Genome Sequencing Identified a 16 Kilobase Deletion on ECA13 Associated with Distichiasis in Friesian Horses

BACKGROUND: Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait. RESULTS: A genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10− 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10− 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder. CONCLUSIONS: This study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance

Case study on the efficacy of a lanthanum-enriched clay (Phoslock®) in controlling eutrophication in Lake Het Groene Eiland (The Netherlands)

Lake Het Groene Eiland was created in the beginning of 2008 by construction of dikes for isolating it from the surrounding 220-ha water body. This so-called claustrum of 5 ha was treated using lanthanum-modified clay (Phoslock®) to control eutrophication and mitigate cyanobacterial nuisance. Cyanobacteria chlorophyll-a were significantly lower in the claustrum than those in the reference water body, where a massive bloom developed in summer, 2008. However, PO4-P and TP did not statistically differ in these two waters. TN and NO3-N were significantly lower in the claustrum, where dense submerged macrophytes beds developed. Lanthanum concentrations were elevated after the applications of the modified clay in the claustrum, but filterable lanthanum dropped rapidly below the Dutch standard of 10.1 μg l−1. During winter, dozens of Canada geese resided at the claustrum. Geese droppings contained an average of 2 mg PO4-P g−1 dry weight and 12 mg NH3-N g−1 dry weight and might present a growing source of nutrients to the water. Constructing the claustrum enabled unrestricted bathing in subsequent three summers, as no swimming bans had to be issued due to cyanobacteria blooms. However, the role of the modified clay in this positive outcome remains unclear, and longevity of the measures questionable.

Virulence and Pathogen Multiplication: A Serial Passage Experiment in the Hypervirulent Bacterial Insect-Pathogen Xenorhabdus nematophila

The trade-off hypothesis proposes that the evolution of pathogens' virulence is shaped by a link between virulence and contagiousness. This link is often assumed to come from the fact that pathogens are contagious only if they can reach high parasitic load in the infected host. In this paper we present an experimental test of the hypothesis that selection on fast replication can affect virulence. In a serial passage experiment, we selected 80 lines of the bacterial insect-pathogen Xenorhabdus nematophila to multiply fast in an artificial culture medium. This selection resulted in shortened lag phase in our selected bacteria. We then injected these bacteria into insects and observed an increase in virulence. This could be taken as a sign that virulence in Xenorhabdus is linked to fast multiplication. But we found, among the selected lineages, either no link or a positive correlation between lag duration and virulence: the most virulent bacteria were the last to start multiplying. We then surveyed phenotypes that are under the control of the flhDC super regulon, which has been shown to be involved in Xenorhabdus virulence. We found that, in one treatment, the flhDC regulon has evolved rapidly, but that the changes we observed were not connected to virulence. All together, these results indicate that virulence is, in Xenorhabdus as in many other pathogens, a multifactorial trait. Being able to grow fast is one way to be virulent. But other ways exist which renders the evolution of virulence hard to predict

Screening the Geomechanical Stability (Thermal & Mechanical) of Shared Multi-user CO2 Storage Assets, a Simple Effective Tool Applied to the Captain Sandstone Aquifer

Multi-user storage systems are anticipated in the near future to permanently store CO2 captured at industrial sources to meet emissions reductions targets. Multiple storage permit applications will be required to exploit the immense potential capacity within extensive CO2 storage assets. To retain 99% of the injected CO2 for 1000 years the geomechanical stability of the sealing strata above the pressurised storage reservoir is a key factor which needs to be included in the geo-engineering design of shared storage assets. The potential for interaction of increased pressure at multiple injection sites needs to be predicted and assessed at a regional scale to assure the integrity at all existing sites before a storage permit is granted. Geomechanical models coupled with the expected fluid pressure response predict the stability of the storage asset during and after injection of CO2 at multiple injection sites, and can be used as a tool to ensure efficient utilisation of the storage capacity. The geomechanical analysis of the thermal stress as well as local and regional fluid pressure changes requires a detailed numerical evaluation, often at a resolution significantly higher than the data available. Coupling of regional-scale static geological models, dynamic multi-phase flow models and detailed geomechanical models requires extensive computational resources. Such models often produce seemingly detailed results, but are usually only one or two realisations of a system populated by a statistically generated parameter set. Limits on time and computational resources prevent more simulations within fixed time and financial budgets. To enable a more time and cost efficient methodology of assessing the geomechanical stability of potential storage sites we present a four-tier modelling approach with increasing complexity that allows an in-depth evaluation of the geomechanical stability at a regional scale of a multi-user storage asset taking into account the fluid pressure increase and the thermal stress impact on the stability of the strata sealing the CO2 store. The tiers include: (1) development of a geo-mechanical facies model of the storage system,(2) development of an analytical geomechanical model for the storage site static stress conditions, (3)fitting an empirical multivariable polynomial function to the analytical modal, and (4) conditioning the empirical function using coupled numerical THM modelling for dynamic stress conditions. The result is look up function which gives the maximum possible fluid pressure as a function of location. This approach significantly simplifies the computational requirements and time for the prediction of geomechanical behaviour. In addition to presenting this methodology, using the Captain Sandstone of the North Sea as an example, three key findings are further examined. Firstly, detailed analysis of the stress changes as a result of cold fluid injection suggests that the redistribution of thermal stress can, in some cases, be beneficial to the storage system depending on the stress bridging which occurs. Secondly, pressure plume migration over time in dipping strata, from deeper injection sites to shallower sites, needs to be taken into account. Thirdly, the nature of the strata underlying the storage formation is critical to the pressure increase in response to the fluid injection. The methodology developed in this paper enables a rapid and efficient screening of the dynamic geomechanical stability and facilitates an efficient coupling to diverse discrete multiphase fluid flow models using commonly available computational resources

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas

Abstract Background Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFβ signaling. Methods To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFβ or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. Results We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFβ monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFβ, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFβ antibody administration attenuates these effects. We show that α-TGFβ acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFβ acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. Conclusions We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165).https://deepblue.lib.umich.edu/bitstream/2027.42/148212/1/40425_2018_Article_493.pd

A missense TGFB2 variant p.(Arg320Cys) causes a paradoxical and striking increase in aortic TGFB1/2 expression.

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder with a range of cardiovascular, skeletal, craniofacial and cutaneous manifestations. LDS type 4 is caused by mutations in TGFβ ligand 2 (TGFB2) and based on the family pedigrees described to date, appears to have a milder clinical phenotype, often presenting with isolated aortic disease. We sought to investigate its molecular basis in a new pedigree. We identified a missense variant p.(Arg320Cys) (NM_003238.3) in a highly evolutionary conserved region of TGFB2 in a new LDS type 4 pedigree with multiple cases of aortic aneurysms and dissections. There was striking upregulation of TGFB1 and TGFB2 expression on immunofluorescent staining, and western blotting of the aortic tissue from the index case confirming the functional importance of the variant. This case highlights the striking paradox of predicted loss-of-function mutations in TGFB2 causing enhanced TGFβ signaling in this emerging familial aortopathy.Raya Al Maskari has a PhD studentship funded by the Omani government.This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/ejhg.2016.14