A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia

Squamous dysplasia of the oral cavity indicates increased risk of progression to squamous cell carcinoma (SCC). An important advance would be the development of a minimally invasive assay for identification of oral SCC and dysplasia. We have investigated the suitability in this context of immunostaining oral smears for minichromosome maintainance proteins (MCMs), sensitive and specific biomarkers of cell cycle entry. Immunohistochemical examination of 66 oral tissue samples showed a greater frequency of Mcm-2 expression in surface layers of moderate/severe dysplasia and SCC compared to benign keratosis/mild dysplasia. Immunocytochemistry for Mcm-2/Mcm-5 was performed on 101 oral smears. Conventional smears included 23 from normal mucosa, benign proliferative disease and mild dysplasia, all of which were MCM negative. Of 52 conventional smears of SCC tissue samples, 18 were inadequate. However, MCM-positive cells were present in 33/34 adequate samples. Of 26 liquid-based cytology smears, 19 out of 20 smears from SCC were adequate and all were MCM positive. Six smears from benign lesions were adequate and MCM negative. We conclude that MCMs are promising markers for early detection of oral SCC and dysplasia, particularly in a liquid-based cytology platform. Detection of MCMs would be amenable to automation and potentially applicable in the developing world. Further studies are now warranted

Competitive aminal formation during the synthesis of a highly soluble, isopropyl-decorated imine porous organic cage

The synthesis of a new porous organic cage decorated with isopropyl moieties (CC21) was achieved from the reaction of triformylbenzene and an isopropyl functionalised diamine. Unlike structurally analogous porous organic cages, its synthesis proved challenging due to competitive aminal formation, rationalised using control experiments and computational modelling. The use of an additional amine was found to increase conversion to the desired cage

Assessing the effectiveness of retrograde autologous priming of the cardiopulmonary bypass machine in isolated coronary artery bypass grafts

Introduction Currently, around 35–80% of patients undergoing cardiac surgery in the UK receive a blood transfusion. Retrograde autologous priming (RAP) of the cardiopulmonary bypass circuit has been suggested as a possible strategy to reduce blood transfusion during cardiac surgery. Methods Data from 101 consecutive patients undergoing isolated coronary artery bypass grafts (where RAP was used) were collected prospectively and compared with 92 historic patients prior to RAP use in our centre. Results Baseline characteristics (ie age, preoperative haemoglobin [Hb] etc) were not significantly different between the RAP and non-RAP groups. The mean pump priming volume of 1,013ml in the RAP group was significantly lower (p&lt;0.001) than that of 2,450ml in the non-RAP group. The mean Hb level at initiation of bypass of 9.1g/dl in patients having RAP was significantly higher (p&lt;0.001) than that of 7.7g/dl in those who did not have RAP. There was no significant difference between the RAP and non-RAP groups in transfusion of red cells, platelets and fresh frozen plasma, 30-day mortality, re-exploration rate and predischarge Hb level. The median durations of cardiac intensive care unit stay and in-hospital stay of 1 day (interquartile range [IQR]: 1–2 days) and 5 days (IQR: 4–6 days) in the RAP group were significantly shorter than those of the non-RAP group (2 days [IQR: 1–3 days] and 6 days [IQR: 5–9 days]). Conclusions In the population group studied, RAP did not influence blood transfusion rates but was associated with a reduction in duration of hospital stay. </jats:sec

Rapid regulation of protein activity in fission yeast

Background: The fission yeast Schizosaccharomyces pombe is widely-used as a model organism for the study of a broad range of eukaryotic cellular processes such as cell cycle, genome stability and cell morphology. Despite the availability of extensive set of genetic, molecular biological, biochemical and cell biological tools for analysis of protein function in fission yeast, studies are often hampered by the lack of an effective method allowing for the rapid regulation of protein level or protein activity. Results: In order to be able to regulate protein function, we have made use of a previous finding that the hormone binding domain of steroid receptors can be used as a regulatory cassette to subject the activity of heterologous proteins to hormonal regulation. The approach is based on fusing the protein of interest to the hormone binding domain (HBD) of the estrogen receptor (ER). The HBD tag will attract the Hsp90 complex, which can render the fusion protein inactive. Upon addition of estradiol the protein is quickly released from the Hsp90 complex and thereby activated. We have tagged and characterised the induction of activity of four different HBD-tagged proteins. Here we show that the tag provided the means to effectively regulate the activity of two of these proteins. Conclusion: The estradiol-regulatable hormone binding domain provides a means to regulate the function of some, though not all, fission yeast proteins. This system may result in very quick and reversible activation of the protein of interest. Therefore it will be a powerful tool and it will open experimental approaches in fission yeast that have previously not been possible. Since fission yeast is a widely-used model organism, this will be valuable in many areas of research

Palaeozoic petroleum systems of the Orcadian Basin to Forth Approaches, Quadrants 6 - 21, UK

This report synthesises the results of the 21CXRM Palaeozoic project to describe the Carboniferous and Devonian petroleum systems of the Orcadian Basin to Forth Approaches area (Quadrants 6 – 21). Petroleum systems of the Orcadian study area that involve significant Palaeozoic elements are not wholly contained within Devonian, Carboniferous and Permian strata. A number of producing fields attest to two main proven petroleum systems; i. Co-sourced Devonian oil (with Jurassic oil) within a Jurassic reservoir: the Beatrice, Jacky and Lybster fields; ii. Jurassic-sourced oil in a Devonian and/or Carboniferous reservoir: the Buchan, Stirling, Claymore, Highlander fields. (Jurassic-sourced oil in a Permian (Zechstein) reservoir is also proven in the Carnoustie, Ettrick and Claymore fields, and in a Rotliegend reservoir in the Dee discovery). A number of additional unproven petroleum system elements are considered in this report; i. Possibilities for Devonian and Carboniferous sourcing or co-sourcing (with Jurassic oil) of Devonian, Carboniferous and Permian (Rotliegend) reservoirs in those areas underlain by proven Palaeozoic source rock; ii. Possibilities for migrated Jurassic and/or Devonian and/or Carboniferous hydrocarbons onto horst blocks and the regional Grampian High, into basement, Palaeozoic or younger reservoirs. Focusing on frontier areas north and east of the Inner Moray Firth and from the north-eastern Forth Approaches to Grampian High, integration of a large volume of seismic, well, geophysical, organic geochemistry, maturity and reservoir property data at regional scale has established: Source rocks A wide extent of potential Devonian lacustrine source rocks mapped seismically from the Inner Moray Firth to the East Orkney Basin and north of the Halibut Horst. Geochemically-typed Devonian-sourced oil shows, oil seep data outside the area of mature Kimmeridge Clay Formation, burial depth and a limited organic geochemistry/maturity dataset indicative of Devonian source rocks that are potentially mature for oil generation outside the Inner Moray Firth. Good quality gas- and oil-prone Carboniferous source rocks are mapped from the Witch Ground Graben to north eastern end of the Forth Approaches. Wells drilled on highs indicate oil-window thermal maturity levels. Oil and gas shows and basin modelling indicate Carboniferous strata buried more deeply in adjacent basins may reach gas maturity levels, with Cenozoic maturation. Key source rock intervals are: o Lower Devonian, lacustrine Struie Formation (Quadrants 11, 12), oil prone. o Middle Devonian, lacustine Orcadia Formation and Eday Group (Quadrants 11- 15 and possibly Quadrants 19, 20), oil prone. o Visean – Namurian (lower-mid Carboniferous) fluvio-deltaic Firth Coal Formation, gas and oil prone. (This unit is age-equivalent of the Scremerston and Yoredale Formations, Cleveland Group source rocks in Quadrants 25-44

Quaternary Heterogeneities: geospatial products for scientists, industry and decision making

Glaciation and permafrost has had a profound impact upon the UK landscape during the Quaternary. Their impact is most relevant within the ‘zone of human interaction’, the surface and near-surface parts of the geological record that humans utilise and exploit for societal and economic gain (e.g. infrastructure development, groundwater, energy, storage and minerals). However, whilst the broad range of glacial and periglacial processes that have affected the UK are known, their spatial influence on the applied properties of the substrate are poorly-understood but have major implications for ground conditions and civil engineering. This lack of understanding is partly due to the complexity of the geological evidence, point or linear approaches to geological investigation and ‘lithostratigraphic’ approaches that have largely-overlooked the significance of heterogeneous products of glaciation and permafrost. Within this project, we are developing a range of national-scale GIS datasets that will highlight the ‘known’ distribution of specific ‘Quaternary Heterogeneities’ in the shallow sub-surface and identify zones of extrapolated susceptibility in areas where data coverage is limited using a series of genetic and geostatistical rules. Spatial data-sets are currently in development for glaciotectonic structure, buried valleys, drift-filled hollows, blockfields and frost weathering. These datasets are aimed at both scientific and applied users (e.g. civil engineers, insurers, hydrogeologists, planners and decision makers), enhancing scientific understanding of glacial and periglacial processes and their spatial influence on the properties of the landscape and sub-surface

Palaeozoic petroleum systems of the central North Sea/Mid North Sea High

This report synthesises the results of the 21CXRM Palaeozoic project to describe the Carboniferous and Devonian petroleum systems of the Central North Sea/Mid North Sea High area (Quadrants 25–44). Focusing on frontier areas to the north of the Southern North Sea gas fields and west of the Auk-Flora ridge, integration of a large volume of seismic, well, geophysical, organic geochemistry, maturity and reservoir property data at regional scale has established: Extensional to strike-slip Devonian and Carboniferous basins cutting across the Mid North Sea High on orientations strongly controlled by basement inheritance, granites and a complex Palaeozoic stress field. Varsican orogenic transpression and inversion was superimposed resulting in a variety of structural trapping styles and burial/uplift histories, and a complicated pre-Permian subcrop map. A widespread spatial and temporal extent of oil and gas mature source rock intervals within the Carboniferous succession particularly; o lower Carboniferous (Visean) coals and mudstones of the Scremerston Formation, dominantly fluvio-deltaic and lacustrine with some marine influence, dominantly gas prone. Gas mature in Quadrant 41 and central-southern Quadrants 42-44 and oil mature in the Forth Approaches and North Dogger Basin o lower-mid Carboniferous (Visean-Namurian) coals and mudstones of the Yoredale and Millstone Grit formations in fluvio-deltaic to marine cycles, gas prone with oil prone intervals. Gas mature in central Quadrant 41 and southern Quadrants 42-43, oil mature across northern Quadrants 41-44, Quadrant 36, 38 and 39. o Lower-mid Carboniferous (Visean-Namurian) mudstones and siltstones of the Cleveland Group, over 1 km thick, deposited in dominantly marine environments. Gas mature to overmature in southern Quadrants 41-44 and modelled as having generated oil and gas. Potentially widespread reservoir intervals of varying reservoir quality. Favourable intervals include the Upper Devonian sandstone of the Buchan Formation expecially where fractured, channels within the fluvio-deltaic lower-mid Carboniferous (Visean-Namurian) Scremerston, Yoredale and Millstone Grit formations, the laterally extensive, high net:gross Fell Sandstone Formation, and possibly turbidites or shoreface sands within marine mudstones/siltstones in southern Quadrants 41-44 (likely tight gas unless early hydrocarbon charged) Widespread opportunities for structural (fault/fold/dip) traps utilising a Silverpit mudstone, or Zechstein evaporite seal as in the Breagh Field. Intraformational Carboniferous seals are documented widely in onshore Carboniferous fields and in some offshore fields and should be further investigated, particularly in mudstone/siltstone-dominated basinal successions with modelled Carboniferous and recent hydrocarbon generation, along with possibilities for stratigraphic traps. Basin modelling predicts oil and gas generation at a variety of times (Carboniferous, Mesozoic and Cenozoic dependent on the well) from lower-mid Carbonferous (Visean-Namurian) strata in Quadrants 41-44. In the Forth Approaches, Quadrant 29/North Dogger basins and on the poorly constrained Devonian-Carboniferous Mid North Sea High, oil window maturity levels are modelled at selected wells in a largely gas-prone sequence, though basinwards gas maturity may be achieved. It is recommended that the contribution and volumetrics of relatively thin oil-prone intervals within the Carboniferous succession be further investigated

Overview of the 21CXRM Palaeozoic Project : a regional petroleum systems analysis of the offshore Carboniferous and Devonian of the UKCS

This report gives an overview of the 21CXRM Palaeozoic Project background, scope and products (Sections 1-3). It explains how the component reports and datasets of the project fit together. Overview technical information (e.g. key diagrams and charts applicable across the reports for each area) is reproduced in Sections 6 and 7 for reference, particularly as background for users of the specialist reports. A visual representation of the regional coverage and quantity of digital Palaeozoic Project products is given in Figure 1