eBank UK: linking research data, scholarly communication and learning

This paper includes an overview of the changing landscape of scholarly communication and describes outcomes from the innovative eBank UK project, which seeks to build links from e-research through to e-learning. As introduction, the scholarly knowledge cycle is described and the role of digital repositories and aggregator services in linking data-sets from Grid-enabled projects to e-prints through to peer-reviewed articles as resources in portals and Learning Management Systems, are assessed. The development outcomes from the eBank UK project are presented including the distributed information architecture, requirements for common ontologies, data models, metadata schema, open linking technologies, provenance and workflows. Some emerging challenges for the future are presented in conclusion

The prospectivity of a potential shale gas play: An example from the southern Pennine Basin (central England, UK)

During the Serpukhovian (late Mississippian) Stage, the Pennine Basin, now underlying much of northern England, consisted of a series of interlinked sub-basins that developed in response to the crustal extension north of the Hercynic orogenic zone. For the current study, mudstone samples of the Morridge Formation from two sub-basins located in the south-eastern part of the Pennine Basin were collected from the Carsington Dam Reconstruction C3 Borehole (Widmerpool Gulf sub-basin) and the Karenight 1 Borehole (Edale Gulf sub-basin). Detailed palynological analyses indicate that aside from the dominant (often 90% or more) heterogeneous amorphous organic matter (AOM), variable abundances of homogeneous AOM and phytoclasts are present. To complement the palynological dataset, a suite of geochemical and mineralogical techniques were applied to evaluate the prospectivity of these potentially important source rocks. Changes in the carbon isotope composition of the bulk organic fraction (δ13COM) suggest that the lower part (Biozone E2a) of Carsington DR C3 is markedly more influenced by terrigenous kerogen than the upper part of the core (Biozones E2a3–E2b1). The Karenight 1 core yielded more marine kerogen in the lower part (Marine Bands E1–E2b) than the upper part (Marine Band E2b). Present day Rock-Eval™ Total Organic Carbon (TOC) surpasses 2% in most samples from both cores, a proportion suggested by Jarvie (2012) that defines prospective shale gas reservoirs. However, when the pyrolysable component that reflects the generative kerogen fraction is considered, very few samples reach this threshold. The kerogen typing permits for the first time the calculation of an original hydrogen index (HIo) and original total organic carbon (TOCo) for Carboniferous mudstones of the Pennine Basin. The most prospective part of Carsington DR C3 (marine bands E2b1–E2a3) has an average TOCo of 3.2% and an average HIo of 465 mg/g TOCo. The most prospective part of Karenight 1 (242.80–251.89 m) is characterized by an average TOCo of 9.3% and an average HIo of 504 mg/g TOCo. Lastly, X-ray diffraction (XRD) analysis confirms that the siliceous to argillaceous mudstones contain a highly variable carbonate content. The palynological, geochemical and mineralogical proxies combined indicate that marine sediments were continuously being deposited throughout the sampled intervals and were punctuated by episodic turbiditic events. The terrestrial material, originating from the Wales-Brabant High to the south of the Pennine Basin, was principally deposited in the Widmerpool Gulf, with much less terrigenous organic matter reaching the Edale Gulf. As a consequence, the prospective intervals are relatively thin, decimetre-to meter-scale, and further high resolution characterization of these intervals is required to understand variability in prospectivitiy over these limited intervals

Functional diversity and co-operativity between subclonal populations of paediatric glioblastoma and diffuse intrinsic pontine glioma cells

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

A networked registration scheme for enhancing trust

Society has widely adopted use of electronic data without sufficient attention to the problems of non-repudiation (NR). A universal, transparent scheme is needed to replace the traditional paper-based model that people are familiar with. A registration scheme is proposed that uses a network of registration servers run in a way that is robust to legal and technical challenge. Any user can register potential electronic evidence with one or more of these servers. This enables a user to later assert that they had the data at the time. Applications encompass intellectual property (IP) protection, file-download-based e-commerce and corporate shareholder communications. Wide availability should induce proper behaviour between parties whether they use the scheme or not

Crystal Structure EPrints: Publication @ Source Through the Open Archive Initiative

Recent advances in crystallographic instrumentation and computational resources have caused an explosion of crystallographic data, as shown by the recent exponential growth of the CSD [1]. However, even this is considered to be lower than expected, following the introduction of area detection. The reason for this is clearly identified as a publication bottleneck, which will become even more severe with developments in high throughput crystallography [2]. As a result of this situation, the user community is deprived of valuable information, and the funding bodies are getting a poor return for their investments! Electronic publishing has helped to make some inroads into the problem, and is already an integral part of chemical and crystallographic publishing. This has dramatically reduced the turnaround time in the publication process, but the system still fails to keep apace of the generation of structural information, mainly because of the continued reliance on traditional protocols for the assembly of manuscripts and their peer review. The need to maintain some kind of review process is clear, and this makes the sometimes-used direct submission of structures to the CCDC “unpopular”. Unlike the mathematical and electronic sciences, the chemical sciences have been reluctant to embrace the 'preprint concept' [3]: the one exception has been the efforts of rapid electronic communications journals. This poster outlines a pre-print procedure for the rapid and effective dissemination of structural information to the scientific community which removes the lengthy peer review process that hampers traditional publication routes, but provides an alternative mechanism. Crystallographic EPrints are built on a concept developed in the Computer Science community [4] whereby an author may reveal to the public archives of information. An Eprint makes available all raw, derived and results data from a crystallographic experiment via a searchable and hierarchical system. At the top searchable level this metadata includes bibliographic and chemical identifier items which allow access to a secondary level of searchable crystallographic items which are directly linked to the associated archived data. Hence the results of a crystal structure determination may be disseminated in a manner that anyone wishing to utilise the information may access the entire archive of data related to it and assess its validity and worth