How analysts think: sense-making strategies in the analysis of temporal evolution and criminal network structures and activities

Analysis of criminal activity based on offenders’ social networks is an established procedure in intelligence analysis. The complexity of the data poses an obstacle for analysts to gauge network developments, e.g. detect emerging problems. Visualization is a powerful tool to achieve this, but it is essential to know how the analysts’ sense-making strategies can be supported most efficiently. Based on a think aloud study we identified ten cognitive strategies on a general level to be useful for designers. We also provide some examples how these strategies can be supported through appropriate visualizations

Developing CCS in the UK and beyond: insights from the UK CCS Research Centre

The UK Carbon Capture and Storage Research Centre co-ordinates a programme of research covering all aspects of CCS in support of basic science and UK government efforts on energy and climate change. This paper will present progress and ‘lessons learned’ from the Centre’s activities, with a particular focus on the development and use of pilot scale facilities and encouraging industrial and other stakeholder engagement in research. It will also highlight key features of an extensive programme of international engagement activities undertaken by the Centre, identifying added value for both the UK CCS community and global development of CCS

Post-combustion carbon dioxide capture cost reduction to 2030 and beyond

Post-combustion CO2 capture (PCC) can be achieved using a variety of technologies. Importantly it is applicable to a wide range of processes and may also be retrofitted in certain cases. This paper covers the use of PCC for low carbon power generation from new natural gas combined cycle (NGCC) plants that are expected to be built in the UK in the 2020s and 2030s and that will run into the 2050s. Costs appear potentially comparable with other low carbon and controllable generation sources such as nuclear or renewables plus storage, especially with the lower gas prices that can be expected in a carbon-constrained world. Non-fuel cost reduction is still, however, desirable and, since CO2 capture is a new application, significant potential is likely to exist. For the NGCC+PCC examples shown in this paper, moving from ‘first of a kind’ (FOAK) to ‘nth of a kind’ (NOAK) gives significant improvements through both reduced financing costs and capital cost reductions. To achieve this the main emphasis needs to be on ‘commercial readiness’, rather than on system-level ‘technical readiness’, and on improvements through innovation activities, supported by underpinning research, that develop novel sub-processes; this will also maintain NOAK status for cost-effective financing. Feasible reductions in the energy penalty for PCC capture have much less impact, reflecting the inherently high levels of efficiency for modern NGCC+PCC plants

Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare salivary cancer. The highest rates of disease recurrence are in patients with NOTCH pathway activation, reported in up to 20%. Novel drugs targeting NOTCH signaling are under investigation in the recurrent/metastatic (R/M) setting. To understand their clinical utility, there is an urgent need to better characterize the disease course and outcomes following current standard of care treatment. METHODS: 120 patients with R/M ACC underwent clinical review at a single UK Cancer Centre. Patients were retrospectively assessed for tumor NOTCH pathway activation using next generation sequencing (NGS) targeting NOTCH1/2/3 genes and/or NOTCH1 intra-cellular domain (NICD1) immunohistochemistry. Demographic and treatment data were extracted from the clinical notes. Kaplan-Meier survival analysis was performed using log rank test. RESULTS: NOTCH pathway activation was identified in 13/120 patients (11 %). In 12/101 patients analyzed by NGS, NOTCH1/3 activating somatic mutations were identified, and a further patient was identified with NICD1 diffuse nuclear staining in whom NGS testing was not possible. Patients with NOTCH pathway activation had shorter median RFS (1.1 vs 3.4 years, p = 0.2032) and significantly reduced median OS from diagnosis (4.0 vs 16.3 years, p < 0.0001). There was significantly reduced median OS from time of disease recurrence/metastasis (1.9 vs 9.6 years, p < 0.0001). CONCLUSION: This study clearly demonstrates a reduction in OS from time of first confirmed disease recurrence/metastasis for patients with NOTCH pathway activated ACC. This provides support for developing new drugs for this sub-group of patients, for whom clinical outcomes are significantly worse and effective treatments are lacking

Parasite and host kinases as targets for antimalarials

Introduction: The deployment of Artemisinin-based combination therapies and transmission control measures led to a decrease in the global malaria burden over the recent decades. Unfortunately, this trend is now reversing, in part due to resistance against available treatments, calling for the development of new drugs against untapped targets to prevent cross-resistance. Areas covered: In view of their demonstrated druggability in noninfectious diseases, protein kinases represent attractive targets. Kinase-focussed antimalarial drug discovery is facilitated by the availability of kinase-targeting scaffolds and large libraries of inhibitors, as well as high-throughput phenotypic and biochemical assays. We present an overview of validated Plasmodium kinase targets and their inhibitors, and briefly discuss the potential of host cell kinases as targets for host-directed therapy. Expert opinion: We propose priority research areas, including (i) diversification of Plasmodium kinase targets (at present most efforts focus on a very small number of targets); (ii) polypharmacology as an avenue to limit resistance (kinase inhibitors are highly suitable in this respect); and (iii) preemptive limitation of resistance through host-directed therapy (targeting host cell kinases that are required for parasite survival) and transmission-blocking through targeting sexual stage-specific kinases as a strategy to protect curative drugs from the spread of resistance

Gásir in Eyjafjörđur: International Exchange and Local Economy in Medieval Iceland

The site of Gásir in Eyjafjörður in northeast Iceland was excavated from 2001–2006, revealing details of one of the larger seasonal trading centers of medieval Iceland. Interdisciplinary investigations of the site have shed light upon the organization of the site and provided confirmation of documentary accounts of both prestige items (gyrfalcons, walrus ivory) and bulk goods (sulphur) concentrated for export. Gásir was a major point of cultural contact as well as economic exchange between Icelanders and the world of medieval Europe, and the zooarchaeological analyses indicated a mix of foodways and the presence of exotic animals and a well-developed provisioning system, which supplied high-quality meat and fresh fish to the traders. The excavations demonstrated an unexpected regional-level economic impact of the seasonally occupied site on the surrounding rural countryside, and contribute to ongoing investigations of the extent and impact of overseas trade in medieval Iceland

Thermal Emittance and Lifetime of Alkali-Antimonide Photocathodes Grown On GaAs and Molybdenum Substrates Evaluated in a -300 kV dc Photogun

CsxKySb photocathodes grown on GaAs and molybdenum substrates were evaluated using a –300 kV dc high voltage photogun and diagnostic beam line. Photocathodes grown on GaAs substrates, with varying antimony layer thickness (estimated range from \u3c 20 nm to \u3e 1 um), yielded similar thermal emittance per rms laser spot size values (~0.4 mm mrad / mm) but very different operating lifetime. Similar thermal emittance was obtained for a photocathode grown on a molybdenum substrate but with markedly improved lifetime. For this photocathode, no decay in quantum efficiency was measured at 4.5 mA average current and with peak current 0.55 A at the photocathode

Generation and Characterization of Magnetized Electron Beam From a DC High Voltage Photogun for Electron Beam Cooling Application

One of the most challenging requirements for the proposed Electron–Ion Collider is the strong cooling of the proton beam, which is key to achieving the collider’s desired luminosity of order 1033–1034cm−2s−1. Magnetized bunched-beam electron cooling could be a means to achieve the required high luminosity, where strong cooling is accomplished inside a cooling solenoid where the ions co-propagate with an electron beam generated from a source immersed in a magnetic field. To increase the cooling efficiency, a bunched electron beam with high bunch charge and high repetition rate is required. This work describes the production and characterization of magnetized electron beam using a compact 300 kV DC high voltage photogun and bi-alkali antimonide photocathode. Beam magnetization was studied using a diagnostic beamline that includes viewer screens for measuring the shearing angle of the electron beamlet passing through a narrow upstream slit. Simulations and corresponding measurements of beam magnetization are presented as a function of laser spot size and magnetic field strength. Correlated beam emittance with magnetic field (0–0.15T) at the photocathode was measured for various laser spot sizes. Measurements of photocathode lifetime were carried out at different magnetized electron beam currents up to 28 mA, and bunch charge up to 0.7 nC (not simultaneously)