Initial 4D seismic results after CO 2 injection start-up at the Aquistore storage site

The first post-CO2-injection 3D time-lapse seismic survey was conducted at the Aquistore CO2 storage site in February 2016 using the same permanent array of buried geophones used for acquisition of three previous pre-CO2-injection surveys from March 2012 to November 2013. By February 2016, 36 kilotons of CO2 have been injected within the reservoir between 3170 and 3370 m depth. We have developed time-lapse results from analysis of the first post-CO2-injection data and three pre-CO2-injection data sets. The objective of our analysis was to evaluate the ability of the permanent array to detect the injected CO2. A “4D-friendly simultaneous” processing flow was applied to the data in an effort to maximize the repeatability between the pre- and post-CO2-injection volumes while optimizing the final subsurface image including the reservoir. Excellent repeatability was achieved among all surveys with global normalized root-mean-square (Gnrms) values of 1.13–1.19 for the raw prestack data relative to the baseline data, which decreased during processing to Gnrms values of approximately 0.10 for the final crossequalized migrated data volumes. A zone of high normalized root-mean-square (nrms) values (0.11–0.25 as compared with background values of 0.05–0.10) is identified within the upper Deadwood unit of the storage reservoir, which likely corresponds to approximately 18 kilotons of CO2. No significant nrms anomalies are observed within the other reservoir units due to a combination of reduced seismic sensitivity, higher background nrms values, and/or small quantities of CO2 residing within these zones

Novel artificial eye service evaluation using patient reported outcome measures

Background This service evaluation explores patient reported outcomes from patients provided with high definition ocular prostheses (artificial eyes). Methods Validated patient questionnaires (FACE-Q, DAS24 and HADS) were utilised to evaluate patient experiences of their new ocular prosthesis. 10 patients were included in the service evaluation, which was conducted between December 2018 and September 2019. Descriptive analysis of the mean and 95% CI was undertaken for all questionnaires. Statistical analysis was performed using SPSS 21 Principal Component Analysis (PCA) for FACE-Q questionnaires. Correlations were significant when factor loading is at α > 0.4. Results A questionnaire response rate of 80% was achieved (n = 8). PCA analysis showed the number of variables tested could be reduced. Two principal components (PC1 and PC2) had very good to excellent internal consistency between variables with factor loading (α = 0.7–0.9). PC1 contained questionnaires 1–7, all of which were highly correlated. PC2 contained question number 8 with a factor loading of α = 0.8. This indicates good reliability, validity and responsiveness. Conclusions We hope to demonstrate the importance of service evaluations with respect to rapidly evolving technological advances in medical devices, pharmaceuticals and imaging modalities. Further feasibility and full clinical studies are required to confirm the positive results of the novel artificial eye service we have evaluated with respect to the traditional approach

A cross-over, randomised feasibility study of digitally printed versus hand-painted artificial eyes in adults: PERSONAL-EYE-S - a study protocol

ackground/objectives: Around 11,500 artificial eyes are required yearly for new and existing patients. Artificial eyes have been manufactured and hand-painted at the National Artificial Eye Service (NAES) since 1948, in conjunction with approximately 30 local artificial eye services throughout the country. With the current scale of demand, services are under significant pressure. Manufacturing delays as well as necessary repainting to obtain adequate colour matching, may severely impact a patient’s rehabilitation pathway to a normal home, social and work life. However, advances in technology mean alternatives are now possible. The aim of this study is to establish the feasibility of conducting a large-scale study of the effectiveness and cost-effectiveness of digitally printed artificial eyes compared to hand-painted eyes. Methods: A cross-over, randomised feasibility study evaluating a digitally-printed artificial eye with a hand-painted eye, in patients aged ≥18 years with a current artificial eye. Participants will be identified in clinic, via ophthalmology clinic databases and two charity websites. Qualitative interviews will be conducted in the later phases of the study and focus on opinions on trial procedures, the different artificial eyes, delivery times, and patient satisfaction. Discussion: Findings will inform the feasibility, and design, of a larger fully powered randomised controlled trial. The long-term aim is to create a more life-like artificial eye in order to improve patients’ initial rehabilitation pathway, long term quality of life, and service experience. This will allow the transition of research findings into benefit to patients locally in the short term and National Health Service wide in the medium to long term

Multi-Scale Stochastic Simulation of Diffusion-Coupled Agents and Its Application to Cell Culture Simulation

Many biological systems consist of multiple cells that interact by secretion and binding of diffusing molecules, thus coordinating responses across cells. Techniques for simulating systems coupling extracellular and intracellular processes are very limited. Here we present an efficient method to stochastically simulate diffusion processes, which at the same time allows synchronization between internal and external cellular conditions through a modification of Gillespie's chemical reaction algorithm. Individual cells are simulated as independent agents, and each cell accurately reacts to changes in its local environment affected by diffusing molecules. Such a simulation provides time-scale separation between the intra-cellular and extra-cellular processes. We use our methodology to study how human monocyte-derived dendritic cells alert neighboring cells about viral infection using diffusing interferon molecules. A subpopulation of the infected cells reacts early to the infection and secretes interferon into the extra-cellular medium, which helps activate other cells. Findings predicted by our simulation and confirmed by experimental results suggest that the early activation is largely independent of the fraction of infected cells and is thus both sensitive and robust. The concordance with the experimental results supports the value of our method for overcoming the challenges of accurately simulating multiscale biological signaling systems

Soft-bound synaptic plasticity increases storage capacity

Accurate models of synaptic plasticity are essential to understand the adaptive properties of the nervous system and for realistic models of learning and memory. Experiments have shown that synaptic plasticity depends not only on pre- and post-synaptic activity patterns, but also on the strength of the connection itself. Namely, weaker synapses are more easily strengthened than already strong ones. This so called soft-bound plasticity automatically constrains the synaptic strengths. It is known that this has important consequences for the dynamics of plasticity and the synaptic weight distribution, but its impact on information storage is unknown. In this modeling study we introduce an information theoretic framework to analyse memory storage in an online learning setting. We show that soft-bound plasticity increases a variety of performance criteria by about 18% over hard-bound plasticity, and likely maximizes the storage capacity of synapses

Lobe Specific Ca2+-Calmodulin Nano-Domain in Neuronal Spines: A Single Molecule Level Analysis

Calmodulin (CaM) is a ubiquitous Ca2+ buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca2+-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca2+-CaM-dependent enzymes: Ca2+/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca2+ and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca2+ ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca2+ and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca2+ signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca2+-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca2+ channels, and to the microscopic injection rate of Ca2+ ions. We also demonstrate that Ca2+ saturation takes place via two different pathways depending on the Ca2+ injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca2+ sensors that can differentially transduce Ca2+ influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca2+-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity

Helicobacter pylori CagA Triggers Expression of the Bactericidal Lectin REG3γ via Gastric STAT3 Activation

Background: Most of what is known about the Helicobacter pylori (H. pylori) cytotoxin, CagA, pertains to a much-vaunted role as a determinant of gastric inflammation and cancer. Little attention has been devoted to potential roles of CagA in the majority of H. pylori infected individuals not showing oncogenic progression, particularly in relation to host tolerance. Regenerating islet-derived (REG)3c encodes a secreted C-type lectin that exerts direct bactericidal activity against Grampositive bacteria in the intestine. Here, we extend this paradigm of lectin-mediated innate immunity, showing that REG3c expression is triggered by CagA in the H. pylori-infected stomach. Methodology/Principal Findings: In human gastric mucosal tissues, REG3c expression was significantly increased in CagApositive, compared to CagA-negative H. pylori infected individuals. Using transfected CagA-inducible gastric MKN28 cells, we recapitulated REG3c induction in vitro, also showing that tyrosine phosphorylated, not unphosphorylated CagA triggers REG3c transcription. In concert with induced REG3c, pro-inflammatory signalling downstream of the gp130 cytokine coreceptor via the signal transducer and activator of transcription (STAT)3 and transcription of two cognate ligands, interleukin(IL)-11 and IL-6, were significantly increased. Exogenous IL-11, but not IL-6, directly stimulated STAT3 activation and REG3c transcription. STAT3 siRNA knockdown or IL-11 receptor blockade respectively abrogated or subdued CagAdependent REG3c mRNA induction, thus demonstrating a requirement for uncompromised signalling via the IL-11/STAT