Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis

Aims/hypothesis The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKTcells. Methods We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. Results The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. Conclusions/interpretation The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis

Detection and impacts of leakage from sub-seafloor deep geological carbon dioxide storage

Fossil fuel power generation and other industrial emissions of carbon dioxide are a threat to global climate1, yet many economies will remain reliant on these technologies for several decades2. Carbon dioxide capture and storage (CCS) in deep geological formations provides an effective option to remove these emissions from the climate system3. In many regions storage reservoirs are located offshore4, 5, over a kilometre or more below societally important shelf seas6. Therefore, concerns about the possibility of leakage7, 8 and potential environmental impacts, along with economics, have contributed to delaying development of operational CCS. Here we investigate the detectability and environmental impact of leakage from a controlled sub-seabed release of CO2. We show that the biological impact and footprint of this small leak analogue (<1 tonne CO2 d?1) is confined to a few tens of metres. Migration of CO2 through the shallow seabed is influenced by near-surface sediment structure, and by dissolution and re-precipitation of calcium carbonate naturally present in sediments. Results reported here advance the understanding of environmental sensitivity to leakage and identify appropriate monitoring strategies for full-scale carbon storage operations

Nondestructive verification of relative burnup values and cooling times of irradiated MTR fuel elements

Sixteen irradiated MTR fuel elements have been examined using nondestructive gamma-ray and neutron techniques. The consistency of declared burnup values and cooling times has been measured. Measured parameters have been identified that best predict the burnup and cooling time values of individual elements and their relative importances have been quantified using established statistical methods of analysis. Various detector systems, including germanium, cadmium telluride, and Be(..gamma..,n) detector, and fission chamber have been used to measure the axial activity profiles

Clinical and genetic analyses in a patient with PAPA syndrome complicated with inflammatory bowel disease

POSTER PRESENTATIO

Multicore Scheduling for Lightweight Communicating Processes

Process-oriented programming is a design methodology in which software applications are constructed from communicating concurrent processes. A process-oriented design is typically composed of a large number of small isolated concurrent components. These components allow for the scalable parallel execution of the resulting application on both shared-memory and distributed-memory architectures. In this paper we present a runtime designed to support process-oriented programming by providing lightweight processes and communication primitives. Our run-time scheduler, implemented using lock-free algorithms, automatically executes concurrent components in parallel on multicore systems. Run-time heuristics dynamically group processes into cache-affine work units based on communication patterns. Work units are then distributed via wait-free work-stealing. Initial performance analysis shows that, using the algorithms presented in this paper, process-oriented software can execute with an efficiency approaching that of optimised sequential and coarse-grain threaded designs

Nondestructive determination of burnup and cooling times of irradiated fuel assemblies

The applicability of nondestructive gamma-ray and neutron techniques for the characterization of irradiated fuel assemblies has been investigated. Consistency of relative cooling times can be verified using specific isotopic ratios. The axial activity profiles of assemblies have been measured using a variety of detectors. Declared burnup values for MTR, BWR, and PWR assemblies have been correlated with the /sup 134/Cs//sup 137/Cs and /sup 154/EU//sup 137/Cs isotopic ratios

Passive neutron assay of irradiated nuclear fuels

Passive neutron assay of irradiated nuclear fuel has been investigated by calculations and experiments as a simple, complementary technique to the gamma assay. From the calculations it was found that the neutron emission arises mainly from the curium isotopes, the neutrons exhibit very good penetrability of the assemblies, and the neutron multiplication is not affected by the burnup. From the experiments on BWR and PWR assemblies, the neutron emission rate is proportional to burnup raised to 3.4 power. The investigations indicate that the passive neutron assay is a simple and useful technique to determine the consistency of burnups between assemblies