Investigation of K0Σ+K^0\Sigma^+ photoproduction with the CBELSA/TAPS experiment

$\gamma (p,K^0)\Sigma^+$ cross section was measured at the CBELSA/TAPS experiment at the ELSA electron stretcher facility. A cusp-like structure was apparent near the $K^*$ production threshold, where the cross section reduced by a factor of four in the forward direction. It is speculated that t-channel $K^*$ exchange, and meson-hyperon dynamically generated states may have large contributions to the cross section. The motivation for the extraction of the beam-target double polarisation observable, $E$, is discussed, and the new experiment, BGO-OD at the ELSA facility is introduced.Comment: 4 pages, 4 figures. Proceedings of NSTAR201

Detection of K+ mesons in segmented electromagnetic calorimeters

The combination of the CrystalBall and TAPS electromagnetic calorimeters were installed in the MAMI A2 hall in 2003. Here they are able to detect the reaction products from photo-induced reactions in combination with the Glasgow photon tagger. In the last two years the MAMI facility was upgraded from 885 MeV to 1.5 GeV, the A2 photon tagger underwent a similar upgrade crossing the threshold for strangeness photoproduction. For the CrystalBall this created a new challenge, to identify K+ mesons above the large background from other charged hadrons, in a situation where the detector setup does not benefit from a magnetic field to help separate particle species. These proceedings outline a novel technique which uses the decay products of the K+ as a strangeness tag

Appraising longitudinal trends in the strategic risks cited by risk managers in the international water utility sector, 2005-2015

We report dynamic changes in the priorities for strategic risks faced by international water utilities over a 10 year period, as cited by managers responsible for managing them. A content analysis of interviews with three cohorts of risk managers in the water sector was undertaken. Interviews probed the focus risk managers' were giving to strategic risks within utilities, as well as specific questions on risk analysis tools (2005); risk management cultures (2011) and the integration of risk management with corporate decision-making (2015). The coding frequency of strategic (business, enterprise, corporate) risk terms from 18 structured interviews (2005) and 28 semi-structured interviews (12 in 2011; 16 in 2015) was used to appraise changes in the perceived importance of strategic risks within the sector. The aggregated coding frequency across the study period, and changes in the frequency of strategic risks cited at three interview periods identified infrastructure assets as the most significant risk over the period and suggests an emergence of extrinsic risk over time. Extended interviews with three utility risk managers (2016) from the UK, Canada and the US were then used to contextualise the findings. This research supports the ongoing focus on infrastructure resilience and the increasing prevalence of extrinsic risk within the water sector, as reported by the insurance sector and by water research organisations. The extended interviews provided insight into how strategic risks are now driving the implementation agenda within utilities, and into how utilities can secure tangible business value from proactive risk governance. Strategic external risks affecting the sector are on the rise, involve more players and are less controllable from within a utility's own organisational boundaries. Proportionate risk management processes and structures provide oversight and assurance, whilst allowing a focus on the tangible business value that comes from managing strategic risks well

Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism

ABSTRACT Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2. Fluorescence in situ hybridization of AAV transgenes was used to identify differences in retinal trafficking and revealed that HS binding was responsible for AAV2 accumulation at the ILM. This mechanism was tested on human ex vivo retinas and showed similar accumulation with HS-binding AAV2 capsid only. To evaluate if HS binding could be applied to other AAV serotypes to enhance their transduction, AAV1 and AAV8 were modified to bind HS with a single-amino-acid mutation and tested in mice. Both HS-binding mutants of AAV1 and AAV8 had higher intravitreal transduction than their non-HS-binding parent capsid due to increased retinal accumulation. To understand the influence that HS binding has on tropism, chimeric AAV2 capsids with dual-glycan usage were tested intravitreally in mice. Compared to HS binding alone, these chimeric capsids displayed enhanced transduction that was correlated with a change in tropism. Taken together, these data indicate that HS binding serves to sequester AAV capsids from the vitreous to the ILM but does not influence retinal tropism. The enhanced retinal transduction of HS-binding capsids provides a rational design strategy for engineering capsids for intravitreal delivery. IMPORTANCE Adeno-associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy is met by intravitreal delivery, but delivery of AAV by this route results in poor transduction outcomes. The inner limiting membrane (ILM) creates a barrier separating the vitreous and the retina. Binding of AAV to heparan sulfate proteoglycan (HSPG) at the ILM may allow the virus to traverse this barrier for better retinal transduction. We show that HSPG binding is correlated with greater accumulation and penetration of AAV in the retina. We demonstrated that this accumulation is conserved across mouse and human retinas and that the addition of HSPG binding to other AAV capsids can increase the number of vectors accumulating at the ILM without dictating tropism

Distribution and Abundance of Larval Burbot and Deepwater Sculpin in Lake Michigan

Samples from seven locations at depths to 21 m, collected over periods of up to 8 years, were used to describe the nearshore distribution and abundance of burbot Lota lota and deepwater sculpin Myoxocephalus thompsoni larvae in Lake Michigan. Based upon power‐plant‐entrainment samples and field collections, burbot larvae (3.0–7.5 mm) occurred from late March to mid‐June, most abundantly in April and May, and most often at water temperatures of 6–12 C. Larvae were collected from the 0.5‐ to 13.5‐m depth strata as far lakeward as the 21‐m bottom contour, the limit of offshore sampling. In eastern Lake Michigan, highest densities (up to 843 larvae/1,000 m3) were at the 1‐m contour; in Green Bay, up to 24,000 larvae/1,000 m3 were detected near the Bark River. High densities of burbot larvae at bottom depths 3 m and less indicated inshore spawning and river spawning at some sites. Deepwater sculpin larvae first occurred in early February and were common in March and April entrainment samples. Larvae (8.0–22.0 mm) were in nearshore waters usually through May at depth strata of 0.5 to 17 m as far lakeward as the 18‐m bottom contour. Most larvae occurred at water temperatures below 6 C. Field densities were low, 5 to 78 larvae/1,000 m3. Deepwater sculpin larvae were pelagic and were dispersed over great distances by currents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141932/1/tafs0162.pd

Reactive Oxygen Species Stimulate Insulin Secretion in Rat Pancreatic Islets: Studies Using Mono-Oleoyl-Glycerol

Chronic exposure (24–72 hrs) of pancreatic islets to elevated glucose and fatty acid leads to glucolipoxicity characterized by basal insulin hypersecretion and impaired glucose-stimulated insulin secretion (GSIS). Our aim was to determine the mechanism for basal hypersecretion of insulin. We used mono-oleoyl-glycerol (MOG) as a tool to rapidly increase lipids in isolated rat pancreatic ß-cells and in the clonal pancreatic ß-cell line INS-1 832/13. MOG (25–400 µM) stimulated basal insulin secretion from ß-cells in a concentration dependent manner without increasing intracellular Ca2+ or O2 consumption. Like GSIS, MOG increased NAD(P)H and reactive oxygen species (ROS). The mitochondrial reductant ß-hydroxybutyrate (ß-OHB) also increased the redox state and ROS production, while ROS scavengers abrogated secretion. Diazoxide (0.4 mM) did not prevent the stimulatory effect of MOG, confirming that the effect was independent of the KATP-dependent pathway of secretion. MOG was metabolized to glycerol and long-chain acyl-CoA (LC-CoA), whereas, acute oleate did not similarly increase LC-CoA. Inhibition of diacylglycerol kinase (DGK) did not mimic the effect of MOG on insulin secretion, indicating that MOG did not act primarily by inhibiting DGK. Inhibition of acyl-CoA synthetase (ACS) reduced the stimulatory effect of MOG on basal insulin secretion by 30% indicating a role for LC-CoA. These data suggest that basal insulin secretion is stimulated by increased ROS production, due to an increase in the mitochondrial redox state independent of the established components of GSIS

Differences in level of confidence in diabetes care between different groups of trainees: the TOPDOC diabetes study

Background There is an increasing prevalence of diabetes. Doctors in training, irrespective of specialty, will have patients with diabetes under their care. The aim of this further evaluation of the TOPDOC Diabetes Study data was to identify if there was any variation in confidence in managing diabetes depending on the geographical location of trainees and career aspirations. Methods An online national survey using a pre-validated questionnaire was administered to trainee doctors. A 4-point confidence rating scale was used to rate confidence in managing aspects of diabetes care and a 6-point scale used to quantify how often trainees would contribute to the management of patients with diabetes. Responses were grouped depending on which UK country trainees were based and their intended career choice. Results Trainees in Northern Ireland reported being less confident in IGT diagnosis, use of IV insulin and peri-operative management and were less likely to adjust oral treatment, contact specialist, educate lifestyle, and optimise treatment. Trainees in Scotland were less likely to contact a specialist, but more likely to educate on lifestyle, change insulin, and offer follow-up advice. In Northern Ireland, Undergraduate (UG) and Postgraduate (PG) training in diagnosis was felt less adequate, PG training in emergencies less adequate, and reporting of need for further training higher. Trainees in Wales felt UG training to be inadequate. In Scotland more trainees felt UG training in diagnosis and optimising treatment was inadequate. Physicians were more likely to report confidence in managing patients with diabetes and to engage in different aspects of diabetes care. Aspiring physicians were less likely to feel the need for more training in diabetes care; however a clear majority still felt they needed more training in all aspects of care. Conclusions Doctors in training have poor confidence levels dealing with diabetes related care issues. Although there is variability between different groups of trainees according to geographical location and career aspirations, this is a UK wide issue. There should be a UK wide standardised approach to improving training for junior doctors in diabetes care with local training guided by specific needs.</p