An Immunohistochemical Study of the Distribution of the Measles Virus Receptors, CD46 and SLAM, In Normal Human Tissues and Subacute Sclerosing Panencephalitis

We have compared the expression of the known measles virus (MV) receptors, membrane cofactor protein (CD46) and the signaling lymphocyte-activation molecule (SLAM), using immunohistochemistry, in a range of normal peripheral tissues (known to be infected by MV) as well as in normal and subacute sclerosing panencephalitis (SSPE) brain. To increase our understanding of how these receptors could be utilized by wild-type or vaccine strains in vivo, the results have been considered with regard to the known route of infection and systemic spread of MV. Strong staining for CD46 was observed in endothelial cells lining blood vessels and in epithelial cells and tissue macrophages in a wide range of peripheral tissues, as well as in Langerhans' and squamous cells in the skin. In lymphoid tissues and blood, subsets of cells were positive for SLAM, in comparison to CD46, which stained all nucleated cell types. Strong CD46 staining was observed on cerebral endothelium throughout the brain and also on ependymal cells lining the ventricles and choroid plexus. Comparatively weaker CD46 staining was observed on subsets of neurons and oligodendrocytes. In SSPE brain sections, the areas distant from lesion sites and negative for MV by immunocytochemistry showed the same distribution for CD46 as in normal brain. However, cells in lesions, positive for MV, were negative for CD46. Normal brain showed no staining for SLAM, and in SSPE brain only subsets of leukocytes in inflammatory infiltrates were positive. None of the cell types most commonly infected by MV show detectable expression of SLAM, whereas CD46 is much more widely expressed and could fulfill a receptor function for some wild-type strains. In the case of wild-type stains, which are unable to use CD46, a further as yet unknown receptor(s) would be necessary to fully explain the pathology of MV infection.

Use of SLAM and PVRL4 and Identification of Pro-HB-EGF as Cell Entry Receptors for Wild Type Phocine Distemper Virus

Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.

The Vertical Distribution and Evolution of Slam Pressure on an Oscillating Wave Surge Converter

The accurate definition of the extreme wave loads which act on offshore structures represents a significant challenge for design engineers and even with decades of empirical data to base designs upon there are still failures attributed to wave loading. The environmental conditions which cause these loads are infrequent and highly non-linear which means that they are not well understood or simple to describe. If the structure is large enough to affect the incident wave significantly further non-linear effects can influence the loading. Moreover if the structure is floating and excited by the wave field then its responses, which are also likely to be highly non-linear, must be included in the analysis. This makes the description of the loading on such a structure difficult to determine and the design codes will often suggest employing various tools including small scale experiments, numerical and analytical methods, as well as empirical data if available.
Wave Energy Converters (WECs) are a new class of offshore structure which pose new design challenges, lacking the design codes and empirical data found in other industries. These machines are located in highly exposed and energetic sites, designed to be excited by the waves and will be expected to withstand extreme conditions over their 25 year design life. One such WEC is being developed by Aquamarine Power Ltd and is called Oyster. Oyster is a buoyant flap which is hinged close to the seabed, in water depths of 10 to 15m, piercing the water surface. The flap is driven back and forth by the action of the waves and this mechanical energy is then converted to electricity.
It has been identified in previous experiments that Oyster is not only subject to wave impacts but it occasionally slams into the water surface with high angular velocity. This slamming effect has been identified as an extreme load case and work is ongoing to describe it in terms of the pressure exerted on the outer skin and the transfer of this short duration impulsive load through various parts of the structure.
This paper describes a series of 40th scale experiments undertaken to investigate the pressure on the face of the flap during the slamming event. A vertical array of pressure sensors are used to measure the pressure exerted on the flap. Characteristics of the slam pressure such as the rise time, magnitude, spatial distribution and temporal evolution are revealed. Similarities are drawn between this slamming phenomenon and the classical water entry problems, such as ship hull slamming. With this similitude identified, common analytical tools are used to predict the slam pressure which is compared to that measured in the experiment.

The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of dietary supplementation with omega-3 fish oils with or without copper on disease activity in systemic lupus erythematosus (SLE). Fish oil supplementation has a beneficial effect on murine models of SLE, while exogenous copper can decrease the formation of lupus erythematosus cells in rats with a hydralazine-induced collagen disease. METHODS: A double blind, double placebo controlled factorial trial was performed on 52 patients with SLE. Patients were randomly assigned to 4 treatment groups. Physiological doses of omega-3 fish oils and copper readily obtainable by dietary means were used. One group received 3 g MaxEPA and 3 mg copper, another 3 g MaxEPA and placebo copper, another 3 mg copper and placebo fish oil, and the fourth group received both placebo capsules. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and peripheral blood samples for routine hematological, biochemical, and immunological indices were taken at baseline, 6, 12, and 24 weeks. RESULTS: There was a significant decline in SLAM-R score from 6.12 to 4.69 (p <0.05) in those subjects taking fish oil compared to placebo. No significant effect on SLAM-R was observed in subjects taking copper. Laboratory variables were unaffected by either intervention. CONCLUSION: In the management of SLE, dietary supplementation with fish oil may be beneficial in modifying symptomatic disease activity.

A randomised interventional trial of ω-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus

Objective: To determine the clinical effect of dietary supplementation with low-dose ?-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus. Methods: A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of ?-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks. Results: In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p

Invariant Information Local Sub-map Filter (IILSF) for Efficient Simultaneous Localisation and Mapping of Large Environments

This paper presents an Invariant Information Local Sub-map Filter (IILSF) as a technique for consistent Simultaneous Localisation and Mapping (SLAM) in a large environment. It harnesses the benefits of sub-map technique to improve the consistency and efficiency of Extended Kalman Filter (EKF) based SLAM. The IILSF makes use of invariant information obtained from estimated locations of features in independent sub-maps, instead of incorporating every observation directly into the global map. Then the global map is updated at regular intervals. Applying this technique to the EKF based SLAM algorithm: (a) reduces the computational complexity of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. Simulation results show that the method was able to accurately fuse local map observations to generate an efficient and consistent global map, in addition to significantly reducing computational cost and data association ambiguities.

Il Piano della Performance nei Comuni medi. La proposta di una nuova configurazione per superare l’inadeguatezza delle prime applicazioni

Il D.Lgs. 150/09 ha inteso dar vita ad una “riforma organica” della PA italiana, improntandone il funzionamento a logiche di programmazione e controllo delle performance. Attorno a tale concetto la riforma ha costruito un Sistema teso a programmare, misurare, controllare, valutare e comunicare la performance degli enti. Il lavoro si focalizza sulla programmazione, e in particolare sullo strumento cardine introdotto dal D.Lgs. 150/09: il Piano della Performance (PdP). Il contributo, basato su una metodologia deduttivo-induttiva, si concentra sui comuni medi italiani, scelti in quanto statisticamente rappresentativi del livello medio di complessità degli enti locali. Sono stati oggetto di indagine i PdP pubblicati sui siti istituzionali degli enti considerati, al fine di verificarne sia il livello di aderenza alle Linee Guida (LG) emanate dalla Commissione Indipendente per la Valutazione, la Trasparenza e l’Integrità delle amministrazioni pubbliche (CIVIT) e dalla Associazione Nazionale Comuni Italiani (ANCI), sia il loro livello di adeguatezza economico-aziendale. Preliminarmente si indagherà il tema della programmazione, sotto il profilo normativo-dottrinale, concentrandosi su soggetti, processi e strumenti. Poi si sposterà il focus sul PdP: dopo aver definito obiettivi, quesiti e metodologia della ricerca, verranno esplicitate le configurazioni di PdP emergenti dalle LG CIVIT e ANCI. Verranno poi illustrati i risultati della ricerca empirica, mettendo in luce il livello di allineamento dei PdP dei comuni medi alle LG, nonché il livello di adeguatezza economico-aziendale degli stessi. Si tratteggeranno quindi alcune brevi conclusioni.

Programmazione e controllo dei gruppi pubblici locali. Dagli strumenti esistenti alle soluzioni innovative per la governance.

Il tema dei servizi pubblici locali è sicuramente centrale nell'attuale contesto socio-economico nazionale ed internazionale, in quanto essi hanno un impatto determinante sulle condizioni di vita dei cittadini e sulla competitività dei sistemi economici. In ragione di ciò, negli ultimi anni in Italia numerose riforme si sono susseguite, con lo scopo di individuare l'assetto più efficace ed efficiente per tale settore. Le suddette riforme hanno così ridisegnato il ruolo degli Enti Locali, che saranno sempre meno gestori diretti e sempre più direttori di una multiforme orchestra composta dalle aziende esterne chiamate a fornire in prima persona le prestazioni agli utenti finali. Il presente lavoro si propone di individuare, anche attraverso una ricerca sui Comuni capoluogo di Emilia-Romagna e Toscana, strumenti di programmazione e controllo in ottica di gruppo che consentano agli Enti Locali di svolgere questo nuovo delicato ruolo. Tali strumenti verranno disegnati sulla base delle necessità informative delle amministrazioni indagate e nel rispetto delle più recenti riforme in tema di programmazione, rilevazione, gestione, controllo, valutazione e comunicazione delle performance pubbliche.

The Characteristics of Wave Impacts on an Oscillating Wave Surge Converter

Wave impacts on an oscillating wave surge converter are examined using experimental and numerical methods. The mechanics of the impact event are identified experimentally with the use of images recorded with a high-speed camera. It is shown that it is the device that impacts the wave rather than a breaking wave impacting the device. Numerical simulations using two different approaches are used to further understand the issue. Good agreement is shown between numerical simulations and experimental measurements at 25th scale.

The structural response of an oscillating wave surge converter to wave slamming

This paper describes the problems in experimentally obtaining hydrodynamic loads on an oscillating wave surge converter during slamming events, with the aim of furthering understanding of full scale hydrodynamic loads that flap type devices must be designed to withstand. Including how hydro-elastic effects and structural response are linked and why they are essential to the measurement of impulsive hydrodynamic loads. A combined experimental and numerical structural response study carried out on a 40th scale Oyster model drew conclusions on the structural vibration observed in the strain gauge load cell measurement. A further structural response study on a piezo electric load measurement device gave an insight into the advantages it could bring to reducing hydro-elastic effects.