CD33M inhibits microglial phagocytosis, migration and proliferation, but the Alzheimer’s disease‐protective variant CD33m stimulates phagocytosis and proliferation, and inhibits adhesion

Funder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268Abstract: CD33 is a Siglec (sialic acid‐binding immunoglobulin‐type lectin) receptor on microglia. Human CD33 can be alternatively spliced into two isoforms: the long isoform (CD33M) and a shorter isoform (CD33m) that lacks the sialic acid‐binding site. CD33m appears to protect against Alzheimer's disease; however, it remains unclear how. To investigate potential mechanisms by which CD33m may confer protection, we expressed the CD33m and CD33M isoforms of human CD33 in mouse BV‐2 and human CHME3 microglial cells and assessed microglia functions. In the BV‐2 cells, CD33M inhibited microglial phagocytosis of beads, synapses, debris and dead cells, while CD33m increased phagocytosis of beads, debris and cells. RNAi knockdown of the endogenous mouse CD33 increased phagocytosis and prevented CD33m's (but not CD33M’s) effect on phagocytosis. CD33M increased cell attachment but inhibited cell proliferation, while CD33m did the opposite. We also found that CD33M inhibited cell migration. In human CHME3 cells, CD33M increased cell attachment, but inhibited phagocytosis, proliferation and migration, whereas CD33m did the opposite. We conclude that CD33M inhibits microglial phagocytosis, inhibits migration and increases adhesion, while CD33m increases phagocytosis, proliferation and inhibits adhesion. Thus, CD33m might protect against Alzheimer's disease by increasing microglial proliferation, movement and phagocytosis of debris and dead cells. imag

Physical simulations of seabed scouring by ice: review and database

This paper summarizes the compilation of information on physical simulations of seabed scouring by ice keels, and the resulting database. Physical simulations are critical for a proper understanding of ice scouring phenomena. A total of 487 scour simulations from twentyeight studies are reported. General information about test facility, soil, keel type, model pipeline, test conditions and results are outlined. The database can be used as a tool to identify knowledge gaps and guide future testing programs, to generate empirical relationships between the parameters involved during this interaction, or to validate numerical models. Copyright \ua9 2012 by the International Society of Offshore and Polar Engineers (ISOPE).Peer reviewed: YesNRC publication: Ye

Flux of multi-year ice past the Molikpaq in the Beaufort sea, 1985-86 season

As part of the environmental monitoring program that supported drilling operations from the Molikpaq at the Amauligak I-65 location during the winter of 1985-86, information about the ice conditions and movements round the structure were collected on an hourly basis. These observations included ice thickness, ice type, partial concentrations, floe sizes and drift rate and direction. In this paper the data were used to assess the flux of ice passing a fixed location. Of particular interest was the amount of multi-year ice present and the relative exposure of the Molikpaq to multi-year ice interactions. In addition to the hourly ice observations, which were representative of a zone within a several km radius of the Molikpaq, detailed observations and video records of ice interactions with the structure were also made. Monthly Canadian Ice Service regional ice charts and drift buoys provided regional data. The various sources of ice data are compared to put the 1985-86 data into a broader context. The total flux of ice through the 2 km radius zone of observation was about 1000 km over the 240 day observation period, of which 30 km was multi-year ice. The flux of multi-year ice that actually interacted with the 100 m wide Molikpaq was about 10 km, the majority of which was second-year ice in November.Peer reviewed: YesNRC publication: Ye

Revisiting the Sanderson pressure-area curve: Defining parameters that influence ice pressure

There is a strong perception in the ice mechanics community that during ice-structure interaction, the ice pressure always decreases as the area of contact increases. This understanding is often based on the pressure-area plot published by Sanderson (1988), which combines a large number of data sources and ice interaction situations on a single plot and shows a definite decrease in pressure with increasing area. This paper examines the data sources in the Sanderson plot as well as some more recent data, and discusses the definitions of global, local, spatial and process pressure-area. It is found that the pressure over a defined local geometric area or over the full global ice contact area can either show no dependence on area or a decrease with increasing area, depending on the interaction scenario. Factors other than area are examined to determine their influence on pressure including the loading rate, aspect ratio, ice failure mode, and ice properties. It is shown that in many cases, these factors are more important than the area in predicting ice pressure. The theory of Palmer et al. (2009) provides a reasonable explanation for some of the observed trends in pressure-area behavior. Examples from field data are provided to illustrate the application of pressure-area relationships for offshore structures in icy waters.Peer reviewed: YesNRC publication: Ye

Review of flexural strength of multi-year ice

Flexural strength from dedicated beam tests and ramming of multi-year floes has been compared. Flexural strength of multi-year ice from beam tests indicates the strength decreases as the size of the beams increases and this is important in comparing flexural strength data from various sources. In terms of relative flexural strength; from strongest to weakest is fresh-water ice, multi-year ice and first-year sea ice. Ship ramming results provide comparative results for flexural strength, even if the absolute values are greater than would be expected given the thickness of the ice. Colder ice floes have greater flexural strength. The MV Arctic ramming tests indicate that multi-year floes in a small area can be quite variable in thickness, temperature and flexural strength. Copyright \ua9 2013 by the International Society of Offshore and Polar Engineers (ISOPE).Peer reviewed: YesNRC publication: Ye

Ice scour simulation database: review and knowledge gap analysis of available numerical models

NRC publication: Ye

Conical structures in ice: Relevant relationships for ISO 19906

Conical shapes are often chosen for structures that are exposed to floating ice, such as offshore drilling platforms, bridge piers and offshore wind turbine foundations. The flexural ice failure promoted by the shape of a cone can lead to lower forces on the structure than compressive failure, which would take place if ice is to encounter a vertical surface. In spite of the wide use of conical structures, many aspects of their performance in ice covered waters remain poorly understood. For example, the ISO 19906 Arctic Offshore Structures standard does not provide guidance with respect to ridge keel loading on cones, or the height to which ice could ride up on a conical structure. With the planned revision of that document presently beginning, it is important to address the guidance gaps in order to include new insights in the revised standard. Previous work by the authors employed a numerical model of ice dynamics in order to predict ice failure patterns and forces on various conical structures. The present work extends those studies and predicts the extent of ice ride-up on the structures; the roles of the waterline width of the structure and ice thickness are discussed. The resulting ice force estimates are comparable to those predicted by an approach recommended in ISO 19906. Both the plastic and elastic beam-bending methods recommended by ISO 19906 for determining ice actions on conical structures require an initial assumption of the maximum height of accumulated rubble. Little guidance is given in ISO 19906, except to note that this height depends on the structure geometry and ice regime. For the present calculations, the chosen rubble height for each ice load calculation is based on the results of the corresponding numerical model run. Previous numerical studies by the authors have also been reviewed and the estimates of ice ride-up heights summarized. Numerical simulations could be expanded to produce a comprehensive range of ride-up values to support users of ISO 19906.Peer reviewed: YesNRC publication: Ye

Ice keel load distribution on cylindrical structures

The ability to reliably predict ice forces generated by ridged ice features is very important for the design of offshore structures in many cold regions. Analytical models have been developed for predicting the loads on a structure due to interaction of an ice ridge keel or rubble, but few data exist for validating these models. In the present paper, the ice keel load distribution across the face of a vertical cylindrical structure is assessed. Ice load data collected in 2002 as part of the STRICE project at Norstr\uf6msgrund lighthouse were examined. Events for which the instrumented part of the lighthouse was responding only to ice keel loading were analysed to quantify horizontal ice keel pressures. The results have been compared with predictions of a numerical model. Numerical modeling is also used to predict the global ice forces and ice failure behavior for ridges of different size. From both full scale field data and numerical simulations of ridge interaction with the lighthouse, a trend of higher forces with increasing keel depths can be seen. In addition to generating larger global loads, larger ridges appear to create greater local loads around the waterline of the cylindrical structure. The load distribution across the lighthouse is not uniform. For some events, the forces on the load panels show a parabolic-type distribution while for others a different load distribution with two maxima is seen.Peer reviewed: YesNRC publication: Ye