Derek A. Fong

Autoantigen microarrays for multiplex characterization of autoantibody responses

We constructed miniaturized autoantigen arrays to perform large-scale multiplex characterization of autoantibody responses directed against structurally diverse autoantigens, using submicroliter quantities of clinical samples. Autoantigen microarrays were produced by attaching hundreds of proteins, peptides and other biomolecules to the surface of derivatized glass slides using a robotic arrayer. Arrays were incubated with patient serum, and spectrally resolvable fluorescent labels were used to detect autoantibody binding to specific autoantigens on the array. We describe and characterize arrays containing the major autoantigens in eight distinct human autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. This represents the first report of application of such technology to multiple human disease sera, and will enable validated detection of antibodies recognizing autoantigens including proteins, peptides, enzyme complexes, ribonucleoprotein complexes, DNA and post-translationally modified antigens. Autoantigen microarrays represent a powerful tool to study the specificity and pathogenesis of autoantibody responses, and to identify and define relevant autoantigens in human autoimmune diseases.

Response of a river plume during an upwelling favorable wind event

The response of a surface-trapped river plume to an upwelling favorable wind is studied using a three-dimensional model in a simple, rectangular domain. Model simulations demonstrate that the plume thins and is advected offshore by the cross-shore Ekman transport. The thinned plume is susceptible to significant mixing because of the vertically sheared horizontal currents. The Ekman dynamics and shear-induced mixing cause the plume to evolve to a quasi-steady uniform thickness, which can be estimated by a critical Richardson number criterion. Although the mixing rate decreases slowly in time, mixing continues under a sustained upwelling wind until the plume is destroyed. Mixing persists at the seaward plume front because of an Ekman straining mechanism in which there is a balance between the advection of cross-shore salinity gradients and vertical mixing. The plume mixing rate observed is similar to the mixing law obtained by previous studies of one-dimensional mixing, although the river plume mixing is essentially two-dimensional.

The alongshore transport of freshwater in a surface-trapped river plume

Abstract The alongshore transport of a surface-trapped river plume is studied using a three-dimensional model. Model simulations exhibit the previously observed rightward veering (in the Northern Hemisphere) of the freshwater and establishment of a downstream geostrophically balanced coastal current. In the absence of any ambient current, the plume does not reach a steady state. The downstream coastal current only carries a fraction of the discharged freshwater; the remaining fraction recirculates in a continually growing “bulge” of freshwater in the vicinity of the river mouth. The river mouth conditions influence the amount of freshwater transported in the coastal current relative to the growing bulge. For high Rossby number [O(1)] discharge conditions, the bulge shape is circular and the coastal current transport is smaller than for the model runs of low Rossby number discharges. For all model runs conducted without an ambient current, the freshwater transport in the coastal current is less than the fr...

The wind-forced response on a buoyant coastal current: Observations of the western Gulf of Maine plume

Abstract The freshwater plume in the western Gulf of Maine is being studied as part of an interdisciplinary investigation of the physical transport of a toxic alga. A field program was conducted in the springs of 1993 and 1994 to map the spatial and temporal patterns of salinity, currents and algal toxicity. The observations suggest that the plumes cross-shore structure varies markedly as a function of fluctuations in alongshore wind forcing. Consistent with Ekman drift dynamics, upwelling favorable winds spread the plume offshore, at times widening it to over 50 km in offshore extent, while downwelling favorable winds narrow the plume width to as little as 10 km. Using a simple slab model, we find qualitative agreement between the observed variations of plume width and those predicted by Ekman theory for short time scales of integration. Near surface current meters show significant correlations between cross-shore currents and alongshore wind stress, consistent with Ekman theory. Estimates of the terms in the alongshore momentum equation calculated from moored current meter arrays also indicate a dominant Ekman balance within the plume. A significant correlation between alongshore currents and winds suggests that interfacial drag may be important, although inclusion of a Raleigh drag term does not significantly improve the alongshore momentum balance.

Laboratory experiments simulating a coastal river inflow

The dynamics of buoyant water entering a rotating basin are studied using a series of laboratory experiments designed to elucidate the alongshore transport mechanisms in river plumes. Inflowing water, which is discharged perpendicular to the tank wall, is observed to form a growing anticyclonic bulge and a coastal current downstream of the bulge. Detailed simultaneous measurements of the velocity and buoyancy fields in the plume confirm that the bulge momentum is in a gradient–wind balance and the coastal current is geostrophic. The growth of the bulge and accumulation of fluid within it coincides with a reduction in coastal current transport to approximately 50 % of the inflow discharge. The bulge is characterized by a depth scale, h ,w hich is proportional to the geostrophic depth, hg, and two time-dependent horizontal length scales, yc, the displacement of the bulge centre from the wall, and rb, the effective radius of the bulge. These two length scales are proportional to the inertial radius, � —‐

High-resolution simulations of a macrotidal estuary using SUNTANS

The parallel, finite-volume, unstructured-grid SUNTANS model has been employed to study the interaction of the tides with complex bathymetry in the macrotidal Snohomish River estuary. The unstructured grid resolves the large-scale, O(10 km) tidal dynamics of the estuary while employing 8 m grid-resolution at a specific region of interest in the vicinity of a confluence of two channels and extensive intertidal mudflats to understand detailed local intratidal flow processes. After calibrating tidal forcing parameters to enforce a match between free surface and depth-averaged velocities at several locations throughout the domain, we analyze the complex dynamics of the confluence and show that the exposure of the intertidal mudflats during low tide induces a complex flow reversal. When coupled with the longitudinal salinity gradient, this flow reversal results in a highly variable salinity field, which has profound implications for local mixing, stratification and the occurrence of fine-scale flow structures. This complex flow is then used as a testbed from which to describe several challenges associated with high resolution modeling of macrotidal estuaries, including specification of high resolution bathymetry, specification of the bottom stress, computation of the nonhydrostatic pressure, accurate advection of momentum, and the influence of the freshwater inflow. The results indicate that with high resolution comes the added difficulty of requiring more accurate specification of boundary conditions. In particular, the bottom bathymetry plays the most important role in achieving accurate predictions when high resolution is employed. 2008 Elsevier Ltd. All rights reserved.

Comparison of Reynolds Stress Estimates Derived from Standard and Fast-Ping ADCPs

Abstract A field experiment was conducted to directly compare the effects of different sampling modes on Reynolds stress estimates calculated from acoustic Doppler current profilers (ADCPs). Two 1.2-MHz ADCPs were deployed concurrently over a fortnightly cycle: one collected single-ping measurements using mode 1 and a second ADCP employed the fast-ping rate mode 12 with subping-averaged data recorded at the same sample rate as the first ADCP. While mode 12 clearly has a lower noise floor for the estimate of mean velocities, it has been an open question whether the averaging of subpings leads to a biased estimate of turbulence quantities, due to the temporal averaging inherent in this approach. Using the variance method, Reynolds stresses were estimated from the two ADCP datasets and compared with stresses computed directly from the velocity records obtained with a pair of fast sampling acoustic Doppler velocimeters (ADVs) collocated with the ADCPs. Mode-12 stresses were more accurate than mode 1 in compar...

A simple model of mixing in stratified tidal flows

We use a simple model of vertical mixing in a stratified tidal flow to study flows that might be observed in shallow estuaries. In the model, flow is driven by a specified surface pressure gradient due to barotropic tidal motions. The model incorporates two means for accomplishing vertical mixing: (1) shear instability and (2) bottom mixed-layer deepening by turbulence produced at the estuary bottom and in the shear layer at the top of the mixed layer. We discuss model results that show how the combined action of shear instability and tidal “stirring” accomplishes vertical mixing. The interaction between the instabilities that develop because of the substantial tidal timescale velocity shear caused by stratification is the key feature of mixing. Shear instability weakens the stability of the mixed layer, allowing stirring to efficiently entrain lighter fluid into the mixed layer. The importance of shear is found to depend on the stability of the water column and on the relative importance of frictional forces.

Horizontal dispersion of a near-bed coastal plume

The transport of scalars in the coastal ocean is considered through the analysis of a vertically constrained plume which disperses laterally. Observations of the plume are made using an autonomous underwater vehicle (AUV) operating in two modes: (i) repeated transects of the plume at a fixed distance from the source; and (ii) a large-scale mapping of the plume development. Together, these measurements define both the variability in the plume centreline (i.e. the meandering) and the growth of the plume around the centreline (i.e. the relative dispersion). The analysis of the measurements suggests that the meandering is well-described by a spatially uniform but temporally variable velocity field, indicating that large-scale flow structures dominate the centreline variability. The growth of the plume downstream is seen to follow a scale-dependent dispersion law, most likely of a compound structure: a 4/3-law in the near field, and a scale-squared law in the far field. This transition between dispersion laws is consistent with the transition from three-dimensional turbulence structures to two-dimensional eddies, which is due to the constraints imposed on the vertical dimension at the site. Comparing the two dispersion processes, the effective dispersion created by meandering is found to be comparable with or larger than the relative dispersion in the near field; but in the far field, the relative dispersion is found to dominate considerations of overall dispersion.

Evaluation of the Accuracy of a Ship-Mounted, Bottom-Tracking ADCP in a Near-Shore Coastal Flow

Abstract The accuracy of an acoustic Doppler current profiler (ADCP) used with an internal bottom-tracking system is considered. The boat speed measured using bottom tracking is extremely accurate, comparable to the speeds measured by a high-resolution, real-time kinematic global positioning system (KGPS). The accuracy in the direction of boat motion reported by the bottom tracking is limited to the accuracy of the internal compass of the ADCP. Directional differences (after correcting for local magnetic declination) are about 3° between the ADCP bottom tracking and KGPS. An error of this magnitude is shown to result in a maximal measurement error in water velocity of less than 6%. Nonetheless, an unexplained water velocity error is observed that is significantly larger than can be explained by a simple compass error. Repeated transects in opposing directions show a bias in measured water velocities in the direction of boat motion. The bias cannot be explained by an error in the compass or the bottom-trac...