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Pulvinones were synthesized (>180) in arrays and evaluated as inhibitors of early stage cell wall biosynthesis enzymes MurA-MurD. Several pulvinones inhibited Mur enzymes with IC(50)'s in the 1-10 microg/mL range and demonstrated antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphyloccus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae.

One of the major objectives of the Deep Basin Experiment, a component of the World Ocean Circulation Experiment, was to quantify the intensity and spatial distribution of deep vertical mixing within the Brazil Basin. In this study, basin-averaged estimates of deep vertical mixing rates are calculated using two independent methodologies and datasets: 1) vertical fluxes are derived from large-scale temperature and density budgets using direct measurements of deep flow through passages connecting the Brazil Basin to surrounding basins and a comprehensive hydrographic dataset within the basin interior and 2) vertical mixing rates are estimated from finescale bathymetry and hydrographic data using a functional relationship between turbulent dissipation and bathymetric roughness, deduced from localized measurements of ocean microstructure obtained during the Deep Basin Experiment. The space‐time mean estimates of vertical mixing diffusivities across representative surfaces within the Antarctic Bottom Water layer fell in the range ; 1‐5(3 1024 m2 s 21) and were indistinguishable k from each other within the estimation uncertainties. The mixing rates inferred from potential temperature budgets update, and are consistent with, earlier estimates that were based on less data. Mixing rates inferred from budgets bounded by neutral surfaces are not significantly different from the former. This implies that lateral eddy fluxes along isopycnals are not important in the potential temperature budgets, at least within the large estimation uncertainties. Unresolved processes, such as cabbeling and low frequency variability, which complicate inference of mixing from large-scale budgets, have been considered. The agreement between diffusivity estimates based on a modeled relationship between bathymetric roughness and turbulent dissipation, with those inferred from large-scale budgets, provides independent confirmation that the mixing rates have been accurately quantified.

An ongoing observational program focused on variability in the subantarctic currents and water masses around southern New Zealand was initiated in May 1998. This paper describes the preliminary results deduced from CTD (conductivity, temperature, depth) data collected during three hydrographic surveys, and moored current and temperature records between 1998 and 1999. An extensive archived data set has also been analysed to provide a hydrographic climatology of the region. The low‐frequency circulation within the subantarctic zone is described, revealing previously unreported flow features: persistent but weak anticyclonic and cyclonic circulations over the Campbell Plateau and a strong cyclonic flow around the western edge of the Bounty Trough. Flow within the Subantarctic Front (SAF) is strongly constrained by the New Zealand bathymetry; diverting to follow the south‐eastern flanks of the Campbell Plateau and crossing to the Bounty Plateau, before separating to join the basin‐scale circulation. ...

A deep, nonlinear warm eddy advecting water that was also anomalously saltier, lower in oxygen, and higher in nutrients relative to surrounding waters was observed in moored current and temperature measurements and in hydrographic data obtained at a site ∼400 km off the coast of northern California. The eddy was reproduced using a nonlinear quasi-geostrophic model, initialized by an iterative procedure using time series of 2-day averaged moored current measurements. The procedure demonstrates how a data assimilative technique synthesizes and enhances the resolution of a relatively sparse data set by incorporating time-dependence and model physics. The model forecast showed significant skill above persistence or climatology for 40 days. Our hypothesis, that the eddy was generated at the coast in winter and subsequently moved 400 km offshore by May, is consistent with the eddy movement diagnosed by the model and with the observations and coastal climatology. The model evolution significantly underpredicted the temperature anomaly in the eddy owing in part to unmodeled salinity compensation in trapped California Undercurrent water. Together, observations and model results show a stable nonlinear eddy in the California Current System that transported water and properties southwestward through the energetic eastern boundary region. Coherent features such as this one may be a mechanism for property transfer between the eddy-rich coastal zone and the eddy desert of the eastern North Pacific Ocean.

Moored observations of currents and temperatures made in the upper 600 rn on eddy-resolving scales over a 2-year period are used to examine the spatial and temporal characteristics of the California Current mesoscale circulation. The observations were made at three principal longitudes: 124oW, 126oW, and 128oW in the vicinity of Point Arena. They bracket the 600-km-wide band of high mesoscale variability found along the eastern boundary of the North Pacific. At all locations, the mesoscale variability was larger than the mean flow, and the spatial modes of variability as determined from empirical orthogonal function analysis consisted of an alongshore mode, a cross-shore mode, and a rotational mode. Observations made near the continental slope (124oW) were dominated by the poleward flowing California Undercurrent, with mesoscale eddies and meanders superposed. The nearshore eddy kinetic energy peaked in a band centered around 60 days. Observations made at 128oW, near the offshore boundary between the energetic mesoscale band and the "eddy desert" of the northeast Pacific, were characterized by small means, fewer eddy events, and a peak in eddy kinetic energy at 120-180 days. The good horizontal resolution of the current meter arrays allowed us to estimate the relative vorticity, horizontal divergence, and Rossby number and therefore to evaluate the relative strength and occurrence of anticyclones and cyclones. We found the mesoscale eddy field to be strongly nonlinear, with Rossby numbers ranging from 0.1 to 0.5. All of the eddies observed at the offshore site were nonlinear, deep, warm anticyclones. Shipboard hydrography revealed the origin of one of these anticyclones to be the California Undercurrent, and this eddy retained its strong anomalies after several months and several hundred kilometers of propagation. Despite the lower incidence of eddies as one moves west from the coast, the eddies that we observed offshore provide evidence for propagation and transport of properties from the coast to the central North Pacific across the California Current System.

Mean net surface heating of the Pacific Ocean shows areas of high heat gain in the eastern tropics and heat loss in the western midlatitudes. For steady state conditions, westward and poleward transport of heat is implied. Mean geostrophic and Ekman fluxes of heat and freshwater through the sides of a western tropical Pacific box bounded by World Ocean Circulation Experiment (WOCE) high-resolution expendable bathythermograph (XBT) transects are presented. Water mass properties of currents transporting heat and freshwater through the enclosed region are seen to be modified in transit. Net transport convergences within the volume of water extending to 800 m in the vertical show a shallow ocean circulation cell (σ θ < 26) with relatively dense subtropical gyre water entering the volume and lighter water leaving in western boundary currents, eastward flowing tropical currents, Ekman flow, and outflow to the Indian ocean. Surface buoyancy fluxes are dominated by freshwater rather than heat fluxes. Freshwater gain through the surface allows warm, salty water to enter in the same density range as cool, fresh water leaving the volume. For steady state conditions the XBT-derived oceanic heat convergence of 0 ± 0.3 PW implies negligible heat loss to the atmosphere. Traditional surface heat flux climatologies predict too much heat gain. Part of the discrepancy may be due to anomolous meteorological conditions during the XBT experiment (1987-1995). Oceanic freshwater divergence of 0.70 ± 0.08 Sv falls in the range of climatological predictions from surface freshwater gain.

A vertically sheared eastward jet in the equatorial Pacific in late 1991 and early 1992 carried relatively fresh water from the western Pacific overriding the saltier surface layer of the central region. Salinity anomalies of about −1.0 psu were observed over a period of several months in a surface layer 50 m thick near the equator. Below this fresh layer them was a steep halocline having very little temperature stratification, so that the density changes were dominated by salinity. In December 1991, eastward surface velocities in the fresh jet at 170°W were 100 cm s−1 with a shear of about 40 cm s−1 in the top 100 m; the core of the jet was about 200 km in width, centered at 1.5°S. The jet decayed and vanished over the next few months, though the surface halocline remained. A simple extension of the familiar 1½-layer model can account for the initial development of the sheared eastward jet. The surface pressure gradient in this initial value problem, tending to accelerate the fluid eastward, dim...

This annual report presents the progress made, to date, in understanding the influences of early Parkinson s disease on all major sensory systems in the same subject cohort. Altered function has now been demonstrated in various sensory domains, most notably olfaction, taste, and vision. Touch and hearing appear not to be influenced by PD, although more data are needed to adequately power these elements of the study. The early sensory alterations found in this study appear to be uninfluenced by LDOPA repletion.

gamma-Secretase inhibitors have been shown to reduce the production of beta-amyloid, a component of the plaques that are found in brains of patients with Alzheimer's disease. A novel series of heterocyclic sulfonamide gamma-secretase inhibitors that reduce beta-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative gamma-secretase substrate.

Objective mapping can remove the equatorial singularity from the problem of estimating geostrophic shear from noisy density measurements. The method uses the complete thermal wind relation, so it is valid uniformly on and off the equator. Errors in the thermal wind balance are due to neglected terms in the momentum balance, which are treated as noise in the inverse problem. The question of whether the geostrophic balance holds near the equator is restated as a need to estimate the size of the ageostrophic noise in the thermal wind equation. Objective mapping formalizes the assumptions about the magnitudes and scales of the geostrophic currents and about the magnitudes and scales of the ageostrophic terms and measurement errors. The uncertainty of the velocity estimates is calculated as part of the mapping and depends on the signal to noise ratio (geostrophic density signal to ageostrophic “noise”) in the data, as well as the station spacing and the scales assumed for the geostrophic velocities. The method is used to map zonal velocity from a mean Hawaii-Tahiti Shuttle density section. These are compared with previous velocity estimates for the same dataset calculated using other techniques. By choosing appropriate scales, the objective map can duplicate previous results. New temperature data are presented from a repeating, high-resolution expendable bathythermograph section crossing the equator at about 170° W with four cruises a year between 1987–1991. There appear to be significant differences between this mean temperature and the shuttle mean temperature. Temperature is converted to density with the aid of a mean T-S relation and geostrophic velocity maps are calculated for the 4-year mean. The mean geostrophic undercurrent obtained from our sections is weaker than in the shuttle estimate and is centered slightly north of the equator. Enforcing symmetry about the equator removes the offset of the current, giving a stronger, but narrow undercurrent. The density field apparently includes significant (O (0.5 kg m−3)) large-scale ageostrophic variability which makes velocity estimates from single cruises poorly determined near the equator.

When my husband and I first came to Kenya during the middle of last year I was convinced that my experience and specialist knowledge of nutrition would be of great value to the African people. Having trained for 4½ years in home economics and dietetics at reputable British colleges and having worked within the profession for 5 years I saw no reason at all why I could not contribute towards bettering the lives of the East African community.

Variability of the subtropical gyre in the South Pacific Ocean was investigated using high-resolution expendable bathythermograph sections along a repeated track between New Zealand and Hawaii. The southern part of the section sampled most of the zonal flow in the subtropical gyre with the eastward flowing branch between New Zealand and Fiji and the westward branch extending north of Fiji to approximately 10°S. The time series began in September 1987 and extended through 1994, averaging four cruises every year. The geostrophic shear field was calculated, relative to 800 m, with the aid of a mean T − S relationship. Variability was present at a broad range of spatial and temporal scales but annual fluctuations were particularly prominent. The authors conclude that 30 snapshots of temperature, measured over a period of seven years, are sufficient to resolve the annual cycle of the gyre-scale circulation along the transect. The shape and intensity of the gyre varied seasonally throughout the water c...