Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug

Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-powder electrostatic process. The AC-SES demonstrated enhanced drug stability under simulated use conditions and consistent drug delivery balanced with coating erosion in a porcine coronary implant model. The initial drug burst was eliminated and drug release was sustained after implantation. The coating was absorbed within 90 days. Following implantation into porcine coronary arteries the AC-SES coating is distributed in the surrounding intimal tissue over the course of several weeks. Computational modeling of drug delivery characteristics demonstrates how distributed coating optimizes the load of drug immediately around each stent strut and extends drug delivery between stent struts. The result was a highly efficient arterial uptake of drug with superior performance to a clinical bare metal stent (BMS). Neointimal thickness (0.17 ± 0.07 mm vs. 0.28 ± 0.11 mm) and area percent stenosis (22 ± 9% vs. 35 ± 12%) were significantly reduced (p < 0.05) by the AC-SES compared to the BMS 30 days after stent implantation in an overlap configuration in porcine coronary arteries. Inflammation was significantly reduced in the AC-SES compared to the BMS at both 30 and 90 days after implantation. Biocompatible, rapidly absorbable stent coatings enable the matching of drug release with coating erosion and provide for the controlled migration of coating material into tissue to reduce vicissitudes in drug tissue levels, optimizing efficacy and reducing potential toxicity.Micell Technologies, Inc.National Institutes of Health (U.S.) (R01 GM49039

SeaWiFS technical report series. Volume 20: The SeaWiFS bio-optical archive and storage system (SeaBASS), part 1

This document provides an overview of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Bio-Optical Archive and Storage System (SeaBASS), which will serve as a repository for numerous data sets of interest to the SeaWiFS Science Team and other approved investigators in the oceanographic community. The data collected will be those data sets suitable for the development and evaluation of bio-optical algorithms which include results from SeaWiFS Intercalibration Round-Robin Experiments (SIRREXs), prelaunch characterization of the SeaWiFS instrument by its manufacturer -- Hughes/Santa Barbara Research Center (SBRC), Marine Optical Characterization Experiment (MOCE) cruises, Marine Optical Buoy (MOBY) deployments and refurbishments, and field studies of other scientists outside of NASA. The primary goal of the data system is to provide a simple mechanism for querying the available archive and requesting specific items, while assuring that the data is made available only to authorized users. The design, construction, and maintenance of SeaBASS is the responsibility of the SeaWiFS Calibration and Validation Team (CVT). This report is concerned with documenting the execution of this task by the CVT and consists of a series of chapters detailing the various data sets involved. The topics presented are as follows: 1) overview of the SeaBASS file architecture, 2) the bio-optical data system, 3) the historical pigment database, 4) the SIRREX database, and 5) the SBRC database

SeaWiFS technical report series. Volume 19: Case studies for SeaWiFS calibration and validation, part 2

This document provides brief reports, or case studies, on a number of investigations and data set development activities sponsored by the Calibration and Validation Team (CVT) within the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Project. Chapter 1 is a comparison with the atmospheric correction of Coastal Zone Color Scanner (CZCS) data using two independent radiative transfer formulations. Chapter 2 is a study on lunar reflectance at the SeaWiFS wavelengths which was useful in establishing the SeaWiFS lunar gain. Chapter 3 reports the results of the first ground-based solar calibration of the SeaWiFS instrument. The experiment was repeated in the fall of 1993 after the instrument was modified to reduce stray light; the results from the second experiment will be provided in the next case studies volume. Chapter 4 is a laboratory experiment using trap detectors which may be useful tools in the calibration round-robin program. Chapter 5 is the original data format evaluation study conducted in 1992 which outlines the technical criteria used in considering three candidate formats, the hierarchical data format (HDF), the common data format (CDF), and the network CDF (netCDF). Chapter 6 summarizes the meteorological data sets accumulated during the first three years of CZCS operation which are being used for initial testing of the operational SeaWiFS algorithms and systems and would be used during a second global processing of the CZCS data set. Chapter 7 describes how near-real time surface meteorological and total ozone data required for the atmospheric correction algorithm will be retrieved and processed. Finally, Chapter 8 is a comparison of surface wind products from various operational meteorological centers and field observations. Surface winds are used in the atmospheric correction scheme to estimate glint and foam radiances

SeaWiFS technical report series. Volume 22: Prelaunch acceptance report for the SeaWFS radiometer

The final acceptance, or rejection, of the Sea-viewing Wide field-of-view Sensor (SeaWiFS) will be determined by the instrument's on-orbit operation. There is, however, an extensive set of laboratory measurements describing the operating characteristics of the radiometer. Many of the requirements in the Ocean Color Data Mission (OCDM) specifications can be checked only by laboratory measurements. Here, the calibration review panel (composed of the authors of this technical memorandum) examines the laboratory characterization and calibration of SeaWiFS in the light of the OCDM performance specification. Overall, the performance of the SeaWiFS instrument meets or exceeds the requirements of the OCDM contract in all but a few unimportant details. The detailed results of this examination are presented here by following the outline of the specifications, as found in the Contract. The results are presented in the form of requirements and compliance pairs. These results give conclusions on many, but not all, of the performance specifications. The acceptance of this panel of the performance of SeaWiFS must only be considered as an intermediate conclusion. The ultimate acceptance (or rejection) of the SeaWiFS data set will rely on the measurements made by the instrument on orbit

SeaWiFS Technical Report Series. Volume 22: Prelaunch Acceptance Report for the SeaWiFS Radiometer

The final acceptance, or rejection, of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) will be determined by the instrument's on-orbit operation. There is, however, an extensive set of laboratory measurements describing the operating characteristics of the radiometer. Many of the requirements in the Ocean Color Data Mission (OCDM) specifications can be checked only by laboratory measurements. Here, the calibration review panel examines the laboratory characterization and calibration of SeaWiFS in the light of the OCDM performance specification. Overall, the performance of the SeaWiFS instrument meets or exceeds the requirements of the OCDM contract in all but a few unimportant details. The detailed results of this examination are presented here by following the outline of the specifications, as found in the Contract. The results are presented in the form of requirements and compliance pairs. These results give conclusions on many, but not all, of the performance specifications. The acceptance by this panel of the performance of SeaWiFS must only be considered as an intermediate conclusion. The ultimate acceptance (or rejection) of the SeaWiFS data set will rely on the measurements made by the instrument on orbit

SeaWiFS technical report series. Volume 28: SeaWiFS algorithms, part 1

This document provides five brief reports that address several algorithm investigations sponsored by the Calibration and Validation Team (CVT) within the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Project. This volume, therefore, has been designated as the first in a series of algorithm volumes. Chapter 1 describes the initial suite of masks, used to prevent further processing of contaminated radiometric data, and flags, which are employed to mark data whose quality (due to a variety of factors) may be suspect. In addition to providing the mask and flag algorithms, this chapter also describes the initial strategy for their implementation. Chapter 2 evaluates various strategies for the detection of clouds and ice in high latitude (polar and sub-polar regions) using Coastal Zone Color Scanner (CZCS) data. Chapter 3 presents an algorithm designed for detecting and masking coccolithosphore blooms in the open ocean. Chapter 4 outlines a proposed scheme for correcting the out-of-band response when SeaWiFS is in orbit. Chapter 5 gives a detailed description of the algorithm designed to apply sensor calibration data during the processing of level-1b data

60 kD Ro and nRNP A Frequently Initiate Human Lupus Autoimmunity

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns

Investigation, Modeling, and Analysis of Integrated Metroplex Arrival and Departure Coordination Concepts

This work involves the development of a concept that enhances integrated metroplex arrival and departure coordination, determines the temporal (the use of time separation for aircraft sharing the same airspace resources) and spatial (the use of different routes or vertical profiles for aircraft streams at any given time) impact of metroplex traffic coordination within the National Airspace System (NAS), and quantifies the benefits of the most desirable metroplex traffic coordination concept. Researching and developing metroplex concepts is addressed in this work that broadly applies across the range of airspace and airport demand characteristics envisioned for NextGen metroplex operations. The objective of this work is to investigate, formulate, develop models, and analyze an operational concept that mitigates issues specific to the metroplex or that takes advantage of unique characteristics of metroplex airports to improve efficiencies. The concept is an innovative approach allowing the NAS to mitigate metroplex interdependencies between airports, optimize metroplex arrival and departure coordination among airports, maximize metroplex airport throughput, minimize delay due to airport runway configuration changes, increase resiliency to disruptions, and increase the tolerance of the system to degrade gracefully under adverse conditions such as weather, traffic management initiatives, and delays in general

SeaWiFS technical report series. Volume 23: SeaWiFS prelaunch radiometric calibration and spectral characterization

Based on the operating characteristics of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS), calibration equations have been developed that allow conversion of the counts from the radiometer into Earth-existing radiances. These radiances are the geophysical properties the instrument has been designed to measure. SeaWiFS uses bilinear gains to allow high sensitivity measurements of ocean-leaving radiances and low sensitivity measurements of radiances from clouds, which are much brighter than the ocean. The calculation of these bilinear gains is central to the calibration equations. Several other factors within these equations are also included. Among these are the spectral responses of the eight SeaWiFS bands. A band's spectral response includes the ability of the band to isolate a portion of the electromagnetic spectrum and the amount of light that lies outside of that region. The latter is termed out-of-band response. In the calibration procedure, some of the counts from the instrument are produced by radiance in the out-of-band region. The number of those counts for each band is a function of the spectral shape of the source. For the SeaWiFS calibration equations, the out-of-band responses are converted from those for the laboratory source into those for a source with the spectral shape of solar flux. The solar flux, unlike the laboratory calibration, approximates the spectral shape of the Earth-existing radiance from the oceans. This conversion modifies the results from the laboratory radiometric calibration by 1-4 percent, depending on the band. These and other factors in the SeaWiFS calibration equations are presented here, both for users of the SeaWiFS data set and for researchers making ground-based radiance measurements in support of Sea WiFS

SeaWiFS technical report series. Volume 13: Case studies for SeaWiFS calibration and validation, part 1

Although the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Calibration and Validation Program relies on the scientific community for the collection of bio-optical and atmospheric correction data as well as for algorithm development, it does have the responsibility for evaluating and comparing the algorithms and for ensuring that the algorithms are properly implemented within the SeaWiFS Data Processing System. This report consists of a series of sensitivity and algorithm (bio-optical, atmospheric correction, and quality control) studies based on Coastal Zone Color Scanner (CZCS) and historical ancillary data undertaken to assist in the development of SeaWiFS specific applications needed for the proper execution of that responsibility. The topics presented are as follows: (1) CZCS bio-optical algorithm comparison, (2) SeaWiFS ozone data analysis study, (3) SeaWiFS pressure and oxygen absorption study, (4) pixel-by-pixel pressure and ozone correction study for ocean color imagery, (5) CZCS overlapping scenes study, (6) a comparison of CZCS and in situ pigment concentrations in the Southern Ocean, (7) the generation of ancillary data climatologies, (8) CZCS sensor ringing mask comparison, and (9) sun glint flag sensitivity study