Synthesis and biological activity of anticoagulant heparan sulfate glycopolymers

Heparin has been used as an anticoagulant drug for more than 70 years. The global distribution of contaminated heparin in 2007, which resulted in adverse clinical effects and over 100 deaths, emphasizes the necessity for safer alternatives to animal-sourced heparin. The structural complexity and heterogeneity of animal-sourced heparin not only impedes safe access to these biologically active molecules, but also hinders investigations on the significance of structural constituents at a molecular level. Efficient methods for preparing new synthetic heparins with targeted biological activity are necessary not only to ensure clinical safety, but to optimize derivative design to minimize potential side effects. Low molecular weight heparins have become a reliable alternative to heparin, due to their predictable dosages, long half-lives, and reduced side effects. However, heparin oligosaccharide synthesis is a challenging endeavor due to the necessity for complex protecting group manipulation and stereoselective glycosidic linkage chemistry, which often result in lengthy synthetic routes and low yields. Recently, chemoenzymatic syntheses have produced targeted ultralow molecular weight heparins with high-efficiency, but continue to be restricted by the substrate specificities of enzymes.

To address the need for access to homogeneous, complex glycosaminoglycan structures, we have synthesized novel heparan sulfate glycopolymers with well-defined carbohydrate structures and tunable chain length through ring-opening metathesis polymerization chemistry. These polymers recapitulate the key features of anticoagulant heparan sulfate by displaying the sulfation pattern responsible for heparin’s anticoagulant activity. The use of polymerization chemistry greatly simplifies the synthesis of complex glycosaminoglycan structures, providing a facile method to generate homogeneous macromolecules with tunable biological and chemical properties. Through the use of in vitro chromogenic substrate assays and ex vivo clotting assays, we found that the HS glycopolymers exhibited anticoagulant activity in a sulfation pattern and length-dependent manner. Compared to heparin standards, our short polymers did not display any activity. However, our longer polymers were able to incorporate in vitro and ex vivo characteristics of both low-molecular-weight heparin derivatives and heparin, displaying hybrid anticoagulant properties. These studies emphasize the significance of sulfation pattern specificity in specific carbohydrate-protein interactions, and demonstrate the effectiveness of multivalent molecules in recapitulating the activity of natural polysaccharides.

Classified one-step modified signed-digit arithmetic and its optical implementation

Based on the two-step modified signed-digit (MSD) algorithm, we present a one-step algorithm for the parallel addition and subtraction of two MSD numbers. This algorithm is reached by classifying the three neighboring digit pairs into 10 groups and then making a decision on the groups. It has only a look-up truth table, and can be further formulated by eight computation rules. A joint spatial encoding technique is developed to represent both the input data and the computation rules. Furthermore, an optical correlation architecture is suggested to implement the MSD adder in parallel. An experimental demonstration is also given. (C) 1996 Society of Photo-Optical instrumentation Engineers.

Late Transition Metals Supported by Aryl Ethers and Phenoxides Bearing Pendant Phosphines: Mechanistic Insights Relevant to Ether C-O Bond Cleavage

Terphenyl diphosphines bearing pendant ethers were prepared to provide mechanistic insight into the mechanism of activation of aryl C–O bonds with Group 9 and Group 10 transition metals. Chapters 2 and 3 of this dissertation describe the reactivity of compounds supported by the model phosphine and extension of this chemistry to heterogenous C–O bond activation.

Chapter 2 describes the synthesis and reactivity of aryl-methyl and aryl-aryl model systems. The metallation of these compounds with Ni, Pd, Pt, Co, Rh, and Ir is described. Intramolecular bond activation pathways are described. In the case of the aryl-methyl ether, aryl C–O bond activation was observed only for Ni, Rh, and Ir.

Chapter 3 outlines the reactivity of heterogenous Rh and Ir catalysts for aryl ether C–O bond cleavage. Using Rh/C and an organometallic Ir precursor, aryl ethers were treated with H2 and heat to afford products of hydrogenolysis and hydrogenation. Conditions were modified to optimize the yield of hydrogenolysis product. Hydrogenation could not be fully suppressed in these systems.

Appendix A describes initial investigations of bisphenoxyiminoquinoline dichromium compounds for selective C2H4 oligomerization to afford α-olefins. The synthesis of monometallic and bimetallic Cr complexes is described. These compounds are compared to literature examples and found to be less active and non-selective for production of α-olefins.

Appendix B describes the coordination chemistry of terphenyl diphosphines, terphenyl bisphosphinophenols, and biphenyl phosphinophenols proligands with molybdenum, cobalt, and nickel. Since their synthesis, terphenyl diphosphine molybdenum compounds have been reported to be good catalysts for the dehydrogenation of ammonia borane. Biphenyl phosphinophenols are demonstrated provide both phosphine and arene donors to transition metals while maintaining a sterically accessible coordination sphere. Such ligands may be promising in the context of the activation of other small molecules.

Appendix C contains relevant NMR spectra for the compounds presented in the preceding sections.

Indicators for management of coral reefs and their applications to marine protected areas

Informed planning and decision-making in the management of natural resources requires an ability to integrate complex interactions in ecosystems and communicate these effectively to stakeholders. This involves coping with three fundamental dilemmas. The first comes from the irregular pulse of nature. The second is the recognition that there are no strictly objective criteria for judging the well-being of an ecosystem. The third is posed by the quest for indicators with some integrative properties that may be used to analyze an ecosystem and impart the information to the relevant resource users. This paper presents some examples of indicators used to: 1) assess the status of a coral reef and, in particular, the state of its fisheries resources; 2) identify reefs that are most threatened by human activities; and 3) evaluate the likelihood of success of management interventions. These indicators are not exhaustive, but illustrate the range of options available for the management of coral reef ecosystems.

Indicators for management of coral reefs and their applications to marine protected areas

Informed planning and decision-making in the management of natural resources requires an ability to integrate complex interactions in ecosystems and communicate these effectively to stakeholders. This involves coping with three fundamental dilemmas. The first comes from the irregular pulse of nature. The second is the recognition that there are no strictly objective criteria for judging the “well-being” of an ecosystem. The third is posed by the quest for indicators with some integrative properties that may be used to analyze an ecosystem and impart the information to the relevant resource users. This paper presents some examples of indicators used to: 1) assess the status of a coral reef and, in particular, the state of its fisheries resources; 2) identify reefs that are most threatened by human activities; and 3) evaluate the likelihood of success of management interventions. These indicators are not exhaustive, but illustrate the range of options available for the management of coral reef ecosystems.

Age and growth estimates of the thorny skate (Amblyraja radiata) in the western Gulf of Maine

The northwest Atlantic population of thorny skates (Amblyraja radiata) inhabits an area that ranges from Greenland and Hudson Bay, Canada, to South Carolina. Despite such a wide range, very little is known about most aspects of the biology of this species. Recent stock assessment studies in the northeast United States indicate that the biomass of the thorny skate is below the threshold levels mandated by the Sustainable Fisheries Act. In order to gain insight into the life history of this skate, we estimated age and growth for thorny skates, using vertebral band counts from 224 individuals ranging in size from 29 to 105 cm total length (TL). Age bias plots and the coefficient of variation indicated that our aging method represents a nonbiased and precise approach for the age assessment of A. radiata. Marginal increments were significantly different between months (Kruskal-Wallis P<0.001); a distinct trend of increasing monthly increment growth began in August. Age-at-length data were used to determine the von Bertalanffy growth parameters for this population: L∞ = 127 cm (TL) and k= 0.11 for males; L∞ = 120 cm (TL) and k= 0.13 for females. The oldest age estimates obtained for the thorny skate were 16 years for both males and females, which corresponded to total lengths of 103 cm and 105 cm, respectively.

Building social and ecological resilience to climate change in Roviana, Solomon Islands: PASAP country activity for Solomon Islands: Brief review: climate change trends and projections for Solomon Islands

As part of the Australian Government’s International Climate Change Adaptation Initiative (ICCAI), the Pacific Adaptation Strategy Assistance Program (PASAP) aims to enhance the capacity of partner countries to assess key vulnerabilities and risks, formulate adaptation strategies and plans, mainstream adaptation into decision-making, and inform robust longterm national planning and decision-making in partner countries. The Department of Climate Change and Energy Efficiency contracted University of Queensland (UQ) and University of California, Santa Barbara (UCSB) to lead the project: “Building social and ecological resilience to climate change in Roviana, Solomon Islands” (2010-2012). Under this project The WorldFish Center was subcontracted to undertake outputs 5 and 6 of Objective three: (5) Review of climate change evidence and projections for the study area and (6) Vulnerability and adaptation assessment for the study area. This report addresses the first of these and comprises a desktop review of climate change evidence and projections for the study area.

An assessment of chemical contaminants, toxicity and benthic infauna in sediments from the St. Thomas East End Reserves (STEER)

This report contains a chemical and biological characterization of sediments from the St. Thomas East End Reserves (STEER) in St. Thomas, U.S. Virgin Islands (USVI). The STEER Management Plan (published in 2011) identified chemical contaminants and habitat loss as high or very high threats and called for a characterization of chemical contaminants as well as an assessment of their effects on natural resources. The baseline information contained in this report on chemical contaminants, toxicity and benthic infaunal community composition can be used to assess current conditions, as well as the efficacy of future restoration activities. In this phase of the project, 185 chemical contaminants, including a number of organic (e.g., hydrocarbons and pesticides) and inorganic (e.g., metals) compounds, were analyzed from 24 sites in the STEER. Sediments were also analyzed using a series of toxicity bioassays, including amphipod mortality, sea urchin fertilization impairment, and the cytochrome P450 Human Reporter Gene System (HRGS), along with a characterization of the benthic infaunal community. Higher levels of chemical contaminants were found in Mangrove Lagoon and Benner Bay in the western portion of the study area than in the eastern area. The concentrations of polychlorinated biphenyls (PCBs), DDT (dichlorodiphenyltrichloroethane), chlordane, zinc, copper, lead and mercury were above a NOAA sediment quality guideline at one or more sites, indicating impacts may be present in more sensitive species or life stages in the benthic environment. Copper at one site in Benner Bay, however, was above a NOAA guideline indicating that effects on benthic organisms were likely. The antifoulant boat hull ingredient tributyltin, or TBT, was found at the third highest concentration in the history of NOAA’s National Status and Trends (NS&T) Program, which monitors the Nation’s coastal and estuarine waters for chemical contaminants and bioeffects. Unfortunately, there do not appear to be any established sediment quality guidelines for TBT. Results of the bioassays indicated significant sediment toxicity in Mangrove Lagoon and Benner Bay using multiple tests. The benthic infaunal communities in Mangrove Lagoon and Benner Bay appeared severely diminished.

Integration of fisheries acoustics surveys and bathymetric mapping to characterize midwater-seafloor habitats of US Virgin Islands and Puerto Rico (2008-2010)

NOAA’s Coral Reef Conservation program (CRCP) develops coral reef management priorities by bringing together various partners to better understand threats to coral reef ecosystems with the goal of conserving, protecting and restoring these resources. Place-based and ecosystem-based management approaches employed by CRCP require that spatially explicit information about benthic habitats and fish utilization are available to characterize coral reef ecosystems and set conservation priorities. To accomplish this, seafloor habitat mapping of coral reefs around the U.S. Virgin Islands (USVI) and Puerto Rico has been ongoing since 2004. In 2008, fishery acoustics surveys were added to NOAA survey missions in the USVI and Puerto Rico to assess fish distribution and abundance in relation to benthic habitats in high priority conservation areas. NOAA’s National Centers for Coastal Ocean Science (NCCOS) have developed fisheries acoustics survey capabilities onboard the NOAA ship Nancy Foster to complement the CRCP seafloor habitat mapping effort spearheaded by the Center for Coastal Monitoring and Assessment Biogeography Branch (CCMA-BB). The integration of these activities has evolved on the Nancy Foster over the three years summarized in this report. A strategy for improved operations and products has emerged over that time. Not only has the concurrent operation of multibeam and fisheries acoustics surveys been beneficial in terms of optimizing ship time and resources, this joint effort has advanced an integrated approach to characterizing bottom and mid-water habitats and the fishes associated with them. CCMA conducts multibeam surveys to systematically map and characterize coral reef ecosystems, resulting in products such as high resolution bathymetric maps, backscatter information, and benthic habitat classification maps. These products focus on benthic features and live bottom habitats associated with them. NCCOS Centers (the Center for Coastal Fisheries and Habitat Research and the Center for Coastal Environmental Health and Biomolecular Research) characterize coral reef ecosystems by using fisheries acoustics methods to capture biological information through the entire water column. Spatially-explicit information on marine resources derived from fisheries acoustics surveys, such as maps of fish density, supports marine spatial planning strategies and decision making by providing a biological metric for evaluating coral reef ecosystems and assessing impacts from pollution, fishing pressure, and climate change. Data from fisheries acoustics surveys address management needs by providing a measure of biomass in management areas, detecting spatial and temporal responses in distribution relative to natural and anthropogenic impacts, and identifying hotspots that support high fish abundance or fish aggregations. Fisheries acoustics surveys conducted alongside multibeam mapping efforts inherently couple water column data with information on benthic habitats and provide information on the heterogeneity of both benthic habitats and biota in the water column. Building on this information serves to inform resource managers regarding how fishes are organized around habitat structure and the scale at which these relationships are important. Where resource managers require place-based assessments regarding the location of critical habitats along with high abundances of fish, concurrent multibeam and fisheries acoustics surveys serve as an important tool for characterizing and prioritizing coral reef ecosystems. This report summarizes the evolution of fisheries acoustics surveys onboard the NOAA ship Nancy Foster from 2008 to 2010, in conjunction with multibeam data collection, aimed at characterizing benthic and mid-water habitats in high priority conservation areas around the USVI and Puerto Rico. It also serves as a resource for the continued development of consistent data products derived from acoustic surveys. By focusing on the activities of 2010, this report highlights the progress made to date and illustrates the potential application of fisheries data derived from acoustic surveys to the management of coral reef ecosystems.

CLADP - THE CAMBRIDGE LINEAR ANALYSIS AND DESIGN PROGRAMS USER REFERENCE MANUAL (4TH ISSUE: APRIL 1983).

CLADP is an engineering software program developed at Cambridge University for the interactive computer aided design of feedback control systems. CLADP contains a wide range of tools for the analysis of complex systems, and the assessment of their performance when feedback control is applied, thus enabling control systems to be designed to meet difficult performance objectives. The range of tools within CLADP include the latest techniques in the field whose central theme is the extension of classical frequency domain concepts (well known and well proven for single loop systems) to multivariable or multiloop systems, and by making extensive use of graphical presentation information is provided in a readily understood form.