The Design and Evaluation of Boronic Acid Derivatives for the Recognition of Cell Surface Carbohydrates for Medicinal Applications

ABSTRACT Carbohydrates in various forms play vital roles in numerous critical biological processes including cell-cell adhesion and communication, embryo development, immune response, etc. Fluorescent sensors for such carbohydrates have a wide range of potential applications including glucose concentration determination, cell labeling and targeting based on carbohydrate biomarkers, as in vitro diagnostic tools, and biomarker-directed cellular imaging. Our group has been interested in the design and synthesis of multi-boronic acid compounds with well-defined three-dimensional scaffolding for the specific recognition of selected carbohydrate biomarkers. Aberrant expression of carbohydrate antigens such as sialyl Lewis X (sLex), sialyl Lewis A (sLea), Lewis X (Lex), and Lewis Y (Ley) have been associated with tumor formation and metastasis in various cancer types.1-4 As such, for our initial design, we have selected sialyl Lewis X (sLex) as our potential target due to implication in the development of liver and colon cancer.5, 6 Herein, we describe the design, synthesis and evaluation of four such compounds, each having about ten linear steps in its synthesis. In addition to the design of fluorescent probes for cell surface carbohydrates, we also have designed lipophilic boronic acid derivatives as potential fusogenic agents. Due to boronic acid¡¯s ability to bind to 1,2 and 1,3 cis diols, we hypothesize that the aliphatic chain should be able to insert into lipid cellular membrane and the boronic acid units should allow for the ¡°attachment to neighboring cells¡± through complexation with cell surface glycans. Such interactions should allow the boronic acid compounds to bring two or more cells together for fusion. Herein, we have described the methodologies of the design of such compounds. INDEX WORDS: Boronic acid, sialyl Lewis X probe, boronolectin, fluorescence, sensor, cell-cell fusion, fusogen, immunotherapy

Dipole-dipole interaction between orthogonal dipole moments in time-dependent geometries

In two nearby atoms, the dipole-dipole interaction can couple transitions with orthogonal dipole moments. This orthogonal coupling accounts for a number of interesting effects, but strongly depends on the geometry of the setup. Here, we discuss several setups of interest where the geometry is not fixed, such as particles in a trap or gases, by averaging over different sets of geometries. Two averaging methods are compared. In the first method, it is assumed that the internal electronic evolution is much faster than the change of geometry, whereas in the second, it is vice versa. We find that the orthogonal coupling typically survives even extensive averaging over different geometries, albeit with qualitatively different results for the two averaging methods. Typically, one- and two-dimensional averaging ranges modelling, e.g., low-dimensional gases, turn out to be the most promising model systems.Comment: 11 pages, 14 figure

AGRICULTURAL PRODUCTION CONTRACTS TO REDUCE NITRATE LEACHING: A WHOLE-FARM ANALYSIS

Ten alternative seed corn contract specifications are evaluated with respect to nitrate leaching and profitability for the processor firm (principal) and contracted grower (agent). A whole-farm optimization and feasibility analysis suggest that contract terms can be used to reduce non-point source pollution.Crop Production/Industries,

Congenital myotonic dystrophy in a national registry

AIM: To describe the neonatal symptoms, developmental problems and chronic multisystem medical morbidities of congenital myotonic dystrophy (CDM) patients registered in the United States National Registry of Myotonic Dystrophy - a disease-specific, self-report program maintained since 2002. Comparisons with the Canadian Paediatric Surveillance Program for CDM are highlighted. METHODS: Genetically confirmed cases of CDM demonstrating symptoms in the first four weeks of life are described. Patients (or their caregivers) and physicians completed survey information at baseline and annually thereafter. RESULTS: Twenty-one patients were included (13 male and eight female), ranging from three to 24 years of age. The CTG trinucleotide repeat number ranged from 940 to 2100. Gastrointestinal, pneumonia and cardiac morbidities were most common. No deaths were noted. CONCLUSIONS: The United States Registry is a valuable resource for clinical research on patients with CDM; however, in contrast with the Canadian Paediatric Surveillance Program, some limitations are identified. ©2010 Pulsus Group Inc. All rights reserved

Innovating new virus diagnostics and planting bed management in the Australian Sweetpotato Industry

The provision of disease free planting material is a key driver of Australia’s burgeoning sweetpotato industry, which currently achieves the highest commercial yields in the world. Australian Sweetpotato Growers Inc. (ASPG) investigated how to improve productivity of on-farm multiplication nurseries (plant beds). Their four-year project also studied virus occurrence and threats to the Australian industry and explored new techniques for detecting viruses. The project worked closely with commercial sweetpotato growers in Queensland and Northern New South Wales, representing 95% of Australia’s production. Queensland scientists monitored grower plant beds over four years, assessing production of planting material (sprouts), and problems, such as plant bed breakdown, that arose during the season. They investigated management options such as sweetpotato root size, plant bed nutrition, irrigation and soil temperatures, in detailed experiments at research facilities and with on-farm collaborators. The virology team surveyed viruses present in the Australian industry, and how they varied geographically and across the season. They compared different diagnostic techniques, including herbaceous indexing, NCM-ELISA and qPCR for accuracy and cost-efficiency. Research demonstrated sprout multiplication could be improved 25% by constructing higher, well-drained plant beds, only covering bedding roots with 3-5 cm of soil, irrigating sparingly early, and keeping soil temperatures between 17-26oC in spring by careful use of plastic covers. The dominant issue was premature plant bed breakdown, particularly with the new, nematode-resistant cultivar Bellevue. The project investigated physiological and pathogenic causes of breakdown and developed guidelines to reduce risk. Surveying found only two main viruses, sweetpotato feathery mottle virus (SPFMV) and sweetpotato leaf curl virus (SPLCV) in commercial cropping areas. North Queensland has two more viruses at least, mainly in home/market garden situations. The Australian industry planting material scheme is free of viruses, and by using pathogen-tested material, virus infections have negligible impact on yields. Herbaceous indexing with Ipomoea setosa is still the most reliable method of detecting sweetpotato viruses but is very time consuming. Molecular technologies such as qPCR proved accurate for two viruses, however for several endemic and exotic viruses, current assays produced too many false negatives, particularly testing asymptomatic sweetpotato material. The molecular technologies are very cost-effective and are rapidly improving. The project developed new virus assays for endemic and exotic viruses not currently in Australia. The project team prepared plant bed and virus management guides, as well as fact sheets and experimental reports, available on ASPG and Hort Innovation websites. They had excellent engagement with well over 85% of current Australian sweetpotato growers, through on-farm visits, and 24 field days and workshops during the project. The project also developed exciting collaborative relationships with sweetpotato researchers at several Australian Universities, neighbouring Pacific countries, and particularly scientists from Louisiana State University. The latter were involved in several reciprocal visits over the four years. Further research into the causes and management of premature breakdown of plant beds would certainly benefit the Australian industry, as would improvement in molecular diagnostic assays for virus detection, to support sweetpotato industry biosecurity

Sweetpotato consumer research: insights to increasing consumption

This report provides an evaluation of the behaviours and purchasing drivers of key sweetpotato consumers defined by Nielsen consumer research as Established Couples (two or more adults with no children 17 and under, and head of house 35-59), Senior Couples (two or more adults with no children 17 or under, and head of house 60 or over), and Independent Singles (one person household 35 or over, no children 17 or under). Research was qualitative in nature. Methods used included focus groups, depth interviews and shop-a-longs. The report found that preferences for sweetpotato amongst these groups were varied. In general a smaller torpedo shaped vegetable was valued for ease of preparation and the convenience of being of sufficient size for a meal for two. Satisfaction with sweetpotato was high with negative comments on quality exceedingly rare within discussions. However, shop-a-longs revealed that some quality issues were apparent at retail such as withered product, pitting and occasionally damage. A display with stock resting in any amount of water was a barrier to purchase for consumers and this was apparent on two out 15 occasions. A high quality sweetpotato was of a deep orange/red colour, had a smooth skin and was extremely dense and hard. An inferior sweetpotato was wrinkly, spongy, pitted and damaged. Awareness of sweetpotato was a relatively recent phenomenon amongst the respondents of this study with most recalling eating the vegetable in the last five to 10 years. Life-time eating patterns emerged as a consequence of childhood food experiences such as growing up with a ‘meat and three’ veg philosophy and traditional Australian meals. However, this was dependent on cultural background and those with ties to diverse cultures were more likely to have always known of the vegetable. Sweetpotato trial and consumption coincided with a breaking away from these traditional patterns, or was integrated into conventional meals such as a baked vegetable to accompany roasts. Increased health consciousness also led to awareness of the vegetable. A primary catalyst for consumption within the Established and Senior Couples groups was the health benefits associated with sweetpotato. Consumers had very little knowledge of the specific health properties of the vegetable and were surprised at the number of benefits consumption provided. Sweetpotato was important for diabetics for its low Glycemic Index status. Top-of-the-mind awareness of the vegetable resulted from the onset of the disease. Increasing fibre was a key motive for this demographic and this provided a significant link between consumption and preventing bowel cancer. For those on a weight loss regime, sweetpotato was perceived as a tasty, satisfying food that was low in carbohydrates. Swapping behaviours where white potato was replaced by sweetpotato was often a response to these health concerns. Other health properties mentioned by participants through the course of the research included the precursor β-carotene and Vitamins A & C. The sweetpotato was appreciated for its hedonic and timesaving qualities. For consumers with a high involvement in food, the vegetable was valued for its versatility in meals. These consumers took pride in cooking and the flavour and texture of sweetpotato lent itself to a variety of meals such as soups, salads, roasts, curries, tagines and so on. Participants who had little time or desire to prepare and cook meals valued sweetpotato because it was an easy way to add colour and variety to the plate and because including an orange vegetable to meals is a shortcut to ensuring vitamin intake. Several recommendations are made to the sweetpotato industry. • Vigorously promote the distinct nutritional and health properties of sweetpotatoes, particularly if they can be favourably compared to other vegetables or foods • Promote the salient properties to specific targets such as diabetics, those that are at risk to bowel cancer, and those embarking on a weight-loss regime. Utilise specialist channels of communication such as diabetic magazines and websites • Promote styles of cooking of sweetpotato that would appeal to traditionalists such as roasts and BBQs • Promote the vegetable as a low maintenance vegetable, easy to store, easy to cook and particularly focusing on it as a simple way to boost the appearance and nutritional value of meals. • Promote the vegetable to high food involvement consumers through exotic recipes and linking it to feelings of accomplishment with cooking • Promote the versatility of the vegetable • Devise promotions that link images and tone of communications with enjoying life to the fullest, having time to enjoy family and grandchildren, and of partaking in social activities • Educate retailers on consumer perceptions of quality and ensuring moisture and mould is not present at displays Qualitative information while providing a wealth of detail cannot be extrapolated to the overall target population and this may be considered a limitation to the research. However, within research theory, effective quantitative design is believed to stem from the insights developed from qualitative studies. • Develop and implement a quantitative study on sweetpotato attitudes and behaviours based on the results of this study

Developing life cycle inventory for life cycle assessment of Australian cotton

Life Cycle Assessment (LCA) is an internationally recognised approach for evaluating the environmental impacts of products and services. In this paper, the potential issues in the development of a consistent and comprehensive life cycle inventory (LCI) data are illustrated in the context of Australian cotton industry. These include diversity and variable nature of farming practices, and the inherent complexities such as the inter-linkages between co-products. For the implementation of LCI, the choices of functional unit and system boundary, definition of regional sub-sectors, methods of energy assessments, and rules of allocations of inputs and emissions are discussed. It is shown that for cotton production, the contribution of on-farm indirect 'chemical' inputs is particularly important, accounting for up to 50–80% of the total energy input in the life cycle. The need for quantified trade off analysis between alternative systems in the LCA context is also emphasized