Bioinformatics Approach for Functional Glycomics

Presentation in the Human Glycomics Proteomics Disease Initiative (HGPI) session

Multivalent ligands of CD22 for targeting of B cells

Multivalent ligands of CD22 for active targeting of B cells. Mary O’Reilly, Wei Hsu Chen, Gladys Completo, Ying Zeng, Satoshi Futakawa and Cory Rillahan and James C. Paulson, Departments of Chemical Physiology and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037

The siglecs comprise 13 members of the immunoglobulin superfamily that recognize sialic acid containing glycans, and are differentially expressed on leukocytes and glial cells. The natural ligands of siglecs typically occur on the same cell (in cis) and/or on adjacent cells (in trans). Cis ligands mask the binding of multivalent synthetic sialoside ligands and are thought to regulate the activity of siglecs as modulators of cell signaling. However, synthetic ligands of sufficient avidity can compete with cis ligands, demonstrating a dynamic equilibrium of cis and trans ligand probes. We have explored the relationship between valency, affinity and geometry for achieving avidity sufficient to compete with cis ligands of CD22 (Siglec-2) in situ. A notable achievement is a hetero-bifunctional ligand approach to create multivalent ligands using antibodies as a protein scaffold. The ligand is comprised of a CD22 ligand, 9-biphenylcarboxyl-NeuAcα2-6Galβ1-4GlcNAc (BPCNeuAc), coupled to an antigen, 4-hydroxy-3-nitrophenylacetic acid (NP) (BPCNeuAc-NP). The BPCNeuAc-NP ligand is able to efficiently assemble complexes of anti-NP antibodies with CD22 on both asialo- and native B cells. Surprisingly, assembly of the tertiary complex occurs with anti-NP IgM (n=10), IgA (n=4) and IgG (n=2). The results suggest that spacing of ligands using an antibody optimizes the contribution of geometry to achieve high avidity with low valency. Other multivalent configurations also show promise for targeting B cells. In particular, liposomes bearing BPCNeuAc ligands bind avidly to B cells and are endocytosed. Thus, BPCNeuAc-lipososomes may prove effective in delivery of therapeutic agents to B cells (Supported by NIH grants GM60938, AI50143 ).
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Of PDRs and Precedent

This Texas Lawyer Legal Research column article discusses the Texas Court of Criminal Appeals’ use of discretionary review powers to discourage out-of-staters from setting up a law practice in Texas and the true anniversary date of the Texas Court of Criminal Appeals

Of PDRs and Precedent

This Texas Lawyer Legal Research column article discusses the Texas Court of Criminal Appeals’ use of discretionary review powers to discourage out-of-staters from setting up a law practice in Texas and the true anniversary date of the Texas Court of Criminal Appeals

A comparison of three heuristics to choose the variable ordering for CAD

Cylindrical algebraic decomposition (CAD) is a key tool for problems in real algebraic geometry and beyond. When using CAD there is often a choice over the variable ordering to use, with some problems infeasible in one ordering but simple in another. Here we discuss a recent experiment comparing three heuristics for making this choice on thousands of examples

De Novo Pudendal Neuropathy After TOT-O Surgery for Stress Urinary Incontinence

Complications from needle placement and exit during a TOT procedure exist and must be considered when placing the needle through the area of the obturator fossa

Southwestern Minnesota Farm Business Management Association 2008 Annual Report

Average net farm income was $190,901 in 2008 for the 99 farms included in this annual report of the Southwestern Minnesota Farm Business Management Association. Average earnings decreased by 21$242,267 in 2007 (Figure 1). 2008 ended a steady trend of increasing year-to-year incomes for these farms from 2001 to 2007. Crop farms, with historically high corn and soybean prices, remained very profitable. However, specialized hog farms, which had been very profitable for the past four years, experienced substantial losses. Highlights of association financial results for 2008: Median net farm income was $178,874, slightly lower than the average, indicating that the average was increased by high profits of the most profitable farms. This effect was not as large as previous years, likely because of losses by larger hog operations. • The difference between the most profitable farms and the least profitable continued to increase. The most profitable 20$449,997 while the least profitable lost $-29,476. • Average gross cash income increased by 20$115,999. The average debt-to-asset ratio improved slightly to 39%, down from 40% (Figure 4). • Corn yields were up but soybean yields were down. Corn averaged 172 bushels per acre compared to 162 in 2007. Soybeans yields decreased to 44 bushels from 49 in 2007 (Figure 5). • Both corn and soybean prices received increased by over 50% to $4.51 for corn and$10.83 for soybeans. • The cost to raise an acre of corn (with land rent) increased by 23% while soybean costs increased by 21%. The cost to produce a bushel of corn on cash rented land increased from $2.58 per bushel in 2007 to$2.90 in 2008, while soybean costs per bushel increased from $6.14 to$7.21. • The average specialized hog operation (those with 70% of sales from hogs or pigs) lost over $150,000 in 2008 (Figure 6). All other farm types with enough farms to report averaged net incomes very close to the association average. • Based on rate of return on assets, crop farms (those with 70$1,000,000, were the least profitable based on rate of return on assets. This group earned an average ROA of 7% compared to 14% for farms that grossed between $500,000 and$1,000,000. • With exceptionally high feed prices, no hog or beef enterprise, with the exception of contract growing of hogs (where the contractor provided the feed) covered even direct costs of production. The report provides additional information on profitability, liquidity, and solvency as well as other whole-farm information and detailed information on crop and livestock enterprises. Also reported are whole-farm financial condition and performance by county, sales size class, type of farm, debt-to-asset ratio, and age of operator.Agricultural Finance, Farm Management,

Broad Autism Phenotypic Traits and the Relationship to Sexual Orientation and Sexual Behavior

Individuals with higher levels of the broad autism phenotype (BAP) have some symptoms of autism spectrum disorder (ASD). Like individuals with ASD, people with higher-BAP may have fewer sexual experiences and may experience more same-sex attraction. This study measured BAP traits, sexual experiences, and sexual orientation in typically developing (TD) individuals to see if patterns of sexual behavior and sexual orientation in higher-BAP resemble those in ASD. Although BAP characteristics did not predict sexual experiences, one BAP measure significantly predicted sexual orientation, β = 0.22, t = 2.72, p = .007, controlling for demographic variables (R2 change = .04, F = 7.41, p = .007), showing individuals with higher-BAP also reported increased same-sex attraction. This finding supports the hypothesis that individuals with higher-BAP resemble ASD individuals in being more likely than TD individuals to experience same-sex attraction

Antenatal Physical Activity Counseling Among Healthcare Providers

Objective: Pregnant women often report a lack of knowledge concerning the safety of exercising during pregnancy. Healthcare providers play an integral role in providing pregnant women with the necessary knowledge to promote antenatal physical activity. Thus, the objective of this study was to assess healthcare providers’ beliefs, attitudes, knowledge and practices related to antenatal physical activity counseling. Study Design: 188 Providers (i.e. obstetricians, midwives, and family medicine physicians) completed a 39 closed-item survey. Characteristics among healthcare providers’ physical activity counseling practices as well as belief, attitudes and knowledge were explored. Results: The majority of all providers agreed that physical activity during pregnancy will result in numerous improved health outcomes for mother and baby. Approximately half of the providers (48%, n = 89) were not familiar with the current national guides recommending that women free of obstetric complications should engage in at least 150 minutes of exercise per week. Only 43% of providers believed their patients followed the advice they are given about physical activity. Over half of the providers reported that they provide in-office physical activity counseling, and FMs provide individualized counseling less often than OBs and CNMs (i.e. 33%, 60%, and 65%, respectively; p = 0.0014). Importantly, 17% (n = 31) of providers reported that they never received professional training in antenatal physical activity counseling and of those that did receive training, 69% (n = 107) claimed their training was fair or poor . Conclusion: Findings from the pre- sent study demonstrate a need for further continuing education opportunities on the current national guide- lines on antenatal physical activity

Low-Speed Measurements of Oscillatory Lateral Stability Derivatives of a 1/7-Scale Model of the North American X-15 Airplane

An investigation to determine the low-speed rolling, yawing, and sideslipping derivatives of a 1/7-scale model which was used to represent the original configuration and a modified configuration of the North American X-15 airplane has been conducted in the Langley free-flight tunnel. The original model was modified to approximately represent the final airplane configuration by reducing the size of the fuselage side fairings and changing the vertical-tail arrangement. The effects of various tail arrangements were determined for both configurations and the effect of small forebody strakes was determined for the modified configuration only