Iowa Lottery Action, Vol. 18, No. 16, Aug. 8-21, 2011

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Iowa Lottery Action Special Edition, May 23, 2011

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Lottery Action Newsletter, Vol. 20, No. 6, April 7-20, 2014

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Lottery Action, Vol. 20, No. 7, April 21-May 4, 2014

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Iowa Lottery Action, May 5-18, 2014, Vol. 20, No. 8

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Lottery Action, May 19-June 1, 2014, Vol. 20, No. 9

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Iowa Lottery Action, Vol. 20, No. 10, June 2 - 15, 2014

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Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is considered an attractive therapeutic target in multiple inflammatory and autoimmune disorders. In addition to its known biologic activities, MIF can also function as a tautomerase. Several small molecules have been reported to be effective inhibitors of MIF tautomerase activity in vitro. Herein we employed a robust activity-based assay to identify different classes of novel inhibitors of the catalytic and biological activities of MIF. Several novel chemical classes of inhibitors of the catalytic activity of MIF with IC(50) values in the range of 0.2-15.5 microm were identified and validated. The interaction site and mechanism of action of these inhibitors were defined using structure-activity studies and a battery of biochemical and biophysical methods. MIF inhibitors emerging from these studies could be divided into three categories based on their mechanism of action: 1) molecules that covalently modify the catalytic site at the N-terminal proline residue, Pro(1); 2) a novel class of catalytic site inhibitors; and finally 3) molecules that disrupt the trimeric structure of MIF. Importantly, all inhibitors demonstrated total inhibition of MIF-mediated glucocorticoid overriding and AKT phosphorylation, whereas ebselen, a trimer-disrupting inhibitor, additionally acted as a potent hyperagonist in MIF-mediated chemotactic migration. The identification of biologically active compounds with known toxicity, pharmacokinetic properties, and biological activities in vivo should accelerate the development of clinically relevant MIF inhibitors. Furthermore, the diversity of chemical structures and mechanisms of action of our inhibitors makes them ideal mechanistic probes for elucidating the structure-function relationships of MIF and to further determine the role of the oligomerization state and catalytic activity of MIF in regulating the function(s) of MIF in health and disease.

Dynamic Tests of a Three-Span Continuous I-Beam Highway Bridge, HR-43, 1959

This paper presents the results of the static and dynamic testing of a three-span continuous I-beam highway bridge. Live load stress frequency curves for selected points are shown, and the static and dynamic load distribution to the longitudinal composite beam members are given. The bridge has four traffic lanes with a roadway width of 48 ft. Six longitudinal continuous WF beams act compositely with the reinforced concrete slab to carry the live load. The beams have partial length cover plates at the piers. Previous research has indicated that beams with partial length cover plates have a very low fatigue strength. It was found in this research that the magnitude of the stresses due to actual highway loads were very much smaller than those computed from specification loading. Also, the larger stresses which were measured occurred a relatively small number of times. These data indicate that some requirements for reduced allowable stresses at the ends of cover plates are too conservative. The load distribution to the longitudinal beams was determined for static and moving loads and includes the effect of impact on the distribution. The effective composite section was found at various locations to evaluate the load distribution data. The composite action was in negative as well as positive moment regions. The load distribution data indicate that the lateral distribution of live load is consistent with the specifications, but that there is longitudinal distribution, and therefore the specifications are too conservative.