Global search algorithm for optimal control

Random-search algorithm employs local and global properties to solve two-point boundary value problem in Pontryagin maximum principle for either fixed or variable end-time problems. Mixed boundary value problem is transformed to an initial value problem. Mapping between initial and terminal values utilizes hybrid computer

Effect of gaseous and solid simulated jet plumes on a 040A space shuttle launch configuration at Mach numbers from 1.6 to 2.2

An experimental investigation was conducted in a 9- by 7-foot supersonic wind tunnel to determine the effect of plume-induced flow separation and aspiration effects due to operation of both the orbiter and the solid rocket motors on a 0.019-scale model of the launch configuration of the space shuttle vehicle. Longitudinal and lateral-directional stability data were obtained at Mach numbers of 1.6, 2.0, and 2.2 with and without the engines operating. The plumes exiting from the engines were simulated by a cold gas jet supplied by an auxiliary 200 atmosphere air supply system, and by solid body plume simulators. Comparisons of the aerodynamic effects produced by these two simulation procedures are presented. The data indicate that the parameters most significantly affected by the jet plumes are the pitching moment, the elevon control effectiveness, the axial force, and the orbiter wing loads

In vivo imaging of protease activity by Probody therapeutic activation.

Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment

Exposure of Bifidobacterium longum subsp. infantis to Milk Oligosaccharides Increases Adhesion to Epithelial Cells and Induces a Substantial Transcriptional Response

Devon Kavanaugh is in receipt of a Teagasc Walsh Fellowship. The authors would also like to acknowledge the support of Science Foundation Ireland under Grant No. 08/SRC/B1393 and the Alimentary Glycoscience Research Cluster (AGRC).peer-reviewedIn this study, we tested the hypothesis that milk oligosaccharides may contribute not only to selective growth of bifidobacteria, but also to their specific adhesive ability. Human milk oligosaccharides (3′sialyllactose and 6′sialyllactose) and a commercial prebiotic (Beneo Orafti P95; oligofructose) were assayed for their ability to promote adhesion of Bifidobacterium longum subsp. infantis ATCC 15697 to HT-29 and Caco-2 human intestinal cells. Treatment with the commercial prebiotic or 3′sialyllactose did not enhance adhesion. However, treatment with 6′sialyllactose resulted in increased adhesion (4.7 fold), while treatment with a mixture of 3′- and 6′-sialyllactose substantially increased adhesion (9.8 fold) to HT-29 intestinal cells. Microarray analyses were subsequently employed to investigate the transcriptional response of B. longum subsp. infantis to the different oligosaccharide treatments. This data correlated strongly with the observed changes in adhesion to HT-29 cells. The combination of 3′- and 6′-sialyllactose resulted in the greatest response at the genetic level (both in diversity and magnitude) followed by 6′sialyllactose, and 3′sialyllactose alone. The microarray data was further validated by means of real-time PCR. The current findings suggest that the increased adherence phenotype of Bifidobacterium longum subsp. infantis resulting from exposure to milk oligosaccharides is multi-faceted, involving transcription factors, chaperone proteins, adhesion-related proteins, and a glycoside hydrolase. This study gives additional insight into the role of milk oligosaccharides within the human intestine and the molecular mechanisms underpinning host-microbe interactions.Science Foundation IrelandTeagasc Walsh Fellowship Programm

Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study

Objectives: To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA).<p></p> Methods Adult PsA patients (≥3 swollen, ≥3 tender joints, active psoriasis) were randomly assigned to subcutaneous injections of placebo, golimumab 50 mg or 100 mg every 4 weeks (q4wks) through week 20. All patients received golimumab 50 or 100 mg beginning week 24. Findings through 2 years are reported. Efficacy evaluations included ≥20% improvement in American College of Rheumatology (ACR20) response, good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), ≥75% improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA-modified Sharp/van der Heijde scores (SHS).<p></p> Results: Golimumab treatment through 2 years was effective in maintaining clinical response (response rates: ACR20 63%–70%, DAS28-CRP 77%–86%, PASI75 56%–72%) and inhibiting radiographic progression (mean change in PsA-modified SHS in golimumab-treated patients: −0.36), with no clear difference between doses. No new safety signals were identified through 2 years. With the study's tuberculosis screening and prophylactic measures, no patient developed active tuberculosis through 2 years.<p></p> Conclusions: Golimumab 50 and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100 mg q4wks added limited benefit. Golimumab safety through up to 2 years was consistent with other antitumour necrosis factor α agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis.<p></p&gt

Shuttle-launch triangular space station

A triangular space station deployable in orbit is described. The framework is comprized of three trusses, formed of a pair of generally planar faces consistine of foldable struts. The struts expand and lock into rigid structural engagement forming a repetition of equilater triangles and nonfolding diagonal struts interconnecting the two faces. The struts are joined together by node fittings. The framework can be packaged into a size and configuration transportable by a space shuttle. When deployed, the framework provides a large work/construction area and ample planar surface area for solar panels and thermal radiators. A plurity of modules are secured to the framework and then joined by tunnels to make an interconnected modular display. Thruster units for the space station orientation and altitude maintenance are provided

Efficiency of Nitrogen Use with Corn on a Tiled and Untiled Soil

Excessive water is one of the largest contributors to the inefficient use of nitrogen in Kentucky. Because of this, nitrogen is often lost by both leaching and,denitrification. The amount, of these losses can be great depending on soil type and weather. Well-drained soils in Kentucky have been shown to lose less nitrogen than poorly drained soils. The nitrogen lost from well drained soils is usually due, to leaching. The nitrogen in the soil, even soon after applying non-nitrate forms of fertilizer N, is mostly in the water soluble nitrate form. When more water falls onto a well-drained soil than the soil can hold, then both water and nitrogen move through the soil below the root zone and are lost for plant use. On poorly-drained soils, the mostly likely method of nitrogen loss is due to denitrification. Nitrogen loss by this mechanism is due to the soil becoming saturated with water (waterlogged) and forcing the air out of the soil. In an effort to survive, some of the microorganisms in the soil take oxygen from nitrate. This process (denitrification) turns the nitrogen into a gas that will diffuse out of the saturated soil and be lost ,into the air. It usually occurs when the soil temperature is above 50°F and the soil is saturated for more than a two day period. If nitrogen fertilizer has been added to the soil prior to the existence of the above conditions, then fairly large amounts of nitrogen can be lost. These conditions are most prevalent in Kentucky on poorly drained soil in April and May. In the past, most farmers have tried to manage this problem by adding excess fertilizer nitrogen to still obtain maximum yields after the loss has been sustained. This management practice may not be economically feasible in the future if nitrogen prices continue to escalate. An alternative management practice used by many farmers is to reduce the amount of nitrogen lost by simply delaying the application of nitrogen until the conditions for denitrification have little chance of occurring. This usually means that the nitrogen is applied in late May or June after the corn has been planted and the risk of waterlogged soil conditions is greatly reduced. To determine the magnitude of such factors, we began an experiment on a poorly drained bottom soil in 1970 to determine 1) the proper rates of preplant nitrogen 2) effectiveness of sidedressing nitrogen and 3) effect of soil tiling on the above two factors

Using pressure pulse seismology to examine basal criticality and the influence of sticky spots on glacial flow

Here we report results of water pressure pulse studies conducted at Storglaciären (Sweden) and West Washmawapta Glacier (British Columbia, Canada). Comparison of pressure pulse records with meteorological conditions at Storglaciären indicates that several periods of increased basal slip activity observed during a 10 day interval of summer 2008 were due to precipitation loading of the glacier surface, rather than to infiltration of surface water to the glacier bed; this indicates that the glacier bed was close to the failure strength for much of this interval. Pressure pulse magnitudes for the two glaciers were well-fit by power law distributions similar to those earlier observed at Trapridge Glacier (and similar in form to the Gutenberg-Richter relationship commonly used in seismology), suggesting that the mechanical processes that give rise to these distributions are robust features of soft-bedded glaciers. In contrast, interevent time distributions for both glaciers diverge from those observed at Trapridge Glacier for short recurrence intervals, suggesting that the factors that govern the rate at which these processes occur differ between glaciers. An examination of pressure pulse characteristics at West Washmawapta Glacier indicates that the establishment of a basal drainage system in summer 2008 resulted in increased stability and reduced sensitivity to meltwater input, suggesting that common assumptions about the relationship between meltwater production and ice flow are oversimplified. These results demonstrate that water pressure pulse observations can provide valuable insight into the dynamics of soft-bedded glaciers

Structure and Oxygen Affinity of Crystalline des-His-146β Human Hemoglobin in the T State *

To correlate directly structure with function, the oxygen affinity and the three-dimensional structure of crystals of the T quaternary state of des-His-146beta human hemoglobin have been determined by polarized absorption microspectrophotometry and x-ray diffraction crystallography. In des-His-146beta, the COOH-terminal histidine residues of the beta chains of hemoglobin A have been removed. Oxygen binding to crystalline des-His hemoglobin is non-cooperative and independent of pH. The oxygen affinity is 1.7-fold greater than that of the crystalline state of hemoglobin A. Removal of His-146beta results in a small movement of the truncated COOH-terminal peptide and in a very small change in quaternary structure. Previously, similar studies on T state crystals of des-Arg-141alpha hemoglobin showed that removal of the COOH termini of the alpha chains results in much larger effects on oxygen affinity and on quaternary structure. Kinetic studies in solution reveal that at pH 7.0, the rates of CO combination with deoxygenated des-His-146beta in the absence and presence of inositol hexaphosphate are 2.5- and 1.3-fold, respectively, more rapid than for hemoglobin A. The values for des-Arg are 7.6- and 3.9-fold. The properties of the T state of hemoglobin both in the crystal and in solution are influenced to a greater degree by the interactions associated with Arg-141alpha than those associated with His-146beta