Development of a protein antigen based pneumococcal vaccine utilizing a polyanhydride nanoparticle delivery platform

Streptococcus pneumoniae is the primary cause of bacterial pneumonia and contributes to millions of deaths worldwide annually. The current capsule polysaccharide based vaccines do provide some protection, but the 7 to 23 valent formulations cannot protect against the over 90 serotypes currently known. Pneumococcal surface protein A (PspA) is a promising candidate for a protein-based vaccine against S. pneumoniae, showing protection in immunized mice and providing the advantage of universal protection from all serotypes of the bacterium. This project shows the results of immunizing CBA/N mice intranasally and subcutaneously with PspA encapsulated into a novel polyanhydride nanoparticle delivery platform in attempt to create a protective protein-based pneumococcal vaccine against bacterial challenge

Covert deformed wing virus infections have long-term deleterious effects on honeybee foraging and survival

Several studies have suggested that covert stressors can contribute to bee colony declines. Here we provide a novel case study and show using radio-frequency identification (RFID) tracking technology that covert deformed wing virus (DWV) infections in adult honeybee workers seriously impact longterm foraging and survival under natural foraging conditions. In particular, our experiments show that adult workers injected with low doses of DWV experienced increased mortality rates, that DWV caused workers to start foraging at a premature age, and that the virus reduced the workers’ total activity span as foragers. Altogether, these results demonstrate that covert deformed wing virus infections have strongly deleterious effects on honey bee foraging and survival. These results are consistent with previous studies that suggested DWV to be an important contributor to the ongoing bee declines in Europe and the US. Overall, our study underlines the strong impact that covert pathogen infections can have on individual and group-level performance in bees

Design optimization of multibody systems by sequential approximation

Abstract. Design optimization of multibody systems is usually established by a direct coupling of multibody system analysis and mathematical programming algorithms. However, a direct coupling is hindered by the transient and computationally complex behavior of many multibody systems. In structural optimization often approximation concepts are used instead to interface numerical analysis and optimization. This paper shows that such an approach is valuable for the optimization of multibody systems as well. A design optimization tool has been developed for multibody systems that generates a sequence of approximate optimization problems. The approach is illustrated by three examples: an impact absorber, a slider-crank mechanism, and a stress-constrained four-bar mechanism. Furthermore, the consequences for an accurate and efficient accompanying design sensitivity analysis are discussed

Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles

Pneumococcal surface protein A (PspA) is a choline-binding protein which is a virulence factor found on the surface of all Streptococcus pneumoniae strains. Vaccination with PspA has been shown to be protective against a lethal challenge with S. pneumoniae, making it a promising immunogen for use in vaccines. Herein, the design of a PspA-based subunit vaccine using polyanhydride nanoparticles as a delivery platform is described. Nanoparticles based on sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH) and 1,8-bis-(p-carboxyphenoxy)-3,6- dioxaoctane (CPTEG), specifically 50:50 CPTEG:CPH and 20:80 CPH:SA, were used to encapsulate and release PspA. The protein released from the nanoparticle formulations retained its primary and secondary structure as well as its antigenicity. The released PspA was also biologically functional based on its ability to bind to apolactoferrin and prevent its bactericidal activity towards Escherichia coli. When the PspA nanoparticle formulations were administered subcutaneously to mice, the animals elicited a high titer and high avidity anti-PspA antibody response. Together, these studies provide a framework for the rational design of a vaccine against S. pneumoniae based on polyanhydride nanoparticles

Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in Drosophila.

Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs

Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in <i>Drosophila</i>.

Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the Drosophila larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs

The UA9 experimental layout

The UA9 experimental equipment was installed in the CERN-SPS in March '09 with the aim of investigating crystal assisted collimation in coasting mode. Its basic layout comprises silicon bent crystals acting as primary collimators mounted inside two vacuum vessels. A movable 60 cm long block of tungsten located downstream at about 90 degrees phase advance intercepts the deflected beam. Scintillators, Gas Electron Multiplier chambers and other beam loss monitors measure nuclear loss rates induced by the interaction of the beam halo in the crystal. Roman pots are installed in the path of the deflected particles and are equipped with a Medipix detector to reconstruct the transverse distribution of the impinging beam. Finally UA9 takes advantage of an LHC-collimator prototype installed close to the Roman pot to help in setting the beam conditions and to analyze the efficiency to deflect the beam. This paper describes in details the hardware installed to study the crystal collimation during 2010.Comment: 15pages, 11 figure, submitted to JINS

Management and Tillage Infl uence Barley Forage Productivity and Water Use in Dryland Cropping Systems

Annual cereal forages are resilient in water use (WU), water use efficiency (WUE), and weed control compared with grain crops in dryland systems. The combined influence of tillage and management systems on annual cereal forage productivity and WU is not well documented. We conducted a field study for the effects of tillage (no-till and tilled) and management (ecological and conventional) systems on WU and performance of forage barley (Hordeum vulgare L.) and weed biomass in two crop rotations (wheat [Triticum aestivum L.]–forage barley–pea [Pisum sativum L.] and wheat–forage barley–corn [Zea mays L.] –pea) from 2004 to 2010 in eastern Montana. Conventional management included recommended seeding rates, broadcast N fertilization, and short stubble height of wheat. Ecological management included 33% greater seeding rates, banded N fertilization at planting, and taller wheat stubble. Forage barley in ecological management had 28 more plants m–2, 2 cm greater height, 65 more tillers m–2, 606 kg ha–1 greater crop biomass, 3.5 kg ha–1 mm–1greater WUE, and 47% reduction in weed biomass at harvest than in conventional management. Pre-plant and post-harvest soil water contents were similar among tillage and management systems, but barley WU was 13 mm greater in 4-yr than 3-yr rotation. Tillage had little effect on barley performance and WU. Dryland forage barley with higher seeding rate and banded N fertilization in more diversified rotation produced more yield and used water more efficiently than that with conventional seeding rate, broadcast N fertilization, and less diversified rotation in the semiarid northern Great Plains