Method of treating fescue toxicosis with domperidone

A novel method for using domperidone, a dopamine receptor antagonist, for treating fescue toxicosis in animals is provided. Fescue toxicosis is caused by animals grazing on endophyte-infected fescue grass. Treatment of the animal with various dosages of domperidone results in effective management of the toxin. The domperidone treatments do not cause any substantial adverse behavioral or neurological side effects in the animal. Domperidone is a more effective treatment for fescue toxicosis than previously-known agents such a metoclopramide and sulpiride

TDRSS momentum unload planning

A knowledge-based system is described which monitors TDRSS telemetry for problems in the momentum unload procedure. The system displays TDRSS telemetry and commands in real time via X-windows. The system constructs a momentum unload plan which agrees with the preferences of the attitude control specialists and the momentum growth characteristics of the individual spacecraft. During the execution of the plan, the system monitors the progress of the procedure and watches for unexpected problems

The development of a program analysis environment for Ada

A unit level, Ada software module testing system, called Query Utility Environment for Software Testing of Ada (QUEST/Ada), is described. The project calls for the design and development of a prototype system. QUEST/Ada design began with a definition of the overall system structure and a description of component dependencies. The project team was divided into three groups to resolve the preliminary designs of the parser/scanner: the test data generator, and the test coverage analyzer. The Phase 1 report is a working document from which the system documentation will evolve. It provides history, a guide to report sections, a literature review, the definition of the system structure and high level interfaces, descriptions of the prototype scope, the three major components, and the plan for the remainder of the project. The appendices include specifications, statistics, two papers derived from the current research, a preliminary users' manual, and the proposal and work plan for Phase 2

Lead iodide X-ray and gamma-ray spectrometers for room and high temperature operation

In this study, we report on the results of the investigation of lead iodide material properties. The effectiveness of zone refining purification methods on the material purity is determined by ICP-MS and ICP-OES and correlated to the electrical and physical material properties. We show that this zone refining method is very efficient in removing impurities from lead iodide and we also determine the segregation coefficient for some of these impurities. Triple axis x- ray diffraction (TAD) analysis has been used to determine the crystalline perfection of the lead iodide after applying various cutting, etching, and fabrication methods. The soft lead iodide crystal was found to be damaged when cleaved by a razor blade, but by using a diamond wheel saw, followed by etching, the crystallinity of the material was improved, as observed by TAD. Low temperature photoluminescence also indicates an improvement in the material properties of the purified lead iodide. Electrical properties of lead iodide such as carrier mobility, were calculated based on carrier- phonon scattering. The results for the electrical properties were in good agreement with the experimental data

Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma

BACKGROUND: Glaucoma is a complex, multifactorial disease characterised by the loss of retinal ganglion cells and their axons leading to a decrease in visual function. The earliest events that damage retinal ganglion cells in glaucoma are currently unknown. Retinal ganglion cell death appears to be compartmentalised, with soma, dendrite and axon changes potentially occurring through different mechanisms. There is mounting evidence from other neurodegenerative diseases suggesting that neuronal dendrites undergo a prolonged period of atrophy, including the pruning of synapses, prior to cell loss. In addition, recent evidence has shown the role of the complement cascade in synaptic pruning in glaucoma and other diseases. RESULTS: Using a genetic (DBA/2J mouse) and an inducible (rat microbead) model of glaucoma we first demonstrate that there is loss of retinal ganglion cell synapses and dendrites at time points that precede axon or soma loss. We next determine the role of complement component 1 (C1) in early synaptic loss and dendritic atrophy during glaucoma. Using a genetic knockout of C1qa (D2.C1qa (-/-) mouse) or pharmacological inhibition of C1 (in the rat bead model) we show that inhibition of C1 is sufficient to preserve dendritic and synaptic architecture. CONCLUSIONS: This study further supports assessing the potential for complement-modulating therapeutics for the prevention of retinal ganglion cell degeneration in glaucoma. Mol Neurodegener 2016 Apr 6; 11(2):2

Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

Miniature gamma-ray camera for tumor localization

The overall goal of this LDRD project was to develop technology for a miniature gamma-ray camera for use in nuclear medicine. The camera will meet a need of the medical community for an improved means to image radio-pharmaceuticals in the body. In addition, this technology-with only slight modifications-should prove useful in applications requiring the monitoring and verification of special nuclear materials (SNMs). Utilization of the good energy resolution of mercuric iodide and cadmium zinc telluride detectors provides a means for rejecting scattered gamma-rays and improving the isotopic selectivity in gamma-ray images. The first year of this project involved fabrication and testing of a monolithic mercuric iodide and cadmium zinc telluride detector arrays and appropriate collimators/apertures. The second year of the program involved integration of the front-end detector module, pulse processing electronics, computer, software, and display