34 research outputs found
An attempt to select suitable elements to characterize an ancient ceramic by neutron activation analysis
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A Philosophy for CNS Radiotracer Design
Conspectus Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test–retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available to predict bioavailability, blood–brain barrier (BBB) permeability, and the associated issues of nonspecific binding and metabolic stability. To evaluate the synthesized chemical library, researchers need to consider high-throughput affinity assays, the analysis of specific binding, and the importance of fast binding kinetics. Finally, we describe how we initially assess preclinical radiotracer imaging, using brain uptake, specific binding, and preliminary kinetic analysis to identify promising radiotracers that may be useful for human brain imaging. Although we discuss these five design components separately and linearly in this Account, in practice we develop new PET-based radiotracers using these design components nonlinearly and iteratively to develop new compounds in the most efficient way possible
Adsorption of gelatin during electrodeposition of copper and tin-copper alloys from acid sulfate electrolyte
International audienceAn acid Cu–Sn deposition bath was developed, and copper and copper–tin coatings were electrodeposited on polycrystalline platinum. The effect of gelatin on copper and copper–tin electrodeposition from acid sulfate solutions has been investigated by a variety of electrochemical methods (voltammetric studies and electrochemical quartz crystal microbalance) as well as by morphologic technique (scanning electron microscopy). The electrochemical results have shown that the overpotential is required when gelatin is added, indicating the presence of interaction between the additive and the coating. From the results of X-ray photoelectron spectroscopy, PM-IRRAS and cyclic voltammetry, gelatin was found to react with metal ions and platinum substrate. Adsorption of gelatin on the coating and platinum substrate is shown. Gelatin adsorption seemed to inhibit the initial nucleation of the copper and copper–tin electrodeposition, allowing homogeneous and smaller crystallites. Addition of gelatin was found to have an effect on reducing copper–tin alloys. The presence of gelatin impacts the crystal size and morphology of Cu–Sn deposits
Influence of organic additives on the initial stages of copper electrodeposition
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NEOLITHIC 'GREENSTONE' AXE BLADES FROM NORTHWESTERN ITALY ACROSS EUROPE: A FIRST PETROGRAPHIC COMPARISON*
Neolithic greenstone in Umbria, from the Bellucci Collection. Petrography, provenance, interpretation
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Nasal neuron PET imaging quantifies neuron generation and degeneration
Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics