65 research outputs found
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Correlation of hole size in support windows with calculated yield strengths
Operating parameters of thin metal foils supported by thick Al grids in use with low energy, high beam current accelerator targets and a comparison between calculated and experimentally determined yield strengths for a series of materials and support grid hole size were investigated. Correlation between theory and experiment was excellent for foils made of Al, Ti, and Havar. Experimental tensile stress is modeled well by theoretical equations describing stress on thin circular membranes stretched to the elastic limit. (Application is in use of low energy accelerators in producing PET radiotracers for hospitals.
Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph
Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents. © 2011 Nature America, Inc. All rights reserved
Unifying view of mechanical and functional hotspots across class A GPCRs
G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors' functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify those sites whose functional role is more clearly detected by considering dynamical and mechanical properties. Of these sites with a genuine mechanical/dynamical character, the top ranking is amino acid 7x52, a previously unexplored, and experimentally verifiable key site for GPCR conformational response to ligand binding. \ua9 2017 Ponzoni et al
Chemogenomic Analysis of G-Protein Coupled Receptors and Their Ligands Deciphers Locks and Keys Governing Diverse Aspects of Signalling
Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs) is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI) is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic) or inhibitory (antagonistic) ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs) 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences
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Quantitative Clinical Evaluation of a Simultaneous PETI MRI Breast Imaging System
A prototype simultaneous PET-MRI breast scanner has been developed for conducting clinical studies with the goal of obtaining high resolution anatomical and functional information in the same scan which can lead to faster and better diagnosis, reduction of unwanted biopsies, and better patient care
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Use of PET in the understanding of Addiction
The objective of this research is to understand the factors contributing to addiction in the human and to understand the effects of addiction on the brain
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Production of Radioactive Iodine.
Probably the most widely used cyclotron produced radiohalogen is I-123. It has gradually replaced I-131 as the isotope of choice for diagnostic radiopharmaceuticals containing radioiodine. It gives a much lower radiation dose to the patient and the gamma ray energy of 159 keV is ideally suited for use in a gamma camera. The gamma ray will penetrate tissue very effectively without excessive radiation dose. For this reason, it has in many instances replaced the reactor produced iodine-131 (Lambrecht and Wolf 1973). A great number of radiopharmaceuticals have been labeled using I-123 and the number is increasing. One of the most promising uses of I-123 is in the imaging of monoclonal antibodies to localize and visualize tumors. However, preclinical and clinical experiences with radiolabeled antibodies have not realized the expectations regarding specificity and sensitivity of tumor localization with these agents. It appears that much of the administered activity is not associated with the tumor site and only a small fraction actually accumulates there. Work continues in this area and tumor-associated antigens can be targets for specific antibody reagents
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Study of coal oxidation by charged particle activation analysis
The technique of Charged Particle Activation Analysis (CPAA) was applied to study the characteristics of low temperature oxidation of coal. The following parameters were investigated: the kinetics of the adsorption of oxygen containing species; the elemental composition of the oxide layer and how deeply it extends into the particle; and the number of reactive sites on or in the surface. The results of this study are in agreement with those of other laboratories. These are summarized as follows: adsorption of oxygen onto most types of coal follow Elovich kinetics, i.e., a rapid uptake followed by a much more gradual uptake; oxygen adsorbed by low rank coals can form phenolic-OH or carbonyl groups; water sorption isotherms on low rank roals have a standard type II sigmoid shape typical of porous adsorbents; heat of desorption for macroscopic amounts of water off most coals is very near that of the heat of vaporization of water; and the apparent activation energies for oxidation are very low. From the data collected a mechanism for low temperature oxidation was proposed
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