Glucagonlike peptide 1 (GLP-1) is a physiological regulator of appetite, and long-acting GLP-1 receptor (GLP-1R) agonists lower food intake and body weight in both human and animal studies. The effects are mediated through brain GLP-1Rs, and several brain nuclei expressing the GLP-1R may be involved. To date, the mapping of the complete location of GLP-1R protein in the brain has been challenged by lack of good antibodies and the discrepancy between mRNA and protein, especially relevant in neuronal axonal processes. Here, we present a specific monoclonal GLP-1R antibody for immunohistochemistry with murine tissue and show detailed distribution of GLP-1R expression, as well as mapping of GLP-1R mRNA by nonradioactive in situ hybridization. Semiautomated image analysis was performed to map the GLP-1R distribution to atlas plates from the Allen Institute for Brain Science. The GLP-1R was abundantly expressed in numerous regions, including the septal nucleus, hypothalamus, and brain stem. GLP-1R protein expression was also observed on neuronal projections in brain regions devoid of any mRNA that has not been observed in earlier reports. Taken together, these findings provide knowledge on GLP-1R expression in neuronal cell bodies and neuronal projections.
We describe the fabrication of the two NuSTAR flight optics modules. The NuSTAR optics modules are glass-graphiteepoxy composite structures to be employed for the first time in space-based X-ray optics by NuSTAR, a NASA Small Explorer schedule for launch in February 2012. We discuss the optics manufacturing process, the qualification and environmental testing performed, and briefly discuss the results of X-ray performance testing of the two modules. The integration and alignment of the completed flight optics modules into the NuSTAR instrument is described as are the optics module thermal shields. OVERVIEW OF THE OPTICS MODULESThe Nuclear Spectroscopy Telescope Array (NuSTAR) is a NASA Small Explorer (SMEX) satellite mission scheduled for launch in February 2012. The NuSTAR experiment contains two telescopes each consisting of an optic and a CdZnTe focal plane detector separated from each other by a 10-meter deployable mast (figure 1). The experiment is an extension and improvement on the design successfully employed in the HEFT balloon experiment (Harrison et al. 2005 1 ). NuSTAR will operate in the 6-79 keV energy band. More details on the mission, the overall instrument design and performance requirements and scientific objectives can be found in Harrison et al. 2010 2 .A blowup of an individual optics module is also shown in figure 1. Each layer of the optic has an upper and lower conic shell (equivalent to the parabola-hyperbola sections of a Wolter-I optic). Each shell is composed of multiple thermally formed glass segments. Each piece of glass is coated with a depth-graded multilayer. The enhanced reflectivity provided by the multilayers, along with the shallow graze angles afforded by the focal length of the optics (10.15 meter) provide high effective area over the NuSTAR energy band of 6-79 keV, and a field of view of 12 arcminutes by 12 arcminutes. There are 133 concentric layers which together form each optic. The glass layers (a glass-epoxy-graphite composite structure) are built up on a Titanium mandrel. Titanium support spiders located on the top and bottom of each optic connect it to the optical bench. The compliant, radially-symmetric spiders accommodate thermal expansion effects as well as dynamic loading. Thin x-ray transparent thermal covers on the entrance and exit apertures of the optic reduce thermal gradients by blocking direct view of the sun and deep space. Two flight modules, FM1 and FM2, were fabricated. A third module, FM0, was fabricated earlier and has Pt/SiC multilayers on the inner 89 layers. FM0 is a potential flight spare and is available to provide for more extensive X-ray characterization than is permitted for either of the flight modules, given the compressed delivery schedule of the optics.
Approximately 382 million people worldwide have diabetes, 1 half of the prevalent cases are not known or diagnosed, half of those diagnosed are not treated, and half of those treated are not controlled. 2,3 One of the reasons for poor treatment compliance is injection anxiety causing 20% of insulin users to sometimes skip their injections, and 10% to restrict their number of injections. 4 As many as 94% of insulin users exhibit symptoms of anxiety, distress, or phobia around blood and injury from injections, 5 22% of insulin users have to mentally prepare themselves for injections, 6 and 33% of insulin users dread their injections. 7 This underlines why it is of high importance to develop needle designs that cause as little fear, injury, and pain as possible. Pain perception is one of the preferred methods to evaluate new needle design. 8-18 Studies have shown how needle diameter correlates with both the magnitude of the perceived pain, typically measured on visual analog scales (VASs), and with pain occurrence, that is, how often the needle causes pain sensation. 11-13 However, pain is a subjective measure with a large number of biasing variables causing data with high variance. Therefore, a high sample size is needed to detect differences in pain, which makes it both costly and time-consuming to carry out the clinical trials. One alternative way to obtain information about the needle impact on tissue is to use animal models, where histology can be used to assess tissue trauma from, for example, a needle insertion. The needle insertion can cause tissue bleeding and initiate inflammation in the tissue. Pig models are especially useful when examining skin disease and wound 531099D STXXX10.
In situ thermal remediation technologies provide efficient and reliable cleanup of contaminated soil and groundwater, but at a high cost of environmental impacts and resource depletion due to the large amounts of energy and materials consumed. This study provides a detailed investigation of four in situ thermal remediation technologies (steam enhanced extraction, thermal conduction heating, electrical resistance heating, and radio frequency heating) in order to (1) compare the life‐cycle environmental impacts and resource consumption associated with each thermal technology, and (2) identify options to reduce these adverse effects. The study identifies a number of options for environmental optimization of in situ thermal remediation. In general, environmental optimization can be achieved by increasing the percentage of heating supplied in off peak electricity demand periods as this reduces the pressure on coal‐based electricity and thereby reduces the environmental impacts due to electricity production by up to 10%. Furthermore, reducing the amount of concrete in the vapor cap by using a concrete sandwich construction can potentially reduce the environmental impacts due to the vapor cap by up to 75%. Moreover, a number of technology‐specific improvements were identified, for instance by the substitution of stainless steel types in wells, heaters, and liners used in thermal conduction heating, thus reducing the nickel consumption by 45%. The combined effect of introducing all the suggested improvements is a 10 to 21% decrease in environmental impacts and an 8 to 20% decrease in resource depletion depending on the thermal remediation technology considered. The energy consumption was found to be the main contributor to most types of environmental impacts; this will, however, depend on the electricity production mix in the studied region. The combined improvement potential is therefore to a large extent controlled by the reduction/improvement of energy consumption.
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